Aim To study the analgesic effect of geraniol on neuropathic pain and to explore the possible mechanism.Method A neuropathic pain rat model of Spared Nerve Injury(SNI) was established to measure changes in the threshold of paw withdrawal before and after i.p.administration of geraniol.Patch clamp whole-cell recording was performed to measure activity of sodium channels using ipsilateral L3/L4/L5 dorsal root ganglion(DRG) cells isolated from the SNI rats.In addition, HEK 293 cells expressing hNav1.7 and hTRPA1 channels were used for measuring the changes in channel activities with or without geraniol by whole-cell patch clamp.Results Geraniol had a fast analgesic effect on hypersensitivity of mechanical pain in the SNI model.It significantly inhibited sodium channels on DRGs isolated from SNI rats and hNav1.7 but not hTRPA1 channels expressed by HEK293 cells.However, high concentrations of geraniol facilitated the activation of HTRPA1 channel stimulated by AITC.Conclusion Geraniol may abirritate hypersensitivity of mechanical pain in the SNI model by specifically inhibiting Nav1.7 channel activity on the DRG cells.

Objective:To explore the status of depression symptoms and related factors of depressive symptoms in middle-aged and elderly disabled people in China and provide references on the preventive cares of depression.Methods:Research data were obtained from the 2018 follow-up data of China Health and Retirement Longitudinal Study(CHARLS).Disabled people were selected as the research object. The scores of center for epidemiological studies depression scale(CES-D) were used to evaluate depressive symptoms. Fourteen variables derived from the 3 dimensions of demographic characteristics, health status, and health related behaviors were utilized in this study.SAS 9.4 were used for descriptive analysis, univariate analysis and Logistic regression analysis.Results:A total of 1 708 middle-aged and elderly disabled people were included, among whom 932(54.5%)were diagnosed with depressive symptoms, and the score of CES-D was (11.45±7.19).Self-rated poor health, self-rated poor memory, life dissatisfaction, physical pain were the risk factors of depressive symptoms ( OR=1.87, 4.22, 1.83, 5.30, 1.75). Male, educational level (middle-high school, high school or above), sleeping duration (6-9 h) were the protective factors of depressive symptoms( OR=0.74, 0.72, 0.10, 0.56). Conclusion:Middle-aged and elderly disabled people in China have a high detection rate of depressive symptoms. Female, lower education background, inadequate amount of sleep, self-rated unsatisfactory healthy, self-rated poor memory, dissatisfaction towards life and suffering from physical pain may be more likely to have depressive symptoms in middle-aged and elderly people with disabilities.

Objective To investigate the benefits of replanning after induction chemotherapy(IC) by analyzing the dosimetric impact of IC on intensity-modulated radiotherapy(IMRT)for locally advanced nasopharyngeal carcinoma(NPC)and the dosimetric characteristics of replanning after IC, and to provide data for the rational design of clinical radiotherapy plans. Methods 16 NPC patients underwent contrast-enhanced CT scan once before and after IC.Target volumes were delineated and the chemotherapy plans were created,defined as Plan-1 and Plan-2,respectively. Then the target structure after IC was copied to Plan-1, generating the third plan, defined as Plan-1-2. The paired t-test was used to compare the dosimetric parameters between Plan-1 and Plan-1-2 and between Plan-2 and Plan-1-2. Results Plan-1 vs. Plan-1-2:Plan-1-2 showed significantly reduced D meanof target volume compared with Plan-1(P<0.05). Plan-1-2 significantly increased D meanand D maxof the spinal cord(P<0.05),although significantly reduced D mean of the brain stem and D maxof the temporal lobes compared with Plan-1. Plan-1-2 also had significantly reduced conformity index(CI)and significantly increased homogeneity index(HI)for the target volume compared with Plan-1(P<0.05). Plan-2 vs. Plan-1-2:Compared with Plan-1-2, Plan-2 significantly increased D meanand D minof gross tumor volume(GTV)and primary GTV(P<0.05)and significantly reduced D meanof the temporal lobes and D maxand D meanof the spinal cord(P<0.05), with D max decreased to 430.48 cGy;Plan-2 had significantly increased CI and significantly reduced HI for the target volume compared with Plan-1-2(all P<0.05). Conclusions IMRT plan-1 after IC has worse dosimetric distribution,while replanning after IC has more dosimetric benefits.

