Glycolytic metabolism enzymes have been implicated in the immunometabolism field through changes in metabolic status. PGK1 is a catalytic enzyme in the glycolytic pathway. Here, we set up a high-throughput screen platform to identify PGK1 inhibitors. DC-PGKI is an ATP-competitive inhibitor of PGK1 with an affinity of K _d = 99.08 nmol/L. DC-PGKI stabilizes PGK1 in vitro and in vivo, and suppresses both glycolytic activity and the kinase function of PGK1. In addition, DC-PGKI unveils that PGK1 regulates production of IL-1β and IL-6 in LPS-stimulated macrophages. Mechanistically, inhibition of PGK1 with DC-PGKI results in NRF2 (nuclear factor-erythroid factor 2-related factor 2, NFE2L2) accumulation, then NRF2 translocates to the nucleus and binds to the proximity region of Il-1β and Il-6 genes, and inhibits LPS-induced expression of these genes. DC-PGKI ameliorates colitis in the dextran sulfate sodium (DSS)-induced colitis mouse model. These data support PGK1 as a regulator of macrophages and suggest potential utility of PGK1 inhibitors in the treatment of inflammatory bowel disease.

Objective To analyze the dosimetric and delivery efficiency differences between IMRT plans based on Halcyon and Trilogy Accelerator for left side breast cancer.Methods A total of 10 patients with left side breast cancer based on the Trilogy platform were retrospectively analyzed.For each patient,plan based on Halcyon was redesigned using Eclipse Version 15.1 TPS.In order to evaluate plan quality,dose coverage of target and dose to organs at risk,monitor unit efficiency,segment size and delivery time were compared.Results Halcyon treatment platform could meet the clinical objective.Dose distribution of the target volume had no significant difference with the Trilogy plans (P＞0.05).Volumes receiving 10 Gy,20 Gy and D of the left lung were significantly reduced(Z=-2.22--1.78,P＜0.05).V5 of heart for Halcyon and Trilogy was(27.80±7.66)％ and (23.18±8.19)％,respectively(Z=-0.71,P＜0.05),while D was (7.03± 1.8)Gy and(7.11±2.40)Gy,respectively(P＞0.05).Halcyon increased the monitor unit from 1 526.2±227.7 by Trilogy to 1 770.5±383.9(Z=-0.71,P＜0.05),but decreased the delivery time from (12.38± 1.49) min by Trilogy to (3.01 ±0.28) min (Z =-3.42,P＜ 0.05).Conclusion Halcyon treatment platform can meet the clinical requirements,reduce dose to normal tissue with high delivery efficiency.

Objective To evaluate the dynamic variation of the dose-volume parameters of the left ventricular myocardium following heart beat in radiotherapy for esophageal cancer. Methods The left ventricular myocardium of 22 patients was contoured on 20 phases (0％-95％) of electrocardiography (ECG) gated heart 4DCT images. The radiotherapy plan was designed on the simulation CT images,and then the dose distribution of radiotherapy plan was imported into MIM Maestro system and 4D dose-volume histogram (DVH) was reconstructed. The variations of position,volume and dice similarity coefficient (DSC) of the left ventricular myocardium were analyzed. The changing ranges of Dmean ,V10,V20 ,V30 and V40 of the left ventricular myocardium during different phases were statistically compared. Results ( 1 ) The biggest displacement of the left ventricular myocardium was in Y axes. The maximum variation rate of volume and DSC of the left ventricular myocardium were (24.23±11. 35)％ and (184.33±128. 61)％ in different phases with statistical significance (both P<0. 05).(2) The maximum variation rate of Dmean of the left ventricular myocardium was (87.05± 38. 34)％ in different phases with the highest rate of 163. 52％ with statistical significance (P<0. 05).(3) The maximum variation values of V10,V20,V30 and V40 of the left ventricular myocardium were (13.64±4. 33)％,(12.84±4. 55)％,(11.62±4. 85)％ and (3.63±2. 56)％ with statistical significance (all P<0. 05). Conclusions The impact of heart beat on the dose-volume parameters of the left ventricular myocardium should be considered during esophageal cancer radiotherapy. Traditional static 3DCT-based assessment of the dose-volume parameters of the left ventricular myocardium can yield relatively large errors, which is probably reduces the prediction efficiency of the dose-volume parameters for radiation-induced heart injury.

Objective: To investigate the potential dosimetric benefits of four-dimensional computed tomography (4DCT) compared to three-dimensional CT (3DCT) in the planning of radiotherapy for external-beam partial breast irradiation (EB-PBI). Methods: Three-DCT and 4DCT scan sets were acquired for 20 patients who underwent EB-PBI. For each patient a conventional 3D conformal plan (3D-CRT) was generated based on end-inhalation phase (EI). The treatment plan based on the 4DCT EI phase images was copied and applied to the end-exhalation phase (EE) and 3DCT images (defined as EB-PBI_EI, EB-PBI_EE, EB-PBI_3D, respectively). Results: The median volumes of the tumour bed based on 3DCT, EI and EE were 20.99 cm^3, 19.28 cm^3, and 18.78 cm^3, respectively. The tumour bed volume based on 3DCT was significantly greater than that of EI and EE volumes (P<0.05). The planning target volumes (PTV) coverage of EB-PBI_3D, EB-PBI_EI and EB-PBI_EE were 96.85%, 97.51%, 97.03%, respectively. The planning target volume (PTV) coverage of EB-PBI_3D was significantly less than that of EB-PBI_EI and EB-PBI_EE (P<0.05). The median homogeneity indexs (HI) based on 3DCT, EI and EE were 0.13, 0.13, 0.13, respectively. The median conformal indexs (CI) based on 3DCT, EI and EE were 0.68, 0.69, 0.68, respectively. The median mean doses (D_mean) based on 3DCT, EI and EE were 36.20 Gy, 36.20 Gy, 36.22 Gy, respectively. However there were no significant differences in the homogeneity index, conformity index and the mean dose of PTV between the three treatment plans (P>0.05). The EB-PBI_3D plan resulted in the largest organs at risk dose (P<0.05). Conclusion There was a significant benefit when using 4DCT to plan 3D-CRT for EB-PBI with regard to reduced non-target organ exposure, and might result in poor dose coverage when the PTV is determined using 3DCT.

