The molecular mechanisms of XBP-1 gene silencing on IRE1α-TRAF2-ASK1-JNK pathways in oral squamous cell carcinoma under endoplasmic reticulum stress

BackgroundProteasome inhibitor Carbobenzoxy-Leu-Leu-leucinal (MG132) induces the unfolded protein response (UPR) in oral squamous cell carcinoma (OSCC). X-box binding protein 1 (XBP1) is a key UPR component that regulates endoplasmic reticulum stress (ER) homeostasis. This study was aimed to investigate the activation of IRE1α-TRAF2-ASK1-JNK pathway by silencing the XBP1 expression in an OSCC cell line.MethodsThe XBP1 specific short hairpin RNA (shRNA) plasmid vector was constructed and then transfected into the Tca-8113 cells. The effect of XBP-1 gene silencing on IRE1α-TRAF2-ASK1-JNK pathway under MG132 induced endoplasmic reticulum stress in Tca-8113 were investigated by real-time RT-PCR or western blot. Cell apoptosis was detected by flow cytometry.ResultsXBP1 expression was reduced in transfected groups and MG132 groups. shRNA-XBP1 induces IRE1α-TRAF2-ASK1 signaling activation to activate pro-apoptotic ASK1-JNK signaling. Moreover, combined shRNA-XBP1 with MG132 further enhanced downregulated XBP1 expression and upregulated activation of ASK1-JNK signaling.ConclusionsSilencing XBP1 expression under MG132 induced ER stress block the XBP1 survival pathway and synergism with MG132 to promote Tca8113 cell apoptosis. These findings provide a therapeutic option in oral squamous cell carcinoma by inhibition of proteasome and XBP1 splicing.     

重症甲型H1N1流感14例临床分析

目的探讨重症甲型H1N1流感的临床特点。方法对我院确诊的14例重症甲型H1N1流感临床特点和治疗进行回顾性分析。结果所有确诊重症甲型H1N1流感病例均有发热等流感样症状,易继发肺部感染等,白细胞(WBC)和淋巴细胞(L)减低,早期给予抗病毒等综合治疗,效果良好。结论重症甲型H lN1流感发病以年轻群体为主,传染性高于季节性流感。早期给予奥司他韦等抗病毒治疗,辅以中药施治,疗效肯定。     

干预性护理在直肠癌手术中的效果与意义

目的：探讨干预性护理在直肠癌手术中的效果与意义。方法：通过对本院2010年5月～2011年5月收治并确诊的52例直肠癌择期手术患者进行回顾性分析,并随机分为干预组和常规组。于术后分析两组的精神状态、患者满意度情况以及并发症情况。结果：①除＂人际关系敏感＂外,干预组的SCL-90自评症状量表的其他指标均优于常规组,且差异具有统计学意义;②干预组的感染并发症发生率低于对照组（P〈0.05）,尤其是阴部感染;③干预组患者的满意程度高于对照组（P〈0.01）。结论：术中干预性护理不仅可以改善直肠癌患者焦虑烦躁的精神状态,而且还可以减少并发症的发生,值得在临床上进行推广。     

Aberrant functional and effective connectivity of the frontostriatal network in unilateral acute tinnitus patients with hearing loss

Brain Imaging and Behavior - The present study combined resting-state functional connectivity (FC) and Granger causality analysis (GCA) to explore frontostriatal network dysfunction in unilateral...     

双环[1.1.1]戊烷衍生物的合成研究进展

双环[1.1.1]戊烷（BCP）是一种具有三维立体结构的桥环骨架,其作为苯环、叔丁基和炔烃的生物电子等排体,已经在药物化学领域得到广泛的应用。随着BCP应用范围的扩大,BCP及其衍生物的合成日益成为研究的热点。本文对BCP衍生物的主要合成策略和方法进行总结,旨在为新药研发人员提供参考。     

三阴性乳腺癌患者超声造影征象及其与抑癌蛋白P53、细胞角蛋白5/6的关系

目的 探讨三阴性乳腺癌(TNBC)患者超声造影征象及其与抑癌蛋白P53、细胞角蛋白5/6(CK5/6)的关系.方法 选取2014年7月—2020年6月于南京医科大学附属江宁医院和南京医科大学第一附属医院超声医学科行乳腺超声造影的98例TNBC患者(研究组)和103例其他分子分型乳腺癌患者(对照组).患者均接受手术治疗,...     

