Objective To explore the molecular mechanism of Xiaojin Pills in the treatment of breast cancer using an integrated network pharmacology and experimental verification.Methods The chemical components and potential targets of Xiaojin Pills were obtained from TCMSP,TCM-ID,ETCM and SwissTargetPrediction databases.Breast cancer related targets were collected from GeneCards,OMIM and KEGG databases.The overlapped targets were imported into STRING database to analysis a protein-protein interaction(PPI).The key targets of PPI networks were screened based on node topology parameter values through Cytoscape 3.8.0.DAVID database was used to analyze the GO and KEGG pathway enrichment to build drug-chemical components-key targets-signaling pathway network.The breast cancer cell lines MDA-MB-231 and SK-BR-3 were used to study the effects of Xiaojin Pills extract on cell apoptosis,migration and invasion,and to verify the key pathway obtained by enrichment analysis.Results Totally 181 chemical components in Xiaojin Pills were obtained,including quercetin,myricetin,pinocembrin and β-sitosterol.615 potential targets were identified for the anti-breast cancer effects of Xiaojin Pills.After overlapping,170 key targets against breast cancer were identified based on the topological analysis,which included SRC,ERK1/2,AKT1,EGFR,etc.KEGG analysis enriched pathways including pathways in cancer,MAPK signaling pathway,endocrine resistance,PI3K-AKT signaling pathway,EGFR tyrosine kinase inhibitor resistance,apoptosis,and HIF-1 signaling pathway,which may play important roles in the therapeutic effects of Xiaojin Pills against breast cancer.GO enrichment was involved in protein phosphorylation,inflammatory response,negative regulation of apoptosis,and positive regulation of ERK1 and ERK2 cascades.Cell experiments showed that Xiaojin Pills further induced mitochondria-dependent apoptosis by inhibiting the activation of MAPK and PI3K-AKT pathways.At the same time,the expressions of ZO-1 and β-catenin increased,and the epithelial-mesenchymal transformation process was reversed to inhibit the metastasis of breast cancer cells.Conclusion The key targets and signaling pathways of Xiaojin Pills in the treatment of breast cancer are studied through network pharmacology combined with in vitro experiments,which provided a basis for further study of its pharmacodynamic material basis,mechanism of action and clinical application.

Using high-energy proton to image the region of interest can directly obtain the accurate estimation of the proton stopping power of the lesions,which is of great significance to reduce the range uncertainty in proton therapy.As a fundamental function of proton computed tomography(CT),radiographic imaging plays a crucial role in assisting clinical positioning.The study develops a compact proton CT detector based on an active array pixel CMOS chip in Monte-Carlo simulation toolkit Geant4,and evaluates the radiographic imaging capability of the system using 180 MeV protons.The angles of tracks are successfully reconstructed.CTP404,CTP528,and the CTP515 of specific materials are used for simulation,obtaining the spatial and density resolutions,and measuring the proton relative stopping power(RSP).The image signal-to-noise ratio is improved when using 2° proton scattering angle cut-off value.The spatial resolution is 3-4 lp/cm measured using CTP528 module.The density resolution is better than 0.05 g/cm3,and the RSP resolution is within 5%when CTP404 module is used.Through the imaging of CTP515 phantom of specific material,it is demonstrated that the system has potential for imaging common human tissues.

Compared with conventional radiotherapy, FLASH radiotherapy has advantages in protecting normal tissues, while the dose rate is increased by more than 100 times. If the shielding design of the treatment room is carried out according to the existing standard, the thickness and cost of the shielding wall will be significantly increased, or even hardly to meet the requirement of the standards, resultsing in the failure of the application of FLASH radiotherapy. By investigating the domestic and foreign standards and literature, this paper analyzes the challenges brought by FLASH radiotherapy technology to the shielding design of radiotherapy treatment room in China. Dose rate control standards adopted by different countries in the shielding design are emphatically compared as well. In several countries, the average dose rate under the actual treatment conditions was considered in the shielding design. In China, the method of instantaneous dose rate taking acount of occupancy factor is adopted. However, if FLASH radiotherapy technology is applied, the requirement of instantaneous dose rate will be difficult to meet. In order to improve the high dose rate radiotherapy technology such as FLASH radiotherapy, the revision of the existing standards is advised if the authorized limits are not changed. To use the average dose rate limit within a certain period of time for control, or to raise the control standard in the case of flash radiotherapy, are also avaliable.