Objective To evaluate the position deviation of multi-leaf collimator (MLC) in volumetric modulated arc therapy for nasopharyngeal carcinoma and to verify a method of detecting the leaf position accuracy.Methods Thirty-two volumetric modulated arc plans of nasopharyngeal carcinoma were randomly selected.A clockwise arc with a gantry range of 181° to 179° and a counterclockwise arc with a gantry range of 179° to 181° were uscd for each plan.Each arc contained two leaf groups,groups A and B.By using the Argus software,the actual MLC leaf positions were extracted from the Dynalog files in the Varian Trilogy accelerator.The planed MLC leaf positions were compared with the actual positions,and the differences were calculated between them.Results The proportions of the leaf position errors within ± 2,± 1.5,± 1 and ± 0.5 mm were 99.99％,99.90％,99.07％ and 93.98％,respectively.The proportions of the leaf position errors within ± 1 mm were 98.08％,100％,98.97％ and 99.01％ for the first therapeutic arc (ARC1),second therapeutic arc (ARC2),A and B groups,respectively.The leaf position errors range of ARC1 and ARC2 were-2.95 to 2.99 and-0.22 to 0.23 mm (t =2.35,P ＜ 0.01).The leaf position errors range of leaf bank A and leaf bank B were-2.95 to 2.68 and-2.92 to 2.99 mm(P ＞ 0.05).Conclusions During the volumetric modulated arc radiotherapy,the leaf positions deviation are in control.The Dynalog files can be used as an effective way to analysis the leafposition errors.

Objective To evaluate the dosimetric effects of target volume delineation with metal clip and seroma,alone or in combination,on external-beam partial breast irradiation (EB-PBI) based on four-dimensional computed tomography (4DCT).Methods Twenty female patients undergoing EB-PBI from 2009 to 2013 were enrolled as subjects.The gross tumor volumes (GTVs),GTVC,GTVS,and GTVC+S,were delineated on 4DCT images at 10 phases using metal clip,seroma,and both of them,respectively.The GTVS on 4DCT images at 10 phases were fused to generate the internal gross tumor volumes (IGTVS),IGTVC,IGTVS,and IGTVC+S.The planning target volumes (PTVS),PTVC,PTVS,and PTVC+S,were obtained via expansion of margin by 15 mm.The three-dimensional conformal radiotherapy plans were made by one physician based on PTVC,PTVS,and PTVC+S on end-inhalation images.The target volume,homogeneity index (HI),conformity index (CI),and doses to organs at risk were compared between the three groups.Results The C+S group had the largest IGTV,PTV,and the ratio of PTV to diseased breast volume,which was followed by the C group and the S group (all P＜ 0.05).The S group had significantly lower doses to the ipsilateral normal breast and lung than the C group and the C+S group (all P＜0.05).There were no significant differences in HI or CI between the three groups (all P＞ 0.05).Conclusions The volume variation caused by target volume dehneation on 4DCT images based on different references has little impact on dose distribution in target volume.However,it has substantial impact on radiation doses to the ipsilateral normal breast and lung.

Objective To study the dosimetric impact of different angle fields in intensitymodulated radiotherapy (IMRT) and the feasibility of beam angle optimization (BAO) for multiple intracranial metastases.Methods In total,11 patients with multiple intracranial metastases were included in these analyses.Two treatment techniques were designed for each patient:the 7 equal spaced fields (BAF group) IMRT,and 7 fields by beam angle optimization (BAO group) IMRT.The dose distribution in the target,the dose to the organs at risk and normal brain tissues,and total MU in two groups were compared to explore the dosimetric differences.Results In comparison to the BAF group,the BAO group reduced the maximum dose to left and right lenses by an average of 45％,37％ (t =-5.707,-4.438,P ＜ 0.05);the mean dose to the left and right eyes were reduced by an average of 42.6％,44.5％ (t =-4.380,-5.638,P ＜0.05);the maximum dose to the right eyes were reduced by an average of 32.5％ (t =-2.518,P ＜ 0.05).The maximum dose of the right optic nerve and the mean dose of normal brain tissue were reduced by an average of 23％ and 3％ (t =-3.105,-3.437,P ＜0.05),respectively.For the target dose,conformity and homogeneity in PTV,no statistical differences were observed between the two groups (P ＞ 0.05).The BAO group reduced the maximum dose of the brainstem and the optic chiasm,as well as the number of MU,however,the differences were not statistically significant (P ＞ 0.05).Conclusions In comparison to the BAF group,the BAO group shows a similar target dose and reduces the dose for the organs at risk.For multiple intracranial metastases,IMRT protocols with BAO are feasible and beneficial.

Objective To explore the effect of respiration on dose accumulation for target volume and normal liver in radiotherapy for hepatocellular carcinoma (HCC) while applying 4D-CT and deformable registration.Methods Nineteen HCC patients who had received transcatheter arterial chemoembolization were enrolled in this study.All patients underwent 3D-and 4D-CT simulation in free breathing.The 3D dose (Dose-3D) was calculated from the treatment planning designed on the 3D-CT image.The Dose-3D then was recalculated on ten phases of 4D-CT images respectively,and the end-inspiration and end-expiration doses were defined as Dose El and Dose-EE.The 4D dose (Dose-4D) was