Effect of Exposure to Agent Orange on the Risk of Monoclonal Gammopathy and Subsequent Transformation to Multiple Myeloma: A Single-Center Experience From the Veterans Affairs Hospital,Detroit

BackgroundMonoclonal gammopathy of undetermined significance (MGUS) is an indolent, premalignant plasma cell disorder with the potential of transforming into symptomatic multiple myeloma (MM). There are multiple risk factors that contribute to transformation. Agent Orange (AO) has been linked with multiple malignant and nonmalignant conditions.Patients and MethodsWe conducted a retrospective chart review of patients with monoclonal gammopathy who were seen at John D. Dingell Veterans Affairs Medical Center (Detroit, Michigan) between 2005 and 2015 with MGUS, smoldering multiple myeloma, and MM. We explored baseline patient characteristics and explored AO exposure. Dates of diagnosis, dates of progression, and expiration dates were recorded to time to progression and overall survival (OS).ResultsWe identified 211 patients with monoclonal gammopathy; 96% were male and 122 were African American. Eleven patients had reported AO exposure. Cumulative risk of progression in the overall population was 1.4% at 1 year. Risk of transformation in the population exposed to AO was significantly higher with a hazard ratio (HR) of 11.19 (95% confidence interval [CI], 2.10-59.47; P = .005). OS was numerically shorter in AO-exposed patients with a median OS of 7 years compared with 11.1 years in those not exposed. However, AO exposure was not associated with OS in multivariable analysis (HR, 0.50; 95% CI, 0.07-3.83; P = .508).ConclusionMonoclonal gammopathy is a premalignant condition with the risk of progressing to MM. Exposure to AO has been implicated in multiple conditions including MM. Our study demonstrates an increased risk of progression in exposed patients.     

江西省锐尖山香圆亲缘关系与群体结构的ISSR分析

目的:利用简单序列重复区间扩增多态性(ISSR)分子标记技术对江西省锐尖山香圆进行亲缘关系和遗传结构分析,为该药材资源的保护和利用提供理论依据。方法:采集江西省4个县6个采样地的22份锐尖山香圆叶片样本,利用试剂盒法提取基因组DNA。利用64条通用ISSR分子标记引物进行聚合酶链式反应(PCR)扩增,运用聚丙烯酰胺凝胶电泳(PAGE)方法检测条带。选择NTsys 2. 10e软件,采用非加权配对算术平均法(UPGMA)计算遗传相似系数并聚类分析。利用Structure 2. 1软件分析群体遗传结构。结果:有48条ISSR引物扩增后获得了产物,多态性条带百分率处于45. 45%～100%。UPGMA聚类分析表明4个县的锐尖山香圆资源不能按照行政区域划分分别聚为一类,群体遗传结构分析表明22份锐尖山香圆群体可以划分为3个类群。结论:江西省锐尖山香圆群体间存在着基因交流,会影响该药材不同地理来源种质资源的遗传结构组成。     

天麻素生物合成的研究进展

天麻素是我国名贵中药材天麻中的一种主要活性成分，具有降血压、抗癫痫、抑制肿瘤、保护神经等多方面的药理活性。随着市场对天麻素需求的不断增长以及传统获取方法固有的问题，导致急需新的方法来解决天麻素生产实际中面临的各项困难。生物合成法是一种有别于传统获取法的新方法，已在天麻素获取上取得了较大进展和成果，故现阶段有必要从天麻素生物合成途径、植物转化法和微生物转化法3个方面，对天麻素生物合成进行系统地阐述，从而为进一步改进和完善天麻素生产方法，以满足人们对其不断增长的需求提供有价值的参考。     

