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22.
目的:探讨长链非编码RNA(long-chain noncoding,lncRNA)PCGEM1 对肺癌A549 细胞恶性生物学行为的影响及其作用机制。方法:收集2016 年3 月至2018 年5 月湖北医药学院附属太和医院胸外科接受手术治疗的62 例肺癌(lung cancer,LC)患者癌组织及相应的癌旁组织标本,并用以上组织构建LC组织芯片。用qPCR检测lncRNA PCGEM1 及miR-148a 在LC组织相应的癌旁组织及LC细胞株中的表达。构建lncRNA PCGEM1 沉默细胞系A549-siPCGEM1 和阴性对照A549-NC,并以A549 细胞作为空白对照(Control 组),用MTT和平板克隆实验检测敲减PCGEM1 对A549 细胞增殖能力的影响,Transwell 和划痕实验检测敲减PCGEM1 对A549 细胞侵袭和迁移能力的影响。使用生物信息学网站StarBase 预测可互补结合PCGEM1的miRNA,再根据Targetscan 网站预测相应可靶向结合miRNA的基因;Western blotting 实验检测TGF-β2/Smad2 信号通路蛋白表达情况。结果:在LC组织中PCGEM1 的表达水平高于癌旁组织而miR-148a 的表达量明显低于癌旁组织(均P<0.05),PCGEM1 在5 种LC细胞株中的表达明显高于人肺成纤维细胞HLF-02(均P<0.05),且以A549 细胞中表达最高。敲减PCGEM1 后,与Control 组和A549-NC 组比较,A549-siPCGEM1 组A549 细胞增殖、侵袭和迁移能力显著降低(均P<0.05)。StarBase 和Targetscan 网站预测结果显示,PCGEM1 可与miR-148a 互补结合,miR-148a 与TGF-β2 存在靶向结合位点。与Control 组和A549-NC组比较,A549-siPCGEM1 组中miR-148a 表达明显升高,TGF-β2 及p-Smad2 蛋白的表达明显降低(均P<0.05)。结论:lncRNA PCGEM1在LC组织和细胞株中高表达,高表达的PCGEM1 可通过下调miR-148a 水平强化TGF β2/Smad2 信号通路,从而促进A549 细胞恶性生物学行为的进展。 相似文献
23.
Xue Wen Ping An Hexuan Li Zijian Zhou Yimin Sun Jian Wang Lixiang Ma Boxun Lu 《神经科学通报》2020,36(12):1414
Expansions of trinucleotide or hexanucleotide repeats lead to several neurodegenerative disorders, including Huntington disease [caused by expanded CAG repeats (CAGr) in the HTT gene], and amyotrophic lateral sclerosis [ALS, possibly caused by expanded GGGGCC repeats (G4C2r) in the C9ORF72 gene], of which the molecular mechanisms remain unclear. Here, we demonstrated that lowering the Drosophila homologue of tau protein (dtau) significantly rescued in vivo neurodegeneration, motor performance impairments, and the shortened life-span in Drosophila expressing expanded CAGr or expanded G4C2r. Expression of human tau (htau4R) restored the disease-related phenotypes that had been mitigated by the loss of dtau, suggesting an evolutionarily-conserved role of tau in neurodegeneration. We further revealed that G4C2r expression increased tau accumulation by inhibiting autophagosome–lysosome fusion, possibly due to lowering the level of BAG3, a regulator of autophagy and tau. Taken together, our results reveal a novel mechanism by which expanded G4C2r causes neurodegeneration via an evolutionarily-conserved mechanism. Our findings provide novel autophagy-related mechanistic insights into C9ORF72-ALS and possible entry points to disease treatment.Electronic supplementary materialThe online version of this article (10.1007/s12264-020-00518-2) contains supplementary material, which is available to authorized users. 相似文献
24.
