Intensive care units(ICU)for various reasons,including the increasing age of admitted patients,comorbidities,and increasingly complex surgical procedures(e.g.,transplants),have become"the epicenter"of nosoco...Intensive care units(ICU)for various reasons,including the increasing age of admitted patients,comorbidities,and increasingly complex surgical procedures(e.g.,transplants),have become"the epicenter"of nosocomial infections,these are characterized by the presence of multidrug-resistant organisms(MDROs)as the cause of infection.Therefore,the perfect match of fragile patients and MDROs,as the cause of infection,makes ICU mortality very high.Furthermore,carbapenems were considered for years as last-resort antibiotics for the treatment of infections caused by MDROs;unfortunately,nowadays carbapenem resistance,mainly among Gram-negative pathogens,is a matter of the highest concern for worldwide public health.This comprehensive review aims to outline the problem from the intensivist's perspective,focusing on the new definition and epidemiology of the most common carbapenem-resistant MDROs(Acinetobacter baumannii,Pseudomonas aeruginosa and Enterobacterales)to emphasize the importance of the problem that must be permeating clinicians dealing with these diseases.展开更多
植物的多向耐药性(Pleiotropic drug resistance,PDR)转运蛋白隶属于ATP结合盒(ATP-binding cassette,ABC)转运蛋白家族的G亚家族。该类蛋白参与植物多种初生、次生代谢物的跨膜运输,在植物的生长发育、响应逆境胁迫、解毒过程中起着重...植物的多向耐药性(Pleiotropic drug resistance,PDR)转运蛋白隶属于ATP结合盒(ATP-binding cassette,ABC)转运蛋白家族的G亚家族。该类蛋白参与植物多种初生、次生代谢物的跨膜运输,在植物的生长发育、响应逆境胁迫、解毒过程中起着重要作用。近年的研究还表明,该蛋白与多种植物对真菌病原的抗性有关。本文以烟草祖先种和重要野生种为研究对象,以拟南芥PDR12蛋白、烟草的PDR1基因为探针,通过搜索同源序列,从数据库中提取烟草及祖先种、重要野生种中的PDR基因、蛋白序列,并通过生物信息学分析手段对其编码蛋白的理化特性、氨基酸序列特征、蛋白结构、功能、启动子序列及表达调控特征进行了分析,并以本氏烟(Nicotiana benthamiana)NbPDR1为代表,预测了该基因启动子的顺式作用元件,以普通烟草(Nicotiana tabacum)NtPDR1基因为例,预测了其基因编辑位点。结果表明,这些PDR基因相似性高,均编码跨膜蛋白,具有典型的跨膜结构域和核酸结合结构域。该基因启动子区有多个与病原真菌诱导、干旱等逆境胁迫响应相关的元件,暗示该基因可能是抗真菌病害、响应逆境胁迫的广谱抗性基因。最后,本文预测的基因编辑位点,为烟草PDR基因的功能研究、基因编辑及抗病育种提供理论基础。展开更多
目的分析凉山州某县HIV-1感染者治疗前耐药情况及影响因素,为制定针对性抗反转录病毒治疗(antiretroviral therapy,ART)方案,减少整体抗病毒治疗失败率提供理论依据。方法选取2022年6—12月间,于凉山州某县医院就诊的拟启动ART的HIV-1...目的分析凉山州某县HIV-1感染者治疗前耐药情况及影响因素,为制定针对性抗反转录病毒治疗(antiretroviral therapy,ART)方案,减少整体抗病毒治疗失败率提供理论依据。方法选取2022年6—12月间,于凉山州某县医院就诊的拟启动ART的HIV-1感染者107例,完善治疗前耐药(pretreatment drug resistance,PDR)基因检测及HIV-1亚型检测,同时收集基线血CD4+T细胞计数、HIV-1病毒载量及常规检查指标,分析PDR总体发生率及相关危险因素。结果107例HIV-1感染者中基因扩增成功101例,成功率为94.4%。101例感染的HIV-1主要基因型为B+C亚型(48/101,47.5%)和CRF07_BC重组型(46/101,45.5%)。共检测出存在耐药基因突变者21例,PDR发生率为20.8%,实际耐药者11(耐药率10.9%)。核苷类逆转录酶抑制剂耐药突变1例为A62V位点。非核苷类逆转录酶抑制剂耐药突变15例,主要突变位点为K103N、Y181C、V179D及V179VD等,分别造成依非韦仑、奈韦拉平、利匹韦林、依曲韦林等药物的不同程度耐药。还有6例为整合酶抑制剂耐药突变,突变位点包含E157Q、A128T及G163R。经单因素及多因素Logistic回归分析,汉族及B+C亚型与发生PDR突变具有相关性,其中汉族为风险因素,B+C亚型为保护性因素。结论凉山州某县初始ART的HIV-1感染者中,存在较大比例的PDR基因突变,除了常见的核苷类及非核苷类逆转录酶抑制剂耐药外还出现了整合酶抑制剂的耐药突变,应该引起高度注意。展开更多
