Ultra-high dose-rate (FLASH) radiotherapy is a new mode of radiotherapy that can control tumors while significantly reducing damage to surrounding normal tissues. Since its official naming in 2014, FLASH radiotherapy research has continued to grow, and in 2019 it entered a period of exponential development. Studies have shown that electrons, photons, and protons can all induce the FLASH effect, but the proton beam can overcome the physical limitations of shallow incident depth and high penetration dose, which is considered to be the most effective solution. This article summarizes previous research results of FLASH proton therapy from the research at the cell, animal and clinical levels, and summarizes the hypothesis of the FLASH effect mechanism, aiming to provide reference for promoting the research and clinical transformation of FLASH proton therapy.

Objective:To compare the relative proportion of direct action (ray particles directly destroy biological molecules such as DNA and indirect action (radical-mediated oxidative damage) in the damage caused by X-ray and proton irradiation of lung cancer cells.Methods:Unirradiated human lung adenocarcinoma A549 cells and human large cell lung cancer NCI-H460 cells were cultured in media containing 0, 0.125, 0.25, 0.5, 0.75 mol/L dimethyl sulfoxide (DMSO) for 1 h to obtain plating efficiency (PE) values, thereby determining whether DMSO affected cell survival. Following pretreatment with each DMSO concentration, cells were exposed to X-ray irradiation at physical doses of 2, 4, 6, 8 Gy and proton irradiation at equivalent doses of 2, 4, 6, 8 GyE, respectively. Survival fractions (SF) and maximum protection (MP) values were calculated to evaluate the effects of varying DMSO concentrations on post-irradiation cell survival and to quantify the contribution of indirect radiation damage mechanisms (higher MP indicates greater indirect effect contribution). PE, SF, and MP values were determined using clonogenic assays. Comparisons among multiple groups were performed using one-way ANOVA followed by Tukey's multiple comparison, and comparisons between irradiation groups were analyzed using independent samples t-tests. Results:The PE of unirradiated cells treated with varying DMSO concentrations showed no statistically significant differences. Following pretreatment at different DMSO concentrations and subsequent irradiation with X-rays or protons, the protective effect of DMSO reached saturation at 0.5 mol/L. At this concentration, comparison of the average MP values across 4 radiation doses revealed: In A549 cells, the MP value was 54.21%±1.73% for X-ray irradiation group and 39.69%±0.72% for proton irradiation group ( t=16.82, P<0.001); in NCI-H460 cells, the MP value was 52.04%±1.00% for X-ray irradiation group and 41.31%±0.70% for proton irradiation group ( t=10.19, P<0.001). Conclusions:Under biologically equivalent doses, proton irradiation demonstrates greater reliance on direct effects in lung cancer cells killing compared with X-ray irradiation.

Ultra-high dose-rate (FLASH) radiotherapy is a new mode of radiotherapy that can control tumors while significantly reducing damage to surrounding normal tissues. Since its official naming in 2014, FLASH radiotherapy research has continued to grow, and in 2019 it entered a period of exponential development. Studies have shown that electrons, photons, and protons can all induce the FLASH effect, but the proton beam can overcome the physical limitations of shallow incident depth and high penetration dose, which is considered to be the most effective solution. This article summarizes previous research results of FLASH proton therapy from the research at the cell, animal and clinical levels, and summarizes the hypothesis of the FLASH effect mechanism, aiming to provide reference for promoting the research and clinical transformation of FLASH proton therapy.

Objective:To compare the relative proportion of direct action (ray particles directly destroy biological molecules such as DNA and indirect action (radical-mediated oxidative damage) in the damage caused by X-ray and proton irradiation of lung cancer cells.Methods:Unirradiated human lung adenocarcinoma A549 cells and human large cell lung cancer NCI-H460 cells were cultured in media containing 0, 0.125, 0.25, 0.5, 0.75 mol/L dimethyl sulfoxide (DMSO) for 1 h to obtain plating efficiency (PE) values, thereby determining whether DMSO affected cell survival. Following pretreatment with each DMSO concentration, cells were exposed to X-ray irradiation at physical doses of 2, 4, 6, 8 Gy and proton irradiation at equivalent doses of 2, 4, 6, 8 GyE, respectively. Survival fractions (SF) and maximum protection (MP) values were calculated to evaluate the effects of varying DMSO concentrations on post-irradiation cell survival and to quantify the contribution of indirect radiation damage mechanisms (higher MP indicates greater indirect effect contribution). PE, SF, and MP values were determined using clonogenic assays. Comparisons among multiple groups were performed using one-way ANOVA followed by Tukey's multiple comparison, and comparisons between irradiation groups were analyzed using independent samples t-tests. Results:The PE of unirradiated cells treated with varying DMSO concentrations showed no statistically significant differences. Following pretreatment at different DMSO concentrations and subsequent irradiation with X-rays or protons, the protective effect of DMSO reached saturation at 0.5 mol/L. At this concentration, comparison of the average MP values across 4 radiation doses revealed: In A549 cells, the MP value was 54.21%±1.73% for X-ray irradiation group and 39.69%±0.72% for proton irradiation group ( t=16.82, P<0.001); in NCI-H460 cells, the MP value was 52.04%±1.00% for X-ray irradiation group and 41.31%±0.70% for proton irradiation group ( t=10.19, P<0.001). Conclusions:Under biologically equivalent doses, proton irradiation demonstrates greater reliance on direct effects in lung cancer cells killing compared with X-ray irradiation.

