ABSTRACT
Warfarin is widely used as an oral anticoagulant in clinic in China. It has narrow therapeutic index, large individual differences on dosage and the variability in warfarin dosage depends on many factors, including gene polymorphism, age, diet habits and so on. For clinicians, how to optimize the individual therapeutic regimen of warfarin is becoming a significant part of their work. In recent years, studies on genetic pharmacogenomics of warfarin are reported frequently. It is found that multiple gene polymorphisms can affect the efficacy of warfarin. We will introduce the gene polymorphism of some warfarin related genes and their effects on warfarin, and the advances of warfarin individual therapeutic regimen will also be discussed here.
ABSTRACT
Warfarin is widely used as an oral anticoagulant in clinic in China. It has narrow therapeutic index, large individual differences on dosage and the variability in warfarin dosage depends on many factors, including gene polymorphism, age, diet habits and so on. For clinicians, how to optimize the individual therapeutic regimen of warfarin is becoming a significant part of their work. In recent years, studies on genetic pharmacogenomics of warfarin are reported frequently. It is found that multiple gene polymorphisms can affect the efficacy of warfarin. We will introduce the gene polymorphism of some warfarin related genes and their effects on warfarin, and the advances of warfarin individual therapeutic regimen will also be discussed here.
ABSTRACT
<p><b>OBJECTIVE</b>To determine the regulatory effects of the circadian clock gene Per1 on cell cycle-related genes and its influence on the proliferation, apoptosis, cycle, and tumorigenicity in vivo of human oral squamous cell carcinoma SCC15 cells.</p><p><b>METHODS</b>Three groups of the short hairpin RNA (shRNA) of lentivirus recombinant plasmids were designed against the RNA of Per1 and then transfected to the SCC15 cells. The optimum interference group was screened through Western blot and quantitative real-time PCR (qRT-PCR) and assigned as the experimental group. The transfected lentivirus plasmid without an interference effect on any gene was set as the control group (Control-shRNA). Untreated SCC15 cells were set as the blank group. The mRNA expressions of cell cycle-related genes, namely, Per1, p53, Cyclin D1, Cyclin E, Cyclin A2, Cyclin B1, CDK1, CDK2, CDK4, CDK6, p16, p21, Wee1, cdc25, E2F, and Rbl1 in each group were detected through qRT-PCR. The cell proliferation, apoptosis, and cell cycle distribution in each group were evaluated through flow cytometry. The cells of the experimental group and the blank group were subcutaneously inoculated in nude mice to observe tumorigenesis.</p><p><b>RESULTS</b>Three groups of Per1-shRNA lentivirus plasmids were constructed successfully. Among the groups, the Per1-shRNA- I group exhibited the highest interference effect, as indicated by qRT-PCR and Western blot analysis. As such, this group was set as the experimental group. The mRNA expression levels of CyclinD1, CyclinE, CyclinB1, CDK1, and Wee1 gene in the Per1-shRNA-I group were significantly higher than those in the Control-shRNA group and the SCC15 group (P < 0.05). By contrast, the mRNA expression levels of p53, Cyclin A2, p16, p21, and cdc25 in the Per1-shRNA-I group were significantly lower than those in the Control-shRNA group and the SCC15 group (P < 0.05). The mRNA expression levels of each gene between the Control-sLRNA group and the SCC15 group did not significantly differ (P > 0.05). The mRNA expression levels of CDK2, CDK4, CDK6, E2F, and Rb1 did not significantly differed in the three groups (P > 0.05). The proliferation index of the Perl-shRNA-I group was significantly higher than those of the Control-shRNA group and the SCC15 group (P < 0.05). The apoptosis index of the Per1-shRNA-I group was significantly lower than those of the Control-shRNA group and the SCC15 group (P < 0.05). The number of S-phase cells in the Per1-shRNA-I group was significantly lower than those of S-phase cells in the Control-shRNA group and the SCC15 group (P < 0.05). The number of G2/M-phase cells in the Per1-shRNA-I group was significantly higher than those of G2/M-phase cells in the Control-shRNA group and the SCC15 group (P < 0.05). Conversely, the proliferation index, apoptotic index, and cell cycle distribution of the cells in the Control-shRNA group did not significantly differ from those of the SCC15 group (P > 0.05). The tumorigenic ability in vivo was significantly enhanced in the Per1-shRNA-I group (P < 0.05).</p><p><b>CONCLUSION</b>Per1 is an important tumor suppressor gene. Per1 can regulate a large number of downstream cell cycle-related genes. The alteration of its expression can affect cell cycle progression, proliferation, apoptosis imbalance, and tumorigenic ability in vivo. Further studies on Per1 may elucidate cancer development and provide novel effective molecular targets for cancer treatment.</p>
Subject(s)
Animals , Humans , Mice , Apoptosis , Carcinoma, Squamous Cell , Cell Cycle , Cell Line, Tumor , Cell Proliferation , Circadian Clocks , Genetics , Cyclin D1 , Mice, Nude , Mouth Neoplasms , Period Circadian Proteins , Genetics , Plasmids , RNA, Small Interfering , Real-Time Polymerase Chain Reaction , TransfectionABSTRACT
Objective To explore the key factors which affect maintenance cost of large-scale medical equipment. Methods The basic factors which affect maintenance cost of medical imagining equipment were summarized. The relationships of them are analyzed and then an interpretative structure mode of each factor was set. Additionally, the multiple relationship and controllability between each factor were also analyzed and the judging standard of key factors was set. Results The maintenance policy and mode were the key factors which affect maintenance cost of medical imagining equipment. Conclusion High quality maintenance for equipment condition and scientific optimization of the maintenance policy are necessary to fundamentally reduce the maintenance cost of large-scale medical equipment.
ABSTRACT
Objective To summarize the methods of in-state maintenance of KODAK CR-400PLUS so that to improve the reliabilityof the equipment.Methods The concrete plans about in-state maintenance on the KODAK CR-400PLUS under the guidelines ofin-state maintenance in combination with the practice conditions were established that to ensure the reliable work of CR.Results Themalfunction rate of CR was decreased and the goal of monitoring the performance degradation degree of the key parts was achieved.Conclusion In-state maintenance is effectively in improving the reliability of CR.