临床药师对乙肝后肝硬化腹水合并肌脓肿患者的药学监护

【摘要】〓临床药师参与1例乙肝后肝硬化腹水合并肌脓肿患者的药学监护,提出抗乙肝病毒采用强效和低耐药的恩替卡韦单药长期治疗;患者凝血功能不好,抗感染治疗上将利奈唑胺更换为万古霉素,并监测万古霉素的血药谷浓度,调整给药剂量和频次等用药建议,提高疗效和减少药品不良反应的发生率。     

Immunization with a Combination of Three Pneumococcal Proteins Confers Additive and Broad Protection against Streptococcus pneumoniae Infections in Mice

Pneumococcal polysaccharide-based vaccines are effective in preventing pneumococcus infection; however, some drawbacks preclude their widespread use in developing and undeveloped countries. Here, we evaluated the protective effects of ATP-dependent caseinolytic protease (ClpP), pneumolysin mutant (ΔA146 Ply), putative lipoate-protein ligase (Lpl), or combinations thereof against pneumococcal infections in mice. Vaccinated mice were intraperitoneally and/or intranasally challenged with different pneumococcal strains. In intraperitoneal challenge models with pneumococcal strain D39 (serotype 2), the most striking protection was obtained with the combination of the three antigens. Similarly, with the intranasal challenge models, (i) additive clearance of bacteria in lungs was observed for the combination of the three antigens and (ii) a combination vaccine conferred complete protection against intranasal infections of three of the four most common pneumococcal strains (serotypes 14, 19F, and 23F) and 80% protection for pneumococcal strain 6B. Even so, immunity to this combination could confer protection against pneumococcal infection with a mixture of four serotypes. Our results showed that the combination vaccine was as effective as the currently used vaccines (PCV7 and PPV23). These results indicate that system immunization with the combination of pneumococcal antigens could provide an additive and broad protection against Streptococcus pneumoniae in pneumonia and sepsis infection models.Streptococcus pneumoniae (pneumococcus) commonly colonizes the upper respiratory tract asymptomatically and was estimated, in 2005, to kill 1.6 million people every year, most of whom were children aged <5 years in developing and undeveloped countries (36). As far as we know, 91 capsular polysaccharide serotypes have been identified in S. pneumoniae (33); among these, serotypes 23F, 19F, 14, and 6B are the four most epidemic strains worldwide (2, 5, 15, 17, 25, 26, 29). Moreover, and of recent concern, the widespread use of antibiotics, leading to the development of antibiotic resistance or multidrug resistance against S. pneumoniae, is increasing (9, 12, 26).Heptavalent protein-polysaccharide conjugate vaccine (PCV7) and 23-valent pneumococcal polysaccharide vaccine (PPV23) are the two vaccines currently being used against S. pneumoniae. Both of these vaccines are polysaccharide-based formulations and effective in preventing invasive pneumococcal infections; however, some drawbacks, such as high cost, the limited polysaccharides covered, poor immunogenicity in the very young and the very old, and serotype replacement (22, 24, 26, 36), limit their wider use.Alternatively, in an attempt to overcome the disadvantages of polysaccharide-based vaccines, a number of studies have been focusing on the screening and evaluation of protein-based vaccine candidates. Pneumococcal protein vaccine candidates, such as nontoxic pneumolysin derivates, pneumococcal surface proteins (PspA and PspC), pneumococcal surface adhesin (PsaA), and ATP-dependent caseinolytic proteases (ClpP), have been studied and shown to provide protection against S. pneumoniae. In addition, another surface protein, putative lipoate-protein ligase (Lpl), has been suggested to be a vaccine candidate, which could effectively elicit a high IgG titer and reduce the blood bacterial load (30). These vaccine candidates are shared by all S. pneumoniae. Of note, it is generally recognized that pneumolysin localized in the cytoplast in a soluble monomer, and its release was dependent on or independent of autolysin (3, 4, 18, 19). A recent study, which showed that pneumolysin was also partially localized on the cell wall (34), strengthened its utility as a vaccine candidate. Additive protections were obtained with combinations of these protein candidates. However, previous evaluations have been based only on intraperitoneal challenge models of pneumococcal disease and were not, to our knowledge, been performed in pneumonia models (7, 10, 13, 20, 23, 30, 37).In the present study, putative lipoate-protein ligase (Lpl), ClpP, and Ply toxoid were expressed, purified, and confirmed to express on all of the pneumococcal strains used here. A focal pneumococcal pneumonia model, mimicking the natural pneumococcal infection, was used to evaluate pneumococci on lung colonization. We also set up models of invasive diseases, which were used to evaluate their systemic protective effects against pneumococcal infections. System vaccination with the combination of three antigens was sufficient to provide complete protection against pneumococcal serotypes 14, 19F, and 23F. In addition, this vaccination regimen conferred protection against the intranasal infection of a mixture of serotypes 14, 6B, 19F, and 23F. We now report the details of the protective effects elicited by ΔA146 Ply, ClpP, Lpl, and combinations thereof against pneumococcal infections.     

