1.Design, synthesis and anti-Alzheimer's disease activity evaluation of cinnamyl triazole compounds
Wen-ju LEI ; Zhong-di CAI ; Lin-jie TAN ; Mi-min LIU ; Li ZENG ; Ting SUN ; Hong YI ; Rui LIU ; Zhuo-rong LI
Acta Pharmaceutica Sinica 2025;60(1):150-163
19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound
2.Research Status of Caenorhabditis elegans Model in Toxicology and Its Applica-tions in Forensic Science
Zhuo LI ; Yi-Ru ZENG ; Zhi-Long SHU ; Xue-Hong SUN ; Kui ZHANG
Journal of Forensic Medicine 2025;41(2):136-143
Caenorhabditis elegans,as an emerging model organism,has been widely used in multiple disciplines such as medicine,life science,and environmental science in recent years,due to its charac-teristics of short life cycle,clear genetic background,highly conserved evolution,complete genome analysis and excellent fitting between experimental data and human results.It also shows unique advan-tages in the field of toxicology.This paper summarizes its advantages in toxicological research starting from the biological characteristics of C.elegans,introduces the toxicological research methods and progress based on the C.elegans model,focuses on demonstrating its applications in environmental fo-rensic medicine and forensic toxicology,and looks forward to the application of the relevant results in the field of forensic science.
3.Clinical application of split liver transplantation: a single center report of 203 cases
Qing YANG ; Shuhong YI ; Binsheng FU ; Tong ZHANG ; Kaining ZENG ; Xiao FENG ; Jia YAO ; Hui TANG ; Hua LI ; Jian ZHANG ; Yingcai ZHANG ; Huimin YI ; Haijin LYU ; Jianrong LIU ; Gangjian LUO ; Mian GE ; Weifeng YAO ; Fangfei REN ; Jinfeng ZHUO ; Hui LUO ; Liping ZHU ; Jie REN ; Yan LYU ; Kexin WANG ; Wei LIU ; Guihua CHEN ; Yang YANG
Chinese Journal of Surgery 2024;62(4):324-330
Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.
4.Clinical application of split liver transplantation: a single center report of 203 cases
Qing YANG ; Shuhong YI ; Binsheng FU ; Tong ZHANG ; Kaining ZENG ; Xiao FENG ; Jia YAO ; Hui TANG ; Hua LI ; Jian ZHANG ; Yingcai ZHANG ; Huimin YI ; Haijin LYU ; Jianrong LIU ; Gangjian LUO ; Mian GE ; Weifeng YAO ; Fangfei REN ; Jinfeng ZHUO ; Hui LUO ; Liping ZHU ; Jie REN ; Yan LYU ; Kexin WANG ; Wei LIU ; Guihua CHEN ; Yang YANG
Chinese Journal of Surgery 2024;62(4):324-330
Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.
