人颅面骨三维有限元模型的建立

目的利用计算机辅助技术,建立颅面骨三维有限元模型,为颌面部火器伤的生物力学分析奠定基础。方法通过薄层螺旋CT扫描正常志愿者颌面部,将获得的颅面骨数据通过Mimics软件进行三维实体重建,利用ANSA软件进行布尔运算,生成颅面骨骼,进行网格划分。结果建立了上颌骨、下颌骨等颅面骨三维有限元模型。结论利用薄层CT,结合Mimics、ANSA软件建立的颅面骨有限元模型真实准确,建立方法实用,可根据枪弹伤情况进行不同的生物力学分析。     

Vascular endothelial growth factor A,secreted in response to transforming growth factor-β1 under hypoxic conditions,induces autocrine effects on migration of prostate cancer cells

Hypoxia and transforming growth factor-β1 (TGF-β1) increase vascular endothelial growth factor A (VEGFA) expression in a number of malignancies. This effect of hypoxia and TGF-β1 might be responsible for tumor progression and metastasis of advanced prostate cancer. In the present study, TGF-β1 was shown to induce VEGFA₁₆₅ secretion from both normal cell lines (HPV7 and RWPE1) and prostate cancer cell lines (DU145 and PC3). Conversely, hypoxia-stimulated VEGFA₁₆₅ secretion was observed only in prostate cancer cell lines. Hypoxia induced TGF-β1 expression in PC3 prostate cancer cells, and the TGF-β type I receptor (ALK5) kinase inhibitor partially blocked hypoxia-mediated VEGFA₁₆₅ secretion. This effect of hypoxia provides a novel mechanism to increase VEGFA expression in prostate cancer cells. Although autocrine signaling of VEGFA has been implicated in prostate cancer progression and metastasis, the associated mechanism is poorly characterized. VEGFA activity is mediated via VEGF receptor (VEGFR) 1 (Flt-1) and 2 (Flk-1/KDR). Whereas VEGFR-1 mRNA was detected in normal prostate epithelial cells, VEGFR-2 mRNA and VEGFR protein were expressed only in PC3 cells. VEGFA₁₆₅ treatment induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in PC3 cells but not in HPV7 cells, suggesting that the autocrine function of VEGFA may be uniquely associated with prostate cancer. Activation of VEGFR-2 by VEGFA₁₆₅ was shown to enhance migration of PC3 cells. A similar effect was also observed with endogenous VEGFA induced by TGF-β1 and hypoxia. These findings illustrate that an autocrine loop of VEGFA via VEGFR-2 is critical for the tumorigenic effects of TGF-β1 and hypoxia on metastatic prostate cancers.     

Clinical outcomes after upgrading from pacemakers to cardiac resynchronization therapy

1 Background and aims

Right ventricular pacing may lead to heart failure (HF). Upgrades from pacemakers to cardiac resynchronization therapy (CRT) were excluded from most randomized, controlled trials. We sought to determine the long‐term outcomes of upgrading from pacemakers to CRT with (CRT‐D) or without (CRT‐P) defibrillation in patients with no history of sustained ventricular arrhythmias.

2 Methods and results

In this observational study, clinical events were quantified in relation to the type of implant (de novo or upgrade) and device type at upgrade (CRT‐P or CRT‐D). Patients underwent CRT implantation (n = 1,545; 1,314 [85%] de novo implants and 231 [15%] upgrades) over a median of 4.6 years [interquartile range: 2.4–7.0]. In analyses of crude event rates, upgrades had a higher total mortality (adjusted hazard ratio [aHR]: 1.33; 95% confidence interval [CI] 0.10–1.61), a higher total mortality or HF hospitalization (aHR: 1.26; 95% CI 1.05–1.51), but similar mortality or hospitalization for major adverse cardiac events (MACEs, aHR: 1.15; 95% CI 0.96–1.38). No group differences emerged in any of these endpoints after propensity score matching. After inverse probability weighting in upgrades, total mortality (HR: 0.55; 95% CI 0.36–0.73), total mortality or HF hospitalization (HR: 0.56; 95% CI 0.34–0.79), and total mortality or hospitalization for MACEs (HR: 0.61; 95% CI 0.40–0.82) were lower after CRT‐D than after CRT‐P.

3 Conclusion

Upgrading from pacemakers to CRT was associated with a similar long‐term risk of mortality and morbidity to de novo CRT. After upgrade, CRT‐D was associated with a lower mortality than CRT‐P.