BACKGROUND:Inherited heart disease has a high prevalence and mortality rate,but its pathogenesis has not yet been clarified.Although relevant animal models have been established to provide a foundation for the pathogenesis research of inherited heart disease,the value of these research results has been significantly reduced due to differences among species.Therefore,a new model is needed to explore its occurrence and development. OBJECTIVE:To review the current role of induced pluripotent stem cells in disease modeling and potential application prospects in various inherited heart diseases. METHODS:The first author searched the relevant articles published nearly 13 years in PubMed from January to March 2023.The search terms were"induced pluripotent stem cell,inherited heart disease,congenital heart disease".Finally,76 articles were included for analysis. RESULTS AND CONCLUSION:Since 2007,when induced pluripotent stem cells were induced from human somatic cells,many studies have been reported on disease-specific induced pluripotent stem cells.Due to the ability of disease-specific induced pluripotent stem cells to reproduce disease phenotypes,they are expected to become a new research tool for in vitro disease modeling,used to analyze pathogenesis and develop auxiliary drugs.In the research of cardiovascular genetic diseases,cardiomyocytes derived from patient-specific induced pluripotent stem cells contain gene mutations that are involved in cardiac dysplasia.Therefore,it can be used as a new tool to study the potential mechanisms of inherited heart disease.Up to now,induced pluripotent stem cells-derived cardiomyocytes have been widely used to study the molecular mechanisms of various genetic heart diseases,such as cardiac electrophysiological diseases,cardiomyopathy,and some syndromic inherited heart diseases.

Objective:To perform testing and clinical application of a volumetric-modulated arc therapy (VMAT) dosimetry verification system based on three-dimensional dose reconstruction of patient anatomical structures.Methods:ArcCheck array calibration was performed. Then, 200 MU was delivered with a 10 cm×10 cm field when the source to center of ArcCheck was 100 cm to calibrate the absolute dose and the dose was simultaneously measured by a FC65-G detector in the center of the ArcCheck. The absolute dose calibration value or the CT value of ArcCheck was adjusted to minimize the differences between the planning and measurement values of FC65-G, reconstructed value by 3DVH and reconstructed percent depth dose by 3DVH. 10 lung and 10 cervical cancer VMAT cases were selected and measured by ArcCheck and FC65-G under the delivery of a TrueBeam LINAC. The three-dimensional doses of all cases were reconstructed by 3DVH and compared with the planning and measurement values.Results:Different array calibration files of ArcCheck exerted different effect upon the two-dimensional dose measured by ArcCheck and three-dimensional dose reconstructed by 3DVH. The optimal reconstructed dose was obtained when self-calibration file was adopted and 249.96 cGy was regarded as the absolute dose calibration value. The deviations of the mean dose (D mean) and D 95% of the target were within ±4.2% and parameters of some organs at risk significantly differed compared with the reconstructed and planning dose for all cases. A negative mean point dose difference was obtained and the reconstructed dose was closer to the measured value. The γ-passing rate of the target for some cases was low, the proportion of regions irradiated by 50% prescription dose was slightly higher and the proportion of other organs was relatively high. Conclusion:The 3DVH model can be accurately established and tested with the acceptance test method in the present study, which can provide detailed information for dose verification.

