阴道念珠菌菌种及香莲方逆转白念珠菌耐药基因组学研究
|
摘要
目的：
主要由白念珠菌引起的外阴阴道念珠菌病是临床常见病、多发病。本研究的主要目的包括：1.了解VVC(包括RVVC)的菌种分布和药敏情况；VVC(包括RVVC)患者的自觉症状(瘙痒和疼痛)与菌种(白念珠菌、非白念珠菌)的关系；2.观察香莲外洗液对白念珠菌耐药菌株的逆转作用；3.从基因水平,揭示香莲外洗液抗真菌的作用机理。
方法：
1.采集广东省中医院皮肤性病科及妇科符合外阴阴道念珠菌病诊断标准的119例患者的白带标本,通过菌种鉴定和药敏检测,了解外阴阴道念珠菌病的菌种分布及药敏情况；通过对瘙痒和疼痛等临床症状进行轻、中、重度的划分并进行统计,明确菌群分布(白念珠菌、非白念珠菌)的不同是否会影响临床症状的严重程度。
2.将香莲外洗液作用于白念珠菌耐药标准株CA17,按照美国临床和实验室标准协会(clinical and laboratory standards institute, CLSI)提出的标准(M27-A3方案),采用肉汤微量稀释法测定氟康唑对原代及每代菌株的MIC值,从而判断不同条件下白念珠菌耐药标准株CA17恢复对氟康唑敏感所需的代数。
3.运用现代分子生物学基因分析相关技术对相关菌株进行多靶点超高通量筛选,通过对原代耐药株、自然转种转变为敏感株的白念珠菌菌株与香莲外洗液作用下转变为敏感株的白念珠菌菌株进行转录组测序,在基因水平揭示香莲外洗液对白念珠菌作用的分子机制,从而揭示香莲外洗液的作用机理。
结果：
1.本研究通过对119例外阴阴道念珠菌病患者的阴道白带标本进行检测,发现白念珠菌97株(81.51%),其次为光滑念珠菌18株(15.13%),热带念珠菌2株(1.68%),近平滑念珠菌2株(1.68%)。药敏试验研究发现,两性霉素B对菌群的敏感性最强,其次依次是伏立康唑、氟康唑、5-氟胞嘧啶、伊曲康唑；本研究对由白念珠菌和非白念珠菌所导致的VVC患者的瘙痒及疼痛严重程度分别进行研究,发现,二者评分差异均无统计学意义(P>0.05)。
2.经香莲外洗液作用后,白念珠菌标准耐药菌株CA17于第6代恢复对氟康唑敏感,而无香莲作用的耐药白念珠菌标准耐药菌株CA17要在第20代才恢复对氟康唑敏感。
3.通过对原代耐药株、与香莲外洗液作用下转变为敏感株的白念珠菌菌株进行转录组测序,发现前者低表达后者高表达的的生物过程主要富集在与细胞氨基酸代谢过程,氨基分解过程,线粒体翻译,有机酸代谢,羧酸代谢,对氧化压力的反应,甘氨酸催化过程,丝氨酸家族氨基酸分解过程,氧化还原反应等过程；前者高表达后者低表达的生物过程主要富集在与细胞氨基酸代谢过程,氨基分解过程,羧酸代谢,有机酸代谢,蛋白质氨基酸糖基化,生物高聚物糖基化,糖基化,氮类复合物合成过程,糖蛋白合成以及代谢等过程。
4.通过对自然转种敏感株、与香莲外洗液作用下转变为敏感株的白念珠菌菌株进行转录组测序,发现在自然转种菌株中低表达香莲外洗液作用菌株中高表达的差异基因的生物过程主要富集在与细胞内转运,核糖体定位,核糖体输出到核外,核糖蛋白复合物的生物合成,横跨膜运输,蛋白质运输,核糖体合成,氧化还原有关；在自然转种株中高表达与香莲外洗液作用菌株中低表达的差异基因的生物过程主要富集在羧酸代谢,有机酸代谢,细胞内氨基酸代谢,氨基代谢,胞内蛋白运输,甘氨酸代谢,蛋白定位。
结论：
1.临床研究发现,白念珠菌仍然是导致阴道念珠菌病的主要病原微生物,这与以往的研究是一致的；两性霉素B对菌群的敏感性最强,其次是伏立康唑、氟康唑、5-氟胞嘧啶、伊曲康唑,由于不同的念珠菌对药物敏感性差异较大,有些菌株对某些药物天然耐药,因此临床上外阴阴道念珠菌病的菌种分布和准确鉴定对抗真菌药物的选择具有重要价值；根据统计结果,尚不能认为白念珠菌和非白念珠菌导致的VVC患者的瘙痒及疼痛严重程度有差别。
2.香莲外洗液能较快诱导耐药菌株恢复对氟康唑的敏感性。除此以外,香莲外洗液对各代转种的耐药菌株,MIC值与原代相同,表明香莲外洗液对耐药菌株作用相对稳定。
3.基因研究方面,无论是与耐药原代株相比,还是同自然转种恢复敏感的菌株相比,香莲外洗液作用下的敏感株差异基因分析,都与目前发现公认的耐药基因不同,提示香莲外洗液对白念珠菌可能有其特异的作用靶点,值得进一步研究。
Object ive
Candida albicans is a kind of most important opportunistic pathogens which can lead to infection of skin、mucosal、central nervous system. With development of society and modern medicine, kinds of technology and broad-spectrum antibiotics are applied into clinic which leads to elevation of incidence rate of mycotic infection. The application of antimycotic drug is widespread day after day. Beacuse of this situation, occurrence of drug resistance is more and more.
VVC is a kind of common disease.Analyzing the distribution and resista nce of infected Candida albicans isolated from patients with vulvovaginal candidiasis(VVC)、analyzing the relationship of level of ache and prurit us and kind of strains、identifing reversal effect of xianglian solution to drug resisitence Candida albicans、discovery of effecting target of xia nglian solution to reverse drug resisitence Candida albicans, which mentio ned above is the subject focused on.
Methods
1.119clinical strains of leucorrhea sample from TCM hospital of Guang dong Province were detected by CHROM agar candida colored culture medium and API/ATB kits, to analyze the distribution and resistance of infected Candida albicans isolated from patients with vulvovaginal candidiasis(V VC); Dividing level of ache and pruritus and grading are for analyzing the relationship of level of pruritus and ache and kinds of Pathogenic bacte rium.
2. Broth microdilution antifungal susceptibility test was used to dete ct MIC of drug-resistant Candida albicans Strains CA17induced by XiangLi an Lotion, to investigate generation of recovery sensitivity to Fluconazol e of drug-resistant Candida albicans Strains CA17.
3. Modern molecular biology technology was used to reveal the molecular mechanism of Xianglian solution in the gene level to Candida albicans, including primary generation resistance strain and sensitive strains which induced by Xianglian solution, sensitive strains which come from subcultivation. Multi-target superelevation flux screening t—echnology was used to construct Xianglian solution gene function mechanism.
Results
1. In119clinical strains of leucorrhea sample, Candida albicans accounts for81.51%, Candida glabrata accounts for15.13%, Candida tropicalis accounts for1.68%, Candida parapsilosis accounts for1.68%. When it confers to susceptibility test, amphotericin was best.The result of analyzing the relationship of level of ache and pruritus and kinds of strain is no value in statistics.