目的探讨替加环素(TGC)联合药物治疗泛耐药鲍曼不动杆菌(PDR-Ab)中枢神经系统感染的效果。方法选取2017-02—2020-02驻马店市第一人民医院收治的108例PDR-Ab中枢神经系统感染患者为研究对象,根据随机数表法分为TGC-头孢哌酮/舒巴坦(CPZ/...目的探讨替加环素(TGC)联合药物治疗泛耐药鲍曼不动杆菌(PDR-Ab)中枢神经系统感染的效果。方法选取2017-02—2020-02驻马店市第一人民医院收治的108例PDR-Ab中枢神经系统感染患者为研究对象,根据随机数表法分为TGC-头孢哌酮/舒巴坦(CPZ/SB)组(TGC-CPZ/SB组)和TGC-异帕米星(ISM)组(TGC-ISM组),比较2组患者入院后24 h内及治疗10 d炎性指标、急性生理功能与慢性健康状况Ⅱ(APACHEⅡ)评分、细菌清除率、不良反应发生情况及临床总有效率。结果治疗10 d后TGC-CPZ/SB组和TGC-ISM组白细胞数(14.33±2.16 vs 12.59±3.10)、C反应蛋白(75.85±16.27 vs 63.16±15.33)、脂多糖(15.58±4.23 vs 12.11±2.34)、降钙素原(2.26±0.77 vs 1.43±0.57)、白细胞介素-6(39.84±5.25 vs 31.42±4.29)比较差异有统计学意义(P<0.05),且均显著低于治疗前(P<0.05);治疗10 d后TGC-ISM组APACHEⅡ评分(11.57±3.28)分,显著低于TGC-CPZ/SB组的(13.66±4.25)分(P<0.05);TGC-ISM组细菌清除率(74.07%)显著高于TGC-CPZ/SB组(55.56%)(P<0.05);2组恶心呕吐、听力减退、头痛、关节痛、视力模糊等不良反应发生率比较差异无统计学意义(P>0.05);TGC-ISM组临床总有效率88.89%,显著高于TGC-CPZ/SB组的70.37%,差异有统计学意义(P<0.05)。结论TGC联合ISM方案治疗PDR-Ab中枢神经系统感染的临床疗效良好,抑炎效果更好,且安全性高。展开更多
DON, as a virulence factor, plays an important role in the infection of Fusarium graminearum in wheat. The infection ability of F. graminearum depends on its capacity of producing DON. The production of DON by F. gram...DON, as a virulence factor, plays an important role in the infection of Fusarium graminearum in wheat. The infection ability of F. graminearum depends on its capacity of producing DON. The production of DON by F. graminearum is significantly decreased in the wheat varieties with scab resistance. In this study, GeneChip analysis indicated that an EST encoding an ATP-binding cassette (ABC) transporter was up-regulated by 45 times in a wheat landrace Wangshuibai, which is resistant to DON accumulation. A pair of EST-derived primers were designed based on the EST sequence, and a clone was then isolated from a wheat genomic DNA TAC library. The TAC clone was sequenced using chromosome walking and gene prediction was conducted using Softberry. A cDNA clone of this gene was subsequently isolated from Wangshuibai induced by DON using gene-specific primers designed according to the untranslated sequence of the gene. The genome size of the gene is 7377 bp, consisting of 19 exons with coding sequences of 4308 bp. It encodes a protein with 1435 amino acid residues and the calculated molecular weight is about 161 kD. BLAST analysis indicated that the gene may belong to pleiotropic drug resistance (PDR) sub-family, and hence designated as TaPDR1 (Triticum aestivum pleiotropic drug resistance). TaPDR1 was located on chromosome 5A of wheat using nullisomic-tetrasomic lines of Chinese Spring. TaPDR1 was up-regulated by induction of both DON and F. graminearum. Expression patterns of TaPDR1 were different in wild-type Wangshuibai and the fast-neutron induced Wangshuibai mutant lacking FHB1, a major QTL of FHB resistance and DON resistance