Objective:To explore the feasibility of applying ArcherQA to independent dose verification of MR-guided online adaptive radiotherapy (ART) plans performed on Elekta Unity 1.5 Tesla (T) magnetic resonance-linear accelerator (MR-Linac).Methods:The dose calculation accuracy of ArcherQA under a specific magnetic field was validated using a homogeneous water phantom. A total of 32 patients who received MR-guided online ART on Elekta Unity were randomly selected by lottery, with 32 offline plans and 177 online plans for five treatment sites (brain, mediastinum, liver, kidney, and vertebral body) enrolled. Finally, the γ pass rates (threshold: 10%; criteria: 3 mm/3% and 2 mm/2%) were compared among the result upon independent dose verification of ArcherQA, measurements of ArcCheck, and calculations using the Monaco treatment planning system (TPS) to quantitatively evaluate the accuracy and efficiency of ArcherQA in independent dose verification of online plans on Elekta Unity.Results:ArcherQA was proven accurate in calculating the dose distribution of therapeutic photon beams under the specific magnetic field. With the 3 mm/3% criterion, the γ pass rates of verification result exceeded 99% in all square fields of a water phantom. Under the stricter 2 mm/2% criterion, the γ pass rates also surpassed 95% in all square fields except 20 cm × 20 cm field. Regarding the verification of treatment plans, the ArcherQA result were found to be highly consistent with those measured or calculated using ArcCheck and Monaco TPS, with the average γ pass rates exceeding 99% under the 3 mm/3% criterion and above 97% under the 2 mm/2% criterion. ArcherQA was acceptably efficient for independent dose verification of online plans, with 50 to 150 s, (108 s on average) required to complete the independent dose verification of 177 online plans.Conclusions:ArcherQA allows for accurately and efficiently calculating the dose distribution of therapeutic photon beams under a specific magnetic field, establishing it as an effective supplementary tool for independent dose calculation of MR-guided offline and online ART plans, thereby ensuring the safety of patient treatment plans.

Adipose progenitor cells(APCs) represent a prominent stromal cellular component of adipose tissue and are now identified as highly heterogenous populations. However, the role of APCs in regulating systemic metabolism remains unknown. Using single cell RNA-sequencing, we investigated the role of the APC subpopulations in regulating development of type 2 diabetes. CD9 + CD55 low APCs are the novel subset identified in this study, which is significantly increased in type 2 diabetic patients. Transplantation of these cells from type 2 diabetic patients into adipose tissue caused glycemic disturbance in mice. Depletion of pathogenic APCs improved obesity-related glycemic disturbance. Collectively, our data provide deeper insights into human APC functionality and highlights APCs as a potential therapeutic target to combat type 2 diabetes. This study has been published in Nature Communications, 2024, 15(1): 4827.

Objective To explore the protective effect of polypeptide Apelin on podocyte mitochondria in diabetic nephropathy and underling mechanisms.Methods Human renal podocytes were divided into four experimental groups:control group,high glucose(HG)group(glucose 25 mmol/L,48 h),Apelin intervention HG group(Ape-lin-13 1 μmol/L,48 h)and Apelin group(Apelin-13 1 μmol/L,48 h).The podocyte apoptosis was observed by TUNEL staining,the expression of mitochondrial membrane protein FUNDC1 was detected by Western blot,and the binding of mitochondrial fission protein DRP1 to FUNDC1 was examined by immunoprecipitation.The 8-week-old male mice were divided into three experimental groups:control group,diabetes group(intraperito-neal injection of streptozotocin 150 mg/kg,only one time)and Apelin intervention DM group(intraperitoneal injection of Apelin-13 0.3 μmol/kg,daily).The morphology of renal was observed by PAS staining and trans-mission electron microscopy.Plasma creatinine(Cr),urea nitrogen,urinary albumin and creatinine were de-tected by ELISA kit.The level of creatinine clearance rate(Ccr)and urinary albumin/creatinine(ACR)was calculated.Results Compared with the control group,the podocyte apoptosis and expression of FUNDC1 in the HG group increased significantly(P＜0.05),and the combination of mitochondrial fission division protein DRP1 to FUNDC1 raised.Meanwhile,compared with the HG group,the number of apoptosis,the expression of FUNDC1(P＜0.05),and the combination of DRP1 to FUNDC1 all reduced in Apelin intervention HG group.Animal experiments showed that the kidney structure of the control group was intact.In the DM group,the num-ber of podocytes decreased significantly,the foot processes were fused and dropped off.In the Apelin intervention DM group,podocyte lesions were less severe than those in the DM group.Compared with the control group,the level of plasma Cr,BUN and urine ACR in the DM group increased,while the level of Ccr decreased significantly(P＜0.05).However,compared with the DM group,the level of above biomarkers in the Apelin intervention DM group was improved(P＜0.05).Conclusions Apelin keeps mitochondrial homeostasis and reduces podocyte ap-optosis by inhibiting the expression of mitochondrial membrane protein FUNDC1,which may contribute to allevia-tion of diabetic nephropathy.