MSP扩增中3种DNA提取法的比较

目的比较标准酚-氯仿、TripureDNA提取法、强碱法3种DNA提取法,研究哪种方法更简单方便,更适合做DNA甲基化特异性PCR（MSP）。方法分别用标准酚-氯仿、TripureDNA提取法、强碱法提取Jurkat细胞株中的DNA,并对3种方法提取的DNA含量、纯度及所需时间进行比较。结果3种方法提取DNA的纯度和完整性都较好,标准酚-氯仿法提取的DNA含量最低,且最费时;强碱法提取的DNA含量最高,并最省时。结论这3种DNA提取法提取的DNA都能够达到做MSP的要求,比较而言,强碱法更具优越性。     

Detection of gastric carcinoma‐associated MG7‐Ag by serum immuno‐PCR assay in a high‐risk Chinese population,with implication for screening

To evaluate gastric carcinoma‐associated antigen, MG7‐Ag, for detection of gastric cancer in a high‐risk population, a population‐based screening of gastric cancer was conducted in Linqu County, Shandong Province, China. In 2002 and 2003, a total of 2,710 participants aged 35–65 years received an endoscopic examination with 5 biopsies taken from standard sites with pathological diagnosis, and serum samples were collected to detect MG7‐Ag by serum‐based Immunopolymerase chain reaction (PCR) assay. The sensitivity and specificity of MG7‐Ag Immuno‐PCR assay in detecting of gastric cancer were assessed. Of 2,710 participants, 148 (5.46%) were determined to be MG7‐Ag positive. The sensitivity of MG7‐Ag Immuno‐PCR assay for the detection of gastric cancer was 77.5% (31 of 40 gastric cancer cases), the specificity was 95.62% (2,553 of 2,670 nongastric cancer subjects) and the accuracy was 73.12%. A total of 24 gastric cancer cases were in Stage I or II, of which 17 (70.8%) were MG7‐Ag positive. However, the proportion of MG7‐Ag positivity in subjects with superficial gastritis, chronic atrophic gastritis, intestinal metaplasia, indefinite dysplasia or dysplasia was ranged from 3.00% to 5.61% in comparison with 77.5% in those with gastric cancer. Our findings suggest that MG7‐Ag was a sensitive and specific serum biomarker and may have a potential for gastric cancer screening in the high‐risk population.     

An efficient and robust analysis of covariance model for baseline adjustment in parallel‐group thorough QT/QTc studies

Baseline adjustment is an important consideration in thorough QT/QTc studies for non‐antiarrhythmic drugs. The time‐matched baseline is often used in practice to adjust for the within‐subject diurnal effects. More recently, the day‐averaged baseline has been proposed in the literature to improve the efficiency of treatment comparisons for the primary and assay sensitivity hypotheses. We recommend an analysis of covariance (ANCOVA) model with change from the time‐matched baseline as the response and both the time‐matched baseline and the day‐averaged baseline as the covariates. This model adjusts for the within‐subject diurnal effects and at the same time is more efficient and robust than the ANCOVA models based on either the time‐matched baseline alone or the day‐averaged baseline alone. Copyright © 2012 John Wiley & Sons, Ltd.     