Objective:To evaluate the volumetric modulated arc therapy (VMAT) dose verification of cervical cancer based on γ rule and dose volume histogram (DVH) and to perform correlation analysis between the evaluation results and the dose differences.Methods:Twenty cervical cancer VMAT plans were selected and performed on TrueBeam Linac. The delivered point and surface dose was measured by FC-65 G and ArcCheck and the results were compared to those calculated by Eclipse. The dose of patients was reconstructed by 3DVH. Then, differences between the reconstructed and plan value of D mean, D 95%, D 98% and D 2% of PTV, V 20Gy of left and right femoral head, V 40Gy of rectum, D 1cm 3 of cord, D 98%, D 2% and D 50% of the 50% prescription iso-dose volume (IDV), were evaluated and 3-dimensional (3D) γ was assessed for each organ. Lastly, Pearson’s correlation coefficient was used to analyze the relationship between point dose difference, 2D γ pass-rate (γ%), γ mean and 3D γ% of each organ and the dose difference. Results:Small differences were found between the point dose measured, reconstructed and the plan value. Differences between D mean of PTV, all dose parameters of IDV and plan values were all within 3% and V 40Gy of rectum showed the largest difference. As for the 3D γ%, the maximum pass rate was found for the left and right femoral head and the maximum variance for cord D 1cm 3. There was a moderate correlation between measured and reconstructed point dose deviation and dose difference of each organ, while no significant correlation was found for 2D γ%. Strong correlation was found between 3D γ% of target and D 50% of PTV/IDV and no correlation was found for other organs. Conclusion:The performance of both γ-and DVH-based evaluation can reveal dose error for dose verification, but both of them have some limitations and should be combined in clinical practice.

Objective:To explore the difference in the complexity of different treatment planning systems, multi-leaf collimator (MLC) types and treatment sites of volume-modulated arc therapy (VMAT), and propose a complexity score for plan quality control.Methods:Statistical analysis of 12 complexity metrics including Monaco and Eclipse, Agility, Millennium and High-definition MLC, nasopharyngeal, lung and cervical cancer was performed. Spearman correlation coefficient between complexity metrics was calculated. Principal component analysis was conducted to reduce the dimensionality of the original data set to the first two principal components and explain its physical meaning. Complexity score based on the principal components was calculated to establish warning and action thresholds for plan quality control. The correlation between complexity metrics and γ pass rate was analyzed.Results:Except cervical cancer aperture sub-regions metric, other metrics had significant differences between Monaco and Eclipse. Monaco MLC had a more regular field but higher MU, smaller leaf gap, and longer leaf travel distance. High-definition MLC with smaller leaf width significantly added MLC aperture-related metrics. The first two principal components explained over 80% of the total variance of the original dataset, complexity score was weighted average of first two principal components. The distribution of complexity score for different equipment and sites was different. The warning threshold was expressed as the average plus standard deviation, and the action threshold was expressed as the average plus 2 standard deviations. Complexity metrics and complexity scores had small correlation with γ pass rate, showing weak or irrelevant but statistically significant. Conclusions:Different planning systems, MLC types, and treatment site complexity metrics are significantly different. The complexity score is a useful tool for plan quality control.

Objective:To evaluate the positive rate of the bronchodilation test (BDT) in asthmatic children with normal forced expiratory volume in 1 second (FEV 1), forced vital capacity (FVC) and FEV 1/FVC, so as to improve the recognition of the importance of the BDT test in asthmatic children with normal FEV 1, FVC and FEV 1/FVC. Methods:Children aged 5-14 who were diagnosed with asthma in the outpatient clinic of Shandong Provincial Hospital Affiliated to Shandong University from September 2018 to August 2019 and willing to receive pulmonary function and BDT examinations were enrolled.Data of pulmonary function of children with normal FEV 1, FVC and FEV 1/FVC were collected to analyze the rate of positive BDT results and the status of small airway function. Results:A total of 1 631 asthmatic children with normal FEV 1, FVC and FEV 1/FVC were enrolled in this study, including 1 414 children with normal pulmonary function and 217 children with small airway dysfunction.Fifteen minutes after the bronchodilator was inhaled, 127 children (87 males and 40 females) showed positive BDT results, accounting for 7.8%.Among these children, 62 cases (28.6%) with co-existing small airway dysfunction showed positive BDT results.The improvement rate of FEV 1 was 8.0% to 11.9% in 132 cases (8.1%). The FEV 1 before bronchodilator inhalation accounted for (98.5±10.3)% of the predicted value.Fifteen minutes after terbutaline sulfate inhalation, the improvement rate was 13.5% (12.5%, 16.2%). The improvement rates of forced expiratory flow at 50% of FVC exhaled (FEF 50, r=-0.339, P<0.01), forced expiratory flow at 75% of forced vital capacity exhaled (FEF 75, r=-0.400, P<0.01), maximum mid-expiratory flow(MMEF, r=-0.375, P<0.01) were negatively correlated with their baseline values.The improvement rate of FEV 1 was not associated with its baseline value ( r=-0.128, P=0.153), but negatively correlated with the baseline value of MMEF ( r=-0.231, P<0.01). Conclusions:BDT results are positive in some asthmatic children with normal FEV 1, FVC and FEV 1/FVC.It is recommended that BDT testing should be conducted as much as possible in the diagnosis and follow-up of children with typical or atypical asthma.In this way, the diagnosis can be confirmed and the current optimal results can be obtained.Meanwhile, small airway function testing is helpful for comprehensive assessment of asthma and its control level.