5.Antimicrobial resistance profile of clinical isolates in hospitals across China:report from the CHINET Antimicrobial Resistance Surveillance Program,2023
Yan GUO ; Fupin HU ; Demei ZHU ; Fu WANG ; Xiaofei JIANG ; Yingchun XU ; Xiaojiang ZHANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Yuling XIAO ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Jingyong SUN ; Qing CHEN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yunmin XU ; Sufang GUO ; Yanyan WANG ; Lianhua WEI ; Keke LI ; Hong ZHANG ; Fen PAN ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Wei LI ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Qian SUN ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanqing ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Hua FANG ; Penghui ZHANG ; Bixia YU ; Ping GONG ; Haixia SHI ; Kaizhen WEN ; Yirong ZHANG ; Xiuli YANG ; Yiqin ZHAO ; Longfeng LIAO ; Jinhua WU ; Hongqin GU ; Lin JIANG ; Meifang HU ; Wen HE ; Jiao FENG ; Lingling YOU ; Dongmei WANG ; Dong'e WANG ; Yanyan LIU ; Yong AN ; Wenhui HUANG ; Juan LI ; Quangui SHI ; Juan YANG ; Abulimiti REZIWAGULI ; Lili HUANG ; Xuejun SHAO ; Xiaoyan REN ; Dong LI ; Qun ZHANG ; Xue CHEN ; Rihai LI ; Jieli XU ; Kaijie GAO ; Lu XU ; Lin LIN ; Zhuo ZHANG ; Jianlong LIU ; Min FU ; Yinghui GUO ; Wenchao ZHANG ; Zengguo WANG ; Kai JIA ; Yun XIA ; Shan SUN ; Huimin YANG ; Yan MIAO ; Jianping WANG ; Mingming ZHOU ; Shihai ZHANG ; Hongjuan LIU ; Nan CHEN ; Chan LI ; Cunshan KOU ; Shunhong XUE ; Jilu SHEN ; Wanqi MEN ; Peng WANG ; Xiaowei ZHANG ; Xiaoyan ZENG ; Wen LI ; Yan GENG ; Zeshi LIU
Chinese Journal of Infection and Chemotherapy 2024;24(6):627-637
Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0% were gram-positive and 71.0% 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) (MRSA,MRSE and MRCNS) was 29.6%,81.9% and 78.5%,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9% of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4% of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had 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 93.1% in the isolates from children and and 95.9% in the isolates from adults.The resistance rate to carbapenems was lower than 15.0% for most Enterobacterales species except for Klebsiella,22.5% and 23.6% of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6% to 10.0%.The resistance rate to imipenem and meropenem was 21.9% and 17.4% for Pseudomonas aeruginosa,respectively,and 67.5% and 68.1% for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.
6.Antimicrobial resistance profile of clinical isolates in hospitals across China:report from the CHINET Antimicrobial Resistance Surveillance Program,2023
Yan GUO ; Fupin HU ; Demei ZHU ; Fu WANG ; Xiaofei JIANG ; Yingchun XU ; Xiaojiang ZHANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Yuling XIAO ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Jingyong SUN ; Qing CHEN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yunmin XU ; Sufang GUO ; Yanyan WANG ; Lianhua WEI ; Keke LI ; Hong ZHANG ; Fen PAN ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Wei LI ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Qian SUN ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanqing ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Hua FANG ; Penghui ZHANG ; Bixia YU ; Ping GONG ; Haixia SHI ; Kaizhen WEN ; Yirong ZHANG ; Xiuli YANG ; Yiqin ZHAO ; Longfeng LIAO ; Jinhua WU ; Hongqin GU ; Lin JIANG ; Meifang HU ; Wen HE ; Jiao FENG ; Lingling YOU ; Dongmei WANG ; Dong'e WANG ; Yanyan LIU ; Yong AN ; Wenhui HUANG ; Juan LI ; Quangui SHI ; Juan YANG ; Abulimiti REZIWAGULI ; Lili HUANG ; Xuejun SHAO ; Xiaoyan REN ; Dong LI ; Qun ZHANG ; Xue CHEN ; Rihai LI ; Jieli XU ; Kaijie GAO ; Lu XU ; Lin LIN ; Zhuo ZHANG ; Jianlong LIU ; Min FU ; Yinghui GUO ; Wenchao ZHANG ; Zengguo WANG ; Kai JIA ; Yun XIA ; Shan SUN ; Huimin YANG ; Yan MIAO ; Jianping WANG ; Mingming ZHOU ; Shihai ZHANG ; Hongjuan LIU ; Nan CHEN ; Chan LI ; Cunshan KOU ; Shunhong XUE ; Jilu SHEN ; Wanqi MEN ; Peng WANG ; Xiaowei ZHANG ; Xiaoyan ZENG ; Wen LI ; Yan GENG ; Zeshi LIU
Chinese Journal of Infection and Chemotherapy 2024;24(6):627-637
Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0% were gram-positive and 71.0% 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) (MRSA,MRSE and MRCNS) was 29.6%,81.9% and 78.5%,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9% of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4% of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had 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 93.1% in the isolates from children and and 95.9% in the isolates from adults.The resistance rate to carbapenems was lower than 15.0% for most Enterobacterales species except for Klebsiella,22.5% and 23.6% of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6% to 10.0%.The resistance rate to imipenem and meropenem was 21.9% and 17.4% for Pseudomonas aeruginosa,respectively,and 67.5% and 68.1% for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.
