Objective To investigate the effect of sodium glucose cotransporter 2 inhibitor(SGLT2i)on cardiac function in T2DM rats with heart failure(HF)by regulating the silencing signaling protein 1/mitochondrial uncoupling protein 2(SIRT1/UCP2)signaling pathway.Methods Forty SD rats were randomly divided into normal control(NC)group,T2DM combined with HF(T2DM-HF)group,SGLT2i group,and SGLT2i+SIRT1 inhibitor(EX527)(SGLT2i+EX527)group.Fasting blood glucose(FBG),cardiac function,and oxidative stress indicators were tested in each group.The pathological morphological changes of myocardial tissue were evaluated by HE and Masson staining,and the expression of SIRT1 and UCP2 proteins in myocardial tissue was evaluated by Western blot.Results Compared with NC group,the T2DM-HF,SGLT2i,and SGLT2i+EX527 groups showed a decrease in body weight(P<0.05)and an increase in cardiac mass index(P<0.05).Compared with T2DM-HF group,the SGLT2i group showed decreased protein expression of FBG,LVESD,LVEDD,LVEDP,MDA,and UCP2(P<0.05),while increased protein expression of LVFS,LVEF,LVSP,±dp/dtmax,SOD,and SIRT1(P<0.05).Compared with SGLT2i group,the SGLT2i+EX527 group showed an increase in FBG,LVESD,LVEDD,LVEDP,MDA,and UCP2 opal levels,while LVFS,LVEF,LVSP,±dp/dtmax,SOD,and SIRT1 opal levels decreased(P<0.05).Conclusions SGLT2i can improve the cardiac function in T2DM rats combined with HF,enhance antioxidant capacity,and exert a protective effect on cardiac function.Its mechanism of action may be related to the regulation of SIRT1/UCP2 signaling pathway.

Objective To investigate the effect of sodium glucose cotransporter 2 inhibitor(SGLT2i)on cardiac function in T2DM rats with heart failure(HF)by regulating the silencing signaling protein 1/mitochondrial uncoupling protein 2(SIRT1/UCP2)signaling pathway.Methods Forty SD rats were randomly divided into normal control(NC)group,T2DM combined with HF(T2DM-HF)group,SGLT2i group,and SGLT2i+SIRT1 inhibitor(EX527)(SGLT2i+EX527)group.Fasting blood glucose(FBG),cardiac function,and oxidative stress indicators were tested in each group.The pathological morphological changes of myocardial tissue were evaluated by HE and Masson staining,and the expression of SIRT1 and UCP2 proteins in myocardial tissue was evaluated by Western blot.Results Compared with NC group,the T2DM-HF,SGLT2i,and SGLT2i+EX527 groups showed a decrease in body weight(P<0.05)and an increase in cardiac mass index(P<0.05).Compared with T2DM-HF group,the SGLT2i group showed decreased protein expression of FBG,LVESD,LVEDD,LVEDP,MDA,and UCP2(P<0.05),while increased protein expression of LVFS,LVEF,LVSP,±dp/dtmax,SOD,and SIRT1(P<0.05).Compared with SGLT2i group,the SGLT2i+EX527 group showed an increase in FBG,LVESD,LVEDD,LVEDP,MDA,and UCP2 opal levels,while LVFS,LVEF,LVSP,±dp/dtmax,SOD,and SIRT1 opal levels decreased(P<0.05).Conclusions SGLT2i can improve the cardiac function in T2DM rats combined with HF,enhance antioxidant capacity,and exert a protective effect on cardiac function.Its mechanism of action may be related to the regulation of SIRT1/UCP2 signaling pathway.

Objective:To explore the effect of a new teaching mode, which includes bridge-in, outcome, pre-test, participation, post-test and summary (BOPPPS), on the online teaching of radiobiology related knowledge for cancer radiotherapy practitioners.Methods:Taking the cell survival curve, cell cycle and radiosensitivity as examples, the radiotherapy practitioners in multiple university-affiliated hospitals were organized to carry out a multicenter prospective randomized control study. All practitioners were randomly divided into BOPPPS group and control group. The courses for BOPPPS group were designed as an online classroom, consisting of pre-class preparation, online teaching and post-class stages. The online teaching stage included video viewing, basic knowledge learning, literature discussion, group discussion and others. The control group employed the traditional teaching mode. The χ2 test was used to compare the consistency of general conditions between the two groups, and nonparametric test was used to compare the differences in scores between two or more groups. Results:The score of the pre-class test was 58.56 ± 0.99. Post-class average score for BOPPPS group was 85.48±0.85 and for control group 77.79±1.10, with the former being higher 7.69 ( Z=5.31, P<0.001) than the latter. The average answer time was (296.62±15.40) s for BOPPPS group and (386.41±21.27) s for control group, with the former being shorter 89.79 s ( Z=3.34, P=0.001) than latter. Subgroup analysis shown that the scores of BOPPPS group were significantly rising, regardless of whether or not the students had studied radiobiology courses. Among the students who have not studied these courses, the scores were rising greatly. Moreover, From the analysis of different positions, it was found that both the scores of BOPPPS group and control group have risen, especially for doctors, deputy chief doctors, physicists and technicians. There were also statistically differences between different degrees, with significantly rise in scores for undergraduate and doctoral students ( Z=3.64, 4.18, P<0.001). Conclusions:The flexible application of BOPPPS teaching mode to the online education of such boring disciplines, like radiobiology, is of great significance to raise the theoretical basis of radiotherapy practitioners.

