ObjectiveTo construct and evaluate a mouse model that simulates the pathological progression of immune checkpoint inhibitor-associated pneumonitis (CIP), in order to address the critical issue of the lack of standardized animal models in this research field. MethodsThirty-five SPF-grade 6-week-old male C57BL/6J mice were randomly assigned to a control group (n=5), a bleomycin (BLM) group (n=15), and a BLM+programmed death-1 (PD-1) monoclonal antibody (BLM+PD-1) group (n=15). Corresponding drugs were administered via intraperitoneal injection for intervention. The general condition, body weight changes, survival rate, and pulmonary histopathological alterations were systematically monitored. ResultsCompared with the BLM group, the BLM+PD-1 group exhibited significantly more severe pulmonary fibrosis, characterized by progressive body weight loss and more severe deterioration of general conditions. Histopathological examination showed that pulmonary inflammation was alleviated 4 weeks post-modeling in the BLM group. In contrast, pulmonary lesions continued to worsen in the BLM+PD-1 group, with no evidence of resolution of inflammation 28 days post-modeling. Quantitative immunohistochemical analysis revealed that the positive expression rate of interleukin-17A (IL-17A) in lung tissues reached 34.28% in the BLM+PD-1 group 14 days post-modeling, which was markedly higher than that in the BLM group (24.02%, P < 0.000 1). The positive expression rate of α-smooth muscle actin (α-SMA) was 12.40% in the BLM+PD-1 group 14 days post-modeling, nearly twice the level in the BLM group (5.87%). 28 days post-modeling, the positive expression rate of α-SMA remained at 7.72% in the BLM+PD-1 group, while it declined to 3.38% in the BLM group. ConclusionThe addition of a PD-1 inhibitor to bleomycin treatment accelerates the progression of pulmonary interstitial fibrosis and effectively recapitulates the pathological process of lung injury and fibrosis driven by aberrant immune activation during clinical immunotherapy. Accordingly, this study successfully establishes a dynamic CIP animal model recapitulating the progression from early inflammatory response to pulmonary fibrosis. This model addresses the critical shortage of animal models for this condition and offers an experimental platform for further mechanistic studies and the development of therapeutic strategies.

Objective To investigate the changes of brain networks function in patients with primary dysmenorrhea(PDM)during menstruation based on topological attributes of brain network.Methods Brain resting-state functional MRI of 57 PDM patients(PDM group)and 50 healthy women(health control[HC]group)were prospectively collected within the first or the second day of menstruation.Clinical scores were obtained and compared between groups.Results Visual analogue scale,cox menstrual symptom scale,self-rating anxiety scale and self-rating depression scale scores in PDM group were all higher than those in HC group(all P＜0.05).At the sparsity of 0.04-0.50,brain networks in both groups conformed to the small world attribute characteristics,and no significant difference of global attributes of brain network was found between groups(all P＞0.05).The node efficiency(Ne)and node degree(Dc)of bilateral posterior cingulate gyrus(PCG),as well as De and node betweenness(Bc)of left middle frontal gyrus(MFG)in PDM group were all higher than those in HC group,while Ne and De of left inferior temporal gyrus in PDM group were lower than those in HC group(all P＜0.01).Compared with HC group,the functional connections between left PCG and right calcarine fissure and surrounding cortex,right lingual gyrus and left MFG,as well as between right PCG and right dorsolateral superior frontal gyrus and left MFG,between right insula and left middle occipital gyrus enhanced in PDM group(all P＜0.001).Conclusion In PDM patients,local brain networks function such as default mode network,central executive network and salience network were over-activated during menstruation,yet the overall brain network still had good coordination and organization.