2. Drug-resistant Candida albicans Strains CA17regained sensitivity to fluconazole after6th passage culture induced by XiangLian Lotion, however, the passage culture of control group without XiangLian Lotion was20th.
3. Compare primary generation resistance strain and sensitive strains which induced by Xianglian solution, the lower expression of gene of primary generation resistance strain concentrates in:The amino acid metabolism process and the aminolysis process, mitochondria translation, organic acid metabolism、carboxylic acid metabolism、glycine catalysis process、serine family amino acids decompose process、redoxreaction process.the lower expression of gene of sensitive strains whichinduced by Xianglian solution concentrates in the amino acid metabolism process and the aminolysis process、 carboxylic acid metabolism、organic acid metabolism、protein amino acids glycosylation、biopolymer glycosylation、nitrogen—compounds synthesis process、glycoprotein synthesis and metabolism process.
4. Compare sensitive strains which come from subcultivation and sensitive strains which induced by Xianglian solution,the lower expression of gene of sensitive strains which come from subcultivation concentrates in: intracellular transport、ribosome allocation、ribosome、nucleoglucoprotein compound biology synthesis、transmembrane transport、protein trafficking、 ribosome synthesis、oxidoreduction;the lower expression of gene of sensitive strains which induced by Xianglian solution concentrates in:carboxylic acid metabolism、organic acid metabolism、intra-cellular amino acid metabolism、 amino-group metabolism、protein transportation transportation、glycine metabolism、proteinum localization.
Conelusion
1. Candida albicans was the most important pathogenic bacterium of vulvovaginal candidiasis(VVC). Other kinds of Candida mycoderma are more and more. Widespread usage of fluconazol is responsible for it. In clinic, we should pay more attention to susceptibility test and rational use of drug to elevate therapeutic efficacy. The result of analyzing the relationship of level of ache and pruritus and kinds of strain is no value in statistics. Compare to other Candida, Candida albicans can not aggratate the level of ache and pruritus.
2. XiangLian Lotion can induce drug-resistant Candida albicans Strains From Vagina to regain sensitivity to Fluconazole quickly.
3. In the process of searching different gene, we find that the different gene between primary generation resistance strain and sensitive strains which induced by Xianglian solution、 sensitive strains which induced by Xianglian solution and sensitive strains which come from subcultivation are different from gene which found already.the target gene which xianglian-soution effects on is different from those found already, which is worth later detailed research.
主要由白念珠菌引起的外阴阴道念珠菌病是临床常见病、多发病。本研究的主要目的包括：1.了解VVC(包括RVVC)的菌种分布和药敏情况；VVC(包括RVVC)患者的自觉症状(瘙痒和疼痛)与菌种(白念珠菌、非白念珠菌)的关系；2.观察香莲外洗液对白念珠菌耐药菌株的逆转作用；3.从基因水平,揭示香莲外洗液抗真菌的作用机理。
方法：
1.采集广东省中医院皮肤性病科及妇科符合外阴阴道念珠菌病诊断标准的119例患者的白带标本,通过菌种鉴定和药敏检测,了解外阴阴道念珠菌病的菌种分布及药敏情况；通过对瘙痒和疼痛等临床症状进行轻、中、重度的划分并进行统计,明确菌群分布(白念珠菌、非白念珠菌)的不同是否会影响临床症状的严重程度。
2.将香莲外洗液作用于白念珠菌耐药标准株CA17,按照美国临床和实验室标准协会(clinical and laboratory standards institute, CLSI)提出的标准(M27-A3方案),采用肉汤微量稀释法测定氟康唑对原代及每代菌株的MIC值,从而判断不同条件下白念珠菌耐药标准株CA17恢复对氟康唑敏感所需的代数。
3.运用现代分子生物学基因分析相关技术对相关菌株进行多靶点超高通量筛选,通过对原代耐药株、自然转种转变为敏感株的白念珠菌菌株与香莲外洗液作用下转变为敏感株的白念珠菌菌株进行转录组测序,在基因水平揭示香莲外洗液对白念珠菌作用的分子机制,从而揭示香莲外洗液的作用机理。
结果：
1.本研究通过对119例外阴阴道念珠菌病患者的阴道白带标本进行检测,发现白念珠菌97株(81.51%),其次为光滑念珠菌18株(15.13%),热带念珠菌2株(1.68%),近平滑念珠菌2株(1.68%)。药敏试验研究发现,两性霉素B对菌群的敏感性最强,其次依次是伏立康唑、氟康唑、5-氟胞嘧啶、伊曲康唑；本研究对由白念珠菌和非白念珠菌所导致的VVC患者的瘙痒及疼痛严重程度分别进行研究,发现,二者评分差异均无统计学意义(P>0.05)。
2.经香莲外洗液作用后,白念珠菌标准耐药菌株CA17于第6代恢复对氟康唑敏感,而无香莲作用的耐药白念珠菌标准耐药菌株CA17要在第20代才恢复对氟康唑敏感。
3.通过对原代耐药株、与香莲外洗液作用下转变为敏感株的白念珠菌菌株进行转录组测序,发现前者低表达后者高表达的的生物过程主要富集在与细胞氨基酸代谢过程,氨基分解过程,线粒体翻译,有机酸代谢,羧酸代谢,对氧化压力的反应,甘氨酸催化过程,丝氨酸家族氨基酸分解过程,氧化还原反应等过程；前者高表达后者低表达的生物过程主要富集在与细胞氨基酸代谢过程,氨基分解过程,羧酸代谢,有机酸代谢,蛋白质氨基酸糖基化,生物高聚物糖基化,糖基化,氮类复合物合成过程,糖蛋白合成以及代谢等过程。
4.通过对自然转种敏感株、与香莲外洗液作用下转变为敏感株的白念珠菌菌株进行转录组测序,发现在自然转种菌株中低表达香莲外洗液作用菌株中高表达的差异基因的生物过程主要富集在与细胞内转运,核糖体定位,核糖体输出到核外,核糖蛋白复合物的生物合成,横跨膜运输,蛋白质运输,核糖体合成,氧化还原有关；在自然转种株中高表达与香莲外洗液作用菌株中低表达的差异基因的生物过程主要富集在羧酸代谢,有机酸代谢,细胞内氨基酸代谢,氨基代谢,胞内蛋白运输,甘氨酸代谢,蛋白定位。
结论：
1.临床研究发现,白念珠菌仍然是导致阴道念珠菌病的主要病原微生物,这与以往的研究是一致的；两性霉素B对菌群的敏感性最强,其次是伏立康唑、氟康唑、5-氟胞嘧啶、伊曲康唑,由于不同的念珠菌对药物敏感性差异较大,有些菌株对某些药物天然耐药,因此临床上外阴阴道念珠菌病的菌种分布和准确鉴定对抗真菌药物的选择具有重要价值；根据统计结果,尚不能认为白念珠菌和非白念珠菌导致的VVC患者的瘙痒及疼痛严重程度有差别。
2.香莲外洗液能较快诱导耐药菌株恢复对氟康唑的敏感性。除此以外,香莲外洗液对各代转种的耐药菌株,MIC值与原代相同,表明香莲外洗液对耐药菌株作用相对稳定。
3.基因研究方面,无论是与耐药原代株相比,还是同自然转种恢复敏感的菌株相比,香莲外洗液作用下的敏感株差异基因分析,都与目前发现公认的耐药基因不同,提示香莲外洗液对白念珠菌可能有其特异的作用靶点,值得进一步研究。
Object ive
Candida albicans is a kind of most important opportunistic pathogens which can lead to infection of skin、mucosal、central nervous system. With development of society and modern medicine, kinds of technology and broad-spectrum antibiotics are applied into clinic which leads to elevation of incidence rate of mycotic infection. The application of antimycotic drug is widespread day after day. Beacuse of this situation, occurrence of drug resistance is more and more.