Objective:Partial stereotactic ablative boost radiotherapy(P-SABR)is a method to deliver SABR boost to the gross tumor boost volume(GTVb), followed by conventionally fractionated radiotherapy to the whole tumor area(GTV). GTVb is the max volume receiving SABR while ensuring the critical organ-at-risk(OAR)falloff to 3 GyE/f. We investigated the potential advantage of proton therapy in treating bulky non-small cell lung cancer(the tumor length greater than 8 cm).Methods:Nine patients with bulky NSCLC treated with photon P-SABR in our institute were selected. For the treatment planning of proton therapy, the GTVb target area was gradually outwardly expanded based on the photon GTVb target area until the dose to critical OARs reached 3 GyE/f. The GTV and CTV areas remained the same as photon plan. A proton intensity-modulated radiation treatment plan(proton-IMPT), a photon intensity-modulated radiation treatment plan(photon-IMRT)and a photon volumetric modulated arc therapy(photon-VMAT)were created for each patient, respectively. The dosimetric parameters of different treatment plans were compared.Results:The volume ratio of GTVb-photon and GTVb-proton to GTV was(25.4±13.4)% and(69.7±30.0)%,respectively( P<0.001). In photon-IMRT, photon-VMAT, and proton-IMPT plan groups, the mean dose of CTV was(76.1±4.9)Gy, (78.2±3.6)Gy, and(84.7±4.9)Gy, respectively; the ratio of tumor volume with Biologic Effective Dose(BED)≥ 90 Gy to GTV volume was(70.7±21.7)%, (76.8±22.1)%,and(97.9±4.0)%,respectively. The actual dose and BED to the tumor area of the proton-IMPT plan group were significantly higher than those of the photon plan group(both P<0.05). Besides, the OARs dose was significantly decreased in the proton-IMPT group, with(49.2±22.0)%, (56.8±19.0)% and(16.1±6.3)% of the whole lung V5 for photon-IMRT, photon-VMAT and proton-IMPT, respectively(all P<0.001). Conclusions:Larger GTV boost target volume, higher BED and reduced OARs dose can be achieved in proton plans compared with photon plans. Proton P-SABR is expected to further improve the local control rate of bulky NSCLC with fewer adverse effects.

Objective:To evaluate the effect of setup errors from daily cone-beam computed tomography (CBCT) on the accumulated dose under different image-guidance (IG) strategies, aiming to investigate the appropriate IG strategies during radiotherapy for the spine metastases.Methods:A total of 720 CBCT scans of 36 vertebral lesions were obtained. All 36 lesions were divided into the simultaneous boosting (PTV 40 Gy/20f, GTV 60 Gy/20f, n=20) and conventional radiotherapy groups (PTV 40 Gy/20f, n=16). The actual fractionated plan was recalculated simulatively after transferring the isocenter of the initial plan according to the interfraction setup error. Under no daily image-guidance (no-DIG) strategies including twice imaging guidance weekly (TIG), initial 5 days then weekly imaging guidance (5D+ WIG), WIG and no imaging guidance (NIG), the dose deviation was calculated between the delivered dose accumulated by each actual fractionated plan and the dose distribution under DIG. The tolerance of dose deviation for the target was within ±5% and the D max of the spinal cord was limited below 45 Gy. Results:Under different image-guidance strategies of TIG, 5D+ WIG, WIG and NIG, the median dose deviation was approximately ±1% for the CTV D 95% and D max of spinal cord. However, the median dose deviation was beyond -5% for the PTV D 95% when conventional radiotherapy was given. The median dose deviation was approximately 10% for the D max of spinal cord and the proportion of cases whose maximum irradiated dose of spinal cord was more than 4500 cGy was ≥70%. Also, the median dose deviation was beyond -5% for the GTV D 95% and PTV D 95% when simultaneous boosting was delivered. Conclusions:Because the dose deviation of CTV and spinal cord is within the tolerance limit, the image-guidance strategies could be chosen according to the clinical practice when conventional radiotherapy is delivered. However, the dose deviation of spinal cord, GTV and PTV exceeds the tolerance limit under no-DIG strategies when simultaneous boosting is delivered. Hence, it is necessary to perform daily IGRT for the spine metastases.

