Objective:To measure and assess relevant radiation doses at the radiotherapy site of the first domestic single-vault proton therapy system.Methods:The radiation levels of the therapy system during and after beam irradiation were measured, and annual effective doses were assessed for personnel at the site.Results:During beam irradiation, the highest radiation dose was detected at the shielded door of the equipment floor, with a gamma radiation level of 2.140 μSv/h and a neutron radiation level of 0.850 μSv/h. Neutron radiation disappeared immediately once the beams stopped. In contrast, the radiation activated originated mostly from gamma rays. A longer time after beams stopped was associated with lower induced radiation intensity at the same location. Furthermore, a farther distance from the irradiated object corresponded to lower induced radiation intensity at the same time. The assessment result reveal that the annual effective doses to the personnel were at the safe level, with physicists exposed to the highest dose of 2.138 mSv.Conclusions:The radiation level at the studied proton therapy site meets the safety requirement, and the treatment can be performed safely at this site.

The hypoxic microenvironment and inflammatory state of residual tumors caused by insufficient radio-frequency ablation(iRFA)are major reasons for rapid tumor progression and pose challenges for immu-notherapy.We retrospectively analyzed the clinical data of patients with hepatocellular carcinoma(HCC)treated with RFA and observed that iRFA was associated with poor survival outcomes and progression-free survival.Using an orthotopic HCC mouse model and a colorectal liver metastasis model,we observed that treatment with melatonin after iRFA reduced tumor growth and metastasis and achieved the best out-comes when combined with anti-programmed death-ligand 1(anti-PD-L1)therapy.In mechanism,melatonin inhibited the expression of epithelial-mesenchymal transitions,hypoxia-inducible factor(HIF)-1 α,and PD-L1 in tumor cells after iRFA.Flow cytometry revealed that melatonin reduced the proportion of myeloid-derived suppressor cells and increased the proportion of CD8+T cells.Transcriptomic analysis revealed an upregulation of immune-activated function-related genes in residual tumors.These findings demonstrated that melatonin can reverse hypoxia and iRFA-induced inflammation,thereby overcoming the immunosuppressive tumor microenvironment(TME)and enhancing the efficacy of immunotherapy.

Objective:To develop multiplex cytokine detection reagents to analyze expression levels of cytokines,angiogene-sis and bone remodeling proteins in relapse/refractory multiple myeloma(RRMM).Methods:Multiplex bead-based immunoassay by flow cytometry was used to develop quantitative detection reagents of multiplex cytokines,which were applied to detect serum samples from 55 RRMM patients and 22 healthy controls.Expression levels of cytokines,angiogenesis,and bone remodeling proteins in pa-tients,and their correlation with clinical characteristics were analyzed.Results:Detection reagents of 10-plex cytokine immunoassay were successfully developed in this study,with average sensitivity of 7.1 pg/ml,average recovery rate of 97.4%,average intra-assay CV of 4.8%,and average inter-assay CV of 9.0%.In addition,results of RRMM samples found that levels of IL-2,IL-17,DKK1,RANKL and OPG were positively correlated with the level of IgG monoclonal protein,and TIMP1 was positively correlated with levels of IgG and IgA monoclonal protein.Conclusion:In this study,ten kinds of cytokine detection reagents with high sensitivity and speci-ficity are developed,and we found that IL-2,IL-17,DKK1,RANKL,OPG and TIMP1 have potential value in tracking disease pro-gression in RRMM.The established development process of multiplex cytokine reagents has important reference significance for ex-panding the development and application of multiplex detection reagents for protein markers in the future.

To improve the transduction efficiency of recombinant adeno-associated virus (rAAV) in NK92 cells, the number of cells, concentration of IL-2 in the medium, and serotype and dosage of rAAV were explored to optimize cell state and viral transfection conditions.Then, zinc chloride (ZnCl2), chloroquine, polyvinyl alcohol (PVA) and genistein with different concentration were added separately during transfection to further improve the viral transduction efficiency.The results showed that, at cell number of 5 × 105, the expression efficiency of enhanced green fluorescent protein (EGFP) was relatively high.When the IL-2 concentration was 1 000 IU/mL, NK92 cells were most suitable for virus transfection. The transduction efficiency of different serotypes of rAAV in NK92 cells was rAAV6, rAAV2 and rAAV9 in descending order.Pretreatment of NK92 cells with genistein could significantly increase the viral transduction efficiency, while the addition of other reagents had no significant effect.Through the optimization of the above conditions, the transduction efficiency of rAAV to NK92 cells could be significantly improved, which provided evidence for functional genetic modification of NK92 cells by rAAV.

