Initial experience with an electron FLASH research extension (FLEX) for the Clinac system.

PURPOSE: Radiotherapy delivered at ultra-high-dose-rates (≥40 Gy/s), that is, FLASH, has the potential to effectively widen the therapeutic window and considerably improve the care of cancer patients. The underlying mechanism of the FLASH effect is not well understood, and commercial systems capable of delivering such dose rates are scarce. The purpose of this study was to perform the initial acceptance and commissioning tests of an electron FLASH research product for preclinical studies. METHODS: A linear accelerator (Clinac 23EX) was modified to include a non-clinical FLASH research extension (the Clinac-FLEX system) by Varian, a Siemens Healthineers company (Palo Alto, CA) capable of delivering a 16 MeV electron beam with FLASH and conventional dose rates. The acceptance, commissioning, and dosimetric characterization of the FLEX system was performed using radiochromic film, optically stimulated luminescent dosimeters, and a plane-parallel ionization chamber. A radiation survey was conducted for which the shielding of the pre-existing vault was deemed sufficient. RESULTS: The Clinac-FLEX system is capable of delivering a 16 MeV electron FLASH beam of approximately 1 Gy/pulse at isocenter and reached a maximum dose rate >3.8 Gy/pulse near the upper accessory mount on the linac gantry. The percent depth dose curves of the 16 MeV FLASH and conventional modes for the 10 × 10 cm2 applicator agreed within 0.5 mm at a range of 50% of the maximum dose. Their respective profiles agreed well in terms of flatness but deviated for field sizes >10 × 10 cm2 . The output stability of the FLASH system exhibited a dose deviation of <1%. Preliminary cell studies showed that the FLASH dose rate (180 Gy/s) had much less impact on the cell morphology of 76N breast normal cells compared to the non-FLASH dose rate (18 Gy/s), which induced large-size cells. CONCLUSION: Our studies characterized the non-clinical Clinac-FLEX system as a viable solution to conduct FLASH research that could substantially increase access to ultra-high-dose-rate capabilities for scientists.

Nifedipine attenuates vascular inflammation via inhibin NF-κB activity / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the effects and related mechanism of nifedipine on vascular inflammation induced by cuff placement.</p><p><b>METHODS</b>Adult male C57BL/6J mice (10 to 12 weeks of age) were assigned to control (no cuff placement without nifedipine), cuff placement (cuff placement without nifedipine) and treatment (cuff placement with nifedipine 1 or 5 mg×kg(-1)×d(-1)) groups. Activity of NF-κB in injured artery was measured 5 days after operation. MCP-1 expression and nuclear translocation of NF-κB were examined in injured artery 7 days after operation.</p><p><b>RESULTS</b>DNA-binding activity of NF-κB was significantly increased in the injured artery 5 days after cuff placement which could be downregulated by nifedipine 5 mg×kg(-1)×d(-1). MCP-1 mRNA expression in the injured arteries was increased 7 days after cuff placement and which could be significantly attenuated by nifedipine 5 mg×kg(-1)×d(-1). Cuff placement decreased the cytoplasmic level of p50, IκBα, IκBβ, and increased the nuclear level of p50. Nifedipine 5 mg×kg(-1)×d(-1) significantly attenuated these changes.</p><p><b>CONCLUSION</b>Our results suggest that high dose nifedipine could suppresses expression of MCP-1 induced by injured arteries via the inhibin NF-κB DNA binding activity, thereby attenuating vascular inflammation.</p>

Carotid remodeling of hypertensive subjects and polymorphism of the angiotensin-converting enzyme gene / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>This study was designed to investigate the relationships between changes in the structure and function of carotid arteries and angiotensin converting enzyme (ACE) gene polymorphism in Chinese hypertensive subjects.</p><p><b>METHODS</b>Multiplex polymerase chain reaction amplification was used to evaluate the ACE gene insertion/deletion (I/D) polymorphism. High-resolution B-mode ultrasound examinations were performed to detect parameters of carotid artery remodeling.</p><p><b>RESULTS</b>Intima-media thickness (IMT) was significantly different among the DD, ID and II genotypes of ACE (DD > ID > II, P < 0.05). Carotid internal diameter, distensibility and stiffness were similar among the DD, ID and II genotypes of ACE (P > 0.05) in hypertensive subjects. The frequency of the DD gene and D allele of ACE were higher in patients with thickening carotid than in patients with normal carotid (70.4% vs 24.1%, and 79.5% vs 40.5%, respectively, P < 0.001). In multiple stepwise regression analysis, independent risk factors for increased carotid IMT in hypertensive subjects were ACE genotypes (P < 0.001), age (P < 0.001) and carotid internal diameter (P = 0.032). Moreover, triglycerides and total cholesterol were higher in patients with the DD genotype than in those with the II genotype (P < 0.05).</p><p><b>CONCLUSIONS</b>The I/D polymorphism of the ACE gene was related to IMT, but not to internal diameter, distensibility and stiffness of the carotid in Chinese hypertensive subjects. ACE gene polymorphism was a main risk factor for increased carotid IMT. These results may imply that there is a link between lipid metabolism and ACE genotype polymorphism in Chinese hypertensive subjects.</p>