Objective:To introduce the clinical dosimetry commissioning methods and results of the 1.5 T MR-linac.Methods:In May, 2019, an Elekta Unity 1.5 T MR-linac was installed in Cancer Hospital, Chinese Academy of Medical Sciences and dosimetry commissioning was performed with magnetic field compatible measuring instruments. Commissioning items include absolute dose calibration, data acquisition and planning system model verification.Results:Absolute dose calibration in magnetic field should be corrected by magnetic field correction factor. The standard output dose of Unity was 87 cGy. Gamma analysis (3%/2 mm) was performed on the beam collection data and the planning system calculation data. The average pass rate of dose verification of standard field test cases was 96.41%, and the TG119 test case was 98.24%. The IROC end to end test case was 97.5%(7%/4 mm).Conclusions:The planning system model and the beam collection data have good consistency. The dose verification results of the standard field and TG119 test cases meet the general tolerance limit requirements of the AAPM TG218 report, and the verification results of the IROC end-to-end test cases meet the IROC center standards.

Objective:To design a drum-shaped applicator through Monte Carlo simulation for breast intraoperative radiotherapy.Methods:Applicator designing process is as follows: first, determined the shape of the applicator based on the geometric characteristics of the breast tumor bed closed to the chest wall; second, calculated the scattering angle and dose rate of the electron beam after passing through a series of scattering foils of different thicknesses to determine the thickness of the scattering foil; thrid, modeled the layer according to the applicator′s geometric characteristics where modulator located, and designed the modulator through the relationship between the geometric characteristics of the layer and the surface dose of the applicator. EGSnrc/BEAMnrc and EGS4/DOSXYZ were employed to model the head of the Mobetron, the layer, the applicator, and to calculate the dose distributions.Results:The applicator has two components. The upper component is a 3cm-diametre cylindrical collimator with 0.5cm wall made of 0.3cm steel and 0.2cm water equivalent material (WEM), a 0.13cm-foil made of tansgen. The lower component is a 4cm-diametre drum made of 0.2cm WEM and a 0.14cm maximum thickness hill-shaped modulator made of steel. When the energy of electron beam was 12MeV, the dose rate was about 90.44 cGy/min, and the depth of the 50% isodose curve was 1cm.Conclusion:The applicator is successfully designed, and can obtain a drum-shaped dose distribution.

Objective:To design a semi-spherical applicator for delivery of semi-spherical dose distributions and assess its dosemetric characteristics.Methods:The applicator was designed in the following way. First, the scattering angle and dose rate of the electron beam having passed through a series of scattering foils of different thicknesses were calculated to determine the thickness of the scattering foil. And then, a series of location model was designed, and the variances of the mean electron energy on the surface of these models were calculated to determine the foil location. Finally, the relationship between the geometric characteristics of the layer and the surface dose on the applicator was established to design the modulator. Monte Carlo (MC) codes EGSnrc/BEAMnrc and EGS4/DOSXYZ were employed to model the head of the Mobetron, the location model, the layer, the semi-spherical applicator, and to calculate the dose distributions.Results:A semi-spherical applicator was designed for electron beam of energy 12 MeV, which consisted of a 2.5 cm diametre cylindrical collimator with 0.5 cm thick wall made of 0.3 cm thick steel and 0.2 cm thick water equivalent material (WEM), a 0.14 cm-thick foil made of tansgen, and a 2.5 cm diametre hollow semi-sphere containing a crescent modulator made of WEM. The dose rate was about 160 cGy/min, and the depth of the 50% isodose curve was 0.85 cm.Conclutions:We designed and performed a MC simulation of a semi-spherical applicator to deliver a semi-spherical dose distribution from a high energy electron beam.