Objective To propose a treatment planning optimization algorithm which can make full use of OAR dose distribution prediction meanwhile improving the output planning quality as much as possible.Methods We had reformulated an FMO function under the guidance of dose distribution prediction and also integrated equivalent uniform dose (gEUD) based on the consideration of prediction uncertainty,for providing optimal solution.Performance of the method was evaluated by comparing the optimized IMRT plan quality of 8 cervical cancers in the term of DVH curves,dose distribution and dosimetric endpoints with the original ones.Results The proposed method had a feasible,fast solution.Compared with original plan,its output plan had better plan quality in better dose homogeneity,less hot spot and further dose sparing for OARs.V30,V45 of rectum was decreased by (6.60±3.53)％ and (17.03±7.44)％,respectively,with the statistically significant difference (t=-4.954,-6.055,P＜0.05).V30,V45 of bladder was decreased by (14.74 ± 5.61) ％ and (14.99 ± 4.53) ％,respectively,with the statistically significant difference (t=-6.945,-8.759,P＜0.05).Conclusions We have successfully developed a predicted dose distribution and equivalent uniform dose-based planning optimization method,which is able to make good use of 3D dose prediction and ensure the output plan quality for intensity modulated radiation therapy.

Objective To establish a three-dimensional (3D) dose prediction model,which can predict multiple organs simultaneously in a single model and automatically learn the effect of the geometric anatomical structure on dose distribution.Methods Clinical radiotherapy plans of patients diagnosed with the same type of tumors were collected and retrospectively analyzed.For every plan,each organs at risk (OAR) voxel was regarded as the study sample and its deposited dose was considered as the dosimetric feature.A regularized multi-task learning method than could learn the relationship among different tasks was employed to establish the relationship matrix among tasks and the correlation between geometric structure and dose distribution among organs.In this experiment,the spinal cord,brainstem and bilateral parotids involved in the intensity-modulated radiotherapy (IMRT) plan of 15 nasopharyngeal cancer patients were utilized to establish the multi-organ prediction model.The relative percentage error between the predicted dose of voxel and the clinical planning dose was calculated to assess the feasibility of the model.Results Ten cases receiving IMRT plans were utilized as the training data,and the remaining five cases were used as the test data.The test results demonstrated a higher prediction accuracy and less data demand.And the average voxel dose errors among the spinal cord,brainstem and the left and right parotids were (2.01±0.02)％,(2.65± 0.02) ％,(2.45± 0.02) ％ and (2.55± 0.02) ％,respectively.Conclusion The proposed model can accurately predict the dose of multiple organs in a single model and avoid the establishment of multiple single-organ prediction models,laying a solid foundation for patient-specific plan quality control and knowledge-based treatment planning.

Objective:To establish a correlation model between MRI and CT images to generate synthetic-CT (sCT) of head and neck cancer during MRI-guided radiotherapy by using generative adversarial networks (GAN).Methods:Images and IMRT plans of 45 patients with nasopharyngeal carcinoma were collected before treatment. Firstly, the MRI (T1) and CT images were preprocessed, including rigid registration, clipping, background removal and data enhancement, etc. Secondly, the cases were trained by GAN, of which 30 cases were randomly selected and put into the network as training set images for modeling and learning, and the other 15 cases were used for testing. The image quality of predicted sCT and real CT were statistically compared, and the dose distribution recalculated upon predicted sCT was statistically compared with that of real planned dose distribution.Results:The mean absolute error of the predicted sCT of the testing set was (79.15±11.37) HU, and the SSIM value was 0.83±0.03. The MAE values of dose distribution difference at different regional levels were less than 1% compared to the prescription dose. The gamma passing rate of the sCT dose distribution was higher than 92% and 98% under the 2mm/2% and 3mm/3% criteria.Conclusions:We have successfully proposed and realized the generation of sCT for head and neck cancer using GAN, which lays a foundation for the implementation of MRI-guided radiotherapy. The comparison of image quality and dosimetry shows the feasibility and accuracy of this method.

