热带念珠菌临床分离株对氟康唑耐药分子机制的研究

Objective This study aimed to investigate the molecular mechanisms responsible for fluconazole resistance in clinical isolates of this pathogenic yeast .Methods A total of 41 Candida tropicalis strains were collected from the clinical laboratory of Taiyuan City Central Hospital .Antifungal susceptibility testing was performed by ATB FUNGU 3 method.The 14 α-demethylase (ERG11) gene in all clinical iso-lates of Candida tropicalis were amplified by PCR,and their nucleotide sequences were determined in order to detect point mutations.Likewise,efflux transporters (CDR1 and MDR1) and ERG11 genes were tested by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) for their expression in Candida tropicalis cells at the mRNA level.Results The fluconazole-resistant rate of 41 Candida tropicalis was 12.2%.The amino acid substitutions in ERG11p of R245K,Y221F and V362I were found in fluconazole-re-sistant isolates.And no amino acid substitution was detected in fluconazole -susceptible ones.The mRNA level of CDR1,MDR1 and ERG11 genes in fluconazole-resistant isolates all showed overexpression compared with fluconazole-susceptible ones.Conclusions Missense mutations in ERG11 gene associated with overexpres-sion of CDR1,MDR1 and ERG11 gene seemed to be responsible for the acquired fluconazole resistance of these clinical isolates.

Objective The aim of the study was to evaluate the characteristics of HIV drug-genotypic resistance among patients taking ifrst-line ARV regimens using polymerase chain reaction and sequencing, and guide to design optimal ARV regimens for these patients.
Methods HIV reverse transcriptase-encoded gene was ampliifed with RT-PCR and ampliifed PCR products were aligned and comparatively analyzed with HIV resistance database to ifnd drug-resistance mutations.
Results Twenty-eight PCR products were amplified and sequenced successfully in 30 serum samples of recruited HIV-infected patients with virologic failure. The resistance rate was 96%, mutations in NRT region were found in 26 patients (93%), while mutations in NNRT region were found in 27 patients (96%). M184V was the most common mutation (86%), K65R was selected in 14%of recruited individuals and TAMs occurred in 50%of patients, which resulted in resistance to NRTIs. Y181C and V179D were the most common mutations in NNRTIs and prevalence was 43%(12/28) and 36%(10/28), respectively, which resulted in cross-resistance to NNRTIs due to low-genetic barrier.
Conclusions Virologic failure may occur in long-term administration of ifrst-line ARV regimens, and drug-resistance mutations can be found in these patients, which resulted in resistance to ifrst-line ARV regimens. We emphasized that HIV viral load assay and resistance assay were important tools to guide healthcare workers to design an optimal second-line ARV regimens for HAART-experienced individuals with virologic failure.

Objective Nucleos(t)ide analogues (NAs) na?ve chronic hepatitis B(CHB) patients were given rescue combination therapy after drug resistance to lamivudine or adefovir. Evolution of HBV mutation patterns and its impact on antiviral effects were studied.
Methods Total of 142 na?ve CHB patients treated with lamivudine were randomly divided into two groups when lamivudine resistance occurred. One group was added with adefovir, the other was switched to entecavir and adefovir. Seventy-two na?ve CHB patients treated with adefovir were randomly divided into two groups when adefovir resistance occurred. One group was added with lamivudine, the other was added with entecavir. HBV polymerase reverse transcriptase mutations associated with resistance were analyed before and after 48 weeks of rescue therapy, respectively.
Results The mutation patterns of M204V/I, M204V+L180M were predominantly found in CHB patients after lamivudine resistance. Meanwhile, the entecavir resistance mutation patterns were also detected. Therefore, patients with lamivudine resistance could develop more diverse drug resistance mutations if they were switched to entecavir and adefovir. The mutation patterns of rtA181 were predominantly found in CHB patients after adefovir resistance and rescure therapy with add-on entecavir was more effective than with add-on lamivudine Conclusions Resistance mutation analysis chould help to choose NAs, reduce resistance and ehance antiviral effects.

Prostate cancer (PCa) is the second most common malignancy among men in the world. Castration-resistant prostate cancer (CRPC) is the lethal form of the disease, which develops upon resistance to ifrst line androgen deprivation therapy (ADT). Emerging evidence demonstrates a key role for the PI3K-AKT-mTOR signaling axis in the development and maintenance of CRPC. This pathway, which is deregulated in the majority of advanced PCas, serves as a critical nexus for the integration of growth signals with downstream cellular processes such as protein synthesis, proliferation, survival, metabolism and differentiation, thus providing mechanisms for cancer cells to overcome the stress associated with androgen deprivation. Furthermore, preclinical studies have elucidated a direct connection between the PI3K-AKT-mTOR and androgen receptor (AR) signaling axes, revealing a dynamic interplay between these pathways during the development of ADT resistance. Thus, there is a clear rationale for the continued clinical development of a number of novel inhibitors of the PI3K pathway, which offer the potential of blocking CRPC growth and survival. In this review, we will explore the relevance of the PI3K-AKT-mTOR pathway in PCa progression and castration resistance in order to inform the clinical development of speciifc pathway inhibitors in advanced PCa. In addition, we will highlight current deifciencies in our clinical knowledge, most notably the need for biomarkers that can accurately predict for response to PI3K pathway inhibitors.

Temozolomide resistance in high grade gliomas

High grade gliomas are always the research focus in the field of neurosurgery due to their poor prognosis despite the current standard therapeutic regimen of surgical resection followed by radiation therapy and chemotherapy.Alkylating agent temozolomide has been established as the standard chemotherapy while its resistance inevitable during treatment.This phenomenon seriously influences the prognosis of patients suffering from high grade gliomas.This review aims to elucidate temozolomide chemoresistance mechanisms through three chapters including O6-methylguanine-DNA methyltransferase (MGMT) methylation,mismatch repair mutation and epigenetic regulation consisting of p21,chromatin and histone,Y-box binding protein-1 and microRNAs.

Advancements in microRNA based cancer therapeutics

Antiplatelet Drug Resistance

Platelet activation plays an important role in arteried thrombosis. Therefore, several million individuals worldwide take antiiplatelet drugs, including aspirin or clopidogrel.

重症监护室病原菌分布及耐药性分析

目的：调查医院重症监护室（ICU）患者临床感染病原菌的分布及耐药趋势，为控制医院感染及临床合理选用抗菌药物提供依据。方法对本院2012年1月至2014年12月 ICU 住院患者送检的各类标本中分离出的病原菌分布及耐药性进行回顾性分析。结果共分离病原菌497株，以革兰阴性杆菌为主占73．24％，革兰阳性球菌51株占10．26％，真菌82株占16．50％。其中以痰标本为主占76．06％，其次是血液标本10．87％，中段尿标本3．62％。革兰阴性杆菌中铜绿假单胞菌居于首位占23．34％，其次为鲍曼不动杆菌12．88％、肺炎克雷伯菌11．47％、嗜麦芽窄食单胞菌5．03％、大肠埃希菌3．22％；超广谱β‐内酰胺酶（ESBLs）检出率分别为38．60％，革兰阳性球菌中金黄色葡萄球菌占2．01％，其中对苯唑西林的耐药率（MRSA）高达100％，未检出万古霉素耐药菌株。结论ICU 为医院感染高发科室，以呼吸道感染为主，病原菌以革兰阴性杆菌为主，大部分细菌对常用抗菌药物表现为高度耐药。加强 ICU 病原学耐药性监测，对指导临床合理使用抗菌药物和预防医院感染具有重要意义。