Objective:To reveal the coupling mechanism of beam temporal profile and tissue oxygen content on radical kinetics, further explain the potential biological basis of the FLASH effect, and provide a reference for beam optimization and treatment planning design of FLASH radiotherapy (FLASH-RT).Methods:TOPAS-nBio v3.0 was used to simulate the physical and chemical processes of electron beams in water, and a full-scale kinetic model was established covering the generation, diffusion, reaction, and quenching of free radicals such as hydroxyl radical (·OH) and hydrated electrons (e aq-). Under different beam temporal profiles (single pulse, multi-pulses, continuous wave irradiation) and different oxygen concentration conditions, the evolution dynamics of free radicals were systematically simulated. At the same time, the data on e aq- content were obtained by experimental measurement of laser absorption spectroscopy to verify the accuracy of the model prediction. Results:The changing trend of e aq- concentration measured in the experiment was highly consistent with the simulation result, verifying the reliability of the constructed model. The beam time structure had a significant impact on the peak value and duration of free radical concentration. The single-pulse structure can cause the free radicals to rapidly increase and then quickly quench in a short time, while the continuous or long-pulse structure can cause the radical concentration to remain at a high level for a long time. The evolution of ·OH was not sensitive to the oxygen environment, while e aq- are greatly affected by the oxygen environment. The scavenging efficiency of free radicals in a hypoxic environment was significantly decreased, leading to an enhanced accumulation of oxidative damage to biological macromolecules. The lifespan of e aq- in an oxygen-rich environment decreased rapidly. Conclusions:Radical kinetics are regulated by both the beam temporal profile and oxygen content. FLASH-RT can utilize single-pulse or multi-pulses intervals to form periodic windows, reducing normal tissue damage by efficiently scavenging free radicals through antioxidants, while free radicals in tumor tissues continuously accumulate and amplify damage, thus generating a selective protective effect.

Objective:To reveal the coupling mechanism of beam temporal profile and tissue oxygen content on radical kinetics, further explain the potential biological basis of the FLASH effect, and provide a reference for beam optimization and treatment planning design of FLASH radiotherapy (FLASH-RT).Methods:TOPAS-nBio v3.0 was used to simulate the physical and chemical processes of electron beams in water, and a full-scale kinetic model was established covering the generation, diffusion, reaction, and quenching of free radicals such as hydroxyl radical (·OH) and hydrated electrons (e aq-). Under different beam temporal profiles (single pulse, multi-pulses, continuous wave irradiation) and different oxygen concentration conditions, the evolution dynamics of free radicals were systematically simulated. At the same time, the data on e aq- content were obtained by experimental measurement of laser absorption spectroscopy to verify the accuracy of the model prediction. Results:The changing trend of e aq- concentration measured in the experiment was highly consistent with the simulation result, verifying the reliability of the constructed model. The beam time structure had a significant impact on the peak value and duration of free radical concentration. The single-pulse structure can cause the free radicals to rapidly increase and then quickly quench in a short time, while the continuous or long-pulse structure can cause the radical concentration to remain at a high level for a long time. The evolution of ·OH was not sensitive to the oxygen environment, while e aq- are greatly affected by the oxygen environment. The scavenging efficiency of free radicals in a hypoxic environment was significantly decreased, leading to an enhanced accumulation of oxidative damage to biological macromolecules. The lifespan of e aq- in an oxygen-rich environment decreased rapidly. Conclusions:Radical kinetics are regulated by both the beam temporal profile and oxygen content. FLASH-RT can utilize single-pulse or multi-pulses intervals to form periodic windows, reducing normal tissue damage by efficiently scavenging free radicals through antioxidants, while free radicals in tumor tissues continuously accumulate and amplify damage, thus generating a selective protective effect.

Objective:To develop a simplified DNA model tailored for Monte Carlo track structure simulations and investigate the influence of microstructural variations at the scale of several base pairs on the physical simulation of proton-induced biological effects, providing a novel approach to enhance the efficiency of modeling and computational processes in proton radiotherapy simulations.Methods:A circular double-helix DNA molecule consisting of 4 362 base pairs was constructed based on the pBR322 plasmid structure. These molecules were evenly distributed without overlap within a spherical region at the center of a water phantom, representing the cellular nucleus. Integrated into the GPU-based gMicroMC code framework, the model facilitated simulations to calculate proton-induced double-strand break (DSB) yields across three distinct models with twist angles of 20°, 36°, and 72° between adjacent nucleotide pairs. Comparative analyses were conducted to assess differences among these models.Results:Intra-model analyses revealed a consistent decrease in proton-induced DSB yields with increasing initial energy. Under proton irradiation at different energies, the DSB yields for the three models followed the order 72°>36°>20°, with intergroup relative differences exceeding 34.6%. Comparative RBE calculations suggested that models with twist angles between 36° and 72° may better replicate proton-induced damage observed in V79 cells.Conclusions:By strategically simplifying the separation of macroscopic and microscopic levels of DNA structure, adjustments to microstructural parameters can be effectively implemented to refine the model, thereby enhancing the efficiency of modeling and physical simulations. This methodology shows potential as a model for simulating relative biological effectiveness (RBE) in proton therapy planning.

