BRAF V600E mutation as a novel mechanism of acquired resistance to ALK inhibition in ALK-rearranged lung adenocarcinoma: A case report

Rationale:Patients with lung adenocarcinoma harboring EML4-ALK rearrangements respond well to multiple ALK tyrosine kinase inhibitors (TKIs). However, the tumor will invariably progress due to acquired resistance. Comprehensive genomic profiling appears to be a promising strategy to reveal the underlying molecular mechanisms of ALK-TKIs resistance.Patient concerns:A patient with right lung adenocarcinoma harboring an ALK rearrangement received targeted therapy with multiple ALK-TKIs. He sought for follow-up treatment after his disease progressed again.Diagnosis:The patient had a tumor diagnosed with stage I (T1bN0M0) lung adenocarcinoma.Interventions:Due to the surgical contraindication, the patient did not undergo surgical resection. Instead, he received crizotinib as the first-line therapy with the progression-free survival of 20 months. Then he switched to alectinib treatment, however the disease rapidly progressed again.Outcomes:Next-generation sequencing was performed and revealed that 7 somatic mutations were identified. Among them, 2 mutations, ALK I1171T and BRAF V600E, may be responsible for the resistance of this patient to ALK-TKIs. BRAF V600E mutation may explain the patient''s resistance to lorlatinib.Lessons:We present a case of ALK-rearranged lung adenocarcinoma with acquired resistance to ALK inhibition, in which the BRAF V600E mutation is a novel resistance mechanism. This provides evidence that BRAF V600E mutation is one mechanism of ALK-TKI resistance.     

The flow characteristics of solid particles used as additives for lubricants in the point contact area

Solid nanoparticles have been applied as anti-wear and friction reduction additives for lubricants. In this paper, the flow characteristics of solid particles used as additives for lubricants were studied. A flow field visualizer based on high speed photography was developed. The particle trajectories in the point contact area were recorded using the flow field visualizer and were compared with the particle trajectories simulated using COMSOL. The results were analyzed and compared with tribological test results. It was found that the experimental results matched well with the simulation results, and the speed of the particles decreased by 60% at the inlet and outlet zones of the contact area. Solid particles were found to experience an unsteady flow in both the inlet and outlet zones and this would contribute to particle sedimentation in those areas, which matches well with the findings of the tribology test, which showed that more particles sedimented in those two areas.

The flow characteristics of solid particles used as lubricant additives under point contact conditions were investigated.     

Association of Resistance Exercise With the Incidence of Hypercholesterolemia in Men

Objective

To examine the associations of resistance exercise, independent of and combined with aerobic exercise, with the risk of development of hypercholesterolemia in men.

2012年我国农村妇女宫颈癌检查状况分析

目的分析我国农村妇女宫颈癌检查项目工作现状。方法利用全国重大公共卫生项目"两癌"检查项目信息直报系统,对2012年宫颈癌检查上报数据进行分析。结果 2012年全国对35~64岁的农村妇女进行宫颈癌检查10 621 482例,任务完成率106.2%,其中东、中、西部任务完成率分别为97.2%、112.9%及102.4%。检查人群中,81.76%的妇女既往从未接受过宫颈癌检查。运用宫颈细胞学检查及醋酸/碘染色(VIA/VILI)方法进行初筛的比例分别为77.17%和18.55%。在宫颈细胞学检查中,运用TBS描述性报告阅片的比例为65.49%,巴氏分级报告的比例为34.51%。宫颈细胞学检查结果异常或可疑病例检出率为3.93%,醋酸/碘染色检查结果异常或可疑病例检出率为11.05%。宫颈癌初筛检查的可疑/异常人群中,分别有17.01%、9.66%的妇女未接受阴道镜及病理学检查。宫颈癌前病变(CINII、III)及宫颈癌检出率124.87/10万、早诊率89.60%。结论多数地区应用宫颈细胞学检查方法作为宫颈癌初筛检查手段,但应用TBS报告结果的比例和异常结果检出率尚需进一步提高,亟需加强参与宫颈癌检查的相关人员技术培训及可疑/阳性人群的管理,进一步提高宫颈癌检查效果。     

TLR4及Hs-CRP对早产亚临床绒毛膜羊膜炎的诊断价值

目的:检测Hs-CRP及TLR4在早产亚临床绒毛膜羊膜炎孕妇外周血、脐血血清中的表达,探讨两者与早产亚临床绒毛膜羊膜炎的关系,评价其预测早产亚临床绒毛膜羊膜炎的可行性.方法:应用流式细胞术检测孕妇外周血、脐血血清中的CDl4+单核细胞上TLR4分子的表达率和平均荧光强度;用胶乳增强免疫比浊法检测外周血及分娩后脐血Hs-CRP含量.结果:早产亚临床绒毛膜羊膜炎孕妇外周血清及脐血中CDl4+单核细胞上TLR4分子的表达率和平均荧光强度及Hs-CRP水平明显高于对照组和早产非感染组,差异均有显著性.亚临床感染组孕妇外周血清及脐血TLR4的MFI与Hs-CRP成正相关.结论:TLR4联合Hs-CRP可作为早期预测感染性早产的指标.     

氧化锆牙科材料改性研究进展

氧化锆因具良好的生物相容性、较高的强度、韧性以及美观效果,被广泛地用作牙科修复材料。随着科学技术的不断发展,氧化锆用于牙科修复材料的研究也有了较大的进展。该文从氧化锆增韧、氧化锆着色和氧化锆基生物活性材料3个方面概述了氧化锆作为牙科修复材料的研究进展,并对其做了进一步展望。     

Exogenous IGF-1 improves tau pathology and neuronal pyroptosis in high-fat diet mice with cognitive dysfunction

Metabolic Brain Disease - Insulin-like growth factor-1 (IGF-1) improves obesity-induced cognitive dysfunction, but its mechanism is not fully clarified. The aim of the study was to reveal whether...