神经外科术后患者静脉输注替考拉宁脑脊液药物浓度研究

目的了解神经外科术后患者静脉输注替考拉宁时脑脊液药物浓度,探讨神经外科手术破坏血脑屏障后是否可增加脑脊液药物浓度,以及药物持续泵入对脑脊液药物浓度的影响。方法选择神经外科术后留置术区/脑室引流管的患者,分为常规给药组(替考拉宁400 mg,30 min泵入,1次/12 h重复给药)和持续给药组(替考拉宁400 mg,30 min泵入,再以200 mg,1次/6 h持续泵入),于给药后相应时间点采集脑脊液标本检测替考拉宁浓度。结果常规给药组脑脊液替考拉宁浓度泵入后即刻浓度为(0.004±0.0123)mg/L,泵入后1 h达峰值(0.712±1.028)mg/L,后逐渐下降,泵入后12、18、24 h分别为(0.254±0.222)、(0.173±0.152)、(0.355±0.207)mg/L。持续给药组脑脊液替考拉宁泵入后即刻浓度为(0.017±0.020)mg/L,4 h后达峰值(0.587±0.255)mg/L,泵入后6、12、18、24 h分别为(0.429±0.416)、(0.325±0.254)、(0.476±0.686)、(0.318±0.464)mg/L,6 h后药物浓度相对稳定,介于(0.318±0.464)~(0.476±0.686)mg/L。常规给药组、持续给药组的AUC0—24 h分别为5.590 mg/L·h、9.082 mg/L·h。两组患者仅峰值附近区域替考拉宁浓度达到凝固酶阴性葡萄球菌(CNS)MIC50,但其浓度高于CNS MIC50的时间占整个给药时间的比例远小于50%;两组患者脑脊液替考拉宁浓度均未能达到金黄色葡萄球菌MIC50。结论持续输注替考拉宁后,患者脑脊液药物浓度较常规给药组有所增加,但仍未能达所要求的MIC;结合血药浓度的实验,血液浓度增高有利于脑脊液药物浓度增加,可考虑适当增加剂量以达到临床治疗目的。     

Dietary Patterns Modulate the Risk of Non-Alcoholic Fatty Liver Disease in Chinese Adults

Although previous studies reported the associations between the intakes of individual foods or nutrients and the risk of non-alcoholic fatty liver disease (NAFLD), the relationship between dietary patterns and NAFLD in the Chinese population has been rarely studied to date. This study aimed to investigate the associations between dietary patterns and the risk of NAFLD in a middle-aged Chinese population. The Study subjects were 999 Chinese adults aged 45–60 years in the Anhui province who participated in the Hefei Nutrition and Health Study. Dietary intake was collected by a semi-quantitative food frequency questionnaire. NAFLD was defined as the presence of moderate-severe hepatic steatosis (by B-ultrasonic examination); the absence of excessive alcohol use (>20 g day⁻¹ in men and 10 g day⁻¹ in women); no use of steatogenic medications within the past six months; no exposure to hepatotoxins; and no history of bariatric surgery. Log-binomial regression analysis was used to examine the association between dietary patterns and NAFLD with adjustment of potential confounding variables. Out of 999 participants, 345 (34.5%) were classified as having NAFLD. Four major dietary patterns were identified: “Traditional Chinese”, “Animal food”, “Grains-vegetables” and “High-salt” dietary patterns. After adjusting for potential confounders, subjects in the highest quartile of the “Animal food” pattern scores had greater prevalence ratio for NAFLD (prevalence ratio (PR) = 1.354; 95% confidence interval (CI): 1.063–1.724; p < 0.05) than did those in the lowest quartile. After adjustment for body mass index (BMI), compared with the lowest quartile of the “Grains-vegetables” pattern, the highest quartile had a lower prevalence ratio for NAFLD (PR = 0.777; 95% CI: 0.618–0.977, p < 0.05). However, the “traditional Chinese” and “high-salt” dietary patterns showed no association with the risk of NAFLD. Our findings indicated that the “Animal food” dietary pattern was associated with an increased risk of NAFLD.     

