Objective:To compare the dosimetric differences between a 3D-printed non-coplanar multi-channel applicator and traditional single-channel/co-planar multi-channel applicators in postoperative vaginal brachytherapy for early-stage endometrial cancer.Methods:CT scan data of 66 patients with stage I endometrial cancer, encompassing 100 3D brachytherapy CT imaging datasets, admitted to Department of Gynecologic Oncology of the Fourth Hospital of Hebei Medical University from December 2021 to June 2024 were retrospectively analyzed. Based on CT images and delineated structures, offline reconstructions of radiotherapy plans were performed for single-channel, coplanar multi-channel, and 3D-printed non-coplanar multi-channel applicators. These 3 radiotherapy plans were optimized, and the high-risk clinical target volume (HR-CTV) coverage (V 100 ≥90%) and doses to organs at risk (rectum, bladder) were compared. The prescription dose was standardized at 600 cGy, with constraints of rectal D 2 cm3 ≤420 cGy and bladder D 2 cm3 ≤480 cGy. Comparison among multiple groups was conducted by ANOVA. Bonferroni method was used to correct P-values for comparison between two groups. Results:When defined as HR-CTV D 90%≥600 cGy, bladder D 2 cm3 was (398.29±76.13)cGy and rectum D 2 cm3 was (402.10±49.77)cGy of the 3D-printed non-coplanar multi-channel group,which were significantly lower than those in the single-channel group [bladder D 2 cm3 (424.09±131.52) cGy, rectum D 2 cm3 (493.11±115.17) cGy] and coplanar group [bladder D 2 cm3 (461.28±134.84) cGy, rectum D 2 cm3 (508.75±119.02) cGy], respectively. When limiting bladder D 2 cm3≤480 cGy, rectal D 2 cm3 was (446.81±78.53 cGy) of the 3D-printed non-coplanar multi-channel group, which was significantly lower than those in the single-channel group [(589.71±153.91) cGy] and the coplanar group [(545.51±122.00) cGy], respectively. Meanwhile, HR-CTV V 100% (94.53%±3.42%) was higher than (91.19%±7.63%) in the coplanar group. When the rectal D 2 cm3 was ≤ 420 cGy, HR-CTV V 100% was (91.92%±4.04%) of the 3D-printed non-coplanar multi-channel group,which was significantly better than (79.23%±13.95%) in the single-channel group and (85.88%±6.86%) in the coplanar group, respectively. Conclusions:The 3D-printed non-coplanar multi-channel applicator significantly reduces bladder and rectal doses while enhancing target coverage, outperforming traditional single-channel and co-planar multi-channel applicators. This innovation provides an optimized solution for individualized precision radiotherapy.

Objective:To compare the dosimetric differences between a 3D-printed non-coplanar multi-channel applicator and traditional single-channel/co-planar multi-channel applicators in postoperative vaginal brachytherapy for early-stage endometrial cancer.Methods:CT scan data of 66 patients with stage I endometrial cancer, encompassing 100 3D brachytherapy CT imaging datasets, admitted to Department of Gynecologic Oncology of the Fourth Hospital of Hebei Medical University from December 2021 to June 2024 were retrospectively analyzed. Based on CT images and delineated structures, offline reconstructions of radiotherapy plans were performed for single-channel, coplanar multi-channel, and 3D-printed non-coplanar multi-channel applicators. These 3 radiotherapy plans were optimized, and the high-risk clinical target volume (HR-CTV) coverage (V 100 ≥90%) and doses to organs at risk (rectum, bladder) were compared. The prescription dose was standardized at 600 cGy, with constraints of rectal D 2 cm3 ≤420 cGy and bladder D 2 cm3 ≤480 cGy. Comparison among multiple groups was conducted by ANOVA. Bonferroni method was used to correct P-values for comparison between two groups. Results:When defined as HR-CTV D 90%≥600 cGy, bladder D 2 cm3 was (398.29±76.13)cGy and rectum D 2 cm3 was (402.10±49.77)cGy of the 3D-printed non-coplanar multi-channel group,which were significantly lower than those in the single-channel group [bladder D 2 cm3 (424.09±131.52) cGy, rectum D 2 cm3 (493.11±115.17) cGy] and coplanar group [bladder D 2 cm3 (461.28±134.84) cGy, rectum D 2 cm3 (508.75±119.02) cGy], respectively. When limiting bladder D 2 cm3≤480 cGy, rectal D 2 cm3 was (446.81±78.53 cGy) of the 3D-printed non-coplanar multi-channel group, which was significantly lower than those in the single-channel group [(589.71±153.91) cGy] and the coplanar group [(545.51±122.00) cGy], respectively. Meanwhile, HR-CTV V 100% (94.53%±3.42%) was higher than (91.19%±7.63%) in the coplanar group. When the rectal D 2 cm3 was ≤ 420 cGy, HR-CTV V 100% was (91.92%±4.04%) of the 3D-printed non-coplanar multi-channel group,which was significantly better than (79.23%±13.95%) in the single-channel group and (85.88%±6.86%) in the coplanar group, respectively. Conclusions:The 3D-printed non-coplanar multi-channel applicator significantly reduces bladder and rectal doses while enhancing target coverage, outperforming traditional single-channel and co-planar multi-channel applicators. This innovation provides an optimized solution for individualized precision radiotherapy.

