关键词：仿制药；一致性评价；原研药

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Histone demethylases are a newly discovered class of non-heme iron enzymes that play an important role in regulating transcription and epigenetic inheritance. We have successfully expressed and purified highly active histone demethylases (HDMs), including the cancerrelevant JMJD2C (GASC1). A detailed enzyme kinetic and inhibition analysis of these HDMs was achieved through a range of fluorescence assays, mass spectrometry, and oxygen consumption measurements. An interesting case of cosubstrate inhibition is observed for these HDMs, with direct relevance to the potential role of alpha-ketoglutarate and HDMs in cancer cells. We have also employed an enzyme-templated approach for specific inhibitor design that takes advantage of the enzyme s substrate specificity. Finally, while the initially tested compounds do not seem to inhibit JMJD2C in MCF7 breast cancer cells, we believe that second generation compounds will be active HDM inhibitors in vivo. The developed specific inhibitors could lead to novel breast cancer therapeutics and can also be used as tools for studying the role of histone demethylases in breast cancer cell proliferation.

关键词：医药；治疗技术；脱甲基酶；乳腺癌

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We have isolated and characterized a population of skeletal muscle- derived stem cells (MDSCs) that display a greatly improved skeletal and cardiac muscle transplantation capacity when compared to skeletal muscle myoblasts. The MDSCs ability to withstand oxidative and inflammatory stresses appears to be the single most important factor for their improved transplantation capacity. Although the true origin of MDSCs remains unclear, their high degree of similarity with blood vessel-derived stem cells suggests their potential origin could be from the vascular wall. We have recently isolated two distinct populations of cells from the vasculature of human skeletal muscle known collectively as human skeletal muscle-derived cells (hMDCs). The two populations are myo-endothelial cells and pericytes and both can repair skeletal and cardiac muscles in a more effective manner than myoblasts, as is observed with murine MDSCs. In the current proposal we intend to evaluate and compare the regeneration capacity of these two hMDC populations after their implantation into the skeletal muscle of immunodeficient/dystrophic (SCID/mdx) mice. We will then investigate the influence that sex has on the regeneration and repair capacity of the hMDCs endowed with the greatest regeneration capacity (either myo-entothelial cells or pericytes). Finally we will investigate the influence that age plays on the regeneration capacity of the cells.

关键词：医药；治疗技术；干细胞疗法

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In response to a request from the public to the Agency for Healthcare Research and Quality (AHRQ) concerning the expanding use of disease-modifying anti-rheumatic drugs (DMARDs) to treat rheumatoid arthritis (RA), a systematic review was undertaken to review the effectiveness and safety of the oral and biologic DMARDs. This summary is based on a systematic review prepared as an update to a review published in 2007. In addition to the material reported in 2007, this update includes articles published after the 2007 report and before January 2011 (a total of 211 studies). This summary, based on the full report of research evidence, is provided to clinicians to inform discussions of options with patients and to assist in decisionmaking along with consideration of a patients values and preferences. Reviews of evidence should not be construed to represent clinical recommendations or guidelines.

关键词：医药；治疗技术；类风湿性关节炎

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Epidemiological evidence has demonstrated an inverse association between serum vitamin D levels and sunlight exposure to prostate cancer incidence. In addition, serum androgen levels and biologically available testosterone decrease significantly in elder men while the incidence rate of prostate cancer increases. These findings lead to the hypothesis that androgen- and vitamin D-mediated signaling events may act together to inhibit prostate tumor initiation and/or development. Using concurrent microarray analyses, we demonstrated that testosterone and 1,25(OH)2D3 co-operate to regulate mRNA and miRNA expression, including some well-defined oncogenes and tumor suppressor genes. Pheno typically, this results in G0/G1 cell cycle arrest and increased neutral lipid accumulation in LNCaP cells, as a consequence of repression of various cell cycle regulators and the up-regulation of PPAR alpha; respectively. This suggests that the cross talk between T and 1,25(OH)2D3 induces cell cycle arrest and promotes cell differentiation in LNCaP cells. It is important ton ote that co-treatment of LNCaP cells with testosterone, 1, 25(OH)2D3 and other standard therapeutics, including bicalutamide, docetaxel and TRAIL did not affect the potencies of these treatments, though there were no synergistic effects either. This suggests that androgen andvitamin D supplementation slow disease progression without affecting the efficacy of standard therapies for prostate cancer. Further analysis is still required to elucidate the underlying mechanisms of T and 1,25(OH)2D3 to modulate key mRNA and miRNA and their significance in prostate tumorigenesis and therapeutic interventions.