Objective:To evaluate the effect of fast cone beam CT (CBCT) scan mode on image quality and registration results, and to establish the scanning pre-settings for fast CBCT.Methods:Three scanning modes were utilized to the CBCT phantom, and the registration accuracy and image quality were quantitatively evaluated. The correlation and consistency of measurement results under different scanning modes were further verified by 278 sets of CBCT data from 33 clinical tumor patients.Results:The maximum deviation between the measurement results of three scanning models and the actual value was 0.70 mm (0.51 mm on average). The measurement results of the same location were consistent among three scanning modes (0.00 mm). For the uniformity, the results of the normal mode were the best (3.62% on average), followed by the fast 1 mode (3.90% on average) and the fast 2 mode (4.84% on average). For the noise, the results of the normal mode were the best (15.69 on average), followed by the fast 2 mode (17.23 on average) and the fast 1 mode (21.74 on average). Regarding the high contrast resolution, the measurement results of three scanning modes were consistent (at least 3 pairs could be distinguished). For the low contrast resolution, the results of the fast 1 mode were the best (1.69 on average), followed by the normal mode (2.10 on average), and the fast 2 mode (2.31 on average). For the geometric accuracy, the measurement results of the three scanning modes were basically consistent with a mean deviation of 0.05 mm. The correlation of the measurement results between normal mode and fast 1 mode was the highest in clinical cases ( R2>0.90, P<0.01) with a high degree of consistency (95% consistency limit of the above two scanning modes< 1 mm threshold). Conclusion:Compared with the normal mode, the fast 1 mode can yield equivalent image quality, consistent registration results, faster scanning speed and lower scanning dose. Therefore, the fast 1 mode is recommended as the scan mode in clinical practice.

Objective:To construct a rat model of hypothalamic obesity by two point electrical damage to the ventromedial hypothalamus and arcuate nucleus.Methods:Twenty adult male SD rats of SPF grade were randomly divided into experimental group and sham operation group.A 25GA (0.45 mm) solid iron needle was used, the needle was coated with an insulating layer, and the tip exposed a 0.5 mm conductive area.With reference to The Rat Brain in Stereotaxic Coordinates and using the stereotactic instrument (AP: -2.6 mm, ML: ± 0.6 mm, DV: -9.6 mm) as the coordinate, 1.5 mA current was continuously applied for 25 s, the ventromedial nucleus (VMH) and arcuate nucleus (ARC) of bilateral brain in SD rats was damaged.During the experiment, the body weight(BW), food intake(FI) and water intake(WI) of the two groups were recorded regularly.The rats were sacrificed on the 28th day after the operation, and the changes of periprenal fat mass and body length were measured.The changes of liver and adipose tissue were detected by HE staining method, leptin by ELISA, leptin receptor(LEPR) by Western blot.Results:(1) The body weight of rats in the experimental group ((427.5±17.7)g) and weight gain ((208.5±14.8)g) were significantly increased compared with the rats in the control group((349.2±17.7)g), ((136.2±21.4)g)on the 28th day after operation ( t=7.661, 6.806, both P<0.001). (2) The daily food intake of rats in the experimental group ((44.2±6.6)g) on the 28th day after surgery was significantly higher than that in the control group ((23.0±3.6)g) ( t=6.918, P<0.001). There was no significant difference of the daily drinking water of rats between experimental group((37.5±12.1)ml) and the control group ((35.0±11.8)ml) ( t=0.361, P=0.726). (3) Perikidney fat mass of experimental group rats ((13.4±2.7)g) significantly increased 28 days after operation compared with control group rats((6.3±0.9)g)( t=4.250, P<0.05). The naso-anal length of experimental group((21.8±0.4)cm) was significantly decreased compared with the control group ((23.4±0.2)cm) ( t=-6.788, P<0.01). The Lee index of the experimental group (348.9±8.5) was significantly higher than that of the control group(305.5±4.3)( t=7.898, P<0.01). (4) The serum leptin content ((8 324.10±159.00)μg/L) of the experimental group rats at 28 days after surgery was significantly higher than that of the control group((2 705.31±407.10)μg/L) ( t=25.712, P<0.001). The lateral hypothalamus area (LHA) LEPR protein expression (1.3±0.1) in the experimental group was significantly higher than that in the control group (0.9±0.1) ( t=4.932, P<0.01). Conclusion:Two-point electrical damage to bilateral VMH and ARC of rats can establish hypothalamic obese rat model.

Objective The IAEA report No.483 describes the latest method of small field dosimetry.The field output factor measurement and correction methods are used to improve the accuracy and consistency of the measurement results for different type detectors.Methods The field output factors from 0.6 cm×0.6 cm to 10 cm× 10 cm were measured using IBA's CC13 ionization chamber,CC01 ionization chamber,PFD semiconductor detector,EFD semiconductor detector and Razor semiconductor detector,respectively.The field output correction factors were used to correct the measurement result.Results Compared with the corrected data,the results of ionization chamber are mainly affected by the volume averaging and the fluence perturbation effect,lead to the measurement result which is 4.70％ lower at 0.6 cm × 0.6 cm;The results of Shielded semiconductors are mainly affected by fluence perturbation effect,lead to the measurement result which is 4.80％ higher at 0.6 cm × 0.6 cm.The results of unshielded semiconductors are mainly affected by energy response and fluence perturbation effect,resulting in lower measurement results at the field size＞0.8 cm×0.8 cm,2.10％ lower at field size of 1.5 cm× 1.5 cm,higher measurement results at field size＜0.8 cm×0.8 cm and 1.1％ higher at field size of 0.6 cm×0.6 cm.Before the correction,the measurement results from different types of detectors are quite different,average standard deviation is 0.016 6.After the correction,the difference among the detectors is significantly reduced,average standard deviation is 0.006 6.Conclusions For detectors such as ionization chambers and semiconductors,the field output correction factors can be used to correct the output factors of the small field to improve the accuracy and consistency of the measurement results.