VVC is a kind of common disease.Analyzing the distribution and resista nce of infected Candida albicans isolated from patients with vulvovaginal candidiasis(VVC)、analyzing the relationship of level of ache and prurit us and kind of strains、identifing reversal effect of xianglian solution to drug resisitence Candida albicans、discovery of effecting target of xia nglian solution to reverse drug resisitence Candida albicans, which mentio ned above is the subject focused on.
Methods
1.119clinical strains of leucorrhea sample from TCM hospital of Guang dong Province were detected by CHROM agar candida colored culture medium and API/ATB kits, to analyze the distribution and resistance of infected Candida albicans isolated from patients with vulvovaginal candidiasis(V VC); Dividing level of ache and pruritus and grading are for analyzing the relationship of level of pruritus and ache and kinds of Pathogenic bacte rium.
2. Broth microdilution antifungal susceptibility test was used to dete ct MIC of drug-resistant Candida albicans Strains CA17induced by XiangLi an Lotion, to investigate generation of recovery sensitivity to Fluconazol e of drug-resistant Candida albicans Strains CA17.
3. Modern molecular biology technology was used to reveal the molecular mechanism of Xianglian solution in the gene level to Candida albicans, including primary generation resistance strain and sensitive strains which induced by Xianglian solution, sensitive strains which come from subcultivation. Multi-target superelevation flux screening t—echnology was used to construct Xianglian solution gene function mechanism.
Results
1. In119clinical strains of leucorrhea sample, Candida albicans accounts for81.51%, Candida glabrata accounts for15.13%, Candida tropicalis accounts for1.68%, Candida parapsilosis accounts for1.68%. When it confers to susceptibility test, amphotericin was best.The result of analyzing the relationship of level of ache and pruritus and kinds of strain is no value in statistics.
2. Drug-resistant Candida albicans Strains CA17regained sensitivity to fluconazole after6th passage culture induced by XiangLian Lotion, however, the passage culture of control group without XiangLian Lotion was20th.
3. Compare primary generation resistance strain and sensitive strains which induced by Xianglian solution, the lower expression of gene of primary generation resistance strain concentrates in:The amino acid metabolism process and the aminolysis process, mitochondria translation, organic acid metabolism、carboxylic acid metabolism、glycine catalysis process、serine family amino acids decompose process、redoxreaction process.the lower expression of gene of sensitive strains whichinduced by Xianglian solution concentrates in the amino acid metabolism process and the aminolysis process、 carboxylic acid metabolism、organic acid metabolism、protein amino acids glycosylation、biopolymer glycosylation、nitrogen—compounds synthesis process、glycoprotein synthesis and metabolism process.
4. Compare sensitive strains which come from subcultivation and sensitive strains which induced by Xianglian solution,the lower expression of gene of sensitive strains which come from subcultivation concentrates in: intracellular transport、ribosome allocation、ribosome、nucleoglucoprotein compound biology synthesis、transmembrane transport、protein trafficking、 ribosome synthesis、oxidoreduction;the lower expression of gene of sensitive strains which induced by Xianglian solution concentrates in:carboxylic acid metabolism、organic acid metabolism、intra-cellular amino acid metabolism、 amino-group metabolism、protein transportation transportation、glycine metabolism、proteinum localization.
Conelusion
1. Candida albicans was the most important pathogenic bacterium of vulvovaginal candidiasis(VVC). Other kinds of Candida mycoderma are more and more. Widespread usage of fluconazol is responsible for it. In clinic, we should pay more attention to susceptibility test and rational use of drug to elevate therapeutic efficacy. The result of analyzing the relationship of level of ache and pruritus and kinds of strain is no value in statistics. Compare to other Candida, Candida albicans can not aggratate the level of ache and pruritus.
2. XiangLian Lotion can induce drug-resistant Candida albicans Strains From Vagina to regain sensitivity to Fluconazole quickly.
3. In the process of searching different gene, we find that the different gene between primary generation resistance strain and sensitive strains which induced by Xianglian solution、 sensitive strains which induced by Xianglian solution and sensitive strains which come from subcultivation are different from gene which found already.the target gene which xianglian-soution effects on is different from those found already, which is worth later detailed research.
引文
[1]Lai C C, Tan C K, Huang Y T, etal. Current challenges in the management of invasive fungal infections[J]. J Infect Chemother,2008,14(2):77-85.
[2]黄海,王彦,李莹,许懿,姜远英.白念珠菌的应激反应与耐药性[J].第二军医大学学报,2010,31(11)：1239-1243.
[3]王彦,黄海,李健峰,温旭东,等.真菌耐药的研究进展.药学服务与研究,2009,9(3)：166-169.
[4]邱芳华,崔颖鹏,陈求刚.651株深部真菌感染菌种分布及耐药性分析[J].中国微生态学杂志,2007,19(2)：211-212.
[5]李志媛.酵母样真菌的分离培养及耐药分析[J].临床肺科杂志,2007,12(9)：1016,1018.
[6]杨蓬勃,胡云建.住院患者真菌感染及耐药性分析[J].中华医院感染学杂志,2007,17(6)：729—731.
[7]路晓钦,黎莉华,周丽.白假丝酵母菌感染分布及耐药性分析[J].中国感染控制杂志,2007,6(6)：419—421.
[8]周燕玲,黄宏君,吴白平.肿瘤病人真菌感染及耐药趋势分析[J].实用预防医学,2007,14(3)：900—921.
[9]张广清.女性泌尿生殖道假丝酵母菌感染及耐药性研究[J].检验医学与临床,2008,5(6)：350—351.
[10]廖万清,顾菊林.深部真菌感染治疗的现状与对策[J].中国感染与化疗杂志,2007,9：101-103
[11]Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis:a persistent public health problem [J].Clin Microbiol Rev,2007,20:133-163.
[12]White TC, Holleman S, Dy F, etal. Resistance mechanisms inclinical isolates of Candida albicans[J].Antimicrob Agents Chemother,2002,46 (6):1704-1713.
[13]Cernicka J, Subik J. Resistance mechanisms in fluconazole resistant Candida albicans isolates from vaginal candidiasis[J]. Int J Antimicrob Agents,2006,27(5):403-408.
[14]Wang YB, Wang H, Guo HY, et al. Analysis of ERG11 gene mutation in Candida albicans. [J]Di Yi Jun Yi Da Xue Xue Bao,2005,25(11):1390.
[15]Perea S, Lopez-Ribot J L, Kirkpatrick W R, etal. Prevalence of molecular mechanisms of resistance to azole antifungal agents in Candida albicans strains displaying high level fluconazole resistance isolated from human immunodeficiency virus infected patients[J]. Antimicrob Agents Chemother,2001,45(10):2676-2684.
