时钟基因Bmal1对鼻咽癌移植瘤放疗敏感性的影响

目的:探讨双向调控时钟基因Bmal1(brain and muscle arnt-like1)对鼻咽癌CNE1裸鼠移植瘤生长的影响及与放疗敏感性的关系。方法:采用慢病毒感染方法,构建Bmal1基因CNE1OE(过表达组)、CNE1OENC(过表达对照组)、CNE1sh3(低表达组)、CNE1shNC(低表达对照组)4株细胞,Western blot验证各组细胞Bmal1蛋白表达情况;4株细胞分别皮下注射相应的4组裸鼠,移植瘤生长后测量其体积;给予6-MeV电子线15 Gy照射裸鼠移植瘤,观察放疗后各组移植瘤体积变化情况。剥离移植瘤,RTPCR及Western blot分别检测Bmal1、P53、P21 mRNA及蛋白表达情况。结果:Western blot结果提示,与各自对照组对比,CNE1OE组Bmal1蛋白过表达,CNE1sh3组Bmal1蛋白低表达,表明细胞转染成功。成功构建裸鼠移植瘤模型,CNE1OE组裸鼠移植瘤体积明显小于CNE1OENC组,CNE1sh3组体积明显大于CNE1shNC组(P<0.05)。放疗后,CNE1OE、CNE1OENC、CNE1shNC组裸鼠移植瘤体积均缩小(P<0.05),其中CNE1OE组缩小最明显。CNE1sh3组放疗前后自身体积变化差异无统计学意义。Bmal1基因、P53及P21的mRNA及蛋白相对表达量在CNE1OE组明显高于CNE1OENC组(P<0.05),CNE1sh3组则明显低于CNE1shNC组(P<0.05)。结论:Bmal1基因过表达能抑制鼻咽癌CNE1裸鼠移植瘤生长,增强其放疗敏感性,可能与P53、P21蛋白上调相关;敲低则促进移植瘤生长,导致其辐射抗拒,可能与P53、P21蛋白下调相关。

Electrical discharge and arc milling with automatic tracking of optimal flushing direction:A novel high-efficiency compound machining method

The arc milling method has the advantages of high machining efficiency and low cost and is independent of the strength and hardness of machined materials.However,frequent electrode back-offs and the risk of workpiece burning may occur if erosion products are not removed promptly.In this study,it was found that the flushing method of the working medium had a significant impact on the machining performance of arc milling.Based on this,a novel highefficiency compound machining method of electrical discharge and arc milling with automatic tracking of the optimal flushing direction was proposed.An automatic tracking optimizer for external working medium injection was designed to determine the optimal external flushing direction according to the feed direction.The influence of flushing methods,working mediums,and machining parameters on the machining efficiency,tool electrode wear rate,machining error,and surface integrity of titanium alloys were investigated.The results indicated that better machining performance and environmental friendliness were achieved using the compound flushing method of outer compressed air and inner deionized water.Additionally,the automatic tracking flushing method in the opposite direction of the feed direction showed superior results compared to other directions.The material removal rate with the opposite direction injection could be increased up to 1.62 times that of the same direction,and the relative electrode wear rate could be reduced by 14.76%.This novel method has broad application prospects for machining parts with difficult-to-cut materials in aerospace and military industries.

Dual sliding mode coordinated control of manipulator grasping system with visual assistance

The operation efficiency of the manipulator is placed in the primary position in automatic production. This paper proposes a coordinated control strategy for joint servo and visual servo to enable timely transfer and accurate gripping in the working area. Aiming at the issues of chattering and slow convergence of traditional sliding mode controller, a fast variable power reaching rate on the basis of the non-singular fast terminal sliding mode controller is proposed, which can effectively reduce the convergence time and chattering. For the purpose of addressing the problem that the traditional visual servo control method is sensitive to the environment, a visual servo controller based on integral sliding mode is proposed, to ensure the favorable positioning accuracy of the manipulator. Based on the two proposed controllers mentioned above, a coordinated control strategy is used to implement the control of the manipulator. Finally, the upper computer software is developed using the C# programming language to monitor the workstation. The feasibility of the above-mentioned method is verified through multiple simulations and experiments.

Chronomodulated chemotherapy for locoregionally advanced nasopharyngeal carcinoma:A phase Ⅱ randomized controlled trial

Objective:To validate the safety and efficacy of chronochemotherapy for locoregionally advanced nasopharyngeal carcinoma(NPC).Methods:Participants for this phase II randomized controlled trial were recruited from the Department of Head and Neck Oncology at the Affiliated Cancer Hospital of Guizhou Medical University.Patients enrolled(128 in total,112 in the final analysis)between April 1,2017,and February 28,2018,were randomly divided into the chronochemotherapy and conventional chemotherapy groups.In the chronochemotherapy group,docetaxel was intravenously administered between 3:30 a.m.and 4:30 a.m.on day 1,followed by intravenous administration of cisplatin between 10:00 a.m.and 10:00 p.m.from day 1to day 5.In addition,5-fluorouracil was administered through a continuous intravenous pump between 10:00 p.m.and 10:00 a.m.(2nd day)from day 1 to day 5.In the conventional chemotherapy group,docetaxel(on day 1),cisplatin(on day 2),and 5-fluorouracil(from day 1 to day 5,120 h in total)were administered without time-specific constraints.Both groups underwent intensitymodulated radiation therapy with 6-MV X-rays.The gross target volume(GTV)comprised the nasopharyngeal GTV and cervical lymph node GTV.The primary endpoint was immune function,quantified by measuring dendritic cell and lymphocyte subsets,whereas the secondary endpoints were therapeutic efficacy and incidence of adverse events.Pearson Chi-square test was applied to compare total events between the groups,Mann-Whitney U test was used to compare the DC subsets and toxicities,and Wilcoxon signed-rank test was used to compare the continuous variables between the two groups.Results:Chronochemotherapy preserved immune function,as evidenced by elevated levels of myeloid dendritic cells(P=0.394)and higher CD4/CD8 ratio(P?0.781).No significant difference in overall response rate,measured as the sum of complete and partial response rates,was observed between the groups(P=0.711).A reduction in the incidence of vomiting(P=0.002),stomatitis(P=0.028),and mucositis(P=0.028)was observed in the chronochemotherapy group.Leukopenia incidence rate was 83.3% and 92.3% in the chronochemotherapy and conventional chemotherapy groups,respectively(P=0.232).Conclusions:In patients with locoregionally advanced NPC,the overall response rate of chronochemotherapy is comparable to that of conventional chemotherapy;however,chronochemotherapy shows fewer adverse events.