Objective:The purpose of this study is to test and assess the model of modeling data of TaiChi accelerator in the Raystation Treatment Planning System(RayStation system)according to the test method and item of TG119 report of American Association Physicians Medicine(AAPM).Methods:The intensity-modulated radiation therapy(IMRT)and volumetric-modulated arc therapy(VMAT)plans of the test cases of different clinical situations,which included the simulated multi target region,prostate target region,head and neck target region,easy type C-shape target region plan and difficult type C-shape target region plan,were designed according to the AAPM TG119 report in the treatment planning system.The deviations of the doses of point and area of the two kinds of plans were measured,and the measured results were compared and analyzed with the recommended standards of AAPM TG119 report.The IBA CC13 ionization chamber and the ArcCHECK matrix ionization chamber were used respectively to verify the point dose and area dose,and the assessment standard was γ passing rate under 3%3mm.The confidence interval was adopted to judge the consistency between the measured dose and the calculated dose.Results:The accuracies of plan dose target,point dose deviation and area dose distribution of tested cases could meet the requirement of the TGl19 report.The deviations of mean doses for the high-dose points of IMRT plan and VMAT plan of tested cases were respectively(0.39±1.02)%and(1.27±0.64)%,and the confidence intervals of them were respectively 2.39%and 2.52%.The average dose deviations of low doses of organ at risk(OAR)of IMRT plan and VMAT plan were respectively(0.53±1.73)%and(0.88±1.11)%,and the confidence intervals were respectively 3.92%and 3.06%.The average γ passing rate under 3%/3mm of IMRT plan and VMAT plan were respectively(99.52±0.366)%and(99.86±0.136)%,and the confidence intervals of them were respectively 1.196%and 0.406%.Conclusion:The TaiChi accelerator performance and the accuracy of Raystation system 6MV FFF model fitting can meet the standard of TG119 report,and the subsequent standards of the quality control of equipment and patients were established according to these tested results,which would provide reference for the improvement of the performance of subsequent accelerator.

Objective:To analyze the effect of sacroiliac joint reduction on the treatment of Tile type C pelvic fractures in children.Methods:A retrospective study was performed to analyze the 28 children [17 males and 11 females with an age of (10.2±3.1) years] with Tile type C pelvic fracture who had been admitted to Department of Orthopaedics, Children's Hospital of Nanjing Medical University from March 2017 to January 2022. The children were divided into a group of 16 cases subjected to non-reduction of the sacroiliac joint (NRSJ) and a group of 12 cases subjected to reduction of the sacroiliac joint (RSJ). The 2 groups were compared in terms of preoperative general data, surgical time, intraoperative bleeding, pelvic diagonal line before and 1 week after surgery, and Cole score for pelvic fracture efficacy at the last follow-up.Results:There was no statistically significant difference in the preoperative general data or in the preoperative pelvic diagonal between the 2 groups, indicating comparability ( P>0.05). The surgical time in group NRSJ [(77.0±12.9) min] was significantly shorter than that in group RSJ [(104.7±24.3) min], the intraoperative bleeding in group NRSJ [(32.8±7.6) mL] significantly less than that in group RSJ [(65.7±13.4) mL], and the pelvic diagonal line [(27.7±5.3) mm] in group NRSJ significantly longer than that in group RSJ [(4.0±1.2) mm] ( P<0.05). The follow-up time was (18.9±3.0) months for group NRSJ and (17.0±2.2) months for group RSJ, showing no statistically significant difference ( P>0.05). The Cole scoring at the last follow-up yielded 2 excellent, 3 good, 5 fair, and 6 poor cases in group NRSJ, significantly worse than those in group RSJ (9 excellent, 2 good, 1 fair, and 0 poor cases) ( P<0.05). Conclusions:Surgical reduction of the sacroiliac joint in children with Tile C pelvic fracture is very important. Compared with non-reduction of the sacroiliac joint, the surgical reduction incurs longer surgical time and more intraoperative bleeding, but leads to higher quality of pelvic reduction, which can further correct the deformity of the pelvic ring and improve the Cole score for pelvic fracture efficacy.