Objective:To explore the amplitude of normal kidney motion in the 3D direction and its influencing factors under free-breathing condition.Methods:Clinical data of 28 patients with a KPS score≥80 who received 4D CT scan from March 2018 to March 2019 were collected. All patients were diagnosed with liver, pancreatic or lung tumors. The kidney was outlined and the geometric center and 3D coordinate values were recorded. The motion of bilateral kidneys in each direction and the 3D direction was calculated. The volume of kidney and surrounding organs, age, sex, height and body mass index (BMI) were recorded. Clinical data were statistically compared by t-test or nonparametric test. Results:The motion of the left and right kidneys in the the sup-inf (SI) direction were the largest up to (8.39±3.18) mm and (7.71±3.55) mm. The motion amplitudes of bilateral kidneys in male patients were significantly larger than those of the female counterparts in the left-right (LR), SI and 3D directions (all P<0.05). The motion amplitudes of bilateral kidneys in patients taller than 165 cm were significantly larger than those of their counterparts with a height of ≤165 cm (all P<0.05). Patients with a BMI≥25 kg/m 2 had significantly larger motion amplitudes of the left kidney in the LR and ant-post (AP) directions compared with those of normal weight counterparts (all P<0.05). The motion amplitude of the left kidney in the AP direction in patients with the left kidney volume of >180 cm 3 was significantly larger than that of patients with smaller left kidney volume ( P=0.014). Age was not significantly associated with kidney motion in each direction ( P>0.05). Conclusions:Kidney motion mainly occurs in the SI direction. The kidney motion amplitudes in male and taller patients are larger. Special attention should be paid to the use of breath motion control device to decrease the normal tissue damage.

Objective:To qualitatively analyze and auto-discriminate intrafraction prostate movement patterns based on transperineal ultrasound (TPUS) technique and linear discriminant analysis (LDA) method, which lays a solid foundation for individualized precise radiotherapy.Methods:A total of 1265 intrafraction motion trajectories and millions of monitoring data were recorded by TPUS from 61 prostate cancer patients. Seven typical patterns were considered: stable at baseline, slight transient excursion, persistent excursion and continuous drift, as well as obvious transient excursion, persistent excursion and continuous drift. Motion trajectory diagrams associated with the displacement-time function were generated by MATLAB programming. Valuable features were selected and different patterns were identified. Discriminant accuracy and receiver operating characteristic (ROC) curve were utilized to evaluate the performance of LDA model.Results:Four movement patterns were found per patient during the whole treatment process, and unstable type was occupied at (35.00±21.49)%. With the increase of treatment times, motion trajectories did not show an increasingly stable trend, and the appearance of different patterns was extremely irregular. After quantitative analysis, discriminant accuracy of LDA method was 90.4% for the training set and 89.5% for the testing set, with a sensitivity of 84.9% and a specificity of 91.1%.Conclusion:Intrafraction movement patterns are characterized by diversity and randomness. The LDA method can be used to discriminate different movement patterns effectively, and the unknown samples can be identified by discriminant equations and centroid coordinates.

Objective:To evaluate the dosimetric properties of intensity-modulated proton therapy (IMPT) plans for simulated treatment planning in patients with ventricular tachycardia (VT) using stereotactic ablative body radiotherapy (SABR), in comparison with the volumetric-modulated arc therapy (VMAT).Methods:A total of 25 gross target volume (GTV) of the apical, anterior, septal, inferior and lateral wall of the left ventricle (LV) were delineated on the CT simulation images of 5 patients with complete data. An additional 5 mm GTV margin was added to the internal target volume (ITV), and an additional 3 mm ITV margin was added to the planning target volume (PTV). VMAT and IMPT plans were designed in each target area. Dose prescription was 25 Gy (RBE) in a single fraction. The dosimetric differences of ITV and organ at risk (OAR) were compared between VMAT and IMPT.Results:The median volume of ITV was 45.40 cm 3(26.72-67.59 cm 3). All plans had adequate target coverage(V 95%Rx≥99%). Compared with the VMAT plans, IMPT reduced the D mean of whole heart, pericardium and non-target cardiac tissues (relative difference) by 44.52%, 44.91% and 60.16%, respectively, which also reduced D 0.03 cm 3 of the left anterior descending artery by 17.58%( P<0.05). After stratified analysis according to the lesion sites, IMPT could still reduce the dose of most OAR. However, the D 0.03 cm 3 of LAD and LCX for the lesions in the anterior wall of LV, the D 0.03 cm 3 of LCX in the inferior wall and D 0.03 cm 3 of LAD in the apical wall did not significantly differ (both P>0.05). Conclusions:Both VMAT and IMPT plans can meet the clinical dosimetric requirements when SABR is simulated in patients with VT. However, IMPT can lower the dose of normal heart tissues, which has the potential benefit of reducing the risk of complications, such as ischemic heart disease, pericarditis/pericardial effusion, etc.