某院耐碳青霉烯类肠杆菌科细菌耐药基因分析

目的研究某院耐碳青霉烯类肠杆菌科细菌(CRE)在细菌耐药方面的分子流行病学特征,为CRE的防控提供依据。方法收集某院2013—2017年细菌室保存的CRE,对其进行多位点序列分型(MLST)、药敏试验、全基因序列测定,选取部分CRE中携带的碳青霉烯耐药基因进行基因环境分析。结果共收集62株CRE,成功复活51株;其中耐碳青霉烯类肺炎克雷伯菌(CRKP)30株,耐碳青霉烯类大肠埃希菌(CREC)9株,耐碳青霉烯类阴沟肠杆菌(CRECL)6株,耐碳青霉烯类其他肠杆菌6株。CRKP MLST主要包括3株ST147、2株ST11;CREC MLST主要包括3株ST167;CRECL MLST主要包括3株ST93、2株ST88。51株CRE对氨苄西林、头孢噻肟的耐药率最高,均为100%。耐碳青霉烯类耐药基因分布:1株携带blaKPC-2,14株携带blaIMP-4,18株携带blaNDM-1,22株携带blaNDM-5,2株携带blaNDM-9,10株携带blaOXA-1,10株携带blaOXA-10,2株携带blaOXA-23,2株携带blaOXA-66。分析blaNDM-1、blaNDM-5、blaNDM-9、blaIMP-4不同菌种的基因环境,发现几种耐药基因各自的基因环境都与已报道的基因环境相似,无明显的菌种间差异性。结论耐药基因通过水平传播能稳定存在于不同的CRE菌株中,对医院感染防控造成一定的威胁。     

不同地理居群新塔花的ITS2和psbA-trnH序列及聚类分析

目的:分析18个不同地理居群新塔花的内转录间隔区(ITS)2和psbA-trnH序列,为其种质资源评价和基原药用植物遗传多样性分析提供参考。方法:试剂盒法提取新塔花基因组DNA,聚合酶链式反应(PCR)扩增ITS2和psbA-trnH间隔区序列,双向测序,拼接,基于Kimura两参数模型(K2P)构建邻接法(NJ)系统发育树。结果:不同地理居群新塔花ITS2和psbA-trnH序列均有种内差异。ITS2序列长度平均为236 bp,检测有9个单倍型,遗传距离为0～0. 022,不同地理居群新塔花聚为两支,XTH3,XTH6,XTH9等10个地理居群聚为一支,XTH4,XTH5,XTH10等8个地理居群聚为另一支。除XTH6的psbAtrnH序列存在6 bp缺失外,其他地理居群的psbA-trnH序列长度均为355 bp,检测有4个单倍型,遗传距离为0～0. 023,不同地理居群新塔花聚为两支,XTH1,XTH3,XTH4等12个地理居群聚为一支,XTH14,XTH17,XTH18聚为另一支。基于ITS2+psbA-trnH组合序列的系统发育(NJ)树显示,不同地理居群的新塔花可分为两支,XTH11,XTH12,XTH16等12个地理居群聚为一支,XTH14,XTH17,XTH18聚为另一支。结论:不同地理居群的新塔花地理位置接近或相似,相对遗传距离较小,亲缘关系较为接近,说明不同地理居群新塔花的亲缘关系及其遗传多样性与地理位置相关。     

Germline variant burden in multidrug resistance transporters is a therapy-specific predictor of survival in breast cancer patients

Multidrug resistance due to facilitated drug efflux mediated by ATP-binding cassette (ABC) transporters is a main cause for failure of cancer therapy. Genetic polymorphisms in ABC genes affect the disposition of chemotherapeutics and constitute important biomarkers for therapeutic response and toxicity. Here we correlated germline variability in ABC transporters with disease-specific survival (DSS) in 960 breast cancer (BRCA), 314 clear cell renal cell carcinoma and 325 hepatocellular carcinoma patients. We find that variant burden in ABCC1 is a strong predictor of DSS in BRCA patients, whereas candidate polymorphisms are not associated with DSS. This association is highly drug-specific for subgroups treated with the MRP1 substrates cyclophosphamide (log-rank p = 0.0011) and doxorubicin (log-rank p = 0.0088) independent of age and tumor stage, whereas no association was found in individuals treated with tamoxifen (log-rank p = 0.13). Structural mapping of significant variants revealed multiple variants at residues involved in protein stability, cofactor stabilization or substrate binding. Our results demonstrate that BRCA patients with high variant burden in ABCC1 are less prone to respond appropriately to pharmacological therapy with MRP1 substrates, thus incentivizing the consideration of genomic germline data for precision cancer medicine.