[16]White TC. The presence of an R467K amino acid substitution and loss of allelic variation correlate with an azole-resistant la nosterol Halpha demethylase in Candida albicans. Antimicrob AgentsChemother,1997,41(7):1488-1494.
[17]Park S, PerlinD S. Establishing surrogate markers for fluconazole resistance in Candida albicans. Microb Drug Resist,2005,11(3):232-238.
[18]Sanglard D, Ischer F, Koymans L, et al. Aminoacid substitution in the cytochrome P-450 lanostero 14 alphademethylase(CYP51A1) from azole-resistant Candida albicans clinical isolates contribute to resistance to azole antifungal agents[J]. Antimicrob Agents Chemother,1998,42(2):241-253.
[19]Hitchcock C A. Cytochrome P-450-dependent 14 alpha-sterol demethylase of Candida albicans and its interaction with azole antifungals[J]. Biochemical Society transactions Biochem Soc Trans,1991,19(3):782-787.
[20]Franz R, Kelly S L, Lamb D C, et al. Multiple Molecular Mechanisms Contribute to a Stepwise Development of Fluconazole Resistance in Clinical Candida albicans Strains[J]. Antimicrobial Agents and Chemotherapy,1998,42(12):3065-3072.
[21]White T C, Marr K A, Bowden R A. Clinical, Cellular, and Molecular Factors That Contribute to Antifungal Drug Resistance[J]. Clinical Microbiology Reviews,1998,11(2): 382-402.
[22]Calabrese D, Bille J, Sanglard D. A novel multidrug efflux transporter gene of the major facilitator superfamily from Candida albicans (FLU1) conferring resistance to fluconazole[Z]. Soc General Microbiol,2000,146(6):2743-2754.
[23]Kakeya H, Miyazaki Y, Miyazaki H, et al. Genetic analysis of azole resistance in the Darlington strain of Candida albicans. [J]Antimicrob Agents Chemother, 2000,44(11):2985-2990.
[24]Xu YH, Chen LM, Li CY. Susceptibility of clinical isolates of Candida species to fluconazole and detection of Candida albicans ERG11 mutations [J]. J Antimicrob Chemother,2008,61:798-804
[25]Asai K, Tsuchimori N, Okonogi K, et al. Formation of azole-resistant Candida albicans by mutation of sterol 14-demethylase P450. [J]Antimicrob Agents Chemother,1999, 43(5):1163-1169.
[26]Marichal P, Koymans L, Willemsens S, eta.1 Contribution of mutations in the cytochrome P45014alphademethylase (Ergllp, Cyp51p) to azole resistance in Candida albicans[J]. Microbiology,1999,145(Pt10):2701-2713.
[27]徐永豪,李春阳.耐唑类药白念珠菌ERG11基因点突变[J].中国真菌学杂志,2006,1(6)：370-373.
[28]Park S, PerlinDS. Establishing surrogate markers for fluconazole resistance in Candida albicans. Microb Drug Resist,2005,11(3):232-238.
[29]黄静,张天托,朱家馨,等.耐氟康唑白念珠菌ERG11基因突变的测序研究[J].中华检验医学杂志.,2007,30(1)：31-32.
[30]周辉,龙铁军.Erg11基因突变与白念珠菌对唑类药物耐药性的初步研究.中国感染与化疗杂志,2007,7(2)：108-110.
[31]李莉,苏维奇.白念珠菌ERG11基因突变与唑类抗真菌药物耐药的关系.中华实用诊断与治疗杂志,2011,25(9)：870-875.
[32]HENRY K W, NICKELS J T, EDLIND T D. Upregulation of ERG genes in Candida species by azoles and other sterol biosyn-thesis inhibitors [J].Antimicrob Agents Chemother, 2000,44(10):2693-2700.
[33]Li X, Brown N, Chau AS, et al. Changes in susceptibility to posaconazole in clinical isolates of Candida albicans. [J] J Antimicrob Chemother.,2004,53(1):74-80.
[34]Prasad R, Gaur NA, Gaur M, etal. Efflux pumps in drug resistance of Candida.Intect uisora )rug Targets,2006,6(2):69-83.
[35]Nakamura K, Niimi M, Niimi K, etal. Functional expression of Candida albicans drug efflux pump Cdrlp in Saccharomyces cerevisiae strain deficient in membrane transporters[J].Antimicrob Agents Chemother,2001,45(12):3366-3374.
[36]Sanglard D, Kuchler K, Pagani J L, etal. Mechanism of resistance to azole antifungal agents in Candida albicans isolate from AIDS patients involve specific multidrug transporters[J]. Antimicrob Agents Chemother,1995,39(6):2378-2386.
[37]贺志彬,廖万清,熊爱君,等.白念珠菌CDR1基因表达与氟康唑耐药的关系[J].上海医学,2004,27(2)：126-128.
[38]王爽.真菌多药耐药相关的外排蛋白基因研究进展[J].中国生物制品学杂志,2008,21(3)：251-253.
[39]秦晓峰,吴建华,贾鑫,等.白念珠菌临床株FLUI基因表达与氟康唑耐药的关系[J].中华皮肤科杂志,2006,9(8)：474.
[40]Douglas LJ. Candida biofilms and their role in infection[J]. Trends Microbiol,2003, 11(1):30-36.
[41]汪长中,邵菁,汪天明,程惠娟.白念珠菌生物被膜基质研究进展.中国真菌学杂志2012,7(3)：178-183.
[42]郑璐.白念珠菌生物被膜及其耐药机制研究进展.儿科药学杂志,2009,15(3)：58-60.
[43]Al-Fattani MA, Douglas LJ.Biofilm matrix of Candida albicans and Candida tropicalis:chemical composition and role in drug resistance [J].J Med Microbiol, 2006,55(Pt 8):999-1008.
[44]王丹敏,靳颖,董小青,等.白色念珠菌生长动力学和形态学观察.武警医学院学报,2010,19(9)：698-700
[45]Chandra J, Kuhn DM, Mukherjee PK, et al. Biofilm formation by the fungal pathogen Candida albicans:development, architecture, and drug resistance[J]. J Bacteriol,2001, 183(18):5385-5394.
[46]Hornby JM, Jensen EC, Lisec AD, et al. Quorum sensing in the dimorphic fungus Candida albicans is mediated by farnesol [J]. ApplEnviron Microbiol,2001,67(7):2982-2992.
[47]陈晓君,谭军艳,马鸣,等.不同培养基对白念珠菌生物被膜产生法尼醇的影响.口腔生物医学,2012,3(2)：68-70
[48]Flemming HC, Wingender J. The biofilm matrix [J]. Nat Rev Microbiol,2010,8(9) 623-633.
[49]郑璐.白念珠菌生物被膜及其耐药机制研究进展.儿科药学杂志,2009,15(3)：58-60
[50]王睿.中国药物应用与监测,2007(5)：5-7.
[51]Donlan RM, Costerton JW. Biofilms:survival mechanisms of clinically relevant microorganisms[J].Clin Microbiol Rev,2002,15(2):167.
[52]Ramage G, Bachmann S, Patterson TF, et al. Investigation of multidrug efflux pumps in relation to fluconazole resistance in Candida albicans biofilms[J]. Antimicrob Chemother,2002,49(6):973.
