In silico repurposing the Rac1 inhibitor NSC23766 for treating PTTG1-high expressing clear cell renal carcinoma

The pituitary tumor-transforming gene 1 (PTTG1), also known as Securin, is considered an oncogene. This study aimed to investigate the role of PTTG1 in clear cell renal cell carcinoma (ccRCC) using in silico bioinformatics approaches. A pan-cancer analysis using The Cancer Genome Atlas (TCGA) data indicated that among all cancer types copy number amplification of PTTG1 gene was most frequently found in ccRCC. However, amplification of PTTG1 gene copy number did not correlate with the increase of mRNA level in ccRCC, and did not predict the patients' overall survival. Instead, ccRCC was correlated with overexpression of PTTG1 mRNA, and its expression level was stage-dependent increased in cancer patients. An outlier analysis using the Oncomine database suggested that PTTG1 mRNA expression served as a good biomarker for ccRCC. Pathway analysis for upregulated genes enriched in PTTG1-high expressing ccRCC patients found that PTTG1 overexpression was associated with mitotic defects. Mining drug sensitivity data using the Cancer Therapeutics Response Portal (CTRP) discovered that PTTG1-high expressing ccRCC cell lines were susceptible to a Rac1 (Ras-related C3 botulinum toxin substrate 1) inhibitor NSC23766. Therefore, this study provides an in silico insight into the role of PTTG1 in ccRCC, and repurposes the Rac1 inhibitor NSC23766 for treating PTTG1-high expressing ccRCC.     

改良肌激动器治疗安氏Ⅱ类Ⅰ分类错(牙合)畸形的X线头影测量分析

目的探讨改良肌激动器矫治早期安氏Ⅱ类Ⅰ分类下颌后缩的错[牙合]畸形的临床疗效。方法选择口腔正畸门诊就诊的安氏Ⅱ类Ⅰ分类下颌后缩的错[牙合]患者20例,年龄在10~12岁之间,平均年龄10.6岁。采用改良肌激动器进行功能矫治,用winceph8.0对矫治前后X线头颅侧位片进行定点测量,所得数据应用SPSS23.0软件进行配对t检验。结果矫治后患者面型改善明显,磨牙基本中性关系,前牙覆[牙合]、覆盖基本正常,治疗后角度测量值SNB、ANB、NA-PA和U1-SN变化,差异有显著性(P<0.01),角度测量值SNA、SNMP、L1-MP、L1-NB、FH-Y轴和Z角变化,无显著性(P>0.05),线距测量值L1-NB、UL-EP和LL-EP跟治疗前比,变化无显著性(P>0.05)。结论改良肌激动器能够矫治早期安氏Ⅱ类Ⅰ分类错[牙合]畸形,值得在临床推广使用。     

微型种植体支抗与口外弓支抗对安氏Ⅱ类1分类错牙合畸形患者的矫治效果对比分析

目的:分析比较微型种植体支抗与口外弓支抗对安氏Ⅱ类1分类错牙合畸形患者的矫治效果。方法:收集笔者医院95例安氏Ⅱ类1分类错牙合畸形患者临床资料,根据其治疗方法将之分为口外弓支抗(MIA组)46例和微型种植体支抗组(HGA组)49例,比较其矫正前后头影测量结果和模型测量结果,矫治时间和不良反应。结果:治疗后,MIA组牙合平面与SN平面夹角(OP-SN)、上颌中切牙牙长轴与SN平面夹角(U1-SN)、上唇突度、下唇突度、上唇最凸点至E线垂直距离(E line-UL)、下唇最凸点至E线垂直距离(E line-LL)、覆牙合(OB)、覆盖(OJ)均小于HGA组(P<0.05),矫治时间短于HGA组(P<0.05),总不良反应发生率与HGA组差异无统计学意义(P>0.05)。结论:对比HGA,MIA对安氏Ⅱ类1分类错牙合畸形患者的矫治效果更佳,且能够缩短矫治时间。     

Interacting with α7 nAChR is a new mechanism for AChE to enhance the inflammatory response in macrophages

Acetylcholine (ACh) regulates inflammation via α7 nicotinic acetylcholine receptor (α7 nAChR). Acetylcholinesterase (AChE), an enzyme hydrolyzing ACh, is expressed in immune cells suggesting non-classical function in inflammatory responses. Here, the expression of PRiMA-linked G4 AChE was identified on the surface of macrophages. In lipopolysaccharide-induced inflammatory processes, AChE was upregulated by the binding of NF-κB onto the ACHE promotor. Conversely, the overexpression of G4 AChE inhibited ACh-suppressed cytokine release and cell migration, which was in contrast to that of applied AChE inhibitors. AChEmt, a DNA construct without enzymatic activity, was adopted to identify the protein role of AChE in immune system. Overexpression of G4 AChEmt induced cell migration and inhibited ACh-suppressed cell migration. The co-localization of α7 nAChR and AChE was found in macrophages, suggesting the potential interaction of α7 nAChR and AChE. Besides, immunoprecipitation showed a close association of α7 nAChR and AChE protein in cell membrane. Hence, the novel function of AChE in macrophage by interacting with α7 nAChR was determined. Together with hydrolysis of ACh, AChE plays a direct role in the regulation of inflammatory response. As such, AChE could serve as a novel target to treat age-related diseases by anti-inflammatory responses.     