基于报告基因的抗CD20单克隆抗体ADCC生物学活性测定方法的建立

利用Jurkat/NFAT-luc+FcγRIIIa转基因细胞系作为效应细胞,WIL2-S细胞系作为靶细胞,通过荧光素酶检测系统(Bio GloTM Luciferase Assay System)进行抗CD20单抗的ADCC生物学活性检测,并对实验条件进行优化及方法学验证。结果显示抗CD20单抗在该方法中存在量效关系,且符合四参数方程式:y=(A-D)/[1+(X/C)B]+D。方法经优化确定靶细胞为WIL2-S细胞,抗体稀释浓度为18 000 ng·m L-1,1∶5倍的稀释倍数,效靶比为6∶1,诱导时间为6 h。该方法具有良好的专属性,8次独立实验的回归分析、线性及平行性均通过统计学检验;4个不同稀释组回收率样本经3次测定,相对效价分别为(44.39±3.93)%、(72.74±2.78)%、(128.28±7.01)%和(168.19±2.70)%,变异系数均小于10%,对应回收率分别为(88.78±7.85)%、(96.99±3.70)%、(102.63±5.61)%和(112.12±1.80)%。本研究利用转基因细胞法成功建立抗CD20单抗ADCC生物学活性检测方法,该方法专属性强、重复性好,准确性高,可作为抗CD20单抗ADCC生物学活性的常规检测方法。     

Refractive index sensing using the metal layer in DVD-R discs

In recent years, grating based bio-sensors have received much attention due to their promising applications in integrated sensing devices. However, production of high quality, large scale and low cost metal gratings is still challenging. Here, we introduce an extremely simple and low cost method to fabricate metal gratings by peeling off the metal layer from a DVD-R disc. An atomic force microscope image shows that the metal layer is a high quality grating, the period and depth of which are 740 nm and 86 nm, respectively. Based on the fabricated metal grating, refractive index sensing is experimentally achieved using two configurations, where either the resonant wavelength or the modulated laser power is measured. The sensitivity of the sensor by wavelength modulation reaches as high as 637 nmRIU⁻¹, which is comparable with or even higher than that of the existing grating coupled sensors. Our method largely reduces the cost to fabricate high quality metal gratings and will promote the development of grating based SPR sensors.

Here, we introduce an extremely simple and low cost method to fabricate metal gratings by peeling off the metal layer from a DVD-R disc.     

磷霉素联合左氧氟沙星对鲍曼不动杆菌生物膜的体外研究

目的探讨磷霉素(FOS)对鲍曼不动杆菌生物膜的破坏作用以及与左氧氟沙星(LFX)的联合杀菌效果。方法选取临床分离鲍曼不动杆菌菌株构建体外生物膜模型,微量肉汤稀释法测定FOS及LFX的最低抑菌浓度(MIC),连续稀释法测定生物膜内活菌计数,结晶紫染色法半定量生物膜。用单因素方差分析进行统计处理。结果生物膜经抗生素作用24 h后,生物膜半定量显示,FOS组及FOS+LFX组吸光度值均少于空白对照组,差异有统计学意义(P<0.01);但LFX组吸光度值与空白对照组比较,差异无统计学意义。FOS组及LFX组的生物膜内活菌计数与空白对照组比较,差异无统计学意义;FOS+LFX组第4,8,24 h膜内活菌计数均少于空白对照组(P<0.01)。结论 FOS能破坏鲍曼不动杆菌已形成的生物膜,并可增强LFX对生物膜内鲍曼不动杆菌的清除作用。     

瑞巴派特分散片的人体药动学及生物等效性

建立了液相色谱-串联质谱法测定健康志愿者口服瑞巴派特分散片(受试制剂)和普通片(参比制剂,膜固思达(R))后的血药浓度,估算两制剂的药动学参数并评价生物等效性.采用随机、开放、双周期交叉试验设计,22名男性健康志愿者单剂量口服受试或参比制剂0.1g后,血样经乙腈直接沉淀蛋白后进行LC-MS/MS分析,利用DAS2.1.1软件计算药动学参数,并进行生物等效性评价.受试和参比制剂在人血浆中瑞巴派特的cmax为(236.9±103.4)和(233.9±105.1) ng/ml,tmax为(2.7±1.1)和(2.9±1.4)h,t1/2为(2.0±0.8)和(2.3±1.5)h,AUC0→12h为(929.0±291.9)和(970.5±353.2) ng·h·ml1.受试制剂的相对生物利用度为(102.6±29.8)％.     