Objective:To analyze the characteristics of prescription about Lingnan Traditional Chinese Medicine (TCM) masters for Biqiu treatment based on data mining, so as to provide reference for the clinical practice and patent drug research and development of rhinorrhea in Lingnan district.Methods:By searching journal documents and medical records in CNKI, VIP, Wanfang, Chinese BioMedical Database (SinoMed) and Duxiu Data Retrieval Platform, we selected the articles and famous TCM medical records that met the criteria on the TCM medical rules of treating Biqiu. We screened database in strict accordance with inclusion and exclusion criteria and extracted prescription information from medical cases. The software Ancient and Modern Consilia Cloud Platform (V 1.5) was used for data mining analysis and medical case standardization, and SPSS Clementine 12.0 software were used to conduct frequency statistics, association analysis and cluster analysis of drugs in medical cases. Results:A total of 31 articles and 42 medical cases including 73 prescriptions were screened. The frequency results showed that there were 40 kinds of high frequency TCMs (frequency more than 5), mainly including drugs for benefiting the qi and strengthening the spleen, medicine to relieve cold and promote nasal passages, which was the same as the frequency statistics of the effects of herbal medicine. Seven drug groups were obtained by cluster analysis. The results of rule analysis showed that 16 association rules for drug pairs and 18 association rules for 3 TCMs pairs were obtained.Conclusions:While treating allergic rhinitis, Lingnan medical doctors focus on tonifying spleen qi, dispersing wind and cold, and promoting the nasal passages, which reflect the treatment theory of cultivating earth and generating gold, and attacking and tonifying. Lingnan medical doctors commonly used Guangdong medicinal herbs, which have distinct regional characteristics. The data mining methods can comprehensively summarize and explore the potential rules of Lingnan prominent practitioners' treatment of allergic rhinitis, and provide reference for guiding the treatment of congested nose and congested nose in TCM.

Objective:To explore application of blended learning mode in the teaching of the general theory of surgery.Methods:Clinical undergraduates from Batch 2015 and Batch 2016 of Medical College of Hunan University of Medicine were taken as participants. One teaching class of Batch 2015 was selected as control group ( n=117), and the traditional teaching method was adopted; one teaching class from Batch 2016 was selected as experimental group ( n=115), and the blended learning model was adopted. The results of two groups' process assessment and final assessment were compared. A questionnaire was conducted among the clinical undergraduates of Batch 2016 who practiced blended learning to evaluate their satisfaction with this learning mode. SPSS 22.0 was used for t test. Results:The experimental group was significantly better than the control group in process assessment and final assessment results [(93.65±3.71) vs. (91.46±5.63); (68.36±8.14) vs. (64.94±8.98)]. The analysis of the questionnaire survey showed that students had a high satisfaction with the blended learning mode, and their approval rate reached over 90%.Conclusion:In the teaching process of clinical course of general theory of surgery, blended learning mode is highly recognized by students, which can significantly improve students' independent learning ability and interest, simultaneously increase students' classroom participation and teacher-student interaction, and finally improve students' professional overall qualities and critical thinking.

Objective To investigate the efficacy and safety of transthoracic minimally invasive occlusion operation guided by transesophageal echocardiography for the treatment of congenital atrial or/and ventricular septal defects (ASD/VSD).Methods The clinical data of a total of 44 patients who underwent surgical occlusion operation from September 2013 to June 2015 were summarized.The whole course of occlusion procedure were dynamically monitored and guided by transesophageal echocardiography.All the patients were followed up regularly by electrocardiogram and echocardiograph.Results Among the 44 patients,43 patients(28 VSDs and 16 ASDs,including one patient suffered with VSD and ASD simultaneously)were occluded successfully,and the other patient with VSD who failed in the surgery was converted to open heart repair.The occlusion operations were finished within 22 to 48 min.The length of incision spaned from 2 to 4.5 cm.The ventilator was used for 1 to 5 hours.The total drainge volumes were recorded each patient from 0 to 50 mL.The postoperative hospitalization stay was 2 to 6 days,and all patients survived and were discharged.During the follow-up of 1 to 12 months, there was no cases with A-V conduction block,valve incompetent,cardiac arrhythmia and residual shunt of heart septel defect.Conclusion Transthoraic mini-invasive surgical occlusion of atrial and ventricular septal defects is a therapeutic method with less trauma,higher safety and feasiblity,faster recovery,and the short-term therapeutic effect is satisfying.