Objective:To evaluate the combined effect of an trajectory log field based(LBF)and two commercial dose reconstruction systems on volume-modulated arc therapy(VMAT)dose verification of lung cancer.Methods:An in-house program was developed to introduce errors in trajectory log of TrueBeam to the origin plan and recalculate the dose of the error plan in treatment planning system(TPS). A total of 18 lung cancer cases treated by two-arc VMAT were selected to perform on LINAC and measured by ArcCheck simultaneously. Then, the reconstructed doses were obtained by 3DVH. The mode of reconstruction was calculated by LFB and Compass. Five of the 18 cases were performed on LINAC two times in four hours and measured by ArcCheck to evaluate the stability of the TrueBeam performance. The 18 plans were recalculated and performed on LINAC with a solid water phantom with 5 cm build-up, 4 cm back scattering thickness and a FC65-G detector in the center. The measured dose by detector was compared with the reconstructed dose by three systems.Results:TheTruebeam performance was stable. For all of the 18 cases, the point dose measured by FC65-G and reconstructed by three systems had a deviation of less than 2% to the TPS calculated. For all of the organs reconstructed by LBF and most organs reconstructed by 3DVH and Compass, the γ pass rate between them and TPS all exceeded 90% under all criteria, as well as the ArcCheck measured results. For all the organ dose difference between reconstructed and TPS, LBF system had the smallest difference, followed by the Compass system except the lung, and the 3DVH had the highest difference.Conclusions:LBF, 3DVH and Compass can reflect the VMAT dose verification results of lung cancer from different perspectives. The combined application of three systems can demonstrate the verification results in an intuitive manner, which is beneficial for subsequent analysis.

Objective:To evaluate the multi-leaf collimator (MLC) performance of TrueBeam accelerator using trajectory log files.Methods:All tests were performed 5 times under different gantry-collimator angle combination. The 1 mm picket fences were constructed by static or dynamic MLC. The control ability for small-field accuracy of accelerator was evaluated. Repeatability was assessed by MLC repeat motion. The movement performance of difference velocities along one direction and the opposite direction were evaluated via a 1 cm picket fences which slipped from -7 cm to 7 cm with a uniform velocity and stopped or immediately back at 7 cm. The MLC performance in a complex program was evaluated by a cross movement test.Results:Both the static and the dynamic picket fences yielded high accuracy. The deviation spectrums of MLC in different gantry angle were consistent, however, an absolute difference of 0.001 1 mm was found. For uniform velocity movement tests with 0°gantry, the RMSE of MLC was increased from 0.015 0 mm to 0.059 8 mm when the speed was accelerated from 5 mm/s to 25 mm/s. Similar results were obtained in non-zero gantry angle. The "overspeed" effect caused by the direction change movement of MLC was less obvious than that caused by speed changed from zero to a uniform velocity movement state. There was no significant change in speed before and after the MLC crossing. The MLC speed fluctuated around the set value, which was independent of the gantry angle.Conclusion:A method for evaluating the performance of MLC using trajectory log files is established, which can evaluate the MLC performance of TrueBeam accelerator and be used for MLC rapid quality control in clinical practice.

