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Pathogenic spectrum and epidemiological characteristics of diarrhea patients in Tianjin during 2015-2017 天津市2015-2017年腹泻患者病原谱及流行病学特征分析
Pub Date : 2019-04-15 DOI: 10.3760/CMA.J.ISSN.1000-6680.2019.04.004
Lu Gao
Objective To investigate the pathogenic spectrum and epidemiological characteristics of acute diarrhea patients in Tianjin. Methods A total of 1 536 stool samples of diarrhea patients were collected from hospitals between 2015 and 2017. Viral nucleic acids were detected by real-time polymerase chain reaction. Selective medium was used to culture bacteria. Drug susceptibility tests were performed by Kirby-Bauer disk diffusion method recommended by the Association for Standardization of Clinical Laboratories. χ2 test was used for statistical analysis. Results In the stool samples of 1 536 cases of diarrhea, one enteric bacterium was detected in 109 samples with the positive rate of 7.10%, one enterovirus was detected in 171 samples with the positive rate of 11.13%, mixed infection was detected in 20 samples with positive rate of 1.30%, including 8 samples with enteric bacterium and enterovirus and 12 samples with double enterovirus. The total detection rate of diarrhea cases was 19.53%. Norovirus, vibrio parahaemolyticus, rotavirus, Salmonella, stellate virus and sapovirus ranked the top six in the detection rate. The total detection rate curve of bacteria showed a single peak, mainly in August, while the total detection rate curve of the virus showed a double peak, which was from May to June and from November to December. The positive rate of bacteria in patients aged over 30 years old was 9.82% (75/764), while that in those aged less than 30 years old was 5.44% (42/772). The difference was statistically significant (χ2=10.451, P<0.01). The positive rate of viral pathogen in patients aged no less than 25 years old was 10.02% (91/908), while that in those aged less than 25 years old was 17.83% (112/628). The difference was statistically significant (χ2=19.755, P<0.01). Salmonella, Shigella and vibrio parahaemolyticus were resistant to ampicillin in varying degrees. Conclusions The positive rate curves of bacteria and virus are obviously different, showing a trend of "bacterial single peak and viral double peak" . Bacteria mainly infect people aged over 30 years old, while the virus mainly infects people under 25 years old. The main pathogens of diarrhea are norovirus, vibrio parahaemolyticus and rotavirus. Key words: Diarrhea; Population surveillance; Pathogen spectrum
目的了解天津市急性腹泻患者的病原谱及流行病学特征。方法收集2015 - 2017年医院腹泻患者粪便标本1 536份。实时聚合酶链反应检测病毒核酸。采用选择性培养基培养细菌。药敏试验采用临床实验室标准化协会推荐的Kirby-Bauer圆盘扩散法。采用χ2检验进行统计学分析。结果1 536例腹泻患者的粪便标本中,检出1种肠道细菌109例,阳性率为7.10%;检出1种肠道病毒171例,阳性率为11.13%;检出混合感染20例,阳性率为1.30%,其中混合感染8例,双感染12例。腹泻病例总检出率为19.53%。诺如病毒、副溶血性弧菌、轮状病毒、沙门菌、星状病毒和萨帕病毒检出率居前6位。细菌总检出率曲线为单峰,主要出现在8月;病毒总检出率曲线为双峰,主要出现在5 - 6月和11 - 12月。30岁以上患者细菌阳性率为9.82%(75/764),30岁以下患者细菌阳性率为5.44%(42/772)。差异有统计学意义(χ2=10.451, P<0.01)。年龄不小于25岁的患者病毒病原体阳性率为10.02%(91/908),年龄小于25岁的患者病毒病原体阳性率为17.83%(112/628)。差异有统计学意义(χ2=19.755, P<0.01)。沙门氏菌、志贺氏菌和副溶血性弧菌对氨苄西林均有不同程度的耐药。结论细菌和病毒的阳性率曲线存在明显差异,呈“细菌单峰、病毒双峰”的趋势。细菌主要感染30岁以上人群,而病毒主要感染25岁以下人群。腹泻的主要病原体为诺如病毒、副溶血性弧菌和轮状病毒。关键词:腹泻;人口监测;病原谱
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引用次数: 0
Treatment status of maternal syphilis infection and factors associated with their adverse pregnant outcomes in Shanghai during 2013-2015 2013-2015年上海市孕产妇梅毒感染治疗现状及其不良妊娠结局相关因素分析
Pub Date : 2019-04-15 DOI: 10.3760/CMA.J.ISSN.1000-6680.2019.04.005
Yibin Gu, Yang Li, Liping Zhu, L. Du, Qi Zhao, Biao Xu
Objective To analyze the factors associated with syphilis treatment compliance and adverse pregnant outcomes among pregnant women with syphilis in Shanghai. Methods The prospective cohort was established based on maternal syphilis monitoring system of Shanghai, which included all the pregnant women diagnosed with syphilis during Jan 2013 to Dec 2015. A total of 1 717 pregnant women with syphilis were recruited at the baseline, and 1 147 of them were followed up during treatment and their pregnancy, and the delivery outcomes were recorded. The information of testing/treatment of pregnant women with syphilis and health outcomes of infants were collected. Chi-square test was used for univariate analysis and logistic regression model was used to identify the factors associated with syphilis treatment and adverse pregnant outcomes. Results A total of 685 participants received syphilis treatment during pregnancy, with the treatment rate of 59.7%. Among them, 397(34.6%) patients underwent two courses of complete treatment. The poor educated, unemployed/job-waiting or multipara population had poor compliance to treatment. Only 34.9% (142/407) of cases diagnosed at last trimester received syphilis treatment and 10.1%(41/407) completed the treatment. The proportion of non-treponemal conversion were higher in subjects who received syphilis treatment during pregnancy than those who did not (39.1%[268/285] vs 3.7%[17/462]). Complete syphilis treatment during pregnancy was protective factor to decrease neonatal death adjusted relative risk ([aRR]=0.05, 95%CI: 0.01-0.37, P=0.003) and prematurity/low birth weight (aRR=0.44, 95%CI: 0.27-0.70, P=0.001). Strong positive non-treponemal result before delivery increased the risks of neonatal death (aRR=12.89, 95%CI: 1.70-100.43, P=0.014) and prematurity/low birth weight (aRR=12.78, 95%CI: 152-5.06, P=0.001). Conclusions Factors such as educational level, employment status, and maternal history will affect the compliance of syphilis treatment during pregnancy. Early diagnosis and complete treatment course of syphilis could improve the pregnant outcomes and the health status of infants. Key words: Syphilis; Mother-to-child transmission; Treatment; Adverse pregnant outcome