Papers published from 1995 to 2012 by six Traditional Chinese Med- icine universities in China： a bibliometric analysis based on science citation index

OBJECTIVE： The quality and quantity of published research papers are important in both scientific and technology fields. Although there are several bibliometric studies based on citation analysis, very few have focused on research related to Traditional Chinese Medicine in China. METHODS： The bibliometric method used in this study included the following focuses： publication outputs for each year, paper type, language of pub- lication, distribution of internationally collaborative countries, sources of funding, authorization num- ber, distribution of institutes regarding collabora- tive publications, research fields, distribution of out-puts in journals, citation data, and h-index RESULTS： A total of 3809 papers published from 1995 to 2012 were extracted from the science cita- tion index （SCI）. The cumulative number of papers from all six universities is constantly increasing. The United States attained the dominant position re- garding complementary and alternative medicine research. The Chinese Academy of Sciences was the greatest participator in collaborative efforts. Re- search field analysis showed that the research main- ly focused on pharmacology pharmacy, chemistry, integrative complementary medicine, plant scienc- es, and biochemistry molecular biology. The Shang- hai University of Chinese Medicine had the most ci- tations. CONCLUSION： In recent years, in terms of SCI pa- pers, the six Traditional Chinese Medicine universi- ties studied here have made great advances in sci- entific research.     

中西医临床医学专业分子生物学实验教学实践

分子生物学是中西医临床医学专业学生重要的专业基础课,分子生物学实验课程是分子生物学理论课的配套课程。文章对中西医临床医学专业分子生物学实验课程设置特点及教学过程中存在的问题进行了探讨,并就实验教学总体思路和目标、教学方式和内容、考核评价体系等方面提出一些改革措施,为提高分子生物学实验的教学质量,培养中西医临床医学专业创新型人才提供参考。     

Effect of IL-10 on formation of foam cell induced by ox-LDL

Atherosclerosis is a chronic disease that causes various cardiovascular complications. It has been realized that cellular and humoral immunity plays crucial roles in atherogenic lesion formation. In this study the effects of lipopolysaccharide (LPS) and interleukin-10 (IL-10) on the formation of foam cells during the early stages of atherosclerosis have been investigated. Macrophage was induced by phorbol myristate acetate (PMA) treatment on THP-1 cells. The cells were further stimulated by ox-LDL, ox-LDL plus LPS, ox-LDL plus IL-10 and LPS. By using an oil red O staining technique, the formation of foam cells was evaluated by lipid granules formation in the cells. The ratio of foam cell formation was increased from (9.77 ± 1.70)% to (16.27 ± 2.27)% after 24 h stimulation with ox-LDL, and the increase was observed with incubating time. The foam cells were significantly increased in the presence of LPS in a dose-dependent manner. The maximum increase of about 40% was observed. However, the significant elevation by LPS was abrogated when IL-10 was added. These results indicated that IL-10 can effectively prevent the formation of foam cells induced by ox-LDL with or without LPS. This study demonstrates that ox-LDL can cause foam cell formation from macrophages in vitro. LPS can significantly accelerate this event. IL-10, an anti-inflammatory cytokine, can inhibit the effect of ox-LDL and LPS. These results indicate that inflammatory effects in blood vessels can speed up foam cell formation. The inhibitive effect of IL-10 is an important factor for delaying atherosclerosis processes.     

中医《温病学》研究性教学课程体系构建探讨

文章探讨了中医《温病学》研究性教学课程体系建设的方法及内容,初步分析了课程建设的要素,为进一步建立中医学研究性教学课程体系进行了有益的探索。