Objective: To achieve quantitative analysis of image quality parameters and establish warning and action thresholds for the on-board imaging (OBI) system of linear accelerator. Methods: The Catphan604 phantom was repeatedly scanned in the Full-Fan and Half-Fan CBCT scanning modes on a Varian EDGE linear accelerator, and the software based on Python language development in-house was utilized to analyze image quality parameters, such as CT number linearity, geometric consistency, slice thickness, spatial resolution, uniformity and low-contrast resolution. The quantitative analysis results of each image quality parameter obtained from 16 times of scanning within 16 months were normalized to the mean and the standard deviations were recorded. A run chart analysis was created to determine the warnings and action thresholds. Results: The software built in-house can quantitatively analyze the image parameters of the two scanning modes of OBI system. The low-contrast resolution of Half-Fan was better than that of Full-Fan, whereas the spatial resolution of Full-Fan was superior to that of Half-Fan. One standard deviation (1σ) was set as the warning threshold and 2 standard deviations (2σ) as the action threshold, respectively. The tolerance level of Half-Fan was smaller than that of Full-Fan. Conclusion Self-developed software enables quantitative analysis of accelerator image quality parameters, establishes warning and action tolerance of quality assurance and provides guidance for image quality assurance under image-guided radiotherapy specification.

Objective To investigate the commissioning and testing of the Eclipse model of an Edge accelerator with high-definition muhi-leaf collimator (HD-MLC).Methods The percentage depth dose (PDD),profile,output factor measured by Razor and CC13 were statistically compared with the standard data.Penumbra,transmission factor (TF),leakage,concave-convex groove,accuracy of movement and dosimetry leaf gap (DLG) were measured with EBT3,electronic portal image device (EPID) and PTW SRS1000&SRS1500.The optimal DLG/TF was acquired when the γ pass rate of test cases was the highest.The point dose of regular fields,intensity-modulated radiation therapy (IMRT) and volume-modulated radiation therapy (VMAT) was verified with FC65-G.The planar dose of these case was verified with Octavius 4D and EBT3.Results The measured PDD data were consistent with the standard data.The measured penumbra of 3 cm and 4 cm square fields was smaller,whereas that of 6 cm square field was larger than the standard values.The left and right edge,field size,center of the field were distributed within the range of-1.0-0.4 mm、0.2-1.7 mm,-0.3-1.9 mm and-0.1-0.8 mm,respectively.The mean penumbra of the left and right MLC in different positions were (2.5±0.042) mm and (2.7±0.005) mm.The leakage of MLC was 0.009-0.016.The measured DLG/TF was 0.1861 cm/0.0116 and the optimal DLG/TF was 0.015 cm/0.014.The differences of point dose of all the test cases except the one which was in the low-dose area were within ±3％.Local and global γ pass rates of all IMRT were 79.81％-100％ and 96.3％-100％ (3％/3 mm),71.3％-98.9％ and 94.3％-99.8％ for VMAT cases.Conclusions This method can accurately test and commission the Eclipse treatment planning model of Edge Linac equipped with HD-MLC.

Objective To establish and evaluate a morning check system for linac based on electronic portal image device (EPID).Methods Delivered fluence maps of open and wedge fields at 10 cm×10 cm field size of Synergy Linac were measured by EPID.Figure features from these two images were extracted with matlab codes and analyzed to realize a quick morning check.The repeatability of dose response and mechanical setup,relationship between gray value and machine unit (MU),accuracy of output and field size test were investigated with both EPID and DailyQA3.The status of Synergy linac was monitored both by DailyQA3 and EPID for two months.Results EPID was able to test the linac consistently with a testing error of 0.50 mm,1.00 mm for field size and center,respectively.Both of the test accuracy for flatness and symmetry was 0.17％.The mechanical accuracy test and dosimetric repeatability test were also consistent.The dose response of EPID was linearly related to the linac output (R2＞0.999).EPID was highly sensitive to the change of output and radiation field size.The measurement deviations between EPID and DailyQA3 were consistent and within clinical acceptable tolerance.Conclusions EPID showed great accuracy and stability on monitoring the performance of linac.The established daily check tool based-on EPID is accurate and reliable for clinical usage.