目的分析上海地区梅毒孕妇梅毒治疗依从性及不良妊娠结局的相关因素。方法以上海市孕产妇梅毒监测系统为基础,建立前瞻性队列,纳入2013年1月至2015年12月诊断为梅毒的所有孕妇。在基线时,共招募了1717名患有梅毒的孕妇,其中1147人在治疗和怀孕期间接受了随访,并记录了分娩结果。收集了孕妇梅毒检测/治疗和婴儿健康结果的信息。卡方检验用于单因素分析,逻辑回归模型用于确定与梅毒治疗和不良妊娠结局相关的因素。结果共有685名受试者在妊娠期间接受了梅毒治疗,治疗率为59.7%,其中397名(34.6%)患者接受了两个疗程的完整治疗。受教育程度低、待业/待业或多胎人群对治疗的依从性较差。在妊娠晚期诊断的病例中,只有34.9%(142/407)接受了梅毒治疗,10.1%(41/407)完成了治疗。妊娠期接受梅毒治疗的受试者的非密螺旋体转化率高于未接受梅毒治疗者(39.1%[268/285]vs 3.7%[17/462])。妊娠期完全梅毒治疗是降低新生儿死亡调整后相对风险([aRR]=0.05,95%CI:0.0.01-0.37,P=0.003)和早产/低出生体重的保护因素(aRR=0.44,95%CI:0.27-0.70,P=0.001)。分娩前强阳性非密螺旋体检查结果增加了新生儿死亡的风险(aRR=12.89,95%CI:1.70-100.43,P=0.014)和早产/低出生体重的风险(a RR=12.78,95%CI:152-5.06,P=0.001,孕妇病史会影响妊娠期梅毒治疗的依从性。梅毒的早期诊断和完整的治疗过程可以改善妊娠结局和婴儿的健康状况。关键词:梅毒;母婴传播;治疗;不良妊娠结局
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引用次数: 1
Comparative study of clinical characteristics between adult patients with adenovirus type 7 and type 55 infections in China during 2012-2018 2012-2018年中国成人7型和55型腺病毒感染临床特征比较研究
Pub Date : 2019-04-15 DOI: 10.3760/CMA.J.ISSN.1000-6680.2019.04.001
Xia Mei, Weiwei Chen, Wen-gang Li, Wen Xu, Zhe Xu, B. Tu, E. Qin, Lei Shi, Peng Zhao, Min Zhao
Objective To compare and explore the differences of clinical characteristics between human adenovirus type 7 (HAdV7) and type 55 (HAdV55) infections in adults, and to provide evidences for clinical management. Methods The data of clinical manifestations, laboratory examinations, chest computed tomography and prognosis of 214 cases with HAdV7 and 235 cases with HAdV55 infections from 2012 to 2018 were retrospectively collected and analyzed. The chi-square test was used for the categorical variables, and the rank sum test was used for the continuous variables of non-normal distribution. Results Compared with patients in HAdV55, those in HAdV7 group displayed more diarrhea (12.1%[26/214] vs 2.6%[6/235], χ2=15.583), more laryngeal lymphatic follicles (33.2%[71/214] vs 17.9%[42/235], χ2=23.566), more tonsil enlargement (56.5%[121/214] vs 20.0%[47/235], χ2=63.870) with secretions (33.2%[71/214] vs 11.5%[27/235], χ2=30.878), more leukocytosis (24.8%[53/214] vs 14.0%[33/235], χ2=8.318), more monocytosis (78.0%[167/214] vs 52.8%[124/235], χ2=31.364), more thrombocytosis (7.1%[15/212] vs 3.8%[9/235], χ2=5.835), more elevated level of C-reactive protein (80.8%[97/120] vs 64.3%[137/213], χ2=10.020), more abnormalities of liver function (alamne aminotransferase [ALT]: 13.5%[28/207] vs 5.6%[13/232], χ2=8.111) and myocardial enzymes (creatine kinase [CK]: 37.6%[77/205] vs 26.4% [61/231], χ2=6.246), creatine kinase isoenzymes ([CK-MB]: 35.6% [73/205] vs 11.1% [24/216], χ2=35.600), and all the differences were statistically significant (all P<0.05, 0.01). Compared with patients in HAdV7 group, those in HAdV55 group displayed longer duration of diseases (7[5] days vs 6[5] days, Z=-2.632), more sore throat (72.8% [171/235] vs 62.1% [133/214], χ2=0.016), more headache (62.1% [146/235] vs 16.4% [35/214], χ2=97.527), more pharyngeal congestion (93.6% [220/235] vs 74.8%[160/214], χ2=30.602), more leukopenia (14.0% [33/235] vs 24.8% [53/214], χ2=8.318), and more elevated level of lactate dehydrogenase (12.6% [29/230] vs 6.3% [13/205], χ2=4.881), more pneumonia (71.5% [168/235] vs 31.8% [68/214], χ2=70.846) (all P<0.05, 0.01). Conclusions The clinical characteristics of HAdV7 and HAdV55 infections in adults are different. The type 55 infection is more likely to develop to pneumonia, while the type 7 infection has wider tissue tropism. Key words: Adenovirus infections, human; Pneumonia, viral; Clinical characteristics; Case analysis
目的比较和探讨成人7型腺病毒(HAdV7)与55型腺病毒(HAdV55)感染的临床特征差异,为临床治疗提供依据。方法回顾性收集2012 ~ 2018年214例HAdV7感染和235例HAdV55感染的临床表现、实验室检查、胸部ct及预后资料进行分析。分类变量采用卡方检验,非正态分布的连续变量采用秩和检验。结果与HAdV55的患者相比,那些在HAdV7集团呈现出更多的腹泻(12.1%(26/214)和2.6%(6/235),χ2 = 15.583),更多的喉淋巴滤泡(33.2%(71/214)和17.9%(42/235),χ2 = 23.566),更多的扁桃体肿大(56.5%(121/214)和20.0%(47/235),χ2 = 63.870)和分泌物(33.2%(71/214)和11.5%(27/235),χ2 = 30.878),更多的白细胞增多(24.8%(53/214)和14.0%(33/235),χ2 = 8.318),更多的单核细胞增多症(78.0%(167/214)和52.8%(124/235),χ2 = 31.364),血小板增多(7.1%[15/212]对3.8%[9/235],χ2=5.835), c反应蛋白水平升高(80.8%[97/120]对64.3%[137/213],χ2=10.020),肝功能异常(谷氨转氨酶[ALT]: 13.5%[28/207]对5.6%[13/232],χ2=8.111),心肌酶(肌酸激酶[CK]: 37.6%[77/205]对26.4% [61/231],χ2=6.246),肌酸激酶同工酶([CK- mb]):35.6% [73/205] vs 11.1% [24/216], χ2=35.600),差异均有统计学意义(P均<0.05,0.01)。与HAdV7组患者相比,HAdV55组患者病程更长(7 bbb d vs 6 bbb d, Z=-2.632),更容易出现喉咙痛(72.8% [171/235]vs 62.1% [133/214], χ2=0.016),更容易出现头痛(62.1% [146/235]vs 16.4% [35/214], χ2=97.527),更容易出现咽阻塞(93.6% [220/235]vs 74.8%[160/214], χ2=30.602),更容易出现白细胞减少(14.0% [33/235]vs 24.8% [53/214], χ2=8.318),更容易出现乳酸脱氢酶升高(12.6% [29/230]vs 6.3% [13/205], χ2=4.881)。肺炎发生率为71.5%[168/235]比31.8% [68/214],χ2=70.846 (P均<0.05,0.01)。结论成人HAdV7和HAdV55感染的临床特点不同。55型感染更容易发展为肺炎,而7型感染具有更广泛的组织亲和性。关键词:腺病毒感染;人;病毒性肺炎;临床特点;案例分析