Objective:To evaluate the robustness of fully automated adaptive planning for Ethos online adaptive radiotherapy (ART) based on the intelligent optimization engine (IOE).Methods:Clinical data of 11 stage ⅠB cervical cancer patients admitted to Peking Union Medical College Hospital between June 2021 and June 2022 were retrospectively analyzed. Original planning images and iterative cone-beam computed tomography (iCBCT) images of each radiotherapy treatment were acquired, and all patient data were imported into the Ethos simulator. IOE-based 9-field automatic plan generation was performed for 11 patients using Ethos, and the generated plans were sent to online adaptive radiotherapy simulation to obtain each online adaptive radiotherapy plan (273 fractions in total) and complete the simulated treatment. For comparison, manual plan design was performed based on the images and contoured structures used for online adaptive radiotherapy planning, and the manually plans created with evenly divided 9 fields. Dosimetric parameters, plan complexity parameters, and Mobius quality assurance (QA) pass rates were collected to compare and evaluate the robustness of the online adaptive radiotherapy plan in terms of organs at risk (OAR), target volume dosimetric parameters, and plan complexity by using paired t-test or rank sum test. Results:The online adaptive plan of cervical cancer had comparable planning target volume (PTV) coverage compared to the manual plan. For the clinical target volume (CTV) D 99%, online adaptive plan was significantly higher than the manual plan [(45.93±0.36) vs. (45.32±0.31) Gy, P<0.001]. For hot dose area, the maximum point dose (PTV D max) of adaptive plan was significantly higher than the manual plan [(49.89±1.25) vs. (48.48±0.77) Gy, P<0.001], but the PTV D 1% of adaptive plan was significantly lower than the manual plan [(47.22±0.29) vs. (47.59±0.48) Gy, P<0.001]. There was no statistical difference in the conformal index ( P=0.967). And there was significant difference in the homogeneity index, with same medians and less dispersion in adaptive plan ( P<0.001). For OAR dose, bladder D mean, rectal V 40 Gy, small intestine D mean of adaptive plan was slightly higher than that of the manual plan; the rectal D mean, small intestine D 2 cm3 of the adaptive plan was slightly lower than that of manual plan; dosimetric parameters of right and left femoral heads, spinal cord and bone marrow of the adaptive plan were better than those of manual plan. The adaptive plan had more monitor units (MU) than the manual plan, but the complexity of the adaptive plan was significantly lower than that of the manual plan (0.135±0.012 vs. 0.151±0.015, P<0.001). For Mobius γ pass rate (5%/3 mm), both adaptive and manual plans met clinical requirements. Conclusion:Ethos cervical cancer online adaptive plan, which is based on the IOE engine, demonstrates good robustness and ensures the quality of online adaptive plans generated for each treatment fraction.

Objective:To evaluate the automatic optimization performance and clinical feasibility of the intelligent optimization engine (IOE) in the Ethos online adaptive radiotherapy platform.Methods:Clinical data of 11 patients with postoperative cervical cancer treated with Halcyon accelerator were retrospectively analyzed. Manual planning was performed for all patients using the 4 full arc volumetric modulated arc therapy (VMAT) (Manual-4Arc) in Eclipse, with a prescription dose of 45 Gy/25F. Patient images and structures were imported into the Ethos simulator, and appropriate clinical goals were added based on clinical requirements. The target coverage was normalized to 95%. Automatic plan generation was conducted using IOE, resulting in 7, 9, and 12 field intensity modulated radiotherapy (IMRT) plans (IMRT-7F、IMRT-9F、IMRT-12F), as well as 2 and 3 arc VMAT plans (VMAT-2Arc、VMAT-3Arc). Dosimetric index comparisons were made between the Manual-4Arc plans and the 5 groups of IOE-generated plans through one-way analysis of variance. Based on the analysis results, Turky post hoc multiple comparisons were performed to evaluate the automatic optimization performance of IOE.Results:In terms of the high dose area, the IMRT-12F plans showed the lowest D 1% for the planning target volume (PTV), and there were significant differences compared to the Manual-4Arc plans ( P=0.004). Regarding target coverage, all groups produced clinical target volume (CTV) plans that met the clinical requirements. Although the Ethos online adaptive plans were normalized during planning, the PTV coverage was slightly insufficient. For organs at risk (OAR) close to the target, such as the bladder, there were significant differences in V 30 Gy, V 40 Gy, and D mean among the 6 groups of plans. The dose ranking for the bladder was generally as follows: IMRT-12F