Objective:To develop a simplified DNA model tailored for Monte Carlo track structure simulations and investigate the influence of microstructural variations at the scale of several base pairs on the physical simulation of proton-induced biological effects, providing a novel approach to enhance the efficiency of modeling and computational processes in proton radiotherapy simulations.Methods:A circular double-helix DNA molecule consisting of 4 362 base pairs was constructed based on the pBR322 plasmid structure. These molecules were evenly distributed without overlap within a spherical region at the center of a water phantom, representing the cellular nucleus. Integrated into the GPU-based gMicroMC code framework, the model facilitated simulations to calculate proton-induced double-strand break (DSB) yields across three distinct models with twist angles of 20°, 36°, and 72° between adjacent nucleotide pairs. Comparative analyses were conducted to assess differences among these models.Results:Intra-model analyses revealed a consistent decrease in proton-induced DSB yields with increasing initial energy. Under proton irradiation at different energies, the DSB yields for the three models followed the order 72°>36°>20°, with intergroup relative differences exceeding 34.6%. Comparative RBE calculations suggested that models with twist angles between 36° and 72° may better replicate proton-induced damage observed in V79 cells.Conclusions:By strategically simplifying the separation of macroscopic and microscopic levels of DNA structure, adjustments to microstructural parameters can be effectively implemented to refine the model, thereby enhancing the efficiency of modeling and physical simulations. This methodology shows potential as a model for simulating relative biological effectiveness (RBE) in proton therapy planning.

Objective To analyze the hemodynamic changes of cerebral arterial collateral circulation and distal perfusion of cerebral arteries after external carotid artery occlusion (EICAO).Methods Ninety-six patients with EICAO were selected as the case group,of which 46 cases of left EICAO (group A),50 cases of right EICAO (group B) and 30 normal volunteers were selected as the control group.Color Doppler ultrasonography (TCD) was used to detect peak systolic velocity (Vs) in the middle cerebral artery (MCA),end diastolic velocity (Vd),mean blood flow velocity (Vm),pulsatility index (PI),hemodynamic parameters of arteries,and opening rate of grade Ⅰ anterior communicating artery (ACOA) and posterior communicating artery (PCOA).Results There were significant differences in Vs,Vm,Vd,and PI among group A,B and C (F =56.046,31.027,39.283,18.614,49.658,24.992,15.035,22.069,P＜ 0.001).The Vs,Vd,Vm,and PI of the left MCA in the group A were significantly lower than those of the left side in the control group (P＜0.01);the Vs,Vd,Vm,and PI of the right MCA in the group B were significantly lower than those of the right side in the control group (P＜0.01).In group A and B,the open rate of simple ACOA in the stage Ⅰ collateral circulation was 26.09％ and 30.00％.The open rate of PCOA alone was 23.91％ and 36.00％,respectively,and the concurrent opening rate of ACOA and PCOA was 36.96％ and 30.00％,respectively,There was no significant difference in the open rate of grade Ⅰ collateral circulation among the three types of blood vessels (x2 =0.223,2.881,0.808,P=0.637,0.090,0.369).The incidence of cerebral infarction at the MCA donor site in the group A was 60.87％ on the left side and 8.70％ on the right side.The data of the left side was significantly higher than that of the right side (x2 =57.165,P＜0.001).The incidence of cerebral infarction at the MCA in the group B was 14.00％ on the left side and 60.00％ on the right side,and the data of the fight side was significantly higher than that of the left side (x2 =43.436,P＜ 0.001).Conclusion Although there is a higher grade Ⅰ collateral circulation opening rate in patients with EICAO,the MCA blood supply area of the distal internal carotid artery is still in a state of low blood flow perfusion,and the incidence of cerebral infarction is also high,so opening the grade Ⅰ collateral circulation does not completely reduce the risk of cerebral infarction in these patients,and these patients are still at high risk of cerebral infarction.

Objective To explore the application value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) and 99Tcm-methylene diphosphonate (99 Tcm-MDP) bone scintigraphy for detecting bone destruction in multiple myeloma (MM).Methods 18 F-FDG PET/CT and 99Tcm-MDP bone scintigraphy results of 27 MM patients were analyzed retrospectively.Inspection areas checked by magnetic resonance imaging (MRI) and X-ray were the limited scopes.The location and number of bone destruction were recorded,and the maximal standardized uptake value (SUVmax) was measured simultaneously.The results were comparatively analyzed.Diagnostic certainty regarding the presence or absence of bone destruction was evaluated according to the reference standard consisting of MRI and X-ray.Results A total of 235 lesions were found according to the reference standard.Of these,227 lesions (97％) were identified by 18F-FDG PET/CT,whereas 187 lesions (80％) were identified by bone scintigraphy,with a significant statistical difference (x2 =32.43,P ＜ 0.05).SUVmax was 8.3 ± 1.7 (4.3 to 18.9).The discovery rates of bone fracture of 18F-FDG PET/CT and bone scintigraphy were 100％ (97/97) and 90％ (87/97),and there was a significant statistical difference between them (x2 =78.09,P ＜ 0.05).Conclusion 18 F-FDG PET/CT is a possible method to detect bone lesions in patients with MM,and is better than 99Tcm-MDP bone scintigraphy.

Objective To investigate the impact of renal function and insulin resistance on serum total homocysteine(tHcy) levels in aged diabetic patients with nephropathy. Methods Serum tHcy, blood glucose, lipids, renal function, serum insulin were measured for 98 elderly patients with type 2 diabetes and 36 normal control subjects. Results (1) Serum tHcy levels were significantly higher in diabetic group than in control group [(17.2?7.6) ?mol/L vs (9.4?3.5)?mol/L,P