Objective:To analyze the dosimetric effects on off-center tumour treatment plan resulting from the MR-Linac-based isocenter position radiotherapy plan.Methods:The cases of 19 patients who were treated in Sun Yat-sen University Cancer Center in 2020 were collected in this study. Two different IMRT plans were designed for each patient with off-center tumor both for group A with planned isocenter position as IMRT and group B with planed target center position as geometric center. The conformity index and homogeneity index of target, the dose normal tissue and the number of MU were compared between two plans.Results:The two IMRT plans met clinical dosimetric requirements. No statistical differences were found both in homogeneity index and conformity index ( P>0.05). Also there was no differences found in doses to normal tissues. However, the MU number (1 149±903, t=2.804, P=0.012) in group A was higher than that in group B (970±652). Conclusions:It is feasible to perform MR-Linac-based off-center treatment plan.

Objective:To investigate the feasibility of applying the ArcherQA three-dimensional (3D) dosimetric verification system in intensity-modulated radiotherapy (IMRT) plans for nasopharyngeal carcinoma (NPC).Methods:A retrospective analysis was conducted for 105 NPC patients′ IMRT plans developed using the Eclipse treatment planning system (TPS). Dose verification was conducted using the ArcherQA system and through portal dosimetry (PD). Moreover, this study compared γ passing rates (criteria: 3 mm/3%, TH = 10%) between ArcherQA and PD and the doses delivered to the target volume ( Dmean, D90%) and organs at risk (OARs) ( Dmean) between ArcherQA and TPS, and analyzed the 3D γ passing rates of each organ at risk calculated by ArcherQA. Results:The average 3D γ passing rate calculated by ArcherQA was (99.04±1.01)%, and the average 2D γ passing rate measured by PD was (99.49±0.78)%, with statistically significant differences ( t=-3.35, P< 0.05). The dosimetric differences to the target volume between ArcherQA and TPS were as follows: the average difference in Dmean to the gross tumor volume (GTV) was (0.57±0.48)%, and the average difference in D90% was (0.65±0.56)%. For the target volume, the average γ passing rate was (97.67±3.43)% for GTV, (97.80±4.35)% for GTVnd-L, (97.82±4.07)% for GTVnd-R, (97.88±2.44)% for CTV1, and (96.64±4.32)% for CTV2. The mean dose difference of each target volume was CTV1 (0.57±0.46)%, GTVnd-L (0.85±0.55)%, GTVnd-R (0.73±0.55)%, and CTV2 (0.88±0.52)%. For OARs, the mean γ passing rate was (99.93±0.22)% for the brainstem, (99.17±2.82)% for the optic chiasm, (100±0)% for the lens, (99.56±1.05)% for the spinal cord, (99.00±2.06)% for the thyroid, and (87.86±10.42)% for the trachea. Statistically significant differences in the average doses to OARs were observed ( t=-14.62 to 4.82, P<0.05), except for those to the left optic nerve, the right hippocampus, and the right parotid gland. Conclusions:Based on the high-performance GPU platform and the Monte Carlo dose algorithm, ArcherQA can provide accurate 3D dose distribution and 3D γ passing rates inside patients according to CT images and provide the dose volume histogram (DVH) of various regions of interest (ROIs). Therefore, the ArcherQA three-dimensional dose verification system can be applied to IMRT plans for NPC. Moreover, it is inducive to improve the treatment efficiency since it does not occupy the accelerator operation time.