Objective:To compare the accuracy and generalized robustness of three predictive models of knowledge-based treatment strategies for radiotherapy for optimized model selection.Methods:The clinical radiotherapy plans of 45 prostate cancer (PC) cases and 25 nasopharyngeal cancer (NPC) cases were collected, and analyzed using three models (Z, L and S model), proposed by Zhu et al, Appenzoller et al and Shiraishi et al, respectively, to predict the dose-volume histogram (DVH) of bladder and rectum on PC cases and that of left and right parotid on NPC cases. The prediction error was measured by the difference of area under the predicted DVH and the clinical DVH curves (|V (pre_DVH)-V (clin_DVH)|), where a smaller prediction error implies a greater prediction accuracy. The accuracies of these three models were compared on the single organ at risk (OAR), and the generalized robustness of models was evaluated and compared by calculating the standard deviation of the prediction accuracy on different OAR. Results:For bladder and rectum, the prediction error of L model (0.114 and 0.163, respectively) was significantly higher than those values of Z and S models (≤0.071, P<0.05); for left parotid gland, the predicted error of S model (0.033) did not present significant difference from those values of Z and L models (≤0.025, P>0.05); for right parotid gland, S model (0.033) demonstrated significantly higher prediction error than those of Z and L models (≤0.028, P<0.05). Regarding different OAR, S model showed a lower standard deviation of prediction accuracy when comparing to Z and L models (0.016, 0.018 and 0.060, respectively). Conclusions:In the prediction of DVH in bladder and rectum of PC, Z and S models were more accurate than L model. In contrast, Z and L models demonstrated higher accuracy than S model in the prediction of left and right parotid glands of NPC. In respect to different OAR, the generalized robustness of S model was superior than the other two models.

Objective To investigate the clinical and epidemiological characteristics of osteosarcoma in China and analyze the incidence and clinical treatment of osteosarcoma.Methods The clinical data of 1 593 patients with osteosarcoma in 7 bone cancer treatment centers from January 2000 to February 2017 were analyzed.We retrieved large samples of documents in the database,extracted the relevant data and compared the data with this study.SPSS 13 software was used for statistical analysis and each factor was tested by x2.Results Of 1 593 patients,984 were males and 609 were females.The ratio of male to female was 1.62∶ 1.The average age was 23.2 years (range from 3-80 years).The peak age of onset was 11-20 years (52.4％).There were 217 elderly patients (＞ 40 years old).The tumors occurred in 1 524 limbs and 69 in axial bone.The most common sites of disease were distal femur 706 cases,proximal tibia 375 cases,distal humerus 117 cases and others 395 cases.There were 1 154 cases (71％) around the knee joint.The axial bone included 18 cases of spine,49 cases of pelvis and 2 cases of rib.Preoperative biopsy was performed in 1 111 cases and incisional biopsy in 280 cases.Preoperative diagnosis could be made in 1 345 cases (84.4％ of all patients,accounting for 96.7％ of biopsy patients).There were 79 cases with metastasis at first visit,accounting for 5％.Preoperative chemotherapy was performed in 1 185 cases (74.4％).With the DIA preoperative chemotherapy 271 cases,DIA+MTX 251 cases,AP 149 cases.220 cases of tumor cell necrosis rate was evaluated after operationaccording to the Huvos classification.There were78 cases of grade Ⅰ,105 cases of Ⅱ grade,35 cases of Ⅲ and 2 cases of grade Ⅳ.There were 1 299 cases undergoingpostoperative chemotherapy (81.5％),1 306 patients undergoinglimb salvage surgery (82％).Thespecific operation with prosthetic replacement is the most common (911 cases,69.8％).The postoperative chemotherapy included DIA+MTX regimen 471 cases,DIA regimen 266 cases and AP regimen 98 cases.Before and after the operation,379 cases were treated with the same chemotherapy regimen and 666 cases were changed.A total of 18 large sample documents were retrieved in Chinese data base (5 684 cases).The sex ratio,age range,peak incidence and location of the disease were similar to those of this study.The average age was 1-2 years old younger.The percentage of lung metastases associated with initial visits washigher.The rate of preoperative and postoperative chemotherapy and limb salvage waslowand the rate of tumor necrosis wasbetter after chemotherapy.A total of 22 large sample literatures were searched in foreign database (12 850 cases).The ratio of men and women is 1.30∶1 and the proportion of women is higher than the domestic data.The average age was 1-2 years older.The ratio of the knee joint was lower.The percentage of lung metastases associated with initial visits washigher.The rate of preoperative and postoperative chemotherapy and limb salvage were similar to that of this study and the rate of tumor necrosis was better after chemotherapy.Conclusion The general situation of the incidence of osteosarcoma (sex,age,location of the disease) is not significantly different from the previous reports both at home and abroad.In the treatment,preoperative and postoperative chemotherapy rate and limb salvage surgery rate have improved significantly compared with the past.The chemotherapy program from the coexistence of various programs,gradually to the DIA+MTX and DIA program as the mainstream program.