Hepatitis B virus-specific T cell responses after stopping nucleos(t)ide analogue therapy in HBeAg-negative chronic hepatitis B

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外周血树突状细胞的诱导及其对T细胞的激发效应

目的建立外周血树突状细胞(Dendritic     

Social media mining in drug development—Fundamentals and use cases

The incorporation of patients' perspectives into drug discovery and development has become critically important from the viewpoint of accounting for modern-day business dynamics. There is a trend among patients to narrate their disease experiences on social media. The insights gained by analyzing the data pertaining to such social-media posts could be leveraged to support patient-centered drug development. Manual analysis of these data is nearly impossible, but artificial intelligence enables automated and cost-effective processing, also referred as social media mining (SMM). This paper discusses the fundamental SMM methods along with several relevant drug-development use cases.     

Ability of 3 Frailty Measures to Predict Short-Term Outcomes in Older Patients Admitted for Post-Acute Inpatient Rehabilitation

ObjectivesTo evaluate the ability of 3 commonly used frailty measures to predict short-term clinical outcomes in older patients admitted for post-acute inpatient rehabilitation.DesignObservational cohort study.Setting and ParticipantsConsecutive patients (n = 207) admitted to a geriatric inpatient rehabilitation facility.MethodsFrailty on admission was assessed using a frailty index, the physical frailty phenotype, and the Clinical Frailty Scale (CFS). Predictive capacity of the frailty instruments was analyzed for (1) nonhome discharge, (2) readmission to acute care, (3) functional decline, and (4) prolonged length of stay, using multivariate logistic regression models and receiver operating characteristic (ROC) curves.ResultsThe number of patients classified as frail was 91 (44.0%) with the frailty index, 134 (64.7%) using the frailty phenotype, and 151 (73.0%) with the CFS. The 3 frailty measures revealed acceptable discriminatory accuracy for nonhome discharge (area under the curve ≥ 0.7) but differed in their predictive ability: the adjusted odds ratio (OR) for nonhome discharge was highest for the CFS [6.2, 95% confidence interval (CI) 1.8-21.1], compared to the frailty index (4.1, 95% CI 2.0-8.4) and the frailty phenotype (OR 2.9, 95% CI 1.2-6.6). For the other outcomes, discriminatory accuracy based on ROC tended to be lower and predictive ability varied according to frailty measure. Readmission to acute care from inpatient rehabilitation was predicted by all instruments, most pronounced by the frailty phenotype (OR 5.4, 95% CI 1.6-18.8) and the frailty index (OR 2.5, 95% CI 1.1-5.6), and less so by the CFS (OR 1.4, 95% CI 0.5-3.8).Conclusions and ImplicationsFrailty measures may contribute to improved prediction of outcomes in geriatric inpatient rehabilitation. The choice of the instrument may depend on the individual outcome of interest and the corresponding discriminatory ability of the frailty measure.     

Correlations between Coffee Consumption and Metabolic Phenotypes,Plasma Folate,and Vitamin B12: NHANES 2003 to 2006

Metabolic syndrome (MetS) is prevalent not only among the overweight and obese but also normal weight individuals, and the phenotype is referred to as a metabolically unhealthy phenotype (MUHP). Besides normal weight individuals, overweight/obese individuals are also protected from MetS, and the phenotype is known as a metabolically healthy phenotype (MHP). Epidemiological studies indicate that coffee and micronutrients such as plasma folate or vitamin B12 (vit. B12) are inversely associated with MetS. However, correlations among coffee consumption metabolic phenotypes, plasma folate, and vit. B12 remain unknown. Our objective was to investigate the correlation between coffee consumption, metabolic phenotypes, plasma folate, and vit. B12 as well as to understand associations between plasma folate, vit. B12, and metabolic phenotypes. Associations among coffee consumption metabolic phenotypes, plasma folate, and vit. B12 were assessed in a cross-sectional study of 2201 participants, 18 years or older, from 2003–2004 and 2005–2006 National Health and Nutrition Examination Surveys (NHANES). MUHP was classified as having > three metabolic abnormalities. Coffee consumption was not associated with metabolic phenotypes, but negatively correlated with several metabolic variables, including BMI (p < 0.001). Plasma folate was positively associated with MUHP (p < 0.004), while vit. B12 was inversely associated with MUHP (p < 0.035). Our results suggest the potential protective impact of coffee on individual components of MetS and indicate a positive correlation between coffee consumption and MUHP among overweight individuals. Identifying possible dietary factors may provide practical and low-cost dietary intervention targets, specifically for early intervention. Larger and randomized intervention studies and prospective longitudinal studies are required to further evaluate these associations.     