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引用次数: 0
Efficacy and safety of high-dose caspofungin in the treatment of invasive pulmonary aspergillosis 大剂量卡泊芬净治疗侵袭性肺曲霉病的疗效和安全性
Pub Date : 2019-03-15 DOI: 10.3760/CMA.J.ISSN.1000-6680.2019.03.002
Ling-Hong Zhou, Xuan Wang, Rui-ying Wang, Hua-zhen Zhao, Ying-Kui Jiang, Jia-Hui Cheng, Jingyun Ye, Li-ping Huang
Objective To investigate the clinical efficacy and safety of high-dose caspofungin (70 mg/d) as initial or salvage treatment for invasive pulmonary aspergillosis. Methods Twenty-one patients with proven or probable invasive pulmonary aspergillosis from June 2014 to October 2017 in Huashan Hospital, Fudan University were retrospectively reviewed. According to the anti-fungal treatment before high-dose caspofungin application, patients were divided into initial treatment group and salvage treatment group. Patients′ clinical data and laboratory data were collected. The characteristics, clinical efficacy, adverse reactions, one-year survival rate and the overall effective rate were evaluated. The prognosis of the two groups was compared by Kaplan-Meier analysis. Results Twenty of the 21 patients opportunistic acquired invasive pulmonary aspergillosis during the treatment of underlying diseases. Five patients were initially treated with high-dose caspofungin for 68 (62) days. At week 12, one patient achieved complete response, 3 patients achieved partial response, and the overall effective rate was 80%(4/5). Sixteen patients received caspofungin as salvage therapy for 66.50 (58) days, of which one patient got complete response at week 12, 10 had partial response, and the overall effective rate was 68.75%(11/16). One-year follow-up showed that no patient died in the initial treatment group, and the one-year survival rate was 100%(5/5). In salvage treatment group, 3 patients died of pulmonary bacterial infections and the one-year survival rate was 81.25%(13/16). During treatment, one patient had elevated total bilirubin, which was possibly associated with high-dose caspofungin. Conclusions High-dose caspofungin regimen has good efficacy and safety, both for initial treatment and salvage therapy in patients with invasive pulmonary aspergillosis. Key words: Invasive pulmonary aspergillosis; Caspofungin; High-dose; Efficacy; Safety
目的探讨大剂量卡泊芬净(70mg /d)作为侵袭性肺曲霉病初始或挽救治疗的临床疗效和安全性。方法回顾性分析2014年6月至2017年10月复旦大学华山医院确诊或疑似侵袭性肺曲霉病患者21例。根据大剂量卡泊芬净应用前的抗真菌治疗情况,将患者分为初始治疗组和抢救治疗组。收集患者的临床资料和实验室资料。观察两组患者的特点、临床疗效、不良反应、1年生存率及总有效率。采用Kaplan-Meier分析比较两组患者的预后。结果21例患者中有20例在治疗基础疾病过程中发生机会性获得性侵袭性肺曲霉病。5例患者最初使用高剂量caspofungin治疗68(62)天。第12周,1例患者完全缓解,3例患者部分缓解,总有效率为80%(4/5)。16例患者接受caspofungin补救性治疗66.50(58)天,其中第12周完全缓解1例,部分缓解10例,总有效率为68.75%(11/16)。1年随访显示,初始治疗组无患者死亡,1年生存率为100%(5/5)。抢救治疗组3例患者死于肺部细菌感染,1年生存率为81.25%(13/16)。在治疗期间,一名患者总胆红素升高,这可能与高剂量卡泊芬金有关。结论大剂量卡泊芬净方案对侵袭性肺曲霉病的初始治疗和抢救治疗均具有良好的疗效和安全性。关键词:侵袭性肺曲霉病;Caspofungin;大剂量;功效;安全
{"title":"Efficacy and safety of high-dose caspofungin in the treatment of invasive pulmonary aspergillosis","authors":"Ling-Hong Zhou, Xuan Wang, Rui-ying Wang, Hua-zhen Zhao, Ying-Kui Jiang, Jia-Hui Cheng, Jingyun Ye, Li-ping Huang","doi":"10.3760/CMA.J.ISSN.1000-6680.2019.03.002","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1000-6680.2019.03.002","url":null,"abstract":"Objective \u0000To investigate the clinical efficacy and safety of high-dose caspofungin (70 mg/d) as initial or salvage treatment for invasive pulmonary aspergillosis. \u0000 \u0000 \u0000Methods \u0000Twenty-one patients with proven or probable invasive pulmonary aspergillosis from June 2014 to October 2017 in Huashan Hospital, Fudan University were retrospectively reviewed. According to the anti-fungal treatment before high-dose caspofungin application, patients were divided into initial treatment group and salvage treatment group. Patients′ clinical data and laboratory data were collected. The characteristics, clinical efficacy, adverse reactions, one-year survival rate and the overall effective rate were evaluated. The prognosis of the two groups was compared by Kaplan-Meier analysis. \u0000 \u0000 \u0000Results \u0000Twenty of the 21 patients opportunistic acquired invasive pulmonary aspergillosis during the treatment of underlying diseases. Five patients were initially treated with high-dose caspofungin for 68 (62) days. At week 12, one patient achieved complete response, 3 patients achieved partial response, and the overall effective rate was 80%(4/5). Sixteen patients received caspofungin as salvage therapy for 66.50 (58) days, of which one patient got complete response at week 12, 10 had partial response, and the overall effective rate was 68.75%(11/16). One-year follow-up showed that no patient died in the initial treatment group, and the one-year survival rate was 100%(5/5). In salvage treatment group, 3 patients died of pulmonary bacterial infections and the one-year survival rate was 81.25%(13/16). During treatment, one patient had elevated total bilirubin, which was possibly