7.Progress in the mechanism of stem cell derived extracellular vesicles in treatment of early onset ovarian insufficiency
Wen-Zhuo ZENG ; Xin-Yi HUANG ; Shu-Li XU ; Xiao-Feng SUN
Medical Journal of Chinese People's Liberation Army 2023;48(12):1467-1472
Premature ovarian insufficient(POI)is one of the important causes of infertility in woman of reproductive age.At present,the clinical treatment of POI is limited and the therapeutic effect is not ideal.Extracellular vesicles derived from stem cells have attracted the attention of many researchers at home and abroad as a new cell-free therapy.Many animal experiment study shows that a variety of extracellular vesicles from stem cells carry microRNAs,lncRNAs,lipids,proteins,and other bioactive substances,improve ovarian function,affect granulosa cell proliferation and apoptosis,promote ovarian angiogenesis,and reduce oxidative stress response,thus playing a therapeutic role on POI.This article will review the mechanisms of extracellular vesicles in treatment of POI,and provide evidence for the application of extracellular vesicles in clinical treatment of POI.
8.Comparison of the predictive value of anthropometric indicators for the risk of benign prostatic hyperplasia in southern China.
Meng-Jun HUANG ; Yan-Yi YANG ; Can CHEN ; Rui-Xiang LUO ; Chu-Qi WEN ; Yang LI ; Ling-Peng ZENG ; Xiang-Yang LI ; Zhuo YIN
Asian Journal of Andrology 2023;25(2):265-270
This study aimed to compare the predictive value of six selected anthropometric indicators for benign prostatic hyperplasia (BPH). Males over 50 years of age who underwent health examinations at the Health Management Center of the Second Xiangya Hospital, Central South University (Changsha, China) from June to December 2020 were enrolled in this study. The characteristic data were collected, including basic anthropometric indices, lipid parameters, six anthropometric indicators, prostate-specific antigen, and total prostate volume. The odds ratios (ORs) with 95% confidence intervals (95% CIs) for all anthropometric parameters and BPH were calculated using binary logistic regression. To assess the diagnostic capability of each indicator for BPH and identify the appropriate cutoff values, receiver operating characteristic (ROC) curves and the related areas under the curves (AUCs) were utilized. All six indicators had diagnostic value for BPH (all P ≤ 0.001). The visceral adiposity index (VAI; AUC: 0.797, 95% CI: 0.759-0.834) had the highest AUC and therefore the highest diagnostic value. This was followed by the cardiometabolic index (CMI; AUC: 0.792, 95% CI: 0.753-0.831), lipid accumulation product (LAP; AUC: 0.766, 95% CI: 0.723-0.809), waist-to-hip ratio (WHR; AUC: 0.660, 95% CI: 0.609-0.712), waist-to-height ratio (WHtR; AUC: 0.639, 95% CI: 0.587-0.691), and body mass index (BMI; AUC: 0.592, 95% CI: 0.540-0.643). The sensitivity of CMI was the highest (92.1%), and WHtR had the highest specificity of 94.1%. CMI consistently showed the highest OR in the binary logistic regression analysis. BMI, WHtR, WHR, VAI, CMI, and LAP all influence the occurrence of BPH in middle-aged and older men (all P ≤ 0.001), and CMI is the best predictor of BPH.