Objective To identify lipid metabolism genes in cerebral infarction;To explore the intervention effect of Huoxue Rongluo Prescription.Methods Multi-chip combined differential analysis(GSE61616,GSE30655)was used to identify lipid metabolism genes in cerebral infarction in combination with Reactome database,and the expression differences of lipid metabolism genes in cerebral infarction were identified and verified in GSE97537 chip;Pearson correlation analysis was used to analyze the correlation of 51 cerebral infarction samples in GSE61616,GSE30655,GSE97537,GSE137595,GSE22255,GSE163614,and GSE78731 datasets;PPI,GO and KEGG analysis of lipid metabolism genes in cerebral infarction were performed through STRING database and R clusterProfiler package.SD rats were made to the model of cerebral infarction,and was administered with Huoxue Rongluo Prescription extract 11.7 g/kg by intragastric administration for 7 days.The symptoms of neurological deficit,the changes of Nissl bodies and the mRNA expressions of PLA2G4A,SPHK1,and PTGES key genes in lipid metabolism in cerebral infarction were observed.Results TSPO,CYP1B1,PLIN2,CH25H,PLA2G4A,ANGPTL4,PTGS1,SPHK1,and PTGES were identified as lipid metabolism genes in cerebral infarction,and were significantly highly expressed and positively correlated in cerebral infarction.Among them,PTGS1,PLA2G4A,and SPHK1 interacted with each other,which were the key genes of lipid metabolism in cerebral infarction;the lipid metabolism gene in cerebral infarction mainly exerted molecular functions such as oxidoreductase activity,iron ion binding,heme binding,etc.,mediating arachidonic acid metabolism,phospholipase D signaling pathway,VEGF signaling pathway,involved in regulation of lipid metabolism process,fatty acid metabolism process,fatty acid derivative metabolism process.The symptoms of neurological deficit in the model rats with cerebral infarction were severe(P<0.001),and Huoxue Rongluo Prescription could effectively improve the neurological deficit of model rats(P<0.001).The Nissl staining indicated that the neuronal structure was abnormal and the number was significantly reduced after cerebral infarction(P<0.001).Huoxue Rongluo Prescription could increase the number of neurons(P<0.001)and repair the neuronal structure.RT-qPCR showed that the key genes of lipid metabolism in cerebral infarction were significantly higher in cerebral infarction(P<0.001),corroborated with the bioinformatics results,and Huoxue Rongluo Prescription could reduce the expression of key lipid metabolism genes of PTGS1,PLA2G4A,and SPHK1(P<0.001,P<0.01,P<0.05).Conclusion Huoxue Rongluo Prescription can down-regulate the expressions of PTGS1,PLA2G4A,SPHK1,exert molecular functions such as oxidoreductase activity,iron ion binding,heme binding,and mediate arachidonic acid metabolism,phospholipase D signaling pathway,and VEGF signaling pathway.It participates in the process of lipid metabolism regulation,fatty acid metabolism,and fatty acid derivative metabolism,increases the number of Nissl bodies,improves the symptoms of neurological deficits,and exerts neuroprotective effects.