associated with high-dose caspofungin. \u0000 \u0000 \u0000Conclusions \u0000High-dose caspofungin regimen has good efficacy and safety, both for initial treatment and salvage therapy in patients with invasive pulmonary aspergillosis. \u0000 \u0000 \u0000Key words: \u0000Invasive pulmonary aspergillosis; Caspofungin; High-dose; Efficacy; Safety","PeriodicalId":10127,"journal":{"name":"Chinese Journal of Infectious Diseases","volume":"37 1","pages":"139-143"},"PeriodicalIF":0.0,"publicationDate":"2019-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42767788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of auranofin combined with antineoplastic vorinostat on bactericidal activities against gram-negative bacteria and study on the target of auranofin 金糠芬联合抗肿瘤伏立诺他对革兰氏阴性菌的抑菌作用及靶菌的研究
Pub Date : 2019-03-15 DOI: 10.3760/CMA.J.ISSN.1000-6680.2019.03.004
Haoran Chen, Zhou Liu, Jiabin Li
Objective To find the target of auranofin with the antibacterial activity against gram-negative bacteria and to investigate the effect of the combination of auranofin and vorinostat on the antibacterial activity against gram-negative bacteria. Methods The strains of E. coli lacking thioredoxin reductase (TrxR) was used to find the target gene. The potential synergies of the combination of auranofin and vorinostat for E. coli strain, A. baumannii strain, P .aeruginosa strain, K. pneumonia strain and multidrug-resistant (MDR) A. baumannii strain were evaluated using susceptibility tests, micro-dilution checkerboard tests and time-kill studies. The genes related to Trx (trxA, trxB, trxC) and the gene expressed glutathione (gor) of E. coli BW25113 strains (WT) were separately knocked out to observe the effect of auranofin on minimum inhibitory concentration (MIC) and the time-kill kinetics of ΔtrxC and Δgor. Furthermore, the complemented strains (C-trxA, C-trxB, C-trxC, C-gor) were used to verify and define the genetic targets. Results According to the results of susceptibility tests, MICs of auranofin were 64 mg/L for E. coli strain BW25113 and K. pneumonia strain ATCC 43816, 128 mg/L for P. aeruginosa strain PA14 and 32 mg/L for both A. baumannii strain ATCC 17978 and A. baumannii strain AB5075. However, MICs of vorinostat are 512 mg/L for all isolates. The fractional inhibitory concentration indexes (FICIs) of the combination of auranofin and vorinostat for E. coli strain BW25113, A. baumannii strain ATCC 17978, MDR A. baumannii strain AB5075, K. pneumonia starin ATCC 43816 and P. aeruginosa strain PA14 were 0.313, 0.375, 0.375, 0.375, and 0.375, respectively, with all values <0.5, which showed synergy. In susceptibility tests of knockout strains, MICs of auranofin for ΔtrxC increased from 64 mg/L to 256 mg/L, decreased to 16 mg/L for Δgor, and no changes for ΔtrxA and ΔtrxB. Auranofin showed the same antibacterial activities against the complemented strains (C-trxC, C-gor) and E. col BW25113, which decreased by about 1.8 lg colong formins units (CFU)/mL of bacterial counts. However, the antibacterial activity of auranofin was significantly reduced for ΔtrxC, and decreased by<1 lg CFU/mL of bacterial counts. For Δgor, bacterial counts decreased 4.6 lg CFU/mL, and the antibacterial activity markedly increased. Conclusions The potential target gene of auranofin against gram-negative bacteria could be trxC, which provides new ideas and methods for the clinical treatment of multidrug-resistant gram-negative bacteria. Key words: Auranofin; Gram-negative bacteria; Thioredoxin reductase; Vorinostat; Synergy
目的探讨金糠蛋白对革兰氏阴性菌的抑菌活性,探讨金糠蛋白与伏立诺他合用对革兰氏阴性菌抑菌活性的影响。方法利用缺乏硫氧还蛋白还原酶(TrxR)的大肠杆菌菌株寻找靶基因。采用药敏试验、微量稀释棋盘棋盘试验和时间杀伤试验,评价了金嘌呤与伏立诺他联合用药对大肠杆菌、鲍曼不动杆菌、铜绿假单胞菌、肺炎克雷伯菌和多药耐药鲍曼不动杆菌的潜在协同作用。分别敲除大肠杆菌BW25113菌株(WT) Trx相关基因(trxA、trxB、trxC)和表达谷胱甘肽(gor)的基因,观察金糠蛋白对ΔtrxC和Δgor最低抑菌浓度(MIC)和时间杀伤动力学的影响。利用互补菌株(C-trxA、C-trxB、C-trxC、C-gor)验证和确定遗传靶点。结果药敏试验结果显示,金黄色葡萄蛋白对大肠杆菌BW25113和肺炎克雷伯菌ATCC 43816的mic值为64 mg/L,铜绿假单胞菌PA14的mic值为128 mg/L,鲍曼不动杆菌ATCC 17978和鲍曼不动杆菌AB5075的mic值为32 mg/L。伏立诺他的mic均为512 mg/L。金嘌呤与伏立诺他联用对大肠杆菌BW25113、鲍曼假单胞菌ATCC 17978、耐多药鲍曼假单胞菌AB5075、肺炎克雷伯菌ATCC 43816和铜绿假单胞菌PA14的分数抑制浓度指数(FICIs)分别为0.313、0.375、0.375、0.375,且均<0.5,表现出协同作用。在敲除菌株的药敏试验中,ΔtrxC对金毒苷的mic从64 mg/L增加到256 mg/L, Δgor对金毒苷的mic降低到16 mg/L, ΔtrxA和ΔtrxB对金毒苷的mic没有变化。金丝桃苷对互补菌株C-trxC、C-gor和大肠杆菌BW25113的抑菌活性相同,均降低约1.8个菌落单位(CFU)/mL。然而,对于ΔtrxC,金糠蛋白的抗菌活性明显降低,细菌计数下降<1 lg CFU/mL。对于Δgor,细菌计数降低4.6 lg CFU/mL,抗菌活性显著提高。结论金糠蛋白抗革兰氏阴性菌的潜在靶基因可能是trxC,为临床治疗多重耐药革兰氏阴性菌提供了新的思路和方法。关键词:萘醌;革兰氏阴性细菌;硫氧还蛋白还原酶;Vorinostat;协同作用