关键词：医药；治疗技术；前列腺癌；细胞疗法

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关键词：乙肝疫苗；天坛生物

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In response to a request from a national professional society regarding the use of procalcitonin in the clinical management of adult and pediatric patients with suspected local or systemic infection, a systematic review of comparative studies (randomized controlled trials and nonrandomized studies) was conducted. The patient populations included critically ill adults with suspected sepsis or other serious bacterial infections, neonates with suspected early neonatal sepsis, patients with upper and lower respiratory tract infections, children with fever of unknown origin, and postoperative patients at risk of infection. Pregnant women, patients with absolute neutropenia and other immunocompromised populations (solid organ and stem-cell transplant recipients, patients with advanced HIV infection/AIDS), and patients with chronic infections such as infective endocarditis were excluded from this review. The systematic review included 18 reports of eligible studies in over 6,000 patients published between January 1, 1990, and December 16, 2011. Outcomes including antibiotic usage, mortality, morbidity, adverse drug effects of antibiotic therapy, and hospital or intensive care unit (ICU) length of stay were assessed. This summary, based on the full report of research evidence, is provided to assist in decisionmaking along with consideration of a patients values and preferences. However, reviews of evidence should not be construed to represent clinical recommendations or guidelines.

关键词：医药；治疗技术；抗生素治疗；降钙素原

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Lymphoepithelioma-like carcinoma of the skin (LELCS) is a rare cutaneous neoplasm microscopically similar to undifferentiated nasopharyngeal carcinoma. It is typically nonaggressive and is treated with wide local excision. However, we present a case of a patient with a regional recurrence and more aggressive LELCS with perineural invasion and positive margins for which he was treated with wide local excision followed by chemoradiation. We discuss the use of chemoradiation for this patient and review the literature, specifically pertaining to treatment of more aggressive cases of LELCS.

关键词：医药；治疗技术；皮肤淋巴上皮癌

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This study was an open-label, single-group, treatment-development project aimed at developing and testing a method for applying virtual reality exposure therapy (VRET) to active duty service members diagnosed with combat post-traumatic stress disorder (PTSD). Forty-two service members with PTSD were enrolled, and 20 participants completed treatment. The PTSD Checklist-Military version, Patient Health Questionnaire-9 for depression, and the Beck Anxiety Inventory were used as outcome measures. Of those who completed post-treatment assessment, 75had experienced at least a 50reduction in PTSD symptoms and no longer met DSM-IV criteria for PTSD at post treatment. Average PSTD scores decreased by 50.4, depression scores by 46.6, and anxiety scores by 36. Intention-to-treat analyses showed that statistically significant improvements in PTSD, depression, and anxiety occurred over the course of treatment and were maintained at follow up. There were no adverse events associated with VRET treatment. This study provides preliminary support for the use of VRET in combat-related PTSD. Further study will be needed to determine the wider utility of the method and to determine if it offers advantages over other established PTSD treatment modalities.

关键词：医药；治疗技术；应激障碍；暴露疗法

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Tuberous Sclerosis Complex (TSC) is a genetic disorder resulting from mutations in either the TSC1 or TSC2 genes. TSC is characterized by abnormal skin pigmentation and tumor formation in multiple organ systems. TheTSC1andTSC2gene products are involved in cell signaling; in particular they are involved in the mammalian target of rapamycin (mTOR) signaling pathway. In TSC, the epidermal basal cells contain a mutant copy of either theTSC1orTSC2gene. A loss of heterozygosity results in constitutive activation of mTOR leading to production of epidermal cells at a faster rate than the ability to slough the dead cells. This overproduction of skin cells, in conjunction with angiogenesis, results in the formation of visible facial angiofibromas over time.

关键词：医药；治疗技术；雷帕霉素；皮肤结节性硬化综合症

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