Objective:To investigate the feasibilityof the adaptive radiotherapy using high-field MR-Linac systems for head neck cancers and perform the evaluation of target coverage and dose criteria.Methods:This study investigated 128 treatment plans of six patients who were treated on 1.5T MR-Linacsystems in Sun Yat-sen University Cancer Center in 2019, compared the differences in target coverage and dose criteria between the dose accumulation in the adaptive radiotherapy using MR-Linac systems and the reference plans, and evaluated the target coverage and dose criteria of each fraction of adaptive plan based on daily MRI anatomy.Results:There was no significant change in the target coverage and dose criteria for each treatment fraction(<1%). However, the change of lens dose was significant (maximum 98%). In addition, the result showed that there was no significant difference in target coverage and dose criteria between the dose accumulation in adaptive radiotherapy using MR-Linac systems and reference plans.In contrast, the average dose to lens was increased by 31.7%.Conclusions:It is feasible to perform adaptive radiotherapy using 1.5T MR-Linacsystems for head neck cancers according tothe evaluation of target coverage and dose criteria. Additionally, since the actual dose tolens was quite different from the reference plan, the lens exposure should be considered in clinical practice.

Objective:To investigate the impacts of electron streaming effect (ESE) on out-of-field dose distribution in 1.5 T MRI-guided radiotherapy.Methods:Firstly, the Monaco v5.40.1 (Elekta AB, Stockholm, Sweden) treatment planning system (TPS) was implemented to investigate the ESE in a square field (5 cm × 5 cm) at the entry and exit sides of a special homogeneous water phantom. Afterward, a retrospective investigation was conducted into one laryngeal cancer case and one breast cancer case who had been treated on a conventional linear particle accelerator (linac). Then doses were recalculated in the Monaco system using a Unity machine model. Meanwhile, the out-of-field skin dose enhancement induced by ESE was investigated.Results:ESE-induced dose variations were observed at both the entry and exit sides of the phantom surface in the presence of a magnetic field, with the ESE on the exit side notably stronger than that on the entry side. For the laryngeal cancer case, the ESE was not notable and had insignificant impacts on the out-of-field skin dose. In contrast, ESE-induced in-air high-dose region outside the body stretched to the chin area for the breast cancer case. This led to the skin dose escalation of the chin at D1 cm 3 454.6 cGy. After the application of 1 cm bolus, the corresponding skin dose of the chin D1 cm 3 reduced to as low as 113.6 cGy, which is almost equivalent to that in the absence of a magnetic field ( D1 cm 3=92.5 cGy). Conclusions:The ESE in a magnetic field can alter out-of-field dose and lead to local dose enhancement along the electron path. Although the ESE had insignificant impacts on the out-of-field dose of the laryngeal cancer case, it reached the chin area of the breast cancer case. ESE can be effectively shielded by adding protective bolus.