Objective:To analyze the clinical efficacy of the distal radius dome osteotomy combined with Vickers ligament release (DRO+ VR) in the treatment of Madelung′s deformity.Methods:A retrospective case series analysis.The clinical data of 15 children with Madelung′s deformity treated in the Children′s Hospital of Nanjing Medical University from January 2012 to August 2023 were collected, and the children were divided into the DRO+ VR group and the other operation group according to the surgical method.The follow-up time was recorded, and the ulnar tilt (UT), lunate subsidence (LS), palmar carpal displacement (PCD), lunate fossa angle (LFA), wrist flexion (WF), wrist extension (WE), and visual analogue scale (VAS) were measured before surgery and at the last follow-up.The independent samples t-test was used for measurement data comparison, and the Fisher′s exact test was used for categorical variable comparison. Results:The follow-up time was 10-96 months, with the time of (27.17±15.51) months in the DRO+ VR group and (48.00±24.06) months in the other operation group.There was no significant difference in preoperative general data, imaging indexes and functional evaluation between the 2 groups (all P>0.05).The comparison of imaging indexes and functional evaluation of children in the DRO+ VR group before surgery and at the last follow-up showed that the differences in UT [(49.00±3.10) ° vs.(31.83±2.40) °], LFA [(34.50±3.78) ° vs.(49.83±4.02) °], LS [(7.29±3.61) mm vs.(2.29±1.48) mm], PCD [(12.06±3.39) mm vs.(4.35±2.37) mm], WF [(61.17±1.47) ° vs.(67.50±3.33) °], WE [(48.67±1.86) ° vs.(60.50±4.42) °], and VAS [(7.33±1.03) points vs.(2.67±0.52) points] were statistically significant (all P<0.05).At the last follow-up, the results of imaging indexes and functional evaluation of the 2 groups showed that the improvement of UT was (17.17±2.32) ° in the DRO+ VR group and (51.78±7.66) ° in the other operation group, which had statistically difference ( t=-2.241, P=0.043). Conclusions:DRO+ VR is an effective approach for treating Madelung′s deformity in children.It can significantly improve children′s imaging indexes and wrist joint function and alleviate pain symptoms.Surgical intervention should be actively considered for patients with severe deformity and pain symptoms related to Madelung′s deformity.

Objective:Hypoxia is a common pathological phenomenon,usually caused by insufficient oxygen supply or inability to use oxygen effectively.Hydroxylated and methoxylated flavonoids have significant anti-hypoxia activity.This study aims to explore the synthesis,antioxidant and anti-hypoxia activities of 6-hydroxygenistein(6-OHG)and its methoxylated derivatives. Methods:The 6-OHG and its methoxylated derivatives,including 4',6,7-trimethoxy-5-hydroxyisoflavone(compound 3),4',5,6,7-tetramethoxyisoflavone(compound 4),4',6-imethoxy-5,7-dihydroxyisoflavone(compound 6),and 4'-methoxy-5,6,7-trihydroxyisoflavone(compound 7),were synthesized by methylation,bromination,methoxylation,and demethylation using biochanin A as raw material.The structure of these products were characterized by 1hydrogen-nuclear magnetic resonance spectroscopy(1H-NMR)and mass spectrometry(MS).The purity of these compounds was detected by high pressure chromatography(HPLC).The antioxidant activity in vitro was investigated by 1,1-diphenyl-2-picrylhydrazyl radical(DPPH)free radical scavenging assay.PC12 cells were divided into a normal group,a hypoxia model group,rutin(1×10-9-1×10-5 mol/L)groups,and target compounds(1×10-9-1×10-5 mol/L)groups under normal and hypoxic conditions.Cell viability was detected by cell counting kit-8(CCK-8)assay,the target compounds with excellent anti-hypoxia activity and the drug concentration at the maximum anti-hypoxia activity were screened.PC12 cells were treated with the optimal concentration of the target compound or rutin with excellent anti-hypoxia activity,and the cell morphology was observed under light microscope.The apoptotic rate was determined by flow cytometry,and the expressions of hypoxia inducible factor-1α(HIF-1α)and vascular endothelial growth factor(VEGF)were detected by Western blotting. Results:The structure of 6-OHG and its 4 methylated derivatives were correct,and the purity was all more than 97%.When the concentration was 4 mmol/L,the DPPH free radical removal rates of chemical compounds 7 and 6-OHG were 81.16%and 86.94%,respectively,which were higher than those of rutin,the positive control.The removal rates of chemical compounds 3,4,and 6 were all lower than 20%.Compared with the normal group,the cell viability of the hypoxia model group was significantly decreased(P<0.01).Compared with the hypoxia model group,compounds 3,4,and 6 had no significant effect on cell viability under hypoxic conditions.At all experimental concentrations,the cell viability of the 6-OHG group was significantly higher than that of the hypoxia model group(all P<0.05).The cell viability of compound 7 group at 1×10-7 and 1×10-6 mol/L was significantly higher than that of the hypoxia model group(both P<0.05).The anti-hypoxia activity of 6-OHG and compound 7 was excellent,and the optimal drug concentration was 1×10-6 and 1×10-7 mol/L.After PC12 cells was treated with 6-OHG(1×10-6 mol/L)and compound 7(1×10-7 mol/L),the cell damage was reduced,the apoptotic rate was significantly decreased(P<0.01),and the protein expression levels of HIF-1α and VEGF were significantly decreased in comparison with the hypoxia model group(both P<0.01). Conclusion:The optimized synthesis route can increase the yield of 6-OHG and obtain 4 derivatives by methylation and selective demethylation.6-OHG and compound 7 have excellent antioxidant and anti-hypoxia activities,which are related to the structure of the A-ring ortho-triphenol hydroxyl group in the molecule.