[53]Mukherjee PK, Chandra J, Kuhn DM, et al. Mechanism of fluconazole resistance in Candida albicans biofilms:phase-specific role of efflux pumps and membrane sterols[J]. Infect Immune,2003,71 (8):4333.
[54]杨继君,陈兴平.外排泵基因在白念珠菌生物膜耐药性产生中的作用.中国皮肤性病学杂志,2008,22(9)：519-521
[55]亓庆国.华西口腔医学杂志,2009,27(2)：191-195
[56]李莹,李德东,王彦.白念珠菌IFD6基因高表达促进生物被膜形成.第二军医大学学报,2010,31(6)：599-603
[57]Cowen LE, Carpenter AE, Matangkasombut O. Genetic architecture of Hsp90-dependent drug resistance[J].Eukaryot Cell,2006,5(12):2184-2188.
[58]姜远英,刘伟,曹永兵.念珠菌的耐药机制及应对策略研究.中国真菌学杂志2011,6(4)：193-197.
[59]朱春香,高平挥,姜远英.白念珠菌基因变异对唑类药物耐受性的研究进展[J]..药学学报,2010,45(7)：821-826.
[60]中华妇产科学会分会感染性疾病协作组.外阴阴道念珠菌病诊治规范(草案)[J].中华妇产科杂志,2004,39(60)：430.
[61]宋春花,常欣峰,韩立民.带下病中医辨证分型与霉菌、滴虫感染的关系分析[J].赣南医学院学报,2010,30(3)：437-438.
[62]王惠珍主编.妇科辨病专方治疗(临床辨病专方治疗丛书).北京：人民卫生出版社,2000：21.
[63]杜小利,朱宁娃.白拟方内服外熏治疗霉菌性阴道炎疗效观察[J].时珍国医国药,2007,18(5)：1205.
[64]张美云.中药内服配合克霉唑栓外用治疗复发性外阴阴道念珠菌病的临床观察[J].大家健康,2011,5(8)：23-24.
[65]符彩霞.中药外洗方配合治疗念珠菌性阴道58例疗效观察[J].中医药导报,2011,17(11)：56-57.
[66]刘芳.中药熏蒸疗法治疗霉菌性阴道炎临床效果分析[J].亚太传统医药,2011,7(11)：61-62.
[67]曹丽君,高丽华.中药六神栓治疗霉菌性阴道炎疗效分析[J].中国误诊学杂志,2008,8(22)：5382.
[68]宋颖.杀虫止痒方治疗霉菌性阴道炎104例[J].陕西中医,2008,(29)5：525-526.
[69]王晶.紫草油治疗外阴阴道念珠菌病50例疗效观察[J].中国现代药物应用,2009,3(13)：94-95.
[70]孙秋,殷召云.150例霉菌性阴道炎的疗效观察[J].光明中医,2009,24(6)：1052.
[71]郭素芬.中西医结合治疗顽固性霉菌性阴道炎76例[J].实用中医药杂志,2010,26(3)：174-175.
[72]万莉洁.中西医结合治疗霉菌性阴道炎的疗效观察[J].中国医药指南,2011,9(36)：175-176.
[73]王磊,赵声兰,陈朝银,等.几种抗艾滋病中药有效成分对解脲支原体和白色念珠菌体外抑制作用的实验研究[J].时珍国医国药,2006,17(5)：767-768.
[74]董小青,刘丽英,陈虹,等.土槿乙酸抗白色念珠菌的敏感性及作用机理的电镜研究[J].天津药学,2008(2)：1-3.
[75]权华,赵靖霞,徐铮,等.盐酸小檗碱与氟康唑协同抗耐药白念珠菌的动物实验研究[J].实用医 药杂志,2011,28(6)：532-535.
76]李丰霞,张宏.汉防己甲素对氟康唑抗白念珠菌活性的增效作用[J].中华皮肤科杂志,2006,39(8)：454-456.
[77]李丰霞,张宏,单孔荣.汉防己甲素对氟康唑抗白念珠菌菌丝相活性的增效作用及其机制研究[J].中国人兽共患病学报,2009,25(1)：13-16.
[78]汪长中,程惠娟,官妍,等.没食子酸抑制白念珠菌生物膜作用的研究[J].中国中药杂志,2009,43(9)：1137-1140.
[79]郑童娇,张虹.4种中药体外抗口腔念珠菌的敏感性研究[J].中国实用口腔科杂志,2008,1(9)：532.
[80]吴岚,周曾同,周永梅,等.苦参碱对白念珠菌生物膜的体外抑制作用[J].上海口腔医学,2009,18(4)：415-418.
[81]解光艳,朱玲玲,孙振新,等.小檗碱苦参碱抗外阴阴道念珠菌病混合菌生物被膜形成作用研究[J].安徽中医学院学报,31(2)：52-55.
[82]王刚生,邓洁华.中药提取组合物(胶囊)对念珠菌及曲霉的体外抗菌实验[J].时珍国医国药,2010,21(4)：884-885.
[83]闻平,陈蕾,俞晓丽,等.胡桃提取物抗白念珠菌作用的机制研究[J].中药药理与临床,2008,24(1)：51-52.
[84]汪长中,程惠娟,官妍,等.穿心莲内酯体外抗白念珠菌生物膜作用的初步研究[J].中国真菌学杂志,2008,3(3)：134.
[85]兰晓明,牟茜,王春波.牡蛎软体中抗菌蛋白对白念珠菌超微结构的影响[J].中国海洋药物杂志,2008,27(1)：55-57.
[86]陆文铨,曹颖瑛,陈海生,等.蒺藜中甾体皂苷TTS-12对白念珠菌生物被膜形成的抑制作用[J].第二军医大学学报,2010,31(2)：132—135.
[87]汪长中,程惠娟,徐颖,等.黄芩苷体外抗白念球菌生物膜作用的研究[J].上海中医药杂志,2008,42(8)：78-80.
[88]汪长中,程惠娟,徐胜利,等.中药水提物对白念珠菌生物膜抑制作用的研究[J].中国微生态学杂志,2009,21(11)：965.
[89]张石群,林辉,苗琦,等.覆盆子提取物联合唑类药物抗真菌活性研究[J].中国真菌学报,2012,7(1)：4-7.
[90]邱莹,于腾.20种中药及其复方抗真菌实验研究[J].济宁医学院学报,2007,30(3)：237-238.
[91]汪长中,程惠娟,官妍.牡丹皮水煎剂对体外白念珠菌生物膜的抑制作用[J].微生物学杂志,2009,29(2)：67.
[92]邓洁华,王刚生,马耀辉,等.中药提取液体外抗肠道念珠菌的作用[J].世界华人消化杂志,2010,(7)：741-743.
[93]解光艳,汪长中,李露天,等.复方百肤青抗外阴阴道念珠菌病[J].时珍国医国药,2012,23(9)：2126-2127.
[94]吴小云,刘志春,马廉兰.知母合剂对白念珠菌的黏附抑制作用[J].时珍国医国药,2012,23(3)：675-676.
[95]汪长中,程惠娟,官妍,等.黄连解毒汤体外对白念珠菌生物膜形成的影响[J].热带病与寄生虫学杂志,2007,5(2)：82.
[96]汪长中,程惠娟,徐颖,等.黄连解毒汤及其单味药对白念珠菌生物膜影响的比较[J].上海中医药杂志,2008(2)：63.