Objective:To develop an HPLC method for the determination of nintedanib in rabbit plasma and study the pharmacoki-netics of nintedanib in rabbits. Methods:The separation was performed on an Agilent ZORBAX SB-C18 column. A mixture of acetoni-trile-0. 1% trifluoroacetic acid-water (35∶ 20∶ 45) was used as the mobile phase at a flow rate of 1. 0 ml·min-1. The detection wavelength was set at 286 nm. Carbamazepine was used as the internal standard and nintedanib was extracted by ethyl acetate from plasma under basic condition. Totally 6 rabbits were given 20 mg·kg-1 nintedanib with intravenous administration. The blood samples were collected from the auricular vein at different time points after the administration. The concentration of nintedanib in plasma was detected by the HPLC method. The pharmacokinetics parameters were analyzed by DAS program. Results: An excellent linear rela-tionship was obtained within the range of 0. 05-10. 00 μg·ml-1(r=0. 999 8). The intra-day RSD was 5. 55%, 4. 53% and 2. 74%and inter-day RSD was 6. 15%, 5. 45% and 3. 15%, respectively for the three concentrations(0. 10, 2. 50 and 7. 50μg·ml-1), and the relative recovery was (98. 50 ± 5. 47)%, (100. 25 ± 4. 54)% and (99. 94 ± 2. 74)%, respectively. The main pharmacokinetics parameters of nintedanib were as follows: Cmaxwas (3.01 ±0.35) μg·ml-1, t1/2 was (4.38 ±1.53) h and AUC0-t was (11.67 ± 1. 71) μg·h·ml-1 . Conclusion:The method is simple, rapid and accurate, and can be used to determine the nintedanib concentra-tion in rabbit plasma and study its pharmacokinetics. Nintedanib is fitted the first-order elimination kinetics in rabbits.

Objective To investigate the adverse effect of different doses of high power microwave(HPM) irradiation on oxidative stress in the brain of Wistar rats in order to contribute to establishing an animal model to evaluate protective agents which will be used for protection against microwave radiation.Methods Eighty male Wistar rats were randomly divided into 16 groups according to factor analysis.The average power density was 0,10,30 and 100 mW/cm2 and the sampling time was 6 h,1,3 and 7 d .The duration of exposure was 6 minutes for each radiation group.After exposure, the rats were sacrificed at each sampling time.Colorimetric method was used to measure the content of malondialdehyde(MDA) and protein carbonyl, the activity of GSH-px, SOD and CAT.Results The content of MDA and protein carbonyl of each radiation group was increased with the radiation dose, but decreased with the sampling time prolonged.The activity of superoxide dismutast(SOD),glutathion peroxidase(GSH-px) and catalase(CAT) in each radiation group was decreased with the radiation dose increased, and with the sampling time prolonged, but increased later.Conclusion Microwave radiation can cause oxidative stress in rats brain, as shown by the oxidative damage of lipid and protein and the decrease in the activity of antioxidant enzymes.Besides, the effect also depends on the radiation dose and sampling time.

Along with the development of science and technology , microwaves are widely used in various fields .Though they have brought much convenience to people , their potential adverse health effects are becoming a concern of governments and researchers .High power microwaves ( HPMs) are widely used in high-tech and new concept weapons , increasing the chance that troops are exposed to HPM environments .It has been clearly confirmed that microwave radiation could cause varying degrees of damage to the nervous system , immune system , cardiovascular system and reproductive system under specific conditions .Therefore , it is of important significance to reduce adverse effects of HPM radiation and improve the combat capability of troops via effective medical protection while doing well in physical protection .According to the mecha-nism and characteristics of microwave radiation damage effects , recent advances in microwave radiation protection are re-viewed in this article , hoping to facilitate research on safer and better drugs .