Objective To evaluate the incidental irradiation to the axillary levels Ⅰ,Ⅱ and Ⅲduring the whole breast radiotherapy after breast conserving surgery(BCS)without axillary lymph node dissection(ALND)in breast cancer(BC)patients.Methods A retrospective analysis was performed on the consecutive 42 cases of T1-2N0M0stage BC patients with sentinel lymphnode biopsy(SLNB)and BCS but without ALND.The axillary lymph nodes of Ⅰ,Ⅱ and Ⅲ were delineated according to RTOG atlas guideline.Three radiotherapy plans including conventional tangential field(CTF),three-dimensional conformal radiotherapy(3D-CRT)and forward-planned intensity-modulated radiotherapy(IMRT)for whole breast irradiation were devised for each case.The Prescription dose was 50 Gy per 25 fractions.Doses to axillary levels(Ⅰ-Ⅲ)were evaluated.Results The mean doses delivered to axillary by the three techniques(CTF,3D-CRT and IMRT)were(40.1 ±6.8),(35.4 ±8.3),(32.9 ±7.0)Gy for level Ⅰ(F＝10.269,P＜0.05),(33.2 ±7.1),(30.6 ±6.7),(30.4 ±7.0)Gy for level Ⅱ(P＞0.05)and(9.6 ±6.8),(6.4 ±4.5),(5.2 ±3.7)Gy for level Ⅲ(F ＝8.377,P ＜0.05),respectively.V50(volume receiving 50 Gy)for the three techniques were 21.3％,27.6％,9.6％for level Ⅰ(F＝13.161,P＜0.05),12.9％,15.9％,8.3％for level Ⅱ(F＝2.750,P＜0.05)and 0.4％,0.1％and 0％for level Ⅲ(P＞0.05),respectively.Conclusions The doses coverage to axillary levelsⅠ-Ⅲwere all limited in the three techniques.Therefore,it is necessary to assess the risk of axillary lymph node metastasis adequately to develop individualized radiotherapy plans.

Objective To apply real-time transperineal ultrasound ( TPUS) to monitor the intra-fractional prostate motion,collect and analyze the data of the prostate motion,aiming to provide evidence for the optimization of the target area and plan of radiotherapy for prostate cancer. Methods TPUS is a non-invasive monitoring technique that utilizes an automatic scanning ultrasound probe to dynamically monitor and correct the motion of organs during radiotherapy. In this study, TPUS was utilized to collect 1588 intra-fractional data of 70 patients with prostate cancer. Prior to each cycle of radiotherapy,CBCT was adopted to correct the errors between intra-factional data by using VMAT. During radiotherapy, real-time ( once per second) ultrasound images were acquired to monitor the 3D motion of the prostate on the x (left+,right-),y (cranial+, caudal-), and z ( abdominal+, dorsal-) axes, emphasizing the analysis of 4D motion of the prostate. Results All patients successfully completed the treatment and data collection. The median time of effective monitoring per faction was 179 seconds (132-286 seconds). During 95% of the monitoring time,the distance of prostate motion was 2. 22 mm in the left direction,2. 17 mm in the right,2. 08 mm in the cranial, 1. 98 mm in the caudal,2. 44 mm in the abdominal and 2. 97 mm in the dorsal direction,respectively. In the x,y and z axes,the percentage of time in which the distance of prostate motion less than 1 mm among the total time was 83. 07%,85. 46% and 78. 27%,respectively,whereas 97. 70%,97. 87% and 96. 45% for＜3 mm, respectively. Conclusions TPUS is a non-invasive real-time monitoring technique,which can detect the 4D motion of the prostate during radiotherapy. By using VMAT,the range of prostate motion is relatively small, and the motion range is less than 3 mm in each direction within 95% of the time.