[97]范瑞强,鲁长明.中药香莲复方抗真菌作用的研究[J].实用医学杂志,1995,11(1)：67-68.
[98]刘宇倩,池凤好,刘绮娜,范瑞强.中药香莲外洗液对40株白色念珠菌的药敏分析[J].广东医学,2010,31(16)：2161-2163.
[99]张文,梁惠,周强,陈建宏,范瑞强.香莲外洗液诱导白色念珠菌耐药菌株恢复对氟康唑的敏感性[J].中华医院感染学杂志,2010,20(10)：1455.
[100]林辉,张石群,苗琪,等.苦寒类中药抗白念珠菌的研究进展[J].中国真菌学杂志,2012,7(3)：184-187.
[101]Richer SS, Galask RP, Messer SA, etal. Antifungal susceptibilities of Candida species causing vulvovaginal and epidemiology of recurrent cases. J Clin Microbiol,2005,43(5):2155-2162.
[102]张文,柏彩英,周强,范瑞强.外阴阴道念珠菌病的菌种分布及耐药性分析.皮肤性病诊疗学杂志.2012,19(3)：139-141.
[103]张力,贺帅.女性阴道念珠菌药敏试验及分析.吉林医学,2011,32(33)：7044.
[104]叶应妩,王毓三.全国临床检验操作规程[M].3版.南京：东南大学出版社,2006：618.
[105]National Committee for Clinical Laboratory Standards. Reference method for broth dilution antifungal susceptibility testing of yeasts:approved standard[S]. NCCLS document M27-A. Wayne Pennsylvania:NCCLS,1997.
[106]李厚敏,刘伟,李若瑜.美国临床实验室标准化委员会2003年版产孢丝状真菌药敏试验方案简介[J].中华检验医学杂志,2005,28(1)：121.
[107]王志远,张宏,张革化.白念珠菌对唑类药物的耐药与对策[J].中国人兽共患病学报,2011,27(12)：1126.
[108]郭建辉,曹毅,陶茂灿.中药癣净散抗真菌作用的研究,中国真菌学杂志,20061(3)：154-15
[109]范瑞强、李丽芸、梁君儿,等.复方香连外洗液和外用霜治疗外阴阴道念珠菌病的临床观察[J].中国皮肤性病学杂志,1996,10(1)：42.
[110]曹先伟,冀朝辉,李若瑜,等.白念珠菌对唑类抗真菌药物的耐药机制探讨[J].中华医院感染学杂志,2007,17(3)：258-261.
[2]黄海,王彦,李莹,许懿,姜远英.白念珠菌的应激反应与耐药性[J].第二军医大学学报,2010,31(11)：1239-1243.
[3]王彦,黄海,李健峰,温旭东,等.真菌耐药的研究进展.药学服务与研究,2009,9(3)：166-169.
[4]邱芳华,崔颖鹏,陈求刚.651株深部真菌感染菌种分布及耐药性分析[J].中国微生态学杂志,2007,19(2)：211-212.
[5]李志媛.酵母样真菌的分离培养及耐药分析[J].临床肺科杂志,2007,12(9)：1016,1018.
[6]杨蓬勃,胡云建.住院患者真菌感染及耐药性分析[J].中华医院感染学杂志,2007,17(6)：729—731.
[7]路晓钦,黎莉华,周丽.白假丝酵母菌感染分布及耐药性分析[J].中国感染控制杂志,2007,6(6)：419—421.
[8]周燕玲,黄宏君,吴白平.肿瘤病人真菌感染及耐药趋势分析[J].实用预防医学,2007,14(3)：900—921.
[9]张广清.女性泌尿生殖道假丝酵母菌感染及耐药性研究[J].检验医学与临床,2008,5(6)：350—351.
[10]廖万清,顾菊林.深部真菌感染治疗的现状与对策[J].中国感染与化疗杂志,2007,9：101-103
[11]Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis:a persistent public health problem [J].Clin Microbiol Rev,2007,20:133-163.
[12]White TC, Holleman S, Dy F, etal. Resistance mechanisms inclinical isolates of Candida albicans[J].Antimicrob Agents Chemother,2002,46 (6):1704-1713.
[13]Cernicka J, Subik J. Resistance mechanisms in fluconazole resistant Candida albicans isolates from vaginal candidiasis[J]. Int J Antimicrob Agents,2006,27(5):403-408.
[14]Wang YB, Wang H, Guo HY, et al. Analysis of ERG11 gene mutation in Candida albicans. [J]Di Yi Jun Yi Da Xue Xue Bao,2005,25(11):1390.
[15]Perea S, Lopez-Ribot J L, Kirkpatrick W R, etal. Prevalence of molecular mechanisms of resistance to azole antifungal agents in Candida albicans strains displaying high level fluconazole resistance isolated from human immunodeficiency virus infected patients[J]. Antimicrob Agents Chemother,2001,45(10):2676-2684.
[16]White TC. The presence of an R467K amino acid substitution and loss of allelic variation correlate with an azole-resistant la nosterol Halpha demethylase in Candida albicans. Antimicrob AgentsChemother,1997,41(7):1488-1494.
[17]Park S, PerlinD S. Establishing surrogate markers for fluconazole resistance in Candida albicans. Microb Drug Resist,2005,11(3):232-238.
[18]Sanglard D, Ischer F, Koymans L, et al. Aminoacid substitution in the cytochrome P-450 lanostero 14 alphademethylase(CYP51A1) from azole-resistant Candida albicans clinical isolates contribute to resistance to azole antifungal agents[J]. Antimicrob Agents Chemother,1998,42(2):241-253.
[19]Hitchcock C A. Cytochrome P-450-dependent 14 alpha-sterol demethylase of Candida albicans and its interaction with azole antifungals[J]. Biochemical Society transactions Biochem Soc Trans,1991,19(3):782-787.
[20]Franz R, Kelly S L, Lamb D C, et al. Multiple Molecular Mechanisms Contribute to a Stepwise Development of Fluconazole Resistance in Clinical Candida albicans Strains[J]. Antimicrobial Agents and Chemotherapy,1998,42(12):3065-3072.
[21]White T C, Marr K A, Bowden R A. Clinical, Cellular, and Molecular Factors That Contribute to Antifungal Drug Resistance[J]. Clinical Microbiology Reviews,1998,11(2): 382-402.
[22]Calabrese D, Bille J, Sanglard D. A novel multidrug efflux transporter gene of the major facilitator superfamily from Candida albicans (FLU1) conferring resistance to fluconazole[Z]. Soc General Microbiol,2000,146(6):2743-2754.
[23]Kakeya H, Miyazaki Y, Miyazaki H, et al. Genetic analysis of azole resistance in the Darlington strain of Candida albicans. [J]Antimicrob Agents Chemother, 2000,44(11):2985-2990.
[24]Xu YH, Chen LM, Li CY. Susceptibility of clinical isolates of Candida species to fluconazole and detection of Candida albicans ERG11 mutations [J]. J Antimicrob Chemother,2008,61:798-804
[25]Asai K, Tsuchimori N, Okonogi K, et al. Formation of azole-resistant Candida albicans by mutation of sterol 14-demethylase P450. [J]Antimicrob Agents Chemother,1999, 43(5):1163-1169.