{"title":"Effect of auranofin combined with antineoplastic vorinostat on bactericidal activities against gram-negative bacteria and study on the target of auranofin","authors":"Haoran Chen, Zhou Liu, Jiabin Li","doi":"10.3760/CMA.J.ISSN.1000-6680.2019.03.004","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1000-6680.2019.03.004","url":null,"abstract":"Objective \u0000To find the target of auranofin with the antibacterial activity against gram-negative bacteria and to investigate the effect of the combination of auranofin and vorinostat on the antibacterial activity against gram-negative bacteria. \u0000 \u0000 \u0000Methods \u0000The strains of E. coli lacking thioredoxin reductase (TrxR) was used to find the target gene. The potential synergies of the combination of auranofin and vorinostat for E. coli strain, A. baumannii strain, P .aeruginosa strain, K. pneumonia strain and multidrug-resistant (MDR) A. baumannii strain were evaluated using susceptibility tests, micro-dilution checkerboard tests and time-kill studies. The genes related to Trx (trxA, trxB, trxC) and the gene expressed glutathione (gor) of E. coli BW25113 strains (WT) were separately knocked out to observe the effect of auranofin on minimum inhibitory concentration (MIC) and the time-kill kinetics of ΔtrxC and Δgor. Furthermore, the complemented strains (C-trxA, C-trxB, C-trxC, C-gor) were used to verify and define the genetic targets. \u0000 \u0000 \u0000Results \u0000According to the results of susceptibility tests, MICs of auranofin were 64 mg/L for E. coli strain BW25113 and K. pneumonia strain ATCC 43816, 128 mg/L for P. aeruginosa strain PA14 and 32 mg/L for both A. baumannii strain ATCC 17978 and A. baumannii strain AB5075. However, MICs of vorinostat are 512 mg/L for all isolates. The fractional inhibitory concentration indexes (FICIs) of the combination of auranofin and vorinostat for E. coli strain BW25113, A. baumannii strain ATCC 17978, MDR A. baumannii strain AB5075, K. pneumonia starin ATCC 43816 and P. aeruginosa strain PA14 were 0.313, 0.375, 0.375, 0.375, and 0.375, respectively, with all values <0.5, which showed synergy. In susceptibility tests of knockout strains, MICs of auranofin for ΔtrxC increased from 64 mg/L to 256 mg/L, decreased to 16 mg/L for Δgor, and no changes for ΔtrxA and ΔtrxB. Auranofin showed the same antibacterial activities against the complemented strains (C-trxC, C-gor) and E. col BW25113, which decreased by about 1.8 lg colong formins units (CFU)/mL of bacterial counts. However, the antibacterial activity of auranofin was significantly reduced for ΔtrxC, and decreased by<1 lg CFU/mL of bacterial counts. For Δgor, bacterial counts decreased 4.6 lg CFU/mL, and the antibacterial activity markedly increased. \u0000 \u0000 \u0000Conclusions \u0000The potential target gene of auranofin against gram-negative bacteria could be trxC, which provides new ideas and methods for the clinical treatment of multidrug-resistant gram-negative bacteria. \u0000 \u0000 \u0000Key words: \u0000Auranofin; Gram-negative bacteria; Thioredoxin reductase; Vorinostat; Synergy","PeriodicalId":10127,"journal":{"name":"Chinese Journal of Infectious Diseases","volume":"37 1","pages":"149-154"},"PeriodicalIF":0.0,"publicationDate":"2019-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43190410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evolution of VP1 gene of coxsackievirus A16 in hand, foot, and mouth disease 手足口病柯萨奇病毒A16 VP1基因的进化
Pub Date : 2019-03-15 DOI: 10.3760/CMA.J.ISSN.1000-6680.2019.03.007
Yang Wang, Yi Li, Chuanmei Peng, Jia Wang, Xiaoye Fu, Wanting Chen
Objective To investigate the genetic evolution of VP1 gene of pathogenic coxsackievirus A16 (CV-A16) strain isolated from clinical hand, foot, and mouth disease (HFMD) patients. Methods A total of 160 HFMD cases with CV-A16-positive results were collected from hospitals in Kunming during January 2015 to June 2017. Fecal samples were collected. Real-time polymerase chain reaction (PCR) was used to detect the CV-A16 virus nucleic acid. The VP1 genes of CV-A16-positive samples were amplified by reverse transcription-PCR. The amplified positive products were sequenced and aligned. The homologies were identified and their subgenotypes were determined. The phylogenetic tree was constructed and homology modeling was conducted. Results All the 160 CV-A16 isolates were B2 subtypes. The genetic distance between detected strains of CV-A16 and the strains in Fujian, Beijing, Nanjing was 0.76. The genetic distance to the strains in Malaysia was 0.78, and to the strains in Australia was 1.86. Homologous modeling revealed that the amino acid sequence of the VP1 gene of the strain had a G227R mutation. Conclusions There is no major genetic variation in the CV-A16 strains during 3 years. CV-A16 isolates are close to those of epidemic strains in Beijing, Fujian and Malaysia, but are far fram the strains from Australia. Key words: Hand, foot and mouth disease; Coxsackievirus A16; VP1 gene; Phylogenetic tree; Homology modeling
目的研究临床手足口病(HFMD)患者分离的致病性柯萨奇病毒A16(CV-A16)株VP1基因的遗传进化。方法收集2015年1月至2017年6月昆明市医院收治的160例CV-A16阳性手足口病患者。收集粪便样本。采用实时聚合酶链式反应(PCR)检测CV-A16病毒核酸。用逆转录聚合酶链式反应扩增CV-A16阳性标本的VP1基因。对扩增的阳性产物进行测序和比对。鉴定了它们的同源性,并确定了它们的亚基因型。构建了系统发育树,并进行了同源性建模。结果160株CV-A16均为B2亚型。检测到的CV-A16菌株与福建、北京、南京菌株的遗传距离为0.76。与马来西亚株系的遗传距离为0.78,与澳大利亚株系的基因距离为1.86。同源模型显示该菌株VP1基因的氨基酸序列具有G227R突变。结论CV-A16菌株在3年内无明显的遗传变异。CV-A16分离株与北京、福建和马来西亚的流行株接近,但与澳大利亚的流行株相差甚远。关键词:手足口病;柯萨奇病毒A16;VP1基因;系统发育树;同源性建模
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引用次数: 0
Epidemiological characteristics and etiology analysis of 11 510 hospitalized children with hand, foot, and mouth disease 11 510例住院手足口病患儿流行病学特征及病因分析
Pub Date : 2019-03-15 DOI: 10.3760/CMA.J.ISSN.1000-6680.2019.03.006
Mei-fen Wang, Zeng-qing Du, Tiesong Zhang, Yunjiao Luo, L. Du, Quan Gan, T. Fu, Junchao Peng, Weiying Ma
