Haplodeletion of Follistatin-Like 1 Attenuates Radiation-Induced Pulmonary Fibrosis in Mice.

PURPOSE: Radiation-induced pulmonary fibrosis (RIPF) is a severe and life-threatening complication of radiation therapy in patients with thoracic cancer; however, the exact molecular mechanisms remain unknown, and there is no effective treatment method in clinic. Here, we assessed the role of follistatin-like 1 (Fstl1) in RIPF. METHODS AND MATERIALS: Protein and messenger RNA levels of Fstl1 in lung tissues from symptomatic RIPF patients, Rhesus macaques, and mice were assessed. Fibrotic and inflammatory responses to radiation-induced lung injury and accumulation of myofibroblasts in Fstl1 haplodeficient (Fstl1+/-) mice were determined. Finally, radiation-induced differentiation and activation of fibroblasts in primary Fstl1+/- lung fibroblasts were evaluated. RESULTS: FSTL1 amounts were significantly increased in serum and/or radiation-injured lung specimens from symptomatic RIPF patients, Rhesus macaques, and mice. Haplodeletion of Fstl1 in Fstl1+/- mice was protective against x-ray-induced lung injury in mice in vivo, as well as myofibroblast activation in vitro. CONCLUSIONS: These findings suggest that Fstl1 plays an important role in lung fibrosis and may offer a potential approach to attenuate RIPF in radiation therapy of patients with thoracic cancer.

Size effect of Au/PAMAM contrast agent on CT imaging of reticuloendothelial system and tumor tissue.

Polyamidoamine (PAMAM)-entrapped Au nanoparticles were synthesized with distinct sizes to figure out the size effect of Au-based contrast agent on CT imaging of passively targeted tissues. Au/PAMAM nanoparticles were first synthesized with narrow distribution of particles size of 22.2 ± 3.1, 54.2 ± 3.7, and 104.9 ± 4.7 nm in diameters. Size effect leads no significant difference on X-ray attenuation when Au/PAMAM was ≤0.05 mol/L. For CT imaging of a tumor model, small Au/PAMAM were more easily internalized via endocytosis in the liver, leading to more obviously enhanced contrast. Similarly, contrast agents with small sizes were more effective in tumor imaging because of the enhanced permeability and retention effect. Overall, the particle size of Au/PAMAM heavily affected the efficiency of CT enhancement in imaging RES and tumors.

Predictive value of mutant p53 expression index obtained from nonenhanced computed tomography measurements for assessing invasiveness of ground-glass opacity nodules.

PURPOSE: To predict p53 expression index (p53-EI) based on measurements from computed tomography (CT) for preoperatively assessing pathologies of nodular ground-glass opacities (nGGOs). METHODS: Information of 176 cases with nGGOs on high-resolution CT that were pathologically confirmed adenocarcinoma was collected. Diameters, total volumes (TVs), maximum (MAX), average (AVG), and standard deviation (STD) of CT attenuations within nGGOs were measured. p53-EI was evaluated through immunohistochemistry with Image-Pro Plus 6.0. A multiple linear stepwise regression model was established to calculate p53-EI prediction from CT measurements. Receiver-operating characteristic curve analysis was performed to compare the diagnostic performance of variables in differentiating preinvasive adenocarcinoma (PIA), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC). RESULTS: Diameters, TVs, MAX, AVG, and STD showed significant differences among PIAs, MIAs, and IACs (all P-values <0.001), with only MAX being incapable to differentiate MIAs from IACs (P=0.106). The mean p53-EIs of PIAs, MIAs, and IACs were 3.4±2.0, 7.2±1.9, and 9.8±2.7, with significant intergroup differences (all P-values <0.001). An equation was established by multiple linear regression as: p53-EI prediction =0.001* TVs +0.012* AVG +0.022* STD +9.345, through which p53-EI predictions were calculated to be 4.4%±1.0%, 6.8%±1.3%, and 8.5%±1.4% for PIAs, MIAs, and IACs (Kruskal-Wallis test P<0.001; Tamhane's T2 test: PIA vs MIA P<0.001, MIA vs IAC P<0.001), respectively. Although not significant, p53-EI prediction has a little higher area under the curve (AUC) than the actual one both in differentiating MIAs from PIAs (AUC 0.938 vs 0.914, P=0.263) and in distinguishing IACs from MIAs (AUC 0.812 vs 0.786, P=0.718). CONCLUSION: p53-EI prediction of nGGOs obtained from CT measurements allows accurately estimating lesions' pathology and invasiveness preoperatively not only from radiology but also from pathology.

Pulse source based on directly modulated laser and phase modulator.

We propose the simple pulse source, in which the pulses generated by large-signal directly modulated laser diode are phase-modulated, and then compressed into short pulses by an optimized length of DCF. On the one hand, phase modulator is used to enhance the negative chirp of large-signal directly modulated pulses. On the other hand, the largesignal directly modulated pulses are used to suppress the pedestal produced by the phase modulator. Using this technique, highly stable 10-GHz 5.5-ps optical pulses are obtained, which suppress pedestal up to 20dB and have a low timing jitter of 184fs.