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Richard Kim Elaine Tan Emily Wang Amit Mahipal Dung-Tsa Chen Biwei Cao Fadzai Masawi Cindy Machado James Yu Dae Won Kim 《The oncologist》2020,25(12):e1893-e1899
Lessons Learned
- The combination of trametinib and sorafenib has an acceptable safety profile, albeit at doses lower than approved for monotherapy.
- Maximum tolerated dose is trametinib 1.5 mg daily and sorafenib 200 mg twice daily.
- The limited anticancer activity observed in this unselected patient population does not support further exploration of trametinib plus sorafenib in patients with hepatocellular carcinoma.
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Ju Zou Daichao Wu Tao Li Xianwen Wang Yan Liu Sijie Tan 《Pathology, research and practice》2019,215(2):229-234
Programmed death ligand 1(PD-L1) mediated immune escape play important roles in the development of cancer. The gene polymorphism of PD-L1, in particular rs4143815 C?>?G, has been associated with the cancer risks, but with conflicting results. Therefore, this meta-analysis was aimed to assess the association between rs4143815 C?>?G and cancer susceptibility. A systematic literature search was performed to select the studies and the pooled odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the strength of association. Eleven eligible studies containing 3711 cases and 3704 controls were enrolled in the meta-analysis. The results suggested that there is a strong association between rs4143815 C?>?G and the cancer risks (G vs. C: OR?=?1.386, 95% CI: 1.132–1.696, p?=?0.002; GG vs. CG?+?CC: OR?=?1.843 95% CI: 1.300–2.613, p?=?0.002; GG?+?CG vs. CC: OR?=?1.280, 95% CI: 1.040–1.576, p?=?0.020). Subgroup analysis based on cancer type suggested that PD-L1 rs4143815 C?>?G might increase the susceptibility to gastric cancer (G vs. C: OR?=?1.842, 95% CI: 1.403–2.418, p?<?0.001) and bladder cancer (G vs. C: OR?=?2.015, 95% CI: 1.556–2.608, p?<?0.001), and genotype GG carriers of PD-L1 rs4143815 C?>?G might have higher risks of HCC (GG vs. CG?+?CC: OR?=?2.226 95% CI: 1.562–3.172, p?<?0.001). PD-L1 rs4143815 C?>?G might confer an increased cancer risk, indicating this SNP may contribute to the pathogenesis of cancer and might be used as a potential biomarker to predict the susceptibility to cancer. 相似文献
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Yuanqing Yao Jun Qian Shunkang Rong Yuwen Huang Bo Xiong Gang Yang Dengqing Zhang Shimin Deng Jie Tan Que Zhu Changming Deng Dichuan Liu Haitao Ran Zhigang Wang Jing Huang 《Ultrasound in medicine & biology》2019,45(2):490-499
Stellate ganglion (SG) modification has been investigated for arrhythmia treatment. In this study, transesophageal SG imaging and intervention were explored using a homemade 30F integrated focused ultrasonic catheter in healthy mongrel canines in vivo. Anatomic details of SGs were ultrasonically imaged and evaluated. SG had a heterogeneous echoic structure and characteristic profiles sketched by hyper-echoic outlines in an ultrasonogram. Left SGs in the experimental group were successfully ablated through the esophagus under ultrasonic guidance provided by the catheter itself. Two weeks after the ablation, the QT and QTc of the experimental group decreased compared with those of the sham group and at baseline (both p values < 0.001). Histologic examination revealed that left SGs were destroyed. No major complications were observed. This approach may be further explored as a method for ganglia remodeling evaluation and as a strategy of ganglia modification for arrhythmia and for other diseases. 相似文献
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Elevated serum levels of Interleukin‐37 are associated with inflammatory cytokines and disease activity in rheumatoid arthritis
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Libin Yang Jun Zhang Jingang Tao Tan Lu 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2015,123(12):1025-1031