[26]Marichal P, Koymans L, Willemsens S, eta.1 Contribution of mutations in the cytochrome P45014alphademethylase (Ergllp, Cyp51p) to azole resistance in Candida albicans[J]. Microbiology,1999,145(Pt10):2701-2713.
[27]徐永豪,李春阳.耐唑类药白念珠菌ERG11基因点突变[J].中国真菌学杂志,2006,1(6)：370-373.
[28]Park S, PerlinDS. Establishing surrogate markers for fluconazole resistance in Candida albicans. Microb Drug Resist,2005,11(3):232-238.
[29]黄静,张天托,朱家馨,等.耐氟康唑白念珠菌ERG11基因突变的测序研究[J].中华检验医学杂志.,2007,30(1)：31-32.
[30]周辉,龙铁军.Erg11基因突变与白念珠菌对唑类药物耐药性的初步研究.中国感染与化疗杂志,2007,7(2)：108-110.
[31]李莉,苏维奇.白念珠菌ERG11基因突变与唑类抗真菌药物耐药的关系.中华实用诊断与治疗杂志,2011,25(9)：870-875.
[32]HENRY K W, NICKELS J T, EDLIND T D. Upregulation of ERG genes in Candida species by azoles and other sterol biosyn-thesis inhibitors [J].Antimicrob Agents Chemother, 2000,44(10):2693-2700.
[33]Li X, Brown N, Chau AS, et al. Changes in susceptibility to posaconazole in clinical isolates of Candida albicans. [J] J Antimicrob Chemother.,2004,53(1):74-80.
[34]Prasad R, Gaur NA, Gaur M, etal. Efflux pumps in drug resistance of Candida.Intect uisora )rug Targets,2006,6(2):69-83.
[35]Nakamura K, Niimi M, Niimi K, etal. Functional expression of Candida albicans drug efflux pump Cdrlp in Saccharomyces cerevisiae strain deficient in membrane transporters[J].Antimicrob Agents Chemother,2001,45(12):3366-3374.
[36]Sanglard D, Kuchler K, Pagani J L, etal. Mechanism of resistance to azole antifungal agents in Candida albicans isolate from AIDS patients involve specific multidrug transporters[J]. Antimicrob Agents Chemother,1995,39(6):2378-2386.
[37]贺志彬,廖万清,熊爱君,等.白念珠菌CDR1基因表达与氟康唑耐药的关系[J].上海医学,2004,27(2)：126-128.
[38]王爽.真菌多药耐药相关的外排蛋白基因研究进展[J].中国生物制品学杂志,2008,21(3)：251-253.
[39]秦晓峰,吴建华,贾鑫,等.白念珠菌临床株FLUI基因表达与氟康唑耐药的关系[J].中华皮肤科杂志,2006,9(8)：474.
[40]Douglas LJ. Candida biofilms and their role in infection[J]. Trends Microbiol,2003, 11(1):30-36.
[41]汪长中,邵菁,汪天明,程惠娟.白念珠菌生物被膜基质研究进展.中国真菌学杂志2012,7(3)：178-183.
[42]郑璐.白念珠菌生物被膜及其耐药机制研究进展.儿科药学杂志,2009,15(3)：58-60.
[43]Al-Fattani MA, Douglas LJ.Biofilm matrix of Candida albicans and Candida tropicalis:chemical composition and role in drug resistance [J].J Med Microbiol, 2006,55(Pt 8):999-1008.
[44]王丹敏,靳颖,董小青,等.白色念珠菌生长动力学和形态学观察.武警医学院学报,2010,19(9)：698-700
[45]Chandra J, Kuhn DM, Mukherjee PK, et al. Biofilm formation by the fungal pathogen Candida albicans:development, architecture, and drug resistance[J]. J Bacteriol,2001, 183(18):5385-5394.
[46]Hornby JM, Jensen EC, Lisec AD, et al. Quorum sensing in the dimorphic fungus Candida albicans is mediated by farnesol [J]. ApplEnviron Microbiol,2001,67(7):2982-2992.
[47]陈晓君,谭军艳,马鸣,等.不同培养基对白念珠菌生物被膜产生法尼醇的影响.口腔生物医学,2012,3(2)：68-70
[48]Flemming HC, Wingender J. The biofilm matrix [J]. Nat Rev Microbiol,2010,8(9) 623-633.
[49]郑璐.白念珠菌生物被膜及其耐药机制研究进展.儿科药学杂志,2009,15(3)：58-60
[50]王睿.中国药物应用与监测,2007(5)：5-7.
[51]Donlan RM, Costerton JW. Biofilms:survival mechanisms of clinically relevant microorganisms[J].Clin Microbiol Rev,2002,15(2):167.
[52]Ramage G, Bachmann S, Patterson TF, et al. Investigation of multidrug efflux pumps in relation to fluconazole resistance in Candida albicans biofilms[J]. Antimicrob Chemother,2002,49(6):973.
[53]Mukherjee PK, Chandra J, Kuhn DM, et al. Mechanism of fluconazole resistance in Candida albicans biofilms:phase-specific role of efflux pumps and membrane sterols[J]. Infect Immune,2003,71 (8):4333.
[54]杨继君,陈兴平.外排泵基因在白念珠菌生物膜耐药性产生中的作用.中国皮肤性病学杂志,2008,22(9)：519-521
[55]亓庆国.华西口腔医学杂志,2009,27(2)：191-195
[56]李莹,李德东,王彦.白念珠菌IFD6基因高表达促进生物被膜形成.第二军医大学学报,2010,31(6)：599-603
[57]Cowen LE, Carpenter AE, Matangkasombut O. Genetic architecture of Hsp90-dependent drug resistance[J].Eukaryot Cell,2006,5(12):2184-2188.
[58]姜远英,刘伟,曹永兵.念珠菌的耐药机制及应对策略研究.中国真菌学杂志2011,6(4)：193-197.
[59]朱春香,高平挥,姜远英.白念珠菌基因变异对唑类药物耐受性的研究进展[J]..药学学报,2010,45(7)：821-826.
[60]中华妇产科学会分会感染性疾病协作组.外阴阴道念珠菌病诊治规范(草案)[J].中华妇产科杂志,2004,39(60)：430.
[61]宋春花,常欣峰,韩立民.带下病中医辨证分型与霉菌、滴虫感染的关系分析[J].赣南医学院学报,2010,30(3)：437-438.
[62]王惠珍主编.妇科辨病专方治疗(临床辨病专方治疗丛书).北京：人民卫生出版社,2000：21.
[63]杜小利,朱宁娃.白拟方内服外熏治疗霉菌性阴道炎疗效观察[J].时珍国医国药,2007,18(5)：1205.
[64]张美云.中药内服配合克霉唑栓外用治疗复发性外阴阴道念珠菌病的临床观察[J].大家健康,2011,5(8)：23-24.
[65]符彩霞.中药外洗方配合治疗念珠菌性阴道58例疗效观察[J].中医药导报,2011,17(11)：56-57.
[66]刘芳.中药熏蒸疗法治疗霉菌性阴道炎临床效果分析[J].亚太传统医药,2011,7(11)：61-62.
[67]曹丽君,高丽华.中药六神栓治疗霉菌性阴道炎疗效分析[J].中国误诊学杂志,2008,8(22)：5382.
[68]宋颖.杀虫止痒方治疗霉菌性阴道炎104例[J].陕西中医,2008,(29)5：525-526.