in chromosome arm 3BS. These results suggested that TaPDR1 might be a candidate gene responsible for DON ac-cumulation resistance. The expression profile showed that TaPDR1 expression was neither induced by hormones typically involved in biotic stress, such as JA and SA, nor by abiotic stresses, such as heat, cold, wounding and NaCl. However, TaPDR1 expression was regulated by Al3+ and [Ca2+], indicating that [Ca2+]i might mediate the signal of TaPDR1 expression.展开更多
文摘Intensive care units(ICU)for various reasons,including the increasing age of admitted patients,comorbidities,and increasingly complex surgical procedures(e.g.,transplants),have become"the epicenter"of nosocomial infections,these are characterized by the presence of multidrug-resistant organisms(MDROs)as the cause of infection.Therefore,the perfect match of fragile patients and MDROs,as the cause of infection,makes ICU mortality very high.Furthermore,carbapenems were considered for years as last-resort antibiotics for the treatment of infections caused by MDROs;unfortunately,nowadays carbapenem resistance,mainly among Gram-negative pathogens,is a matter of the highest concern for worldwide public health.This comprehensive review aims to outline the problem from the intensivist's perspective,focusing on the new definition and epidemiology of the most common carbapenem-resistant MDROs(Acinetobacter baumannii,Pseudomonas aeruginosa and Enterobacterales)to emphasize the importance of the problem that must be permeating clinicians dealing with these diseases.
文摘目的分析凉山州某县HIV-1感染者治疗前耐药情况及影响因素,为制定针对性抗反转录病毒治疗(antiretroviral therapy,ART)方案,减少整体抗病毒治疗失败率提供理论依据。方法选取2022年6—12月间,于凉山州某县医院就诊的拟启动ART的HIV-1感染者107例,完善治疗前耐药(pretreatment drug resistance,PDR)基因检测及HIV-1亚型检测,同时收集基线血CD4+T细胞计数、HIV-1病毒载量及常规检查指标,分析PDR总体发生率及相关危险因素。结果107例HIV-1感染者中基因扩增成功101例,成功率为94.4%。101例感染的HIV-1主要基因型为B+C亚型(48/101,47.5%)和CRF07_BC重组型(46/101,45.5%)。共检测出存在耐药基因突变者21例,PDR发生率为20.8%,实际耐药者11(耐药率10.9%)。核苷类逆转录酶抑制剂耐药突变1例为A62V位点。非核苷类逆转录酶抑制剂耐药突变15例,主要突变位点为K103N、Y181C、V179D及V179VD等,分别造成依非韦仑、奈韦拉平、利匹韦林、依曲韦林等药物的不同程度耐药。还有6例为整合酶抑制剂耐药突变,突变位点包含E157Q、A128T及G163R。经单因素及多因素Logistic回归分析,汉族及B+C亚型与发生PDR突变具有相关性,其中汉族为风险因素,B+C亚型为保护性因素。结论凉山州某县初始ART的HIV-1感染者中,存在较大比例的PDR基因突变,除了常见的核苷类及非核苷类逆转录酶抑制剂耐药外还出现了整合酶抑制剂的耐药突变,应该引起高度注意。
文摘目的探讨替加环素(TGC)联合药物治疗泛耐药鲍曼不动杆菌(PDR-Ab)中枢神经系统感染的效果。方法选取2017-02—2020-02驻马店市第一人民医院收治的108例PDR-Ab中枢神经系统感染患者为研究对象,根据随机数表法分为TGC-头孢哌酮/舒巴坦(CPZ/SB)组(TGC-CPZ/SB组)和TGC-异帕米星(ISM)组(TGC-ISM组),比较2组患者入院后24 h内及治疗10 d炎性指标、急性生理功能与慢性健康状况Ⅱ(APACHEⅡ)评分、细菌清除率、不良反应发生情况及临床总有效率。结果治疗10 d后TGC-CPZ/SB组和TGC-ISM组白细胞数(14.33±2.16 vs 12.59±3.10)、C反应蛋白(75.85±16.27 vs 63.16±15.33)、脂多糖(15.58±4.23 vs 12.11±2.34)、降钙素原(2.26±0.77 vs 1.43±0.57)、白细胞介素-6(39.84±5.25 vs 31.42±4.29)比较差异有统计学意义(P<0.05),且均显著低于治疗前(P<0.05);治疗10 d后TGC-ISM组APACHEⅡ评分(11.57±3.28)分,显著低于TGC-CPZ/SB组的(13.66±4.25)分(P<0.05);TGC-ISM组细菌清除率(74.07%)显著高于TGC-CPZ/SB组(55.56%)(P<0.05);2组恶心呕吐、听力减退、头痛、关节痛、视力模糊等不良反应发生率比较差异无统计学意义(P>0.05);TGC-ISM组临床总有效率88.89%,显著高于TGC-CPZ/SB组的70.37%,差异有统计学意义(P<0.05)。结论TGC联合ISM方案治疗PDR-Ab中枢神经系统感染的临床疗效良好,抑炎效果更好,且安全性高。