Objective To study the prevalence trends and etiology of hand, foot, and mouth disease (HFMD) in hospitalized children. Methods The clinical data of 11 510 cases of children hospitalized with HFMD from 2008 to 2017 in Department of Infection Diseases of Kunming Children′s Hospital were collected, and to retrospectively analyze the characteristics, time distribution and pathogen distribution of the cases. Results Of the 11 510 children with HFMD, 6 100 were male and 5 410 were female. There were 9 814 cases under 3 years old, 1 696 over 3 years old. HFMD occurred throughout the year. The peak months of the disease were April to July, with the time distribution of single peak. There were 4 690 severe cases and 3 452 critical cases, accounting for 70.34%. The main pathogens detected were enteroviruses A71 (EV-A71), coxsackievirus A16 (CV-A16) and other enteroviruses (EV), with 3 803 cases (36.02%), 1 122 cases (10.63%) and 3 401 cases (32.21%) respectively. EV-A71 and CV-A16 infections dominated from 2008 to 2013, while EV-A71 and other EV infection dominated from 2014 to 2017. Conclusions EV-A71, CV-A16 and other EV are the main pathogens of HFMD in Kunming. Critical HFMD cases are mainly caused by EV-A71 infection. Key words: Hand, foot and mouth disease; Enterovirus; Epidemic characteristics
目的了解住院儿童手足口病(手足口病)的流行趋势及病因学。方法收集昆明儿童医院感染科2008 - 2017年收治的11 510例手足口病患儿的临床资料,回顾性分析病例特点、时间分布及病原菌分布。结果11 510例手足口病患儿中,男6 100例,女5 410例。3岁以下9 814例,3岁以上1 696例。手足口病全年都有发生。发病高峰期为4 ~ 7月,时间呈单峰分布。重症病例4 690例,危重病例3 452例,占70.34%。检出的主要病原体为肠病毒A71 (EV-A71)、柯萨奇病毒A16 (CV-A16)和其他肠病毒(EV),分别为3 803例(36.02%)、1 122例(10.63%)和3 401例(32.21%)。2008 - 2013年以EV- a71和CV-A16感染为主,2014 - 2017年以EV- a71和其他EV感染为主。结论EV- a71、CV-A16等EV是昆明地区手足口病的主要致病菌。手足口病危重病例主要由EV-A71感染引起。关键词:手足口病;肠病毒;流行特点
{"title":"Epidemiological characteristics and etiology analysis of 11 510 hospitalized children with hand, foot, and mouth disease","authors":"Mei-fen Wang, Zeng-qing Du, Tiesong Zhang, Yunjiao Luo, L. Du, Quan Gan, T. Fu, Junchao Peng, Weiying Ma","doi":"10.3760/CMA.J.ISSN.1000-6680.2019.03.006","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1000-6680.2019.03.006","url":null,"abstract":"Objective \u0000To study the prevalence trends and etiology of hand, foot, and mouth disease (HFMD) in hospitalized children. \u0000 \u0000 \u0000Methods \u0000The clinical data of 11 510 cases of children hospitalized with HFMD from 2008 to 2017 in Department of Infection Diseases of Kunming Children′s Hospital were collected, and to retrospectively analyze the characteristics, time distribution and pathogen distribution of the cases. \u0000 \u0000 \u0000Results \u0000Of the 11 510 children with HFMD, 6 100 were male and 5 410 were female. There were 9 814 cases under 3 years old, 1 696 over 3 years old. HFMD occurred throughout the year. The peak months of the disease were April to July, with the time distribution of single peak. There were 4 690 severe cases and 3 452 critical cases, accounting for 70.34%. The main pathogens detected were enteroviruses A71 (EV-A71), coxsackievirus A16 (CV-A16) and other enteroviruses (EV), with 3 803 cases (36.02%), 1 122 cases (10.63%) and 3 401 cases (32.21%) respectively. EV-A71 and CV-A16 infections dominated from 2008 to 2013, while EV-A71 and other EV infection dominated from 2014 to 2017. \u0000 \u0000 \u0000Conclusions \u0000EV-A71, CV-A16 and other EV are the main pathogens of HFMD in Kunming. Critical HFMD cases are mainly caused by EV-A71 infection. \u0000 \u0000 \u0000Key words: \u0000Hand, foot and mouth disease; Enterovirus; Epidemic characteristics","PeriodicalId":10127,"journal":{"name":"Chinese Journal of Infectious Diseases","volume":"37 1","pages":"160-162"},"PeriodicalIF":0.0,"publicationDate":"2019-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45384087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinical characteristics of patients with positive blood culture for Mycobacterium tuberculosis in a general hospital 某综合医院血培养结核分枝杆菌阳性患者的临床特点
Pub Date : 2019-03-15 DOI: 10.3760/CMA.J.ISSN.1000-6680.2019.03.003
Yuzhen Xu, Qing-luan Yang, Yuanyuan Liu, Qianqian Liu, Qiaoling Ruan, Yan Gao, L. Shao, Wenhong Zhang, Hong Liu
Objective To retrospectively analyze the clinical and laboratory characteristics of patients with positive blood culture results for Mycobacterium tuberculosis (M.tb). Methods The clinical laboratory database of patients suspected with disseminated tuberculosis from January 2009 to January 2017 in Huashan Hospital affiliated with Fudan University were collected and analyzed. The clinical manifestations, laboratory characteristics and outcomes between disseminated tuberculosis patients with positive blood culture (positive blood culture group) for M. tb and negative results (negative blood culture group) were compared. T test, Mann-Whitney U test and Fisher exact test were used for statistical analysis. Results A total of 5 589 patients suspected with M. tb infection had peripheral blood culture for mycobacterium. Positive blood culture for M. tb was found in 26 disseminated tuberculosis patients, while 6 patients finally identified as nontuberculous mycobacterium (NTM) with species identification, and 22 disseminated tuberculosis patients with negative blood