Middle Aged
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Male
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Humans
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Aged
;
Prostatic Hyperplasia
;
Obesity/epidemiology*
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Body Mass Index
;
China/epidemiology*
;
Waist-Height Ratio
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ROC Curve
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Waist Circumference
;
Risk Factors
9.Optimization of processing technology of braised Rehmanniae Radix based on multiple indexes and response surface technology and correlation between components and color.
Yang XIE ; Ling-Yun ZHONG ; Xiao XUE ; Zhuo WANG ; Jin-Ju SONG ; Jia-Qing LI ; Qing ZHANG ; Yi-Bin WANG ; Yan ZENG
China Journal of Chinese Materia Medica 2022;47(18):4927-4937
This study aims to explore the key factors influencing the processing of braised Rehmanniae Radix, optimize the processing, and determine the correlation between the components in different processed products and chroma values, which is expected to add quantitative indexes for the processing of braised Rehmanniae Radix and better control the processing. The weights of the indexes catalpol, rehmannioside D, verbascoside, isoacteoside, 5-hydroxymethylfurfural, reducing sugar, and appearance were calculated based on analytic hierarchy process(AHP) in combination with coefficient of variation, and the overall desirability(OD) was obtained. Box-Behnken design was used to explore the optimal amount of water added, time for soaking with rice wine, and steaming time in the processing of braised Rehmanniae Radix. Colorimeter was employed to determine the chroma of 17 samples and raw samples, and SPSS, Prism, and other software to investigate the correlation between the components in braised Rehmanniae Radix and the chroma values. The results showed that each factor influenced the processing, and the influence followed the order of steaming time>amount of water added>time for soaking with rice wine. The optimal processing process is as below: A total of 100 g medicinal material was added with 7 times of water, followed by soaking with rice wine for 5 h and steaming in a pot for 6 h. The correlation analysis suggested the extremely significantly positive correlation between L~* and content of catalpol, between a~* and 5-hydroxymethylfurfural content, and between b~* and catalpol content, and the extremely significantly negative correlation between L~* and the content of 5-hydroxymethylfurfural and reducing sugar, and between b~* and the content of 5-hydroxymethylfural and reducing sugar. In this experiment, response surface methodology was used to optimize the processing technology of braised Rehmanniae Radix and the optimized process was rational and feasible. The content of chemical components in braised Rehmanniae Radix was significantly correlated with the chroma. This study provided a new method for the quality evaluation of braised Rehmanniae Radix.
Drugs, Chinese Herbal/chemistry*
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Excipients
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Furaldehyde/analogs & derivatives*
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Iridoid Glucosides
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Plant Extracts
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Rehmannia/chemistry*
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Sugars
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Technology
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Water
10.Research advances on the interaction between Pseudomonas aeruginosa bacteriophages and the host.
Xi SHI ; Zhuo ZENG ; Yi Ming ZHANG ; Zi Chen YANG ; Yi Zhi PENG
Chinese Journal of Burns 2022;38(9):849-853
Pseudomonas aeruginosa is the most common pathogen of burn wound infection. It can encode a variety of virulence factors and is highly pathogenic, which can lead to poor prognosis and high mortality. In order to research a new method to combat Pseudomonas aeruginosa infection, researchers have observed a wide range of interactions between the bacteriophages and the host. Bacteriophages influence and even dominate the structure, movement, and metabolism of host bacteria through a variety of mechanisms, catalyze the evolution of the host, and are also an important factor in host environmental adaptability and pathogenicity. In this paper, the interaction between Pseudomonas aeruginosa bacteriophages and the host is reviewed from the single cell level and the population level. Understanding these interactions could provide new idea for the treatment of Pseudomonas aeruginosa clinical infections, provides a basis for future development of antimicrobial agents and guides the treatment of burn infections.
Bacteriophages
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Burns/therapy*
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Humans
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Pseudomonas Infections/microbiology*
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Pseudomonas Phages
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Pseudomonas aeruginosa
;
Virulence Factors

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