核医学分子影像在分化型甲状腺癌中的应用现状与进展

分化型甲状腺癌因其发病率逐年升高而引人关注,核医学诊疗是其诊疗过程中重要的一环。随着新型示踪剂的发展,核医学分子影像检查对于在体显示甲状腺癌特定的分子特征及表达水平有重要价值,并可实现基于在体分子特征评估指导下的精准靶向治疗。现就核医学分子影像在评估分化型甲状腺癌分化表型特征和非分化表型特征两方面的应用与进展进行综述。     

Novel method for DNA methylation analysis using high‐performance liquid chromatography and its clinical application

The aim of this study was to develop a new methodology that is suitable for DNA methylation diagnostics and to demonstrate its clinical applicability. We developed a new anion‐exchange column for high‐performance liquid chromatography (HPLC) with electrostatic and hydrophobic properties. Both cytosine and thymine, corresponding to methylated and unmethylated cytosine after bisulfite modification, respectively, are captured by electrostatic interaction and then discriminated from each other by their hydrophobic interactions. The DNA methylation levels of synthetic DNA were quantified accurately and reproducibly within 10 minutes without time‐consuming pretreatment of PCR products, and the measured values were unaffected by the distribution of methylated CpG within the synthetic DNA fragments. When the DNA methylation status of the FAM150A gene, a marker of the CpG island methylator phenotype specific to clear cell renal cell carcinoma (ccRCC), was examined in 98 patients with ccRCC, bulk specimens of tumorous tissue including cancer cells showing DNA methylation of the FAM150A gene were easily identifiable by simply viewing the differentiated chromatograms, even when the cancer cell content was low. Sixteen ccRCC showing DNA methylation more frequently exhibited clinicopathological parameters reflecting tumor aggressiveness (ie, a larger diameter, higher histological grade, vascular involvement, renal vein tumor thrombi, infiltrating growth, tumor necrosis, renal pelvis invasion and higher pathological TNM stage), and had significantly lower recurrence‐free and overall survival rates. These data indicate that HPLC analysis using this newly developed anion‐exchange column could be a powerful tool for DNA methylation diagnostics, including prognostication of patients with cancers, in a clinical setting.     

120名中国人磺胺二甲嘧啶N-乙酰化表型分析

 目的：对120名健康志愿者进行了N-乙酰化表型分析。方法：以磺胺二甲嘧啶（SM₂）为探针药物，用HPLC测得受试者3h尿样，6h后尿样及血样中SM₂及乙酰化磺胺二甲嘧啶（Ac-SM₂），以Ac-SM₂摩尔百分数（Ac-SM₂％）为分型指标。结果：作频数图后，受试者均呈明显两态分布，3种样品中Ac-SM₂％值小于72％，85％，50％者被分为慢代谢者，120名受试者中慢代谢者分别为22，20，21人，对3种样品的相关分析表明方法之间相关性达0．9以上。结论：经综合分析，20名受试者可明确划分出慢代谢者，占16．6％。此研究结果将为进一步探讨应用咖啡因作为探针药物以及进一步的基因分析打下了一定基础，同时也有助于进一步明确中国人N-乙酰化分型的情况。     

红细胞谱细胞的筛选与建立

目的：通过对献血员和部分血站职工及团体普查Ｒｈ、Ｄｕｆｆｙ、Ｋｉｄｄ等１２个血型系统抗原,筛选和建立红细胞谱细胞。方法：采用盐水法、木瓜酶法、间接Ｃｏｏｍｂｓ法及中和、吸收、放散等试验。结果：筛出９个组Ｏ型Ｒｈ表型（Ｒ１Ｒ１、Ｒ２Ｒ２、Ｒ１Ｒ２、Ｒ１ｒ、Ｒ２ｒ、Ｒ１Ｒ＾ｚ、Ｒ２ｒ＾ｚ、ｒｒ、ｒｒ’）和２９种抗原（Ｄ、Ｃ、Ｅ、ｃ、ｅ、Ｃ＾ｗ、Ｍ、Ｎ、Ｓ、ｓ、Ｐ１、Ｌｅ＾ａ、Ｌｅ＾ｂ、Ｋ、ｋ、Ｋｐ＾ａ     

HIV-1广谱中和活性感染者假病毒的中和表型分析

目的分析HIV-1广谱中和活性感染者基于膜蛋白基因(env)的假病毒对自体血浆和代表性广谱单克隆中和抗体(bm NAbs)的中和表型。方法单基因组扩增(SGA)广谱中和活性感染者第0月血浆的env基因并克隆至pc D-NA~(TM)3.1 Directional TOPO表达载体,将env表达质粒与HIV-1骨架质粒p SG3△env共转染293T/17细胞制备假病毒,用假病毒分别与自体连续时间点血浆和代表性bm NAbs进行中和实验分析中和表型。结果共获得11株功能性假病毒,假病毒对8个连续时间点自体血浆的中和敏感性呈现先升高(第0~15月),后下降(第16~32月),之后再上升(第33~45月)的波动。所有假病毒对10E8、PGT121和VRC01中和敏感(IC_(50)6μg/m L);各有18.2%(2株)的假病毒对12A21和2G12高度敏感(IC_(50)1μg/m L);所有病毒均对PGT135呈中和抗性。结论假病毒对当前时间点血浆的中和敏感性低,对之后时间点血浆中和敏感性增强,提示感染者体内病毒与中和抗体的动态进化过程。同一时间点假病毒对特定bm-NAbs的敏感性差异明显,提示感染者准种毒株间中和表型的复杂性。