culture results were enrolled during the same period as control. The mean age ([49.1±10.1] years old vs[38.3±17.1] years old, t=2.460, P=0.018), the proportion of diagnosed with fever of unknown origin at admission (FUO) (65.0%[13/20] vs 13.6%[3/22], P=0.001), the proportion of diagnosed with focal infection (30.0%[6/20] vs 86.4%[19/22], P=0.001), the proportion of patients with other diseases (75.0%[15/20] vs 22.7%[5/22], P=0.002), the proportion of patients with hematological diseases (35.0%[7/20] vs 4.5%[1/22], P=0.018) and the proportion of patients with tumor (20%[4/20] vs 0[0/22], P=0.043) in the positive blood culture group were significantly different from those in the negative blood culture group. Laboratory examinations of the percentage of neutrophils, the percentage of lymphocytes, the percentage of monocytes, the value of neutrophil/lymphocyte, the level of hemoglobin, the level of erythrocyte sedimentation rate, the level of C-reactive protein, the level of procalcitonin and the positive rate of T-SPOT.TB in positive blood culture groups were significantly different from those in negative blood culture group (all P<0.05). Conclusions Peripheral blood M. tb culture is more likely to be positive for those elder disseminated tuberculosis patients with hematological diseases or tumors, and those with increase of neutrophil counts and inflammation markers but reduction of lymphocyte counts and hemoglobin. Key words: Mycobacterium tuberculosis; Blood culture; Disseminated tuberculosis
目的回顾性分析血培养阳性结核分枝杆菌患者的临床和实验室特点。方法收集2009年1月至2017年1月复旦大学附属华山医院疑似播散性结核病患者的临床实验室数据库并进行分析。比较结核分枝杆菌血培养阳性(血培养阳性组)与阴性(血培养阴性组)弥散性结核患者的临床表现、实验室特征及转归。采用T检验、Mann-Whitney U检验和Fisher精确检验进行统计分析。结果5 589例疑似结核分枝杆菌感染患者行外周血分枝杆菌培养。26例弥散性结核患者血培养结核分枝杆菌阳性,6例经菌种鉴定最终鉴定为非结核分枝杆菌(NTM),同期纳入22例血培养阴性的弥散性结核患者作为对照。平均年龄([49.1±10.1]岁vs[38.3±17.1]岁,t=2.460, P=0.018),入院时诊断为不明原因发热的比例(FUO) (65.0%[13/20] vs 13.6%[3/22], P=0.001),诊断为局灶性感染的比例(30.0%[6/20]vs 86.4%[19/22], P=0.001),合并其他疾病的比例(75.0%[15/20]vs 22.7%[5/22], P=0.002),合并血液病的比例(35.0%[7/20]vs 4.5%[1/22]),P=0.018),阳性血培养组肿瘤患者比例(20%[4/20]vs 0[0/22], P=0.043)与阴性血培养组差异有统计学意义。实验室检查:中性粒细胞百分比、淋巴细胞百分比、单核细胞百分比、中性粒细胞/淋巴细胞值、血红蛋白水平、红细胞沉降率水平、c反应蛋白水平、降钙素原水平、T-SPOT阳性率。阳性血培养组与阴性血培养组结核发生率差异有统计学意义(P<0.05)。结论老年弥散性结核伴血液病或肿瘤患者外周血结核分枝杆菌培养阳性,中性粒细胞计数和炎症标志物升高,淋巴细胞计数和血红蛋白降低。关键词:结核分枝杆菌;血培养;播散性肺结核
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引用次数: 0
Clinical features and prognostic factors in patients with liver abscess and acquired immunodeficiency syndrome 肝脓肿合并获得性免疫缺陷综合征的临床特点及预后因素分析
Pub Date : 2019-03-15 DOI: 10.3760/CMA.J.ISSN.1000-6680.2019.03.005
M. Cai
Objective To investigate the clinical features and prognostic factors in patients with acquired immunodeficiency syndrome (AIDS) and liver abscess. Methods The clinical data of AIDS patients with liver abscess admitted in Beijing You-an Hospital during January 2013 to December 2017 were retrospective analyzed to reveal the clinical manifestations, etiologies, imaging features, therapeutic effects and prognostic factors. T test, χ2 test or Fisher exact test were used for statistical analyses. Results A total of 76 patients were recruited. The most common clinical manifestations were fever (72 cases), chills (48 cases), anorexia (42 cases) and abdominal pain (35 cases). Liver abscesses were mainly located in right lobe (57 cases), then in left lobe (11 cases), in both right and left lobes (6 cases) and in caudate lobe (2 cases). Lobulation or division was seen in 19 cases and gas formation was seen in 5 cases. Single abscess was identified in 56 cases. Positive culture results were obtained in 15.5% (9/58) from liver pus and 6.0% (4/67) from blood samples. Thirteen strains of pathogens were detected by liver pus culture, including 9 strains of Staphylococcus, 3 strains of Candida and 1 strain of Mycobacterium. Six strains of pathogens were detected by blood culture, including 5 strains of Staphylococcus and 1 strain of Corynebacterium. The main complications included acute kidney injury (10 cases) and septic shock (6 cases). Sixty-one cases were treated with antibiotics plus imaging-guided percutaneous aspiration, drainage or surgery, of whom 57 cases were effective. Fifteen cases were treated with antibiotics alone, of whom 12 cases were effective. Septic shock (OR=70.16, 95%CI: 4.77-1 032.06, P<0.01), respiratory failure (OR=68.41, 95%CI: 2.40-1 946.53, P=0.01) and gas formation (OR=23.36, 95%CI: 1.30-420.16, P=0.03) were independent risk factors for poor prognosis. Conclusions The clinical features of AIDS patients with liver abscess are uncharacteristic. Bacteria are the main pathogens. Septic shock, respiratory failure and gas formation are independent risk factors for poor prognosis. Imaging-guided percutaneous aspiration, drainage combined with antibiotic therapy is safe and effective. Key words: Acquired immunodeficiency syndrome; Liver abscess; Prognosis; Clinical feature; Treatment