Objective To investigate the dynamic expression of telomere repeat binding factor 1 (TRF1) and telomeric repeat binding factor 2 (TRF2) in the development and progression of bronchopulmonary dysplasia (BPD) in neonatal rats and to clarify its role in BPD alveolar dysplasia.Methods The neonatal rat BPD model (n =40) was induced by using neonatal SD rats with inhaled oxygen concentration of 85％.The control group was prepared by inhaled air (n =40).In the two groups,10 rats were randomly selected from 1 day,3 days,7 days,and 14 days after the experiment.The lung tissue samples were collected,HE staining was performed to observe the pathological changes,and the alveolar development degree was evaluated by radial alveolar counting (RAC).Immunohistochemistry was used to observe the localization and expression of TRF1 and TRF2.Western Blot and real-time quantitative PCR (RT-PCR) were used to detect the expression levels of TRF1 and TRF2 proteins and genes in lung tissue.Results Immunohistochemical staining showed that TRF1 was mainly localized in the nucleus of alveolar epithelial cells and bronchial epithelial cells.TRF2 protein was found in the nucleus and cytoplasm of alveolar epithelial cells and bronchial epithelial cells.The expression was significantly higher than that of the control group.Compared with the control group,the TRF1 and TRF2 proteins increased significantly from 1d (TRF1 in control group:0.163 ±0.022,in model group:0.251 ±0.022;TRF2 in control group:0.156 ±0.012,in model group:0.240 ±0.018) to 14d (TRF1 in control group:0.193 ± 0.024,in model group:0.230 ± 0.025;TRF2 in control group:0.225 ± 0.017,in model group:0.350 ±0.012) rather than the control group (P ＜ 0.05).The mRNA expression levels of TRF1 and TRF2 increased continuously from 1d to 7d of hyperoxia exposure (TRF1 in control group:0.946 ± 0.028,in model group:1.590 ± 0.228;TRF2 in control group:0.834 ± 0.083,in model group:1.783 ±0.262) and decreased at 14d (TRF1 in control group:2.217 ± 0.225,in model group:1.259 ± 0.217,P＜0.05;TRF2 in control group:2.143 ±0.250,in model group:0.997 ±0.199,P ＜0.05).Conclusion In the developmental stage of BPD,TRF1 and TRF2 act as negative regulators of telomere length,and protein levels are up-regulated,which suggest that they be involved in the pathological process of BPD alveolar dysplasia.

Background and objective Lung cancer is a common malignant tumor all over the world, and Ca2+is a critical regulator for apoptosis of cancer cells. hTe monitoring of cytoplastic Ca2+level in real-time will contribute to further investigate the molecular mechanisms of apoptosis mediated by Ca2+in lung cancer cells. To evaluate the Ca2+indicator lfuo-3 and lfuo-4 in the process of H2O2 induced the apoptosis of lung adenocarcinoma A549 cells. hTe cytoplastic Ca2+concentration ([Ca2+]i) was determined in real-time, and the correlations between [Ca2+]i and cell apoptosis were investigated. hTe differences in lfuorescence intensity and measured value were compared between the two Ca2+indicators. Methods Cells were loaded with the Ca2+indicator lfuo-3 or lfuo-4 for 1 h, and then stimulated with 50 mM H2O2. Laser scanning confocal microscope was applied to perform real-time monitoring on the variation of [Ca2+]i in selected cells. DAPI staining was used to observe apop-tosis in H2O2 treated cells. Results Our results showed that the lfuorescence intensity of lfuo-4 was stronger than that of lfuo-3 in the same condition of dye concentration, loading time and image acquisition parameters before or atfer H2O2 stimulation. hTe cytoplastic [Ca2+]i was rapidly elevated in H2O2 stimulated A549 cells. hTe range of [Ca2+]i in selected cells loaded with lfuo-3 was 112.2 nM-1,069.6 nM, and that in selected cells loaded with lfuo-4 was 7.6 nM-505.4 nM. Moreover, the apoptotic rate was signiifcantly increased in H2O2 treated cells, compared with untreated ones (P<0.01). Conclusion In summary, H2O2 promoted Ca2+release in A549 cells, and induced cell apoptosis. Ca2+indicator lfuo-4 was probably more applicable to measure [Ca2+]i in cells with less content of Ca2+.