Interleukin‐37 (IL‐37) is closely associated with several inflammatory diseases. However, the role of IL‐37 in the pathogenesis of rheumatoid arthritis (RA) remains unclear. The aim of this study was to assess the associations between serum levels of IL‐37 and disease activity, inflammatory cytokines, and bone loss in patients with RA. Serum cytokines levels were examined by Enzyme‐linked immunosorbent assay (ELISA). Radiographic bone erosion was assessed using the van der Heijde‐modified Sharp score and bone mineral density (BMD) was measured using DXA. Serum IL‐37 levels in RA patients were significantly higher than those in HCs (p < 0.001), and were significantly positively correlated with clinical parameters of disease activity and serum levels of IL‐17 and IL‐23. In addition, serum IL‐37 levels were significantly higher in patients with stage IV of radiographic bone erosion than those with stage III and stage I–II, and they were significantly higher in those with osteopenia and osteoporosis than in those with normal BMD. Our results suggest that serum IL‐37 levels were increased in patients with RA and were positively associated with disease activity, IL‐17/IL‐23 and bone loss in RA, suggesting that IL‐37 may play a critical role in the pathogenesis of RA. 相似文献
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Sharisse M. Arnold Rehring Liza M. Reifler Jennifer H. Seidel Karen A. Glenn John F. Steiner 《Academic pediatrics》2019,19(5):572-580
ObjectiveClinical specialty societies recommend long-acting reversible contraceptives (LARCs) as first-line contraception for adolescent women. We evaluated whether a combined educational and process improvement intervention enhanced LARC placement in primary care within an integrated health care system.MethodsThe intervention included journal clubs, live continuing education, point-of-care guidelines, and new patient materials. We conducted a retrospective cohort study across 3 time periods: baseline (January 2013?September 2015), early implementation (October 2015–March 2016), and full implementation (April 2016–June 2017). The primary outcome was the proportion of LARCs placed by primary care clinicians among women aged 13 to 18 years compared with gynecology clinicians.ResultsKaiser Foundation Health Plan of Colorado cared for approximately 20,000 women aged 13 to 18 years in each calendar quarter between 2013 and 2017. Overall, LARC placement increased from 7.0 per 1000 members per quarter at baseline to 13.0 per 1000 during the full intervention. Primary care clinicians placed 6.2% of all LARCs in 2013, increasing to 32.1% by 2017 (P < .001), including 45.5% of contraceptive implants. Clinicians who attended educational sessions were more likely to adopt LARCs than those who did not (17.9% vs 6.4% respectively, P = .009). Neither overall LARC placement rates (relative risk, 1.9; 95% confidence interval, 0.7?5.6) nor contraceptive implant rates (relative risk, 3.0; 95% confidence interval, 0.9?9.8) increased significantly in clinicians who attended educational activities.ConclusionsThis multimodal intervention was associated with increased LARC placement for adolescent women in primary care. The combination of education and process improvement is a promising strategy to promote clinician behavior change. 相似文献
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Dry powder inhalers (DPIs) are gaining popularity for the delivery of drugs. A cost effective and efficient delivery device is necessary. Developing new DPIs by modifying an existing device may be the simplest way to improve the performance of the devices. The aim of this research was to produce a new DPIs using computational fluid dynamics (CFD). The new DPIs took advantages of the Cyclohaler® and the Rotahaler®. We chose a combination of the capsule chamber of the Cyclohaler® and the mouthpiece and grid of the Rotahaler®. Computer-aided design models of the devices were created and evaluated using CFD. Prototype models were created and tested with the DPI dispersion experiments. The proposed model 3 device had a high turbulence with a good degree of deagglomeration in the CFD and the experiment data. The %fine particle fraction (FPF) was around 50% at 60?L/min. The mass median aerodynamic diameter was around 2.8–4?μm. The FPF were strongly correlated to the CFD-predicted turbulence and the mechanical impaction parameters. The drug retention in the capsule was only 5–7%. In summary, a simple modification of the Cyclohaler® and Rotahaler® could produce a better performing inhaler using the CFD-assisted design. 相似文献
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