BACKGROUND: Currently, the morphologic characteristics of the torn discoid lateral meniscus remain unclear, andmorphological indexes used to evaluate the discoid lateral meniscus tears still need to be explored. OBJECTIVE: To discuss the specificity and sensitivity of discoid lateral meniscal tears in children using morphological indexes. METHODS: Seventy-three patients (seventy-six knees) with torn discoid lateral meniscus underwentarthroscopy and MRI data of knee examinations were retrospectively reviewed. All MR images were double-blinded, independently, retrospectively analyzed by attending radiologist (doctor A) and sports physician (doctor B). The following morphological signs of discoid lateral meniscus, such as a internal displaced free edge sign, a hypertrophic free edge sign and a hypertrophied-horn sign, were selected to evaluate the discoid lateral meniscus tears. The likelihood of the discoid lateral meniscus tears was analyzed on basis of arthroscopic findings constituted the gold standard. Sensitivity, specificity and accuracy of MRI diagnosis of the discoid lateral meniscus tears by two physicians were calculated, and the consistency of diagnosis results by two physicians was evaluated using the Kappa statistics.RESULTS AND CONCLUSION: (1) The sensitivity, specificity and accuracy in the diagnosis of discoid lateral meniscustears by internal displaced free edge sign for doctor A were 19%, 94% and 53%, respectively, and for doctor B were 21%, 97% and 55%. (2) The sensitivity, specificity and accuracy in the diagnosis of discoid lateral meniscus tears by hypertrophic free edge sign for doctor A were 52%, 100% and 74%, respectively, and for doctor B were 57%, 97% and 75%. (3) The sensitivity, specificity and accuracy in the diagnosis of discoid lateral meniscus tears by hypertrophied-horn sign for doctor A were 26%, 97% and 58%, respectively, and for doctor B were 24%, 100% and 58%. (4) The sensitivity, specificity and accuracy in the diagnosis of discoid lateral meniscus tears by binding morphological index for doctor A were 86%, 91% and 87%, respectively, and for doctor B were 88%, 94% and 91%. (5) The Kappa statistics for discoid lateral meniscus tears respectively demonstrated a good inter-observer agreement (K > 0.75, P < 0.001). (6) These findings suggest that single morphological index used to evaluate the discoid lateral meniscus tears shows a good specificity, but which also shows a low sensitivity, while a binding morphological index can significantly improve the diagnostic sensitivity. Morphological characteristics may be reliable indexes to evaluate the discoid lateral meniscal tears in children.

BACKGROUND:Currently, the morphologic changes of the discoid lateral meniscus (DLM) remain unclear, and morphological indexes used to evaluate the injuries of DLM stil need to be explored. OBJECTIVE:To compare the MR imaging difference between symptomatic and asymptomatic DLM in adults, and to select reliablemorphologicalparametersfor assessing DLM. METHODS:A total of 36 patients (36 knees) with a symptomatic DLM (study group)and 34 patients (34 knees) with an asymptomatic DLM (control group) were included in this study. GE Healthcare Centricity RIS/PACKS System was used to measure the primary morphological parameters of two patients with DLM on coronal MR imaging. Intergroup comparison was performed with the Wilcoxon test. RESULTS AND CONCLUSION:On the coronal MR imaging, the width of the body portion and height of the free edge of the DLM was significantly increased in the study group compared with the control group (P< 0.001), while the height of the peripheral portion which connects with the capsule of the DLM was significantly decreased in the study group compared with the control group (P= 0.002). The heightof the middle of the DLM and the width of the lateral femoral condyle showed no significant differences between the both groups (P> 0.05). The width ratio of the body of the DLM to the lateral femoral condyle and the height ratio of height of the free edge to the middle of the DLM were significantly increased in thestudy group compared with the control group (P< 0.001), while the height ratio of the peripheral portion to the middle for the DLM was significantly decreased compared with the control group (P< 0.001). These findings suggest that compared with asymptomatic discoid lateral meniscus, the width of the body portion and the height of the free edge for the DLM are increased;however,the height of the peripheral portion which connects with the capsule of the DLM is decreased. The width ratio of the body portion of the DLM to the lateral femoral condyle and the height ratio of the free edge to the middle for the DLM may be reliable morphological parameters for the assessment of the DLM in adults.

Objective To investigate α-interferon (α-IFN) and cyclooxygenase-2 (COX-2)inhibitor celecoxib synergistically inhibit the growth of human liver cancer SMMC-7721 cells xenografts and tumor angiogenesis in a nude mouse model.Methods The effects of celecoxib and α-interferon on tumor volumes and weight were observed.The expressions of VEGF and Cox-2 were determined by immunohistochemistry and RT-PCR,and the effect of α-interferon on MVD also was observed by immunohisto chemistry.Results During the period of observation tumor volume increased progressively in control group,while it was suppressed obviously in other drug treatment groups.The average tumor volume was significantly smaller in celecoxib + α-IFN group than that in IFN group,celecoxib group and control group (P ＜ 0.01,respectively),its inhibitory rate was 61.84％.Immunohistochemistry showes that the VEGF and MVD was significantly smaller in celecoxib + IFN group than that in α-IFN group,celecoxib group and control group (P ＜ 0.01,respectively).RT-PCR shows that the COX-2mRNA and VEGF mRNA pression was lower in the celecoxib + α-IFN group than in α-IFN group,celecoxib group and control group (P ＜ 0.01).Conclusions The COX-2 inhibitor celecoxib and α-interferon synergistically reduces xenografts growth of human liver cancer SMMC-7721 cells effectively via suppressing tumor growth and angiogenesis.