Objective:To analyze the differences in dosimetric quality and plan complexity of volumetric modulated arc therapy (VMAT) plans based on Halcyon 2.0 and Truebeam for different treatment sites of the patients.Methods:Halcyon 2.0 VMAT plans in head & neck, chest, abdomen, and pelvis treatment sites of 49 cases were retrospectively selected and the VMAT plans were re-designed based on Truebeam with the same optimization parameters. The differences in dosimetric metrics and plan complexity between the two types of plans were compared and analyzed. P<0.05 was considered as statistically significant. Results:In terms of PTV, Halcyon 2.0 plans showed better homogeneity index (HI), conformal index (CI) in the head & neck and chest. Besides, Halcyon 2.0 plans yielded better D 98% and CI in the abdomen and better D 2% in the pelvis. For organs at risk (OAR), the D 20% and D mean of bilateral lungs, and D meanof heart for Halcyon 2.0 plans in the chest were lower than those for Truebeam plans (all P<0.05). For the complexity metrics, the median average aperture area variability (AAV) of Halcyon 2.0 plans in the head & neck, abdomen and pelvis were 0.414, 0.425 and 0.432, which were better than 0.385, 0.368 and 0.361 of Truebeam plans in the corresponding sites, respectively. In the abdomen and pelvis, Halcyon 2.0 plans showed better median modulation complexity score (MCS) than Truebeam plans (0.320 vs. 0.268, 0.303 vs. 0.282; both P<0.05). The median small aperture score (SAS) for all plans of Halcyon 2.0 were better than that of Truebeam plans (all P<0.05), and the median plan average beam area (PA) of all plans of Halcyon 2.0 were larger than that of Truebeam plans (all P<0.05). Conclusions:Compared with conventional fractionated VMAT plans based on Halcyon 2.0 and Truebeam, Halcyon 2.0 plans have similar or even better dosimetric quality. However, Halcyon 2.0 plans have lower plan complexity, which makes it an advantage in clinical application.

Objective:To evaluate the clinical application of online adaptive radiotherapy based on iterative cone-beam computed tomography (iCBCT) for the pelvic malignancies.Methods:This was a prospective clinical trial of iCBCT guided online adaptive radiotherapy for pelvic malignancies in Department of Radiation Oncology, Peking Union Medical College Hospital. Clinical data of 13 patients with pelvic malignancies who received online adaptive radiotherapy from August to November, 2022 were preliminarily analyzed (2 cases of cervical cancer, 4 postoperative cervical cancer, 3 postoperative endometrial cancer, 3 bladder cancer and 1 prostate cancer). The feasibility of online adaptive radiotherapy, adaptive radiotherapy time, the frequency and magnitude of edits for organs at risk and target volume, target volume coverage and organs at risk doses were analyzed. Statistical analysis was performed by SPSS software. Data conforming to normal distribution were described by Mean±SD, and data with non-normal distribution were expressed by M ( Q1, Q3). Data with homogeneous variances were analyzed by t-test, and data with non-normal distribution or heterogeneous variances were analyzed by nonparametric test. Results:The average adaptive time was 15 min and 38 s (from acceptance of acquired CBCT scan to completion of the final plan selection). 85.4% (830/972 fractions) of influencer structures (system-defined organs adjacent to and with high impact on the generation of clinical target volume and planning target volume, primarily bladder, rectum and small intestine in pelvic neoplasms) automatically generated by artificial intelligence required no edits or minor editors, and 89.8% (491/547 fractions) of clinical target volume automatically generated by artificial intelligence required no edits or minor editors. The adapted plan was adopted in 98.5% (319/324 fractions) of radiotherapy fractions. Compared with the scheduled plan, the adapted plan showed better target volume coverage and reduced the dose of organs at risk.Conclusions:iCBCT guided online adaptive radiotherapy for the pelvic malignancies can be achieved within clinically acceptable timeslots. In addtion, better dose coverage of target volume shows the advantages of online adaptive radiotherapy.