Dan Azagury Tara E Mokhtari Luis Garcia Ulysses S Rosas Trit Garg Homero Rivas John Morton 《Surgery》2019,165(3):565-570
Background
Laparoscopic Roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy, and laparoscopic adjustable gastric banding all lead to substantial weight loss in obese patients. Long-term weight loss can be highly variable beyond 1-year postsurgery. This study examines and compares the frequency distribution of weight loss and lack of treatment effect rates after laparoscopic Roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy, and laparoscopic adjustable gastric banding.Methods
A total of 1,331 consecutive patients at a single academic institution were reviewed from a prospectively collected database. Preoperative data collected included demographics, body mass index, and percent excess weight loss. Postoperative BMI and %EWL were collected at 12, 24, and 36 months. Percent excess weight loss was analyzed by the percentiles of excess weight lost, and the distribution of percent excess weight loss was evaluated in 10% increments. Lack of a successful treatment effect was defined as <25% excess weight loss.Results
Of the 1,331 patients, 72.4% (963) underwent laparoscopic Roux-en-Y gastric bypass, 18.3% (243) laparoscopic sleeve gastrectomy, and 9.4%(125) laparoscopic adjustable gastric banding. Mean percent excess weight loss was greatest for laparoscopic Roux-en-Y gastric bypass, followed by laparoscopic sleeve gastrectomy, and then by laparoscopic adjustable gastric banding at every time point: at 2 years mean percent excess weight loss was 77.9± 24.4 for laparoscopic Roux-en-Y gastric bypass, 50.8 ± 25.8 for laparoscopic sleeve gastrectomy, and 40.8± 25.9 for laparoscopic adjustable gastric banding (P < .0001). The rates of a successful treatment effect s for laparoscopic Roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy, and laparoscopic adjustable gastric banding were 0.9%, 5.2%, and 24.3% at 1 year; 0.3%, 11.1%, and 26.0% at 2 years; and 1.0%, 25.3%, and 30.2% at 3 years. At 1 year, the odds ratio of lack of a successful treatment effect of laparoscopic sleeve gastrectomy versus laparoscopic Roux-en-Y gastric bypass was 6.305 (2.125–19.08; P?=?.0004), the odds ratio for laparoscopic adjustable gastric banding versus laparoscopic Roux-en-Y gastric bypass was 36.552 (15.64–95.71; P < .0001), and the odds ratio for laparoscopic adjustable gastric banding versus laparoscopic sleeve gastrectomy was 5.791 (2.519–14.599; P < .0001). At 2 years, the odds ratio for laparoscopic sleeve gastrectomy versus laparoscopic Roux-en-Y gastric bypass increased to 70.7 (9.4–531.7; P < .0001), the odds ratio for laparoscopic adjustable gastric banding versus laparoscopic Roux-en-Y gastric bypass increased to 128.1 (16.8–974.3; P < .0001), and the odds ratio for laparoscopic adjustable gastric banding versus laparoscopic sleeve gastrectomy decreased to 1.8 (0.9–3.6; P?=?.09).Conclusion
This study emphasizes the existing variability in weight loss across bariatric procedures as well as in the lack of a treatment effect for each procedure. Although laparoscopic adjustable gastric banding has the greatest rate of a lack of a successful treatment effect, the rate remained stable over 3 years postoperatively. Laparoscopic sleeve gastrectomy showed a doubling in the rate of a lack of a successful treatment effect every year reaching 25% at year 3. The rates for lack of a successful treatment effect for laparoscopic Roux-en-Y gastric bypass remained stable at about 1% for the first 3 years postoperatively. 相似文献25.
Fraudulent business practices, such as those leading to the Enron scandal and the
conviction of Bernard Madoff, evoke a strong sense of public outrage. But fraudulent or
dishonest actions are not exclusive to the realm of big corporations or to evil
individuals without consciences. Dishonest actions are all too prevalent in everyone’s
daily lives, because people are constantly encountering situations in which they can gain
advantages by cutting corners. Whether it’s adding a few dollars in value to the stolen
items reported on an insurance claim form or dropping outlier data points from a figure to
make a paper sound more interesting, dishonesty is part of the human condition. Here, we
explore how people rationalize dishonesty, the implications for scientific research, and
what can be done to foster a culture of research integrity. 相似文献
26.
27.
骨碎补是历代临床常用中药,具有疗伤止痛、补肾强骨、消风祛斑等功效。其主要含黄酮、苯丙素、三萜、酚酸及其苷等类化学成分,现代研究表明骨碎补具有抗骨质疏松、促进骨折愈合、促软骨再生、护牙健齿、保护肾功能、抗炎、防治中毒性耳聋、降血脂等多种生物活性,开发前景广阔。本文对近年来骨碎补的化学成分、药理作用及临床应用研究进行综述,以期为骨碎补的进一步深入系统的研究和开发利用提供依据。 相似文献
28.
29.
Yasmine Yousef Etienne St-Louis Robert Baird Emily R. Smith Elena Guadagno Dickens St-Vil Dan Poenaru 《Journal of pediatric surgery》2019,54(4):831-837
Background
The Lancet Commission on Global Surgery highlighted global surgical need but offered little insight into the specific surgical challenges of children in low-resource settings. Efforts to strengthen the quality of global pediatric surgical care have resulted in a proliferation of partnerships between low-and middle-income countries (LMICs) and high-income countries (HICs). Standardized tools able to reliably measure gaps in delivery and quality of care are important aids for these partnerships. We undertook a systematic review (SR) of capacity assessment tools (CATs) focused on needs assessment in pediatric surgery.Methods
A comprehensive search strategy of multiple electronic databases was conducted per PRISMA guidelines without linguistic or temporal restrictions. CATs were selected according to pre-defined inclusion criteria. Articles were assessed by two independent reviewers. Methodological quality of studies was appraised using the COSMIN checklist with 4-point scale.Results
The search strategy generated 16,641 original publications, of which three CATs were deemed eligible. Eligible tools were either excessively detailed or oversimplified. None used weighted scores to identify finer granularity between institutions. No CATs comprehensively included measures of resources, outcomes, accessibility/impact and training.Discussion
The results of this study identify the need for a CAT capable of objectively measuring key aspects of surgical capacity and performance in a weighted tool designed for pediatric surgical centers in LMICs.Type of Study
Systematic Review.Level of Evidence
II. 相似文献30.