Preparing anti-SARS-CoV-2 agent EIDD-2801 by a practical and scalable approach,and quick evaluation via machine learning

EIDD-2801 is an orally bioavailable prodrug, which will be applied for emergency use authorization from the U.S. Food and Drug Administration for the treatment of COVID-19. To investigate the optimal parameters, EIDD-2801 was optimized via a four-step synthesis with high purity of 99.9%. The hydroxylamination procedure was telescoped in a one-pot and the final step was precisely controlled on reagents, temperature and reaction time. Compared to the original route, the yield of the new route was enhanced from 17% to 58% without column chromatography. The optimized synthesis has been successfully determinated on a decagram scale: the first step at 200 g and the final step at 20 g. Besides, the relationship between yield and temperature, time, and reagents in the deprotection step was investigated via Shapley value explanation and machine learning approach-decision tree method. The results revealed that reagents have the greatest impact on yield estimation, followed by the temperature.     

SP联合CBL在骨外科临床实践教学中的应用研究

目的探讨标准化病人(standard patient,SP)结合案例式教学(case-based learning,CBL)在骨外科临床实践教学中的应用效果。方法选取2018—2019学年于我院骨科实习的南京医科大学2014级临床医学专业学生50人作为研究对象。随机将其均分为试验组和对照组两组,每组各25人。试验组采用SP+CBL相结合教学方法;对照组采用传统CBL授课方法。在教学结束后,请所有参与试验的学生对课程进行评价,并从理论和操作两方面对学生进行考核。结果两组学生的理论考试成绩无明显差异,不具统计学意义(P>0.05)。但试验组学生的临床技能操作考核成绩高于对照组(P<0.01)。试验组学生对SP+CBL教学在激发学习兴趣、增强解决实际问题能力及提高骨外科实践教学质量等方面的满意度显著高于对照组(P<0.01)。结论SP+CBL教学优于传统CBL教学,可以显著提高学习的积极性,有助于提高骨外科临床实践教学的效果。     

Adiposity is not beneficial to bone mineral density in 0–5 year old Chinese children: The Jiangsu bone health study

ObjectiveData on obesity in relation to bone mineral density(BMD) in infants and preschool children were sparse in China. The objective of this study was to examine the associations between body mass index (BMI) and BMD.Subjects and methodsThis was a large population-based multicenter study in which the representative children aged 0–5 years were recruited from 13 Children’s Health Care Centers by a stratified cluster random-sampling method in Jiangsu Province, China. BMD was measured by using quantitative ultrasound. The association of BMD with BMI and obesity were evaluated using multiple linear regression and logistic regression analysis taking into account the effects of confounders. The relations between age, weight, height, BMI and BMD were analyzed by using Pearson’s correlation and further tested using partial correlation in the additive model.ResultsA total of 5,289 children (2786 boys and 2503 girls) were recruited. The BMD was positively linear relation with age, length/height, and was inversely linear relation with BMI (r = 0.711, P < 0.001; r = 0.727, P < 0.001; r = −0.318, P < 0.001, respectively). The BMD gradually increased when the weight was in the range within 21.2 kg, but started to gain slowlyand even decreased when the weight was over 21.2 kg. After adjusting for confounders, compared with control group, children with obesityhad higher odds of low BMD (OR 95%CI: 2.73 (1.57, 4.76), P < 0.001), the speed of sound (SOS)value in children with obesity was lower 47.45 (β = −47.45, 95%CI = −85.07, −9.83, P = 0.013).ConclusionsAdiposity was not advantageous for bone mineral density in 0-5-year-old Chinese children.