LY3214996 relieves acquired resistance to sorafenib in hepatocellular carcinoma cells

Background: Sorafenib, an oral multi-kinase inhibitor of rapidly accelerated fibrosarcoma; vascular endothelial growth factor receptor-2/3, platelet-derived growth factor receptor, c-Kit, and Flt-3 signaling, is approved for treatment of advanced hepatocellular carcinoma (HCC). However, the benefit of sorafenib is often diminished because of acquired resistance through the reactivation of ERK signaling in sorafenib-resistant HCC cells. In this work, we investigated whether adding LY3214996, a selective ERK1/2 inhibitor, to sorafenib would increase the anti-tumor effectiveness of sorafenib to HCC cells.Methods: The Huh7 cell line was used as a cell model for treatment with sorafenib, LY3214996, and their combination. Phosphorylation of the key kinases in the Ras/Raf/MAPK and PI3K/Akt pathways, protein expression of the cell cycle, and apoptosis migration were assessed with western blot. MTT and colony-formation assays were used to evaluate cell proliferation. Wound-healing assay was used to assess cell migration. Cell cycle and apoptosis analyses were conducted with flow cytometry.Results: LY3214996 decreased phosphorylation of the Ras/Raf/MAPK and PI3K/Akt pathways, including p-c-Raf, p-P90RSK, p-S6K and p-eIF4EBP1 activated by sorafenib, despite increased p-ERK1/2 levels. LY3214996 increased the anti-proliferation, anti-migration, cell-cycle progression, and pro-apoptotic effects of sorafenib on Huh7^R cells.Conclusions: Reactivation of ERK1/2 appears to be a molecular mechanism of acquired resistance of HCC to sorafenib. LY3214996 combined with sorafenib enhanced the anti-tumor effects of sorafenib in HCC. These findings form a theoretical basis for trial of LY3214996 combined with sorafenib as second-line treatment of sorafenib-resistant in advanced HCC.     

面动脉颊瓣修复口腔颌面部缺损的临床观察

目的探讨面动脉颊瓣修复口腔颌面部缺损的临床可靠性和修复效果。方法回顾分析淮安市第二人民医院口腔科2012年7月至2019年9月面动脉颊瓣修复口腔癌病灶切除术后缺损的患者15例,收集患者基本信息、病理诊断结果、手术时间、手术出血量及住院时间等资料,仔细临床检查,观察术区创口愈合情况,术后随访完善张口度功能检查,随访至少1年。数据采用SPSS 19.0统计软件分析处理,结果以x±s表示。结果观察随访面动脉颊瓣修复口腔颌面部缺损15例,平均手术时间(5.49±0.76)h,手术出血量约平均(382.67±63.86)mL,术中或术后输血3例,平均住院时间(17.73±2.49)d。面动脉颊瓣最大为8 cm×4 cm的三角形肌皮瓣。术后2周皮瓣均存活无坏死、血运良好,皮瓣存活率100%。术后1年复诊,医师检查患者张口度情况,15例患者张口度(3.86±0.14)cm,均在正常范围内。但3例男性患者提出术后皮瓣表面生长毛发,带来不适感,均在可以接受范围。位于口角以下颊部的供区瘢痕与面部纹路位置重叠。结论面动脉颊瓣可修复口腔中下部的中小缺损,皮瓣供区手术创伤小,皮瓣成活率高,可在口腔癌病灶切除后同期修复,术后张口功能恢复良好,瘢痕不明显。     

Optimize the management of urological tube-related emergencies during the coronavirus disease 2019 (COVID-19) pandemic