目的探讨艾滋病合并肝脓肿的临床特点及影响预后的因素。方法对北京佑安医院2013年1月至2017年12月收治的艾滋病肝脓肿患者的临床资料进行回顾性分析,揭示其临床表现、病因、影像学特点、治疗效果及预后因素。采用T检验、χ2检验或Fisher精确检验进行统计分析。结果共招募76名患者。最常见的临床表现为发热(72例)、发冷(48例)、厌食(42例)和腹痛(35例)。肝脓肿主要位于右叶(57例),然后是左叶(11例),左右叶各6例,尾状叶2例。小叶或分裂19例,气体形成5例。56例中发现单个脓肿。肝脓液培养阳性率为15.5%(9/58),血液培养阳性率6.0%(4/67)。肝脓液培养共检出病原菌13株,其中葡萄球菌9株,念珠菌3株,分枝杆菌1株。血培养共检出6株病原菌,其中葡萄球菌5株,棒状杆菌1株。主要并发症包括急性肾损伤(10例)和感染性休克(6例)。61例采用抗生素加影像学引导下经皮穿刺、引流或手术治疗,其中57例有效。单用抗生素治疗15例,其中12例有效。败血症休克(OR=70.16,95%CI:4.77-1032.06,P<0.01)、呼吸衰竭(OR=68.41,95%CI:2.40-1946.53,P=0.01)和气体形成(OR=23.36,95%CI:1.30-420.16,P=0.03)是预后不良的独立危险因素。结论艾滋病合并肝脓肿的临床特点不典型。细菌是主要的病原体。败血症休克、呼吸衰竭和气体形成是预后不良的独立危险因素。影像学引导下经皮穿刺引流联合抗生素治疗是安全有效的。关键词:获得性免疫缺陷综合症;肝脓肿;预后;临床特征;治疗
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引用次数: 0
Protective effect of bone marrow mesenchymal stem cells derived exosomes on alcohol-induced hepatic injury 骨髓间充质干细胞来源的外泌体对酒精性肝损伤的保护作用
Pub Date : 2019-02-15 DOI: 10.3760/CMA.J.ISSN.1000-6680.2019.02.007
Xiao-ya Jin, Yong-ping Chen, Feng-Bin Lu, Yingxiao Chen, Lu Chen, Lei Zhang, Yu Huang, J. Gan
Objective To evaluate therapeutic effects of bone marrow mesenchymal stem cells (MSC) derived exosomes on alcohol-induced liver injury. Methods Eighteen male C57BL/6 mice aged 6 to 8 week were randomly divided into control group, model group and exosomes group, with 6 mice in each group. The mice in the model group and the exosomes group were fed with Lieber-DeCarli ad libitum diet (Dyets Inc.) for 4 weeks, followed by gavage a bolus of ethanol at day 26, 27 and 28. The mice in the control group matched the alcohol-derived calories with dextran-maltose. Meanwhile, the mice in exosomes group were injected with MSC-exosomes via the tail vein at day 14 and 26. After the experiment, serum levels of alanine aminotransferase (ALT) and aspartate aminotransaminase (AST) were detected, and the pathological changes of liver tissues were observed. The expressions of nuclear factor erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1), CD63, CD81, TSG101 and Cytochrome C were analyzed by Western blot, and mRNA levels of Nrf-2, HO-1, interleukin (IL)-10 and IL-17 were analyzed by real-time polymerase chain reaction(RT-PCR). The commercial kits were used to detect serum IL-10, IL-17 levels and liver tissue malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) oxidative stress indicators. The numbers of regulatory T cell (Treg) and help T (Th)17 cells in the liver were analyzed by flow cytometry. One-way analysis of variance was used for comparison between groups. Results MSC-exosomes expressed positive markers CD63, CD81 and TSG101, but did not express the negative markers Cytochrome C. The serum ALT and AST levels in model group were (87.3±25.1) U/L and (223.2±43.5) U/L, respectively, while those in exosomes group were (47.7±12.0) U/L and (128.2±33.6) U/L, respectively. The differences between the two groups were both statistically significant (F=12.818 and 12.226, respectively, both P<0.05). Compared with control group, the SOD activity and GSH level in the model group significantly decreased with statistically significant differences (F=4.245 and 24.074, respectively, both P<0.05). Lieber-DeCarli ethanol feeding significantly increased intrahepatic MDA level in the model mice, which was reversed by MSC-exosomes supplementation, and the difference was statistically significant (F=36.675, P<0.05). Compared with control group, the intrahepatic protein expressions of Nrf-2 and HO-1 in model group were significantly decreased, while the expressions in exosomes group were obviously increased. The differences were statistically significant (F=33.623 and 14.960, respectively, both P<0.05). The expression trends of Nrf-2 and HO-1 mRNA were the same as those of protein expressions (F=20.784 and 276.336, respectively, both P<0.05). The proportions of liver Treg/Th17 in the control group, model group and exosomes group were 4.3±0.9, 0.4±0.2, and 3.4±0.5, respectively. The differences among groups were statistically significant (F=64.
目的探讨骨髓间充质干细胞外泌体对酒精性肝损伤的治疗作用。方法6 ~ 8周龄雄性C57BL/6小鼠18只,随机分为对照组、模型组和外泌体组,每组6只。模型组和外泌体组小鼠连续4周饲喂Lieber-DeCarli无限制日粮(diets Inc.),并于第26、27、28天灌胃乙醇。对照组的老鼠用葡聚糖麦芽糖来匹配酒精衍生的卡路里。同时,外泌体组小鼠于第14天和第26天通过尾静脉注射msc -外泌体。实验结束后检测血清丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)水平,观察肝脏组织病理变化。Western blot检测核因子-红细胞2相关因子2 (Nrf-2)、血红素加氧酶-1 (HO-1)、CD63、CD81、TSG101和细胞色素C的表达,实时聚合酶链反应(RT-PCR)检测Nrf-2、HO-1、白细胞介素(IL)-10和IL-17的mRNA水平。采用商品化试剂盒检测血清IL-10、IL-17水平及肝组织丙二醛(MDA)、谷胱甘肽(GSH)、超氧化物歧化酶(SOD)氧化应激指标。流式细胞术检测肝脏中调节性T细胞(Treg)和辅助性T (Th)17细胞的数量。组间比较采用单因素方差分析。结果msc -外泌体表达CD63、CD81和TSG101阳性标记物,不表达细胞色素c阴性标记物。模型组血清ALT和AST水平分别为(87.3±25.1)U/L和(223.2±43.5)U/L,外泌体组血清ALT和AST水平分别为(47.7±12.0)U/L和(128.2±33.6)U/L。两组比较差异均有统计学意义(F=12.818、12.226,P均<0.05)。与对照组比较,模型组SOD活性和GSH水平显著降低,差异有统计学意义(F=4.245、24.074,P均<0.05)。Lieber-DeCarli乙醇喂养显著提高了模型小鼠肝内MDA水平,而补充msc -外泌体则相反,差异有统计学意义(F=36.675, P<0.05)。与对照组比较,模型组大鼠肝内Nrf-2、HO-1蛋白表达明显降低,外泌体组大鼠肝内Nrf-2、HO-1蛋白表达明显升高。差异有统计学意义(F=33.623、14.960,P均<0.05)。Nrf-2和HO-1 mRNA的表达趋势与蛋白表达趋势一致(F=20.784、276.336,P均<0.05)。对照组、模型组和外泌体组肝脏Treg/Th17比例分别为4.3±0.9、0.4±0.2和3.4±0.5。组间差异有统计学意义(F=64.227, P<0.05)。与对照组比较,模型组大鼠血清蛋白和肝内IL-17基因表达均显著升高,但经msc外泌体处理后,这一现象被逆转。差异有统计学意义(F=15.581、40.095,P均<0.05)。Lieber-DeCarli乙醇饲喂后血清IL-10蛋白水平和肝内IL-10基因表达显著降低,低于外泌体组。差异有统计学意义(F=98.268、153.743,P均<0.05)。结论间充质干细胞外泌体移植可减轻酒精性肝损伤。其机制可能涉及通过调节Nrf-2/HO-1和使Treg和Th17细胞平衡正常化来减少肝脏氧化应激。关键词:肝病;酒精;炎症;免疫力;骨间充质干细胞;外来体;氧化应激
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中华传染病杂志
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