[69]王晶.紫草油治疗外阴阴道念珠菌病50例疗效观察[J].中国现代药物应用,2009,3(13)：94-95.
[70]孙秋,殷召云.150例霉菌性阴道炎的疗效观察[J].光明中医,2009,24(6)：1052.
[71]郭素芬.中西医结合治疗顽固性霉菌性阴道炎76例[J].实用中医药杂志,2010,26(3)：174-175.
[72]万莉洁.中西医结合治疗霉菌性阴道炎的疗效观察[J].中国医药指南,2011,9(36)：175-176.
[73]王磊,赵声兰,陈朝银,等.几种抗艾滋病中药有效成分对解脲支原体和白色念珠菌体外抑制作用的实验研究[J].时珍国医国药,2006,17(5)：767-768.
[74]董小青,刘丽英,陈虹,等.土槿乙酸抗白色念珠菌的敏感性及作用机理的电镜研究[J].天津药学,2008(2)：1-3.
[75]权华,赵靖霞,徐铮,等.盐酸小檗碱与氟康唑协同抗耐药白念珠菌的动物实验研究[J].实用医 药杂志,2011,28(6)：532-535.
76]李丰霞,张宏.汉防己甲素对氟康唑抗白念珠菌活性的增效作用[J].中华皮肤科杂志,2006,39(8)：454-456.
[77]李丰霞,张宏,单孔荣.汉防己甲素对氟康唑抗白念珠菌菌丝相活性的增效作用及其机制研究[J].中国人兽共患病学报,2009,25(1)：13-16.
[78]汪长中,程惠娟,官妍,等.没食子酸抑制白念珠菌生物膜作用的研究[J].中国中药杂志,2009,43(9)：1137-1140.
[79]郑童娇,张虹.4种中药体外抗口腔念珠菌的敏感性研究[J].中国实用口腔科杂志,2008,1(9)：532.
[80]吴岚,周曾同,周永梅,等.苦参碱对白念珠菌生物膜的体外抑制作用[J].上海口腔医学,2009,18(4)：415-418.
[81]解光艳,朱玲玲,孙振新,等.小檗碱苦参碱抗外阴阴道念珠菌病混合菌生物被膜形成作用研究[J].安徽中医学院学报,31(2)：52-55.
[82]王刚生,邓洁华.中药提取组合物(胶囊)对念珠菌及曲霉的体外抗菌实验[J].时珍国医国药,2010,21(4)：884-885.
[83]闻平,陈蕾,俞晓丽,等.胡桃提取物抗白念珠菌作用的机制研究[J].中药药理与临床,2008,24(1)：51-52.
[84]汪长中,程惠娟,官妍,等.穿心莲内酯体外抗白念珠菌生物膜作用的初步研究[J].中国真菌学杂志,2008,3(3)：134.
[85]兰晓明,牟茜,王春波.牡蛎软体中抗菌蛋白对白念珠菌超微结构的影响[J].中国海洋药物杂志,2008,27(1)：55-57.
[86]陆文铨,曹颖瑛,陈海生,等.蒺藜中甾体皂苷TTS-12对白念珠菌生物被膜形成的抑制作用[J].第二军医大学学报,2010,31(2)：132—135.
[87]汪长中,程惠娟,徐颖,等.黄芩苷体外抗白念球菌生物膜作用的研究[J].上海中医药杂志,2008,42(8)：78-80.
[88]汪长中,程惠娟,徐胜利,等.中药水提物对白念珠菌生物膜抑制作用的研究[J].中国微生态学杂志,2009,21(11)：965.
[89]张石群,林辉,苗琦,等.覆盆子提取物联合唑类药物抗真菌活性研究[J].中国真菌学报,2012,7(1)：4-7.
[90]邱莹,于腾.20种中药及其复方抗真菌实验研究[J].济宁医学院学报,2007,30(3)：237-238.
[91]汪长中,程惠娟,官妍.牡丹皮水煎剂对体外白念珠菌生物膜的抑制作用[J].微生物学杂志,2009,29(2)：67.
[92]邓洁华,王刚生,马耀辉,等.中药提取液体外抗肠道念珠菌的作用[J].世界华人消化杂志,2010,(7)：741-743.
[93]解光艳,汪长中,李露天,等.复方百肤青抗外阴阴道念珠菌病[J].时珍国医国药,2012,23(9)：2126-2127.
[94]吴小云,刘志春,马廉兰.知母合剂对白念珠菌的黏附抑制作用[J].时珍国医国药,2012,23(3)：675-676.
[95]汪长中,程惠娟,官妍,等.黄连解毒汤体外对白念珠菌生物膜形成的影响[J].热带病与寄生虫学杂志,2007,5(2)：82.
[96]汪长中,程惠娟,徐颖,等.黄连解毒汤及其单味药对白念珠菌生物膜影响的比较[J].上海中医药杂志,2008(2)：63.
[97]范瑞强,鲁长明.中药香莲复方抗真菌作用的研究[J].实用医学杂志,1995,11(1)：67-68.
[98]刘宇倩,池凤好,刘绮娜,范瑞强.中药香莲外洗液对40株白色念珠菌的药敏分析[J].广东医学,2010,31(16)：2161-2163.
[99]张文,梁惠,周强,陈建宏,范瑞强.香莲外洗液诱导白色念珠菌耐药菌株恢复对氟康唑的敏感性[J].中华医院感染学杂志,2010,20(10)：1455.
[100]林辉,张石群,苗琪,等.苦寒类中药抗白念珠菌的研究进展[J].中国真菌学杂志,2012,7(3)：184-187.
[101]Richer SS, Galask RP, Messer SA, etal. Antifungal susceptibilities of Candida species causing vulvovaginal and epidemiology of recurrent cases. J Clin Microbiol,2005,43(5):2155-2162.
[102]张文,柏彩英,周强,范瑞强.外阴阴道念珠菌病的菌种分布及耐药性分析.皮肤性病诊疗学杂志.2012,19(3)：139-141.
[103]张力,贺帅.女性阴道念珠菌药敏试验及分析.吉林医学,2011,32(33)：7044.
[104]叶应妩,王毓三.全国临床检验操作规程[M].3版.南京：东南大学出版社,2006：618.
[105]National Committee for Clinical Laboratory Standards. Reference method for broth dilution antifungal susceptibility testing of yeasts:approved standard[S]. NCCLS document M27-A. Wayne Pennsylvania:NCCLS,1997.
[106]李厚敏,刘伟,李若瑜.美国临床实验室标准化委员会2003年版产孢丝状真菌药敏试验方案简介[J].中华检验医学杂志,2005,28(1)：121.
[107]王志远,张宏,张革化.白念珠菌对唑类药物的耐药与对策[J].中国人兽共患病学报,2011,27(12)：1126.
[108]郭建辉,曹毅,陶茂灿.中药癣净散抗真菌作用的研究,中国真菌学杂志,20061(3)：154-15
[109]范瑞强、李丽芸、梁君儿,等.复方香连外洗液和外用霜治疗外阴阴道念珠菌病的临床观察[J].中国皮肤性病学杂志,1996,10(1)：42.
[110]曹先伟,冀朝辉,李若瑜,等.白念珠菌对唑类抗真菌药物的耐药机制探讨[J].中华医院感染学杂志,2007,17(3)：258-261.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |