Radiotherapy plays a significant role in treating malignant tumor.With continuous advancements in radiotherapy technology and the development of systemic therapies,many patients with tumor who occurred distant metastases have been able to achieve long-term survival.At the same time,the curative effect of stereotactic radiation therapy(SRT)has demonstrated increasingly notable benefits for patients with advanced distant metastatic cancers.Recently,domestic radiotherapy equipment obtained significant development,and SRT has been a technical highlight of multiple domestic radiotherapy equipment.Under the support of the National Key R&D Program of China,the Radiotherapy Equipment and Technology Branch of the Chinese Association of Medical Equipment organized experts from the relevant fields to formulate this guideline,aiming to standardize the clinical application of domestically innovative integrated radiotherapy equipment in utilizing SRT for metastatic cancers.

Objective To screen the active chemical components with potential therapeutic effects against lung cancer in tea and to provide new insights into the treatment and prevention of lung cancer.Methods Based on net-work pharmacology,the main active components from 13 types of tea samples were analyzed using liquid chromatog-raphy-mass spectrometry(LC-MS).The targets of these small molecules were obtained from the BATMAN-TCM da-tabase to construct a"component-target-disease"network.Lung cancer-related disease targets were retrieved from the GeneCard and Malacard databases followed by Gene Ontology(GO)functional and KEGG pathway enrichment analyses of potential pharmacological targets.A protein-protein interaction(PPI)network was constructed using the STRING database.The molecular docking was employed to screen small molecules with potential anti-cancer ac-tivity,and their potential inhibition to proliferation of human non-small cell lung cancer cell line A549 and human large cell lung cancer cell line H460.Results A total of 37 active components and 429 targets were identified in tea,with 182 overlapping targets associated with lung cancer.GO analysis revealed that these targets were primarily involved in biological processes such as cell proliferation,response to stimuli,and metabolic processes.KEGG pathway analysis indicated that these targets were mainly enriched in the p53 signaling pathway,ErbB signaling pathway,and PI3K-Akt signaling pathway.PPI network analysis identified key targets including MAPK1,AKT1,SRC,MAPK3,and p53.Molecular docking screened coumestrol as a molecule capable of binding to human estro-gen receptor 2(ESR2),and its inhibitory effect on the proliferation of A549 and H460 cells was experimentally validated(P＜0.000 1).Conclusions The active components in tea may intervene in the development and progres-sion of lung cancer through a multi-component,multi-target,and multi-pathway mechanism,The results suggests po-tential components against lung cancer in tea,which may be applied in the prevention of human lung cancer.

Radiotherapy plays a significant role in treating malignant tumor.With continuous advancements in radiotherapy technology and the development of systemic therapies,many patients with tumor who occurred distant metastases have been able to achieve long-term survival.At the same time,the curative effect of stereotactic radiation therapy(SRT)has demonstrated increasingly notable benefits for patients with advanced distant metastatic cancers.Recently,domestic radiotherapy equipment obtained significant development,and SRT has been a technical highlight of multiple domestic radiotherapy equipment.Under the support of the National Key R&D Program of China,the Radiotherapy Equipment and Technology Branch of the Chinese Association of Medical Equipment organized experts from the relevant fields to formulate this guideline,aiming to standardize the clinical application of domestically innovative integrated radiotherapy equipment in utilizing SRT for metastatic cancers.

At present,precise radiotherapy has been widely used through the development with many years,but the existing technique still is limited by the limitation of tolerance dose of normal tissues,which cannot achieve the optimal goal of treating tumor.Flash radiotherapy(Flash-RT)is one kind of radiotherapy technique that uses the beam with ultra-high dose rate(UHDR)to conduct irradiation,which can furthest treat tumors while significantly reduce radiation injury of normal tissues.But until now,the biological mechanism,key physical parameters and triggering mechanism of Flash-RT are still unclear,and its principle and clinical translational application are still in the stage of research.This review clarified the technological advance and clinical translational application of Flash-RT research through summarized the relevant research of Flash-RT.

The Flash radiotherapy(Flash-RT),which is the key breakthrough in the basic field of radiotherapy technique,which is expected to cause a new major transformation in the field of radiotherapy.In this paper,we reviewed the latest research advances of the application and the mechanism exploration of Flash-RT in tumor treatment.Current studies have found that both the Flash-RT with electron beams and photon and the Flash-RT with proton can reduce injury of normal tissue than radiotherapy with conventional dose-rate,but the relevant mechanisms are not yet clearly understood,which includes but not limited to oxygen depletion,DNA damage,cellular senescence,apoptosis and immune response.The difference of Flash-RT injury between tumor tissue and normal tissue further reduces the limitations of radiotherapy,and reduces the adverse reaction and complication compared with conventional radiotherapy,which has wide application prospects.

Objective:To investigate the regulatory role of mesenchymal stem cells(MSCs)on radiation-induced lung injury in mice by the ferroptosis pathway.Methods:The mice were divided into normal control group,MSCs-treated group(MSCs group),single irradiation group(IR group)and IR combined with MSCs group(IR+MSCs group)according to random number table method before irradiation.A mouse model of radiation-induced lung injury was constructed using whole thorax irradiation with cobalt 60(60Co)(20Gy each time),and TNF-α and IL-6 levels of mouse were detected by enzyme-linked immunosorbent assay(ELISA).The injury of lung tissue in mice was assessed using hematoxylin eosin(HE)staining and Masson staining.Western Blot was used to examine the expression levels of ferroptosis-related proteins in lung tissue,including nuclear factor erythroid NF-E2 related factor 2(Nrf2),4-Hydroxynonenal(4-HNE)and glutathione peroxidase 4(GPX4).The expression level of prostaglandin-endoperoxide synthase 2 Gene(PTGS2)in the lung tissue of mice was detected by using quantitative polymerase chain reaction(qPCR),and the level of reactive oxygen species(ROS)in the lung tissue of mice was detected after radiation by using dihydroethidium(DHE),and the level of malondialdehyde(MDA)content in the lung tissue was detected after radiation.And then,the level of oxidative damage in the lung tissue of mice was assessed.Results:Elisa results showed the serum TNF-α and IL-6 levels in mice after irradiation in IR group were significantly higher than those in normal control group(F=53.60,10.65,P＜0.05),respectively.The HE and MSCs staining of pathological analysis showed that MSCs treatment could significantly relieve both early radiation-induced pneumonitis and advanced pulmonary fibrosis.After radiation,the 4-HNE expression level was upregulation and the Nrf2 expression level was downregulation in the lung tissues of mice,whereas MSCs were able to significantly reduce the 4-HNE expression and upregulate the Nrf2 expression.The mRNA expression level and MDA content of the ferroptosis gene PTGS2 were significantly increased,which were significantly higher than those of normal control group,while MSCs were able to significantly reduce its expression,and the differences were statistically significant(F=105.8,7.693,P＜0.05).Conclusion:MSCs is able to relieve significantly ionizing radiation-induced ferroptosis of lung epithelial cells,thereby relieve radiation-induced lung injury.

Objective:To investigate the relationship between mild cognitive impairment (MCI) and body mass index (BMI) in older adult patients with type 2 diabetes mellitus (T2DM).Methods:A total of 327 patients with T2DM who received treatment in Wuyunshan Sanatorium from January 2016 to May 2019 were included in the T2DM group. Patients in theT2DM group were subdivided into an MCI group ( n = 73) and a non-MCI group ( n = 254) according to whether they had MCI. An additional 100 older adult volunteers who concurrently received physical examination were included in the control group. Sex, age, years of education, monthly family income, body mass index, living habits (drinking, smoking) and laboratory indexes were compared among the groups. The influential factors of MCI in patients with T2DM were analyzed by logistic regression model. The predictive value of BMI for MCI in older adult patients with T2DM was evaluated by receiver operating characteristic (ROC) curve. Results:Age, monthly family income, the proportion of patients with a history of diabetes mellitus, BMI, fasting blood glucose, glycosylated hemoglobin (HbA1C), low-density lipoprotein cholesterol (LDL-C) in the T2DM group were (73.10 ± 9.56) years old, 8 926 yuan RMB, 189/327, (24.18 ± 2.64) kg/m 2, (6.96 ± 0.88) mmol/L, (7.10 ± 0.84)%, (7.32 ± 0.84) mmol/L, respectively, which were higher than those in the control group [(68.28 ± 8.21) years old, 6 715 yuan RMB, 13/100, (22.30 ± 1.74) kg/m 2, (4.51 ± 0.72) mmol/L, (5.62 ± 0.68)%, (7.04 ± 0.67) mmol/L, t = 4.554, χ2 = 18.601, 61.654, t = 6.668, t = 25.360, 16.077, 3.049, all P < 0.05]. In the MCI group, the proportion of patients having a monthly family income < 5 000 yuan RMB, the proportion of patients having a history of diabetes mellitus, BMI, HbA1c value were 29/73, 60/73, (24.92 ± 2.43) kg/m 2, (7.54 ± 0.88)%, respectively , while they were 70/254, 129/254, (23.77 ± 2.59) kg/m 2, (6.92 ± 0.81)%, respectively in the non-MCI group. There were significant differences in these indexes between MCI and non-MCI groups ( χ2 = 6.144, 22.927, t = 3.389, 5.652, all P < 0.05). Multivariate logistic regression analysis showed that BMI and HbA1c were the influential factors of MCI complicated by T2DM in older adult patients ( OR = 0.274, 0.192, both P < 0.05). Monthly family income and family history of diabetes mellitus were not closely related to the development of MCI in older adult patients with T2DM ( OR = - 0.154, 0.093, both P > 0.05). The ROC curve revealed that when BMI value was 24.49 kg/m 2, Youden index was the largest (0.510), the corresponding sensitivity was 83.86%, and the specificity was 67.12%. The area under the ROC curve was 0.766 [95% CI (0.699 - 0.832)]. Conclusion:BMI is an influential factor of MCI development in older adult patients with T2DM, and may be one of the important indicators for early prediction of MCI.

Objective:To explore the regulatory effect of glutathione S-transferase P1(GSTP1) on the radiosensitivity of mouse Lewis lung cancer (LLC) cells.Methods:GSTP1-shRNA lentivirus and negative control lentivirus were used to respectively infect the LLC cells, and stable transgenic strains were selected. Real-time PCR and Western blot were conducted to quantitatively measure the expression levels of GSTP1 mRNA and protein in the LLC cells to verify the knockdown effect. The cell counting kit-8(CCK-8) assay was used to detect cell viability after irradiation. The colony formation assay was utilized to assess the cell proliferation ability after irradiation. Flow cytometry was performed to assess the level of cell apoptosis after irradiation. The tumor-bearing mice were established and irradiated to detect the changes in the tumor volume after irradiation. TUNEL staining was employed to detect the level of tumor apoptosis after irradiation. Immunofluorescence was used to detect the number of CD 4+ CD 8+ T cells in the tumor after irradiation. Results:Real-time PCR and Western blot showed that after shRNA lentivirus interference, the expression levels of GSTP1 mRNA and protein were significantly down-regulated. Down-regulation of GSTP1 reduced cell viability and proliferation, and increased the rate of cell apoptosis after irradiation. The tumor volume of the tumor-bearing mice after irradiation in the GSTP1 knockdown group was significantly smaller than that in the NC group, whereas the tumor apoptosis rate was significantly higher and the number of infiltrating CD 4+ CD 8+ T cells in the tumor was remarkably higher compared with those in the control group. Conclusion:Knockdown of GSTP1 can significantly increase the radiosensitivity of LLC cells and enhance the infiltration of lymphocytes in tumor tissues.

The segmentation of organs at risk is an important part of radiotherapy. The current method of manual segmentation depends on the knowledge and experience of physicians, which is very time-consuming and difficult to ensure the accuracy, consistency and repeatability. Therefore, a deep convolutional neural network (DCNN) is proposed for the automatic and accurate segmentation of head and neck organs at risk. The data of 496 patients with nasopharyngeal carcinoma were reviewed. Among them, 376 cases were randomly selected for training set, 60 cases for validation set and 60 cases for test set. Using the three-dimensional (3D) U-NET DCNN, combined with two loss functions of Dice Loss and Generalized Dice Loss, the automatic segmentation neural network model for the head and neck organs at risk was trained. The evaluation parameters are Dice similarity coefficient and Jaccard distance. The average Dice Similarity coefficient of the 19 organs at risk was 0.91, and the Jaccard distance was 0.15. The results demonstrate that 3D U-NET DCNN combined with Dice Loss function can be better applied to automatic segmentation of head and neck organs at risk.

Objective To investigate the association and mechanism between glutathione S-transferase P1(GSTP1) and radiation-induced lung injury.Methods Two effective GSTP1 siRNAs were designed and synthesized.The normal lung epithelial cell line BEAS-2B cells were transfected with GSTP1 siRNA (experimental group,siRNA-1,siRNA-2) and negative control siRNA (negative control group,NC).Western blot was performed to detect the expression levels of GSTP1 protein and EMT-related proteins.CDNB was adopted to evaluate the activity of GSTs.DCFH-DA probe was used for incubation.Flow cytometry was conducted to detect the median fluorescence intensity (MFI) and cellular apoptosis.Annexin-v/PI staining was utilized for incubation.MTT assay was performed to measure the proliferation of BEAS-2B,and the growth curve was drawn based on the results.Results After radiation,compared with the NC group,the ROS level and MFI were significantly higher in experimental group (6774.66±399.60 vs.8759.00±256.96 vs.9967.67±735.11,P＜0.05).In the experimental group,the percentage of cellular apoptosis was remarkably higher than that in the NC group (12.3± 1.16 vs.17.38± 1.65 vs.22.88± 1.20,P＜0.05).MTT assay demonstrated that the OD values in the experimental group were significantly lower than that in the NC group everyday.Further more,the level of EMT process is higher in the experimental group.Conclusions Interfering with the GSTP1 expression in lung epithelial cells can increase the intracellular ROS level,increase the percentage of cellular apoptosis,and reduce the cell proliferation rate following γ-radiation.Besides,it can also promote the epithelial mesenchymal transition in lung epithelial cells.The down-regulation of GSTP1 protein expression level probably aggravates the radiationinduced lung cell injury and promotes the epithelial mesenchymal transition.