款冬花炮制前后总生物碱含量比较

目的:建立款冬花总生物碱含量测定方法,并对款冬花生品和炮制品的含量进行比较研究。方法:采用酸性染料比色法,检测波长:417.5 nm。结果:款冬花总生物碱在6.75~135.00μg范围内呈良好的线性关系,回归方程:y=85.228x-0.0401(r=0.9995)。款冬花生品样品中总生物碱平均含量为0.1070mg·g-1,蜜炙品样品中总生物碱平均含量为0.1633 mg·g-1,甘草炙品样品中总生物碱平均含量为0.0861 mg·g-1。结论:该方法经方法学验证可用于款冬花中总生物碱含量的测定。款冬花生品经炮制后,总生物碱含量发生变化,且炮制方法不同,总生物碱含量变化不同。蜜炙品的总生物碱含量最高,生品次之,甘草炙品最低。     

Comparison analysis of first-line asparaginase- versus non-asparaginase-based regimens for early-stage extranodal NK/T-cell lymphoma

Annals of Hematology - The present study investigated the efficacy and toxicity profile of first-line asparaginase (ASP)-based versus non-ASP-based regimens in treating early-stage extranodal...     

Quantitative Metabolomics Reveals Heart Failure With Midrange Ejection Fraction as a Distinct Phenotype of Heart Failure

BackgroundHeart failure with midrange ejection fraction (HFmrEF) has been recently acknowledged as a separate phenotype, but metabolomics evaluation of this subtype remains largely unexamined.MethodsA quantitative metabolomics study on amino acids and acylcarnitines was performed to characterize different states of heart failure (HF) in 628 participants. Both multivariate orthogonal partial least squares- discriminant analysis and univariate Mann-Whitney U test were used to explore reliable metabolic profiles associated with different HF states. The resulting metabolites were further refined to obtain diagnostic metabolite scores (DMSs) with the use of ordinal logistic regression. Lasso-penalized regression was applied to produce a survival-associated prognostic metabolite score (PMS). The Cox proportional hazards model, Kaplan-Meier curves, and time-dependent receiver operating characteristics were used for a comprehensive assessment of prognostic value using PMS versus traditional clinical biomarkers.ResultsThe optimized models identified a panel of 15 differential metabolites that were shared across different HF states, whereas some metabolites were associated with a specific state. PMS consisting of 9 metabolites demonstrated an appreciably better prognostic value (hazard ratio [HR] 1.62, 95% confidence interval [CI] 1.25-2.1) vs the natural logarithm of N-terminal pro–B-type natriuretic peptide (Ln[NT-proBNP]; HR 1.23, 95% CI 0.94-1.61; P < 0.001). The overall area under the receiver operating characteristic curve value of PMS was superior to that of Ln(NT-proBNP) in risk prediction for patients with HFmrEF and HF with reduced ejection fraction (HFrEF) subtypes (P < 0.001).ConclusionsTargeted metabolomics has provided a novel understanding of the molecular mechanism underlying HF. Both DMS and PMS clearly demonstrated HFmrEF as a distinct phenotype between a mild HF with preserved ejection fraction state and a severe HFrEF state. PMS exhibited superior prognostic value than Ln(NT-proBNP). Further investigation is needed with independent large-scale validation.     

埃索美拉唑与奥美拉唑根除幽门螺杆菌疗效比较的Meta分析

目的:对以埃索美拉唑和奥美拉唑为基础疗程为1周的三联/四联疗法根除幽门螺杆菌的疗效进行系统评价。方法:检索Pubmed、Embase数据库、Cochrane图书馆临床对照试验资料库、中国知网、维普数据库和万方数据库,检索时限从建库至2013年10月,搜集公开发表的有关埃索美拉唑与奥美拉唑对比治疗幽门螺杆菌感染的随机对照临床试验。应用Rev Man 5.2软件对符合条件的纳入研究进行Meta分析。结果:共5项研究符合入选标准。Meta分析结果表明,与奥美拉唑相比,埃索美拉唑与适当的抗菌疗法联合用药根除幽门螺杆菌疗效更好(OR=2.59,95%可信区间:1.27~5.29,P=0.009)。埃索美拉唑与奥美拉唑治疗引发的不良反应发生率比较差异无统计学意义(OR=1.23,95%可信区间:0.72~2.09,P=0.45)。结论:埃索美拉唑较奥美拉唑根除幽门螺杆菌感染效果更好,但尚需进一步在前瞻性随机对照临床试验中加以验证。