2型糖尿病肺癌患者生存期影响因素分析

目的探讨2型糖尿病肺癌患者生存期及其影响因素。方法选取2014年至2016年在我院诊断的T2DM合并肺癌的患者43为观察组,同期诊断单纯肺癌不合并T2DM的患者40为对照组,查阅患者的一般资料,调查所有可能影响患者预后的危险因素,如年龄、性别、肺癌TNM分期、病理分型、远处转移、合并症、吸烟、治疗情况、血糖及控制血糖的方法等,随访患者的生存情况。结果观察组PFS时间为7.8±5.1月,对照组PFS时间为11.1±6.1月,观察组PFS时间明显短于对照组;观察组OS时间为15.0±7.5月,对照组OS时间为18.5±8.8月,观察组OS时间明显短于对照组。Cox回归分析发现,患者生存时间与是否合并糖尿病、远处转移、病理分期有关,差异具有统计学意义(P<0.05),而年龄、性别、是否吸烟、病理分型等对总生存期的影响较差,差异无统计学意义((P>0.05),Kaplan-Meier分析结果显示:合并T2DM的肺癌患者PFS明显低于单纯未合并T2DM的肺癌患者,远处转移的的肺癌患者PFS明显低于无远处转移的肺癌患者,IV期的肺癌患者低于II期的肺癌患者,II期肺癌患者低于I期的肺癌患者。结论T2DM合并肺癌无论是无进展生存期还是总生存期均低于单纯肺癌不合并T2DM的患者,T2DM合并肺癌患者除了传统的因素如远处转移、肿瘤TNM分期等影响肺癌患者的预后外,T2DM也是影响肺癌患者预后的独立危险因素。     

Functional characterization of CEP250 variant identified in nonsyndromic retinitis pigmentosa

Retinitis pigmentosa (RP) is the most common manifestation of inherited retinal diseases with high degree of genetic, allelic, and phenotypic heterogeneity. CEP250 encodes the C‐Nap1 protein and has been associated with various retinal phenotypes. Here, we report the identification of a mutation (c.562C>T, p.R188*) in the CEP250 in a consanguineous family with nonsyndromic RP. To gain insights into the molecular pathomechanism underlying CEP250 defects and the functional relevance of CEP250 variants in humans, we conducted a functional characterization of CEP250 variant using a novel Cep250 knockin mouse line. Remarkably, the disruption of Cep250 resulted in severe impairment of retinal function and significant retinal morphological alterations. The homozygous knockin mice showed significantly reduced retinal thickness and ERG responses. This study not only broadens the spectrum of phenotypes associated with CEP250 mutations, but also, for the first time, elucidates the function of CEP250 in photoreceptors using a newly established animal model.     

侵袭性真菌病修订定义——欧洲癌症研究和治疗组织／侵袭性真菌感染协作组和美国国立变态反应和感染病研究院真菌病研究组（EORTC／MSG）共识组

侵袭性真菌病（IFD）是真菌感染致死的重要原因，明确和统一此类疾病的诊断定义是提高临床研究质量的重要因素，标准的定义可加强该类研究的一致性和可重复性。2002年EORTc／MSG共同发表了有关免疫缺陷患者IFD定义的国际共识，由于诊断技术的发展以及该领域的发展需要对原定义进行修订。此次修订始于2003年，经过专家多次讨论，于2005年初稿获得通过。经过6个月的意见反馈和商榷后，修订定义终稿获得批准。修订后的定义保留了诊断IFD原定义的3个级别：确诊（proven）、拟诊（probable）和疑似（possible），其中对拟诊的定义进行了扩展，并限制了疑似定义的范围。侵袭性真菌病确诊定义适用于任何患者，不考虑患者是否存在免疫缺陷的情况，而拟诊及疑似定义仅适用于存在免疫缺陷的患者。此次修订力图促进临床和流行病学研究，也可作为高危患者中其他感染的有用模式。     

注射用益气复脉(冻干)与氯化丁基胶塞相容性研究中抗氧剂和硫化剂的含量测定

目的 建立注射用益气复脉（冻干）药品中氯化丁基橡胶塞用抗氧剂2,6-二叔丁基-4-甲基苯酚（BHT）和硫化剂对-特辛基苯酚的含量测定方法,并对其稳定性进行考察。方法 采用ACQUITY UPLC BEH C₁₈柱,以乙腈-0.2%甲酸水为流动相梯度洗脱,体积流量0.3 mL/min,柱温35℃,检测波长280 nm。结果 BHT和对特-辛基苯酚质量浓度在0.4～20μg/mL线性关系良好（r > 0.999）;准确度试验平均回收率分别为99.3%、101.9%,精密度及耐用性结果均符合要求;注射用益气复脉（冻干）稳定性考察样品中BHT和对-特辛基苯酚含量均小于限度值。结论 所建立的方法准确可靠,可用于注射用益气复脉（冻干）中BHT和对-特辛基苯酚的含量测定。     