Objective: To investigate the effects of milrinone on levels of inflammatory factors and liver and renal function after CPB in rheumatic heart disease patients for valve replacement. Methods: From January 2014 to January 2016, 80 patients received valve replacement in the Central Hospital of Chongqing Three Gorges were randomly divided into observation group and control group by block randomization grouping method, with 40 patients in each group.The patients in the observation group were pumped intravenously with milrinone 0.5μg·kg^-1·min^-1 for 72h after surgery, while the patients in the control group were not pumped.The serum levels of IL-6, IL-8, IL-10, TNF-α were detected by ELISA before operation and on 0d, 1d, 3d, 5d after operation, respectively.The levels of ALT, AST, Scr were also detected at the same time.Moreover, the time for operation, extracorporeal circulation, interruption, mechanical ventilation, ICU and hospital were also compared between the two groups. Results: The levels of TNF-α, IL-6, IL-8 and IL-10 increased immediately after operation in both groups[control group: (14.97±5.14)pg/mL, (52.45±10.37)pg/mL, (34.10±8.38)pg/mL, (32.27±8.45)pg/mL; observation group: (16.05±5.71)pg/mL, (54.39±8.56)pg/mL, (33.80±7.69)pg/mL, (31.48±5.94)pg/mL, t=-0.628, -0.644, 0.116, 0.342], and the peak values of TNF-α, IL-6 and IL-8 reached on the first day after operation in both two groups[control group: (52.07±10.18)pg/mL, (96.04±26.45)pg/mL, (91.14±18.28)pg/mL, (48.10±9.78)pg/mL; observation group: (50.37±12.98)pg/mL, (93.66±24.10)pg/mL, (83.16±16.28)pg/mL, (46.68±9.25)pg/mL, t=0.559, 0.295, 1.458, 0.473], and the peak value of IL-10 reached on the 3rd day after operation(t=-3.577), the differences were statistically significant on the 3rd day after operation[control group: (36.03±9.39)pg/mL, (59.56±14.38)pg/mL, (53.91±13.16)pg/mL, (85.55±16.49)pg/mL; observation group: (36.70±4.33)pg/mL, (36.20±3.85)pg/mL, (42.91±7.30)pg/mL, (101.33±10.81)pg/mL, t=-0.289, 7.017, 3.267, -3.577]. The levels of ALT, AST and Scr increased immediately after operation in both groups[control group: (38.51±5.12)U/L, (40.23±5.03)U/L, (62.27±5.02)μmol/L; observation group: (39.20±4.67)U/L, (39.6±4.94)U/L, (73.61±4.04)μmol/L, t=0.114, 0.243, 0.630], there were tatistically significant difference between the two groups on the 5th day after operation[control group: (61.45±5.27)U/L, (54.20±7.0)U/L, (86.45±9.01)μmol/L; observation group: (36.20±3.85)U/L, (34.85±7.12)U/L, (83.7±11.07)μmol/L, t=11.231, 9.224, 5.647], and on the fifth day, the levels of ALT, AST and Scr in the observation group dropped to normal, while only the level of Scr in the control group dropped to normal.There were no statistically significant differences in the time of operation, extracorporeal circulation, interruption, mechanical ventilation between two groups (t=0.267, 0.151, 0.187, 0.773, all P>0.05). However, there were statistically significant differences in the time of ICU and hospital [control group: (54.90±16.84)h, (14.35±3.01)d, observation group: (44.05±7.06)h, (10±1.86)d, t=8.149, 13.042, all P<0.05]. Conclusion Milrinone can obviously improve the inflammatory reaction in surgical trauma tissues caused by IL-6, IL-8, IL-10, TNF-α, and can protect liver, renal tissue from injury, moreover, it can decrease the incidence of postoperative complications and the length of hospital stay.