基金Supported by the National Natural Science Foundation of China (Grant No. 30330380)Programme of Introducing Talents of Discipline to Universities (Grant No. B08025)+3 种基金Chinese High Technology Research and Development Program of China (Grant No. 2006AA10Z1F6)Natural Science Foundation of Jiangsu Province (Grant No. BK2006720)Important National Science & Technology Specific Projects of Transgenic Research (Grant No. 2009Zx08002-001B)McKnight Foundation CCRP Program
文摘DON, as a virulence factor, plays an important role in the infection of Fusarium graminearum in wheat. The infection ability of F. graminearum depends on its capacity of producing DON. The production of DON by F. graminearum is significantly decreased in the wheat varieties with scab resistance. In this study, GeneChip analysis indicated that an EST encoding an ATP-binding cassette (ABC) transporter was up-regulated by 45 times in a wheat landrace Wangshuibai, which is resistant to DON accumulation. A pair of EST-derived primers were designed based on the EST sequence, and a clone was then isolated from a wheat genomic DNA TAC library. The TAC clone was sequenced using chromosome walking and gene prediction was conducted using Softberry. A cDNA clone of this gene was subsequently isolated from Wangshuibai induced by DON using gene-specific primers designed according to the untranslated sequence of the gene. The genome size of the gene is 7377 bp, consisting of 19 exons with coding sequences of 4308 bp. It encodes a protein with 1435 amino acid residues and the calculated molecular weight is about 161 kD. BLAST analysis indicated that the gene may belong to pleiotropic drug resistance (PDR) sub-family, and hence designated as TaPDR1 (Triticum aestivum pleiotropic drug resistance). TaPDR1 was located on chromosome 5A of wheat using nullisomic-tetrasomic lines of Chinese Spring. TaPDR1 was up-regulated by induction of both DON and F. graminearum. Expression patterns of TaPDR1 were different in wild-type Wangshuibai and the fast-neutron induced Wangshuibai mutant lacking FHB1, a major QTL of FHB resistance and DON resistance in chromosome arm 3BS. These results suggested that TaPDR1 might be a candidate gene responsible for DON ac-cumulation resistance. The expression profile showed that TaPDR1 expression was neither induced by hormones typically involved in biotic stress, such as JA and SA, nor by abiotic stresses, such as heat, cold, wounding and NaCl. However, TaPDR1 expression was regulated by Al3+ and [Ca2+], indicating that [Ca2+]i might mediate the signal of TaPDR1 expression.