BackgroundTo introduce and determine the value of optimized strategies for the management of urological tube-related emergencies with increased incidence, complexity and operational risk during the global spread of coronavirus disease 2019 (COVID-19).MethodsAll emergent urological patients at Tongji Hospital, Wuhan, during the period of January 23 (the beginning of lockdown in Wuhan) to March 23, 2020, and the corresponding period in 2019 were recruited to form this study’s COVID-19 group and control group, respectively. Tongji Hospital has the most concentrated and strongest Chinese medical teams to treat the largest number of severe COVID-19 patients. Patients in the control group were routinely treated, while patients in the COVID-19 group were managed following the optimized principles and strategies. The case incidence for each type of tube-related emergency was recorded. Baseline characteristics and management outcomes (surgery time, secondary complex operation rate, readmission rate, COVID-19 infection rate) were analyzed and compared across the control and COVID-19 periods.ResultsThe total emergent urological patients during the COVID-19 period was 42, whereas during the control period, it was 124. The incidence of tube-related emergencies increased from 53% to 88% (P<0.001) during the COVID-19 period. In particular, the incidence of nephrostomy tube-related (31% vs. 15%, P=0.027) and single-J stent-related problems (19% vs. 6%, P=0.009) increased significantly. The mean surgery times across the two periods were comparable. The number of secondary complex operations increased from 12 (18%) to 14 (38%) (P=0.028) during the COVID 19-period. The number of 2-week postoperative readmission decreased from 10 (15%) to 1 (3%) (P=0.049). No participants contracted during the COVID-19 period.ConclusionsUrological tube-related emergencies have been found to have a higher incidence and require more complicated and dangerous operations during the COVID-19 pandemic. However, the optimized management strategies introduced in this study are efficient, and safe for both urologists and patients.     

Progress on ocular siRNA gene‐silencing therapy and drug delivery systems

Age‐related macular degeneration (AMD) and glaucoma are global ocular diseases with high blindness rate. RNA interference (RNAi) is being increasingly used in the treatment of these disorders with siRNA drugs, bevasiranib, AGN211745 and PF‐04523655 for AMD, and SYL040012 and QPI‐1007 for glaucoma. Administration routes and vectors of gene drugs affect their therapeutic effect. Compared with the non‐viral vectors, viral vectors have limited payload capacity and potential immunogenicity. This review summarizes the progress of the ocular siRNA gene‐silencing therapy by focusing on siRNA drugs for AMD and glaucoma already used in clinical research, the main routes of drug delivery and the non‐viral vectors for siRNA drugs.     

病房护士发生职业性肌肉骨骼疾患工作场所的MAPO指数评估及影响因素分析

目的评估病房手工搬运患者护士发生职业性肌肉骨骼疾患(WMSDs)工作场所的MAPO指数,并了解工作场所中WMSDs发生的影响因素。方法采用便利抽样法,于2019年3—5月选取某三甲医院26个病区的317名护士为研究对象。以一般资料调查表、MAPO评估方法、米尺为研究工具,采用现场调查和测量法,对病房手工搬运患者护士发生WMSDs工作场所的情况进行综合评估。依据MAPO指数将病区分为红灯、黄灯、绿灯3个风险等级,亮黄灯代表有必要执行中期和长期干预计划,亮红灯意味着必须执行短期干预计划。对病房手工搬运患者护士发生WMSDs的影响因素采用多因素Logistic回归分析。结果本研究共发放问卷317份,回收有效问卷265份,有效回收率为83.6%。265名病房护士中,76.2%(202/265)的护士发生WMSDs。有13个(50.0%,13/26)病区亮红灯,包含158名(59.6%,158/265)护士;6个(23.1%,6/26)病区亮黄灯,包含92名(34.7%,92/265)护士;7个(26.9%,7/26)病区亮绿灯,包含15名(5.7%,15/265)护士。多因素Logistic回归分析显示,MAPO指数和病房分值是病房护士发生WMSDs的影响因素(OR值分别为1.056、1.571;P<0.05)。结论病房护士工作场所发生WMSDs的风险较高,建议从病床类型、床间距、辅助设备、护理人力资源配置和职业防护培训方面入手来减少护士WMSDs的发生。     

Establishment of nomograms for the prediction of useful hearing loss in patients with neurofibromatosis type 2

Journal of Neuro-Oncology - Treatment for vestibular schwannoma (VS) in patients with neurofibromatosis type 2 (NF2) is extremely challenging due to the high risk of hearing loss. The aim of this...