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@#[摘 要] 目的：探讨miR-620对乳腺癌MCF-7细胞放射敏感性的影响及其机制。方法：收集2017年3月至2018年3月在海南省儋州市人民医院手术切除的21例乳腺癌患者的癌及癌旁组织标本，以及乳腺癌细胞MCF-7、BCaP-37和乳腺上皮细胞HBL-100，采用qPCR法检测癌组织和细胞中miR-620和生长抑制因子4（ING4）mRNA的表达。利用脂质体转染技术，分别将miR-620抑制剂（anti-miR-620）和抑制剂阴性对照（anti-miR-NC）、anti-miR-620和ING4小干扰RNA（si-ING4）、anti-miR-620和小干扰RNA阴性对照序列（si-NC）转染至MCF-7细胞，经放射处理后（依次记为IR+anti-miR-620组、IR+anti-miR-NC组、IR+anti-miR-620+si-ING4组、IR+anti-miR-620+si-NC组），利用克隆形成实验、MTT法和FCM分别检测细胞放射敏感性、细胞增殖活力、细胞周期分布和凋亡率。双荧光素酶报告基因实验和WB法验证miR-620和ING4的靶向关系。结果：与癌旁组织和HBL-100细胞比较，乳腺癌组织和细胞中miR-620表达均显著升高（均P<0.01）、ING4 mRNA表达均显著降低（均P<0.01）。与IR+anti-miR-NC组比较，IR+anti-miR-620组MCF-7细胞增殖活力、S期细胞比例均显著降低（均P<0.01），细胞凋亡率、G0-G1期细胞比例、放射敏感性均显著升高（均P<0.01）。与IR+anti-miR-620+si-NC组比较，IR+anti-miR-620+si-ING4组MCF-7细胞增殖活力、S期细胞比例均显著升高（均P<0.01），细胞凋亡率、G0-G1期细胞比例和放射敏感性均显著降低（均P<0.01）。双荧光素酶报告基因实验证明ING4是miR-620的靶基因，miR-620靶向负性调控ING4表达。结论：敲减miR-620可能通过上调ING4表达抑制乳腺癌MCF-7细胞增殖，并促进细胞凋亡和放射敏感性。
ABSTRACT
Objective: The objective of this paper was to investigate hub genes of postmenopausal osteoporosis (PO) utilizing benchmarked dataset and gene regulatory network (GRN). Materials and Methods: To achieve this goal, the first step was to benchmark the dataset downloaded from the ArrayExpress database by adding local noise and global noise. Second, differentially expressed genes (DEGs) between PO and normal controls were identified using the Linear Models for Microarray Data package based on benchmarked dataset. Third, five kinds of GRN inference methods, which comprised Zscore, GeneNet, context likelihood of relatedness (CLR) algorithm, Partial Correlation coefficient with Information Theory (PCIT), and GEne Network Inference with Ensemble of trees (Genie3), were described and evaluated by receiver operating characteristic (ROC) and precision and recall (PR) curves. Finally, GRN constructed according to the method with best performance was implemented to conduct topological centrality (closeness) for the purpose of investigate hub genes of PO. Results:A total of 236 DEGs were obtained based on benchmarked dataset of 20,554 genes. By assessing Zscore, GeneNet, CLR, PCIT, and Genie3 on the basis of ROC and PR curves, Genie3 had a clear advantage than others and was applied to construct the GRN which was composed of 236 nodes and 27,730 edges. Closeness centrality analysis of GRN was carried out, and we identified 14 hub genes (such as TTN, ACTA1, and MYBPC1) for PO. Conclusion: In conclusion, we have identified 14 hub genes (such as TN, ACTA1, and MYBPC1) based on benchmarked dataset and GRN. These genes might be potential biomarkers and give insights for diagnose and treatment of PO
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Objective To investigate the clinical effect of levosimendan in perioperative aortic and/or mitral valvereplacement. Methods Patients undergoing open heart aortic and/or mitral valve replacement in our hospitalfrom January 2018 to December 2019 were enrolled. 45 patients in the control group received routineperioperative treatment based on dopamine, while 45 patients in the research group received continuousperioperative administration of levosimendan injection for 24h on the basis of routine treatment. The leftventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVDd) and left ventricular end-systolicdiameter (LVDs) were evaluated by color doppler echocardiography before and one week after surgery.Postoperative mechanical ventilation weaning time, length of ICU stays, number of vasoactive drugs used andwithdrawal time; indexes of liver and kidney function before and on the day after surgery to 10 days after surgery;use of in vitro support techniques such as aortic balloon pulsation (IABP), continuous renal replacement therapy(CRRT) and extracorporeal membrane oxygenation (ECMO) within 5 days of perioperative period. Results Theimprovement of LVDs and LVEF in the study group using levosimendan one week after the operation wassignificantly better than that in the control group (P value was 0.013 and 0.001, respectively), and fewer kinds ofvasoactive drugs were needed (P<0.001), and the risk of postoperative AKI in the study group was significantlylower than that in the control group (P=0.047). Conclusion The perioperative use of levosimendan can effectivelypromote the recovery of cardiac systolic function and reduce the risk of postoperative AKI.
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The purpose of this study is to find out whether there are broad cross-reactivity between antibacterial and nonantibacterial sulfonamide agents, the method of the study contained two parts, one is literature research mainlyfrom PubMed database by using the MeSH terms (“Drug name” + allergy); (“Drug name” + hypersensitivity);(“Drug name” + cross-allergenicity) and (“Drug name + cross-reactivity), the search drugs included somecommonly seen medication such as carbonic anhydrase inhibitor, COX-2 inhibitor, loop diuretic, sulfonylurea,thiazide and certain antiviral drugs; the other parts of this thesis is to conduct a statistical review, we screen outpatients who have a previous allergic history of antimicrobial sulfonamides from hospital medical record systemduring Jan 1st, 2015 to Dec 31th, 2016, we did a descriptive statistics of general patients medical information,analyze the suspect cases which patients present potential allergic reaction after using non-antimicrobialsulfonamides agents. Result of literature research reveal there are no convincing evidences and research toconfirm there are bored allergenicity between non-antimicrobial sulfonamides and antimicrobial sulfonamide inthe aspects of chemical structure, immunological study, and large scale population study as well; Result ofhospital patient’s statistics found out there are only 3 suspected cases that the patients were having adverseeffect during their pharmacotherapy from 506 cases. However, we did not found any strong correlation of broadallergenicity between non-antimicrobial sulfonamides and antimicrobial sulfonamides from these suspectedcases. Conclusion: There is minimal evidence of cross-reactivity between the antimicrobial sulfonamides and thenon-antimicrobial sulfonamides. However, the non-antimicrobial sulfonamides are rarely implicated inhypersensitivity reactions as well, so it is impossible to say with certainty that cross-reactivity does not occur.