Population pharmacokinetics of theophylline in adult Chinese patients with asthma and chronic obstructive pulmonary disease

Background Theophylline has a narrow therapeutic range and large interindividual variability in blood levels, so a thorough understanding of its pharmacokinetic characteristics is essential. Population pharmacokinetic (PPK) approaches could achieve it and many PPK studies of theophylline have been reported in infants. However, none was conducted in Chinese adults and none has explored the effect of CYP1A2 genotypes on the PPK characteristics of theophylline in adults. Objective To evaluate the PPK characteristics of theophylline and to assess the possible influence of covariates, including CYP1A2 genotypes, on theophylline clearance in Chinese adult patients. Setting The study is conducted at the department of respiration in Zhujiang Hospital, Guangzhou, China. Methods Theophylline concentrations were obtained from eligible patients and were measured by high performance liquid chromatography. The polymorphisms of ??3860G?>?A, ??163C?>?A, C5347T (CYP1A2*1B) and G-3113A were genotyped using a direct sequencing method. Then, CYP1A2 genotypes, age, fat-free mass (FFM) and other covariates were used to develop a PPK model by NONMEM software. Bootstrap analysis was used to asses the accuracy and prediction of the PPK model. Main outcome measure The concentration and clearance of theophylline. Results A total of 134 theophylline concentrations from 95 patients were obtained. The final model was as follows: CL/F(L/h)?=?4.530?×?(FFM/56.1)^0.75 ×?0.713^CYP1A2*1B, the inter-individual variability in clearance/bioavailability (CL/F) was 44.0%, and the residual variability was 9.8%. The final model was proved to be reliable by bootstrap analysis. Conclusion Theophylline clearance was significantly associated with FFM and CYP1A2*1B genotypes in Chinese adult patients.     

Effect of Dibutyl Phthalate on the Tolerance and Lipid Accumulation in the Green Microalgae <Emphasis Type="Italic">Chlorella vulgaris</Emphasis>

Offshore oil exploration creates threats to coastal ecosystems, including increasing urbanization and associated effluent releases. Genotoxicity biomarkers in mussels were determined across a gradient of coastal zone influences of offshore petroleum exploration in southeastern Brazil. Coastal ecosystems such as estuaries, beaches and islands were seasonally monitored for genotoxicity evaluation using the brown mussel Perna perna. The greatest DNA damage (5.2%?±?1.9% tail DNA and 1.5‰? ±?0.8‰ MN) were observed in urban estuaries, while Santana Archipelago showed levels of genotoxicity near zero and is considered a reference site. Mussels from urban and pristine beaches showed intermediate damage levels, but were also influenced by urbanization. Thus, mussel genotoxicity biomarkers greatly indicated the proposed oil exploration and urbanization scenarios that consequently are genetically affecting coastal organisms.     

温针灸对类风湿性关节炎大鼠血清免疫球蛋白及滑膜组织中VCAM-1的影响

目的:观察温针灸对类风湿性关节炎(Rheumatoid arthritis,RA)大鼠血清免疫球蛋白及滑膜组织中血管细胞黏附分子-1(vascular cell adhesion molecule-1,VCAM-1)的影响,探讨温针灸改善类风湿性关节炎的作用机制。方法:选取清洁级3月龄SD健康大鼠60只,雌雄各半,体质量(208±4.5)g,先适应性喂养1周,然后按照数字表法随机抽取15只为正常组进行常规喂养,其余大鼠进行模型复制,并随机分为模型组、针刺组和温针灸组,每组15只。采用皮内注射牛Ⅱ型胶原接种诱发制备大鼠类风湿性关节炎模型。温针灸组于造模后第1天取"足三里""肾俞"和"悬钟"温针灸治疗,采用手针,刺激量以大鼠耐受为度,日1次,共治疗21 d。针刺组针刺方法同温针灸组,不用艾灸。模型组不给予任何处理。疗程结束后滑膜取材,采用MD-100自动生化分析仪检测血清中IgG、IgM和IgA的含量,以免疫组化法检测VCAM-1在滑膜组织中的表达。结果:与正常组比较,模型组大鼠血清IgG、IgM、IgA含量和滑膜组织中VCAM-1表达水平显著升高(P0.05);与模型组比较,温针灸组和针刺组大鼠血清IgG、IgM、IgA含量和滑膜组织中VCAM-1表达水平显著降低(P0.05);与针刺组比较,温针灸组大鼠血清IgG、IgM、IgA含量和滑膜组织中VCAM-1表达水平降低幅度更明显(P0.05)。结论:温针灸可升高RA大鼠血清IgG、IgM和IgA的含量,抑制VCAM-1在滑膜组织中的表达,可能是温针灸通过调节RA大鼠慢性炎症以改善关节损伤的调节机制之一。     