Objective:To analyze characteristics and trends of histopathological diagnosis of adult renal biopsy in Beijing from 2008 to 2020.Methods:A total of 4 652 cases of adult renal biopsy were collected from three hospitals in Beijing between 2008 and 2020. The patients were divided into three age groups: 18-40 years, 40-65 years and≥ 65 years; and also divided into three period: 2008-2011, 2012-2015, and 2016-2020. The pathological characteristics and changes of renal biopsy were analyzed in three age groups at different periods.Results:Among 4 652 cases primary glomerular disease accounted for 81.8%, the membranous nephropathy (MN, 32.4%, 1 509/4 652), IgA nephropathy (IgAN, 29.2%, 1 356/4 652) and minor glomerular abnormalities (MGA, 11.3%, 526/4 652) were the top three pathological types. The overall proportion of MN and diabetic nephropathy (DN) increased from 20.3% and 2.3% in 2008-2011 to 37.3% and 10.1% in 2016-2020) (χ2=99.9 and 96.1, both P<0.01), respectively. For age group 18-40 years, the MN and DN increased from 11.2% and 1.6% in 2008-2011 to 24.7% and 5.5% in 2016-2020 (χ2=32.7 and 20.7, both P<0.01), respectively. For age group 40-65 years the MN and DN increased from 26.6% and 3.2% in 2008-2011 to 41.5% and 13.1% in 2016-2020 (χ2=39.1 and 57.3, both P<0.01), respectively. For age group≥65 years the MN was the most common pathological type in the three periods, fluctuating between 41.3% and 55.0% (χ2=5.2, P=0.08); and DN increased from 0(0/63) in 2008-2011 to 7.5%(22/292) in 2016-2020 (χ2=8.1, P=0.02). Conclusion:The renal biopsy data show that membranous nephropathy and diabetic nephropathy are the most common primary and secondary adult glomerular diseases in Beijing recently.

Objective:To characterize the imaging distortion of the 1.5T magnetic resonance imaging-guided linear accelerator (MR-Linac) and to analyze the influence of MR-Linac and peripheral devices on the geometric distortion.Methods:Specialized MRI imaging distortion phantom and analysis software were applied. The baseline of imaging distortion within diameter spherical volume (DSV) around the center of the magnet was established. The influence of the beam generation system, mechanical system and peripheral devices on the imaging distortion was analyzed. The long-term stability of imaging distortion was tested on the MR-Linac.Results:Imaging distortion of the MR-Linac was increased with the increasing distance to the center of the magnet. Within DSV 400 mm, few test points surpassed 1 mm imaging distortion in 3D directions. However, imaging distortion surpassed 2 mm in part of region within DSV 400-500 mm, with the largest distortion over 7 mm. Imaging distortion of the MR-Linac remained unchanged within 7 months after installation. And the influence of the MR-Linac and peripheral devices on the imaging distortion was only observed in the overall largest distortion within DSV 400-500 mm.Conclusions:Cautions should be taken during the application of high-field MR-Linac in patients whose tumor location is over 20 cm from the ISO center. Imaging distortion of the MR-Linac remains stable within 7 months after installation. The influence of the MR-Linac and peripheral devices on the imaging distortion is trivial, which can be neglected in clinical practice.

Objective To explore the efficacy and adverse effects of nimotuzumab combined with chemotherapy and radiotherapy in the treatment of locally advanced cervical cancer.Methods Sixty patients with stage Ⅲ cervical cancer by the histopathologic diagnosis were collected,and they were randomly divided into two groups using the random number table method.The control group (n =30)using intensity-modulated radiotherapy,intracavitary afterloading therapy and periodic chemotherapy,the observation group (n =30)in addition to the intensity-modulated radiotherapy,intracavitary afterloading therapy and periodic chemotherapy, the nimotuzumab (200 mg)was given to the patients before weekly radiotherapy.All patients were received 6 to 7 times of treatment.Results The curative effects of all the patients were evaluated after radiotherapy 3 months.In the observation group,there were 20 cases of CR,5 cases of PR,4 cases of SD,1 case of PD,the total effective rate (CR +PR)was 83.3%.In the control group,there were 1 8 cases of CR,3 cases of PR,6 cases of SD,3 cases of PD,the total effective rate was 70.0%.The difference was statistically significant (χ2 =8.356,P <0.05).The main adverse reactions in the observation group and control group included slight radioactive proctitis (1 6.7% vs 1 3.3%),radioactive cystitis (1 0.0% vs 1 0.0%),nausea and vomiting (50.0% vs 46.7%),reduction of white blood cells (40.0% vs 43.3%),with no significant differences (χ2 =3.357,P =0.71 9;χ2 =2.71 7,P =0.925;χ2 =5.882,P =0.623;χ2 =4.728,P =0.687).There were no skin rashes and allergic reactions.Conclusion Nimotuzumab can enhance the locally stage cervical cancer patients′sensitivity on radiotherapy,which can increase the efficacy and doesn′t increase adverse
reaction obviously.