Analysis of AcrB in Klebsiella pneumoniae reveals natural variants promoting enhanced multidrug resistance

Infections caused by Klebsiella pneumoniae are often difficult to manage due to the high frequency of multidrug resistance, often conferred by efflux pumps. In this study, we analyzed sequence variations of the major RND family multidrug efflux pump AcrB from 387 assembled K. pneumoniae genomes. We confirm that AcrB is a highly-conserved efflux pump in K. pneumoniae, and identified several variants that were prevalent in clinical isolates. Molecular dynamics analyses on two of these variants (L118M and S966A) suggested conformational changes that may correlate with increased drug efflux capabilities. The L118M change resulted in enhanced protein rigidity while the flexibility of drug binding pockets was stable or increased, and the interactions between the proximal pockets and water molecules were stronger. For S966A, the significantly enlarged proximal pocket suggested higher drug accommodation ability. Consistent with these predictions, the L118M and S966A variants conferred a slightly increased ability to grow in the presence of tetracycline and to survive cefoxitin exposure when overexpressed. In summary, our results suggest that the emergence of enhanced-function AcrB variants may be a potential risk for increased antibiotic resistance in clinical K. pneumoniae isolates.     

Expressions of conventional vitellogenin and vitellogenin-like A in worker brains are associated with a nursing task in a ponerine ant

In eusocial insect colonies, non-reproductive workers often perform different tasks. Tasks of an individual worker are shifted depending on various factors, e.g., age and colony demography. Although a vitellogenin (Vg) gene play regulatory roles in both reproductive and non-reproductive division of labours in a honeybee, it has been shown that the insect Vg underwent multiple gene duplications and sub-functionalisation, especially in apical ant lineages. The regulatory roles of duplicated Vgs were suggested to change evolutionarily among ants, whereas such roles in phylogenetically basal ants remain unclear. Here, we examined the expression patterns of conventional Vg (CVg), Vg-like A, Vg-like B and Vg-like C, as well as Vg receptor, during the task shift in an age-dependent manner and under experimental manipulation of colony demography in a primitive ant Diacamma sp. Expressions of CVg and Vg-like A in a brain were associated with a nursing task. It is suggested that associations of brain expressions of these Vgs with worker tasks were acquired in the basal ant lineage, and that such Vg functions could have sub-functionalised in the derived ant lineage.     

基于团队定位分工模式的情景模拟培训在心肺复苏中的应用

目的探讨基于团队定位分工模式的情景模拟教学在心肺复苏实践中的应用。方法将57名护士按能级及专科技能分A,B,C 3个级别,不同级别的3名护士与1名医生组成的4人抢救小组,进行团队式情景模拟心肺复苏培训,比较实施前后抢救小组开始心肺复苏到建立静脉通路、连接心电监护建立人工气道、首次给入复苏药物的时间以及危重患者抢救质量评分;医生对护士抢救的综合满意度,护士对工作的满意度情况。结果培训后建立静脉通路、连接心电监护、建立人工气道以及首次给入复苏药物的时间较培训前均明显缩短,危重患者抢救质量检查评分明显提高,差异有统计学意义(P<0.05);医生对护士抢救的综合满意度提高,护士对工作满意度由85.97%提高到95.26%。结论基于团队定位分工模式情景模拟教学的实施有利于提高护士的团队配合能力,缩短各项抢救措施的落实时间,提高医生对护士抢救的综合满意度,以及护士对工作的满意度。     

功能和固定矫治器联合矫治安氏Ⅱ类1分类骨性错畸形

目的 通过对功能和固定矫治器联合矫治恒牙列早期安氏Ⅱ类1分类骨性错(牙合)畸形的研究,探讨发育期骨性错(牙合)畸形一期矫治的优越性。方法 应用双(牙合)垫矫治器或斜面导板结合方丝弓矫治器对12例恒牙列早期安氏Ⅱ类1分类骨性错(牙合)联合矫治,对治疗前后头颅侧位定位片进行分析。结果 SNB角增加1.28°,FMA角无明显改变,OP-SN值变大,Go-Pog、Go-Ar都呈显著性增大,前牙覆盖减少7.26mm,上下唇至审美平面距离显著减小。结论 利用功能矫治器和固定矫治器联合一期矫治恒牙列早期安氏Ⅱ类1分类骨性错(牙合),,同样可收到双期矫治的效果。