舒郁抑斑方对慢性心理应激促发动脉粥样硬化大鼠的保护作用

舒郁抑斑方(SYYB)对伴有慢性心理应激的冠心病患者有较好的治疗作用。为观察SYYB对慢性心理应激促发大鼠动脉粥样硬化(athero-sclerosis,As)早期病变形成及其炎症反应的影响,采用高脂饵食+维生素D3(VD3)腹腔注射建立大鼠As早期病变模型(As),在此基础上采用不可预知慢性应激刺激法(As+CUMS),观察慢性心理应激是否加重大鼠病变及SYYB(6.6,13.2,26.4 mg·kg~(-1))的干预作用。采用悬尾实验和新奇实验法观察大鼠行为学改变,检测血清应激激素促肾上腺素(adrenocortico-tropic hormone,ACTH)、皮质醇(cortisol,Cor)、去甲肾上腺素(noradrenaline,NE)的含量,称量胸腺、肾上腺的质量,综合评价SYYB对模型大鼠心理应激的影响。取主动脉弓HE染色观察血管组织病理改变,测定血清甘油三酯(triglycerides,TG)、总胆固醇(total cholesterol,TC)、高密度脂蛋白(HDL-C),评价SYYB对大鼠As病变的影响。检测血清高敏C反应蛋白(high-sensitivity C-reactive protein,hs CRP)、白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6),评价SYYB对As大鼠炎症反应的影响。实验结果显示,与空白组相比,As组TC,TG含量增高,HDL-C明显降低,HE染色可见主动脉壁增厚。As+CUMS组TC,TG含量显著增高,HDL-C明显降低,HE染色可见主动脉弓内膜增厚,泡沫细胞形成,行为学评价及血清应激激素检测结果显示动物存在慢性应激反应,该实验As+CUMS模型复制成功。SYYB可降低血清中TC,TG含量,减轻主动脉泡沫细胞、钙化灶及炎性细胞浸润,对血清中ACTH和Cor,NE有明显的降低作用,同时有效降低了血清中动脉粥样硬化相关的炎性标志物hs-CRP,IL-1和IL-6。提示SYYB对心理应激促发As大鼠的保护作用,其作用与改善神经-内分泌网络平衡及调节相关炎症反应有关。     

中医药治疗干眼症研究进展

近年来人们对干眼症的关注与日俱增,中医药发挥其传统优势,运用内治,外治,针灸等方法,达到机体脏腑功能平衡,气血津液充足,化生泪液有源,泪液不乏。但是,目前中医学对于干眼症的研究还存在一些问题。第一,干眼的疗效评价标准参照西医学标准,中医方面尚无统一标准。第二,干眼症的中医辨证分型也无统一标准,数据可信度难以保证。第三,临床的研究设计多为小样本,科研设计不够严谨,缺乏相关的动物实验研究。干眼症是多种原因诱发的疾病,已经逐步引起人们的重视,但就其发病的病因及机制应更进一步的深入研究。治疗上应在中医整体观念的指导下,运用辨证施治同时结合现代医学理论。应统一干眼症的辨证分型及疗效评价标准,增加临床观察指标的客观性及可信度,同时临床学者及科研工作者应尝试采取大样本,多中心的随机对照实验,让研究结果更有说服力,也应该尝试更多的动物实验研究,运用先进的科学技术及方法研究本病的病理生理状况,预防等,将其结果转化为临床可用的知识,为干眼症的诊疗开辟新的篇章。     

中原帖氏飞针聚气针法治疗椎动脉型颈椎病60例

目的:观察中原帖氏飞针聚气针法治疗椎动脉型颈椎病的临床疗效。方法:选取2014年4月—2016年6月郑州市中医院疼痛科、针灸科门诊及河南省重竞技运动管理中心收治的椎动脉型颈椎病患者60例,随机分为治疗组和对照组,每组30例。治疗组给予中原帖氏飞针聚气针法治疗,对照组给予指切进针法治疗。结果:治疗组ESCV评分优于对照组(P0.05);治疗组治疗后椎动脉、基底动脉收缩期峰值血流速度优于对照组(P0.05);治疗组有效率优于对照组(P0.05)。结论:中原帖氏飞针聚气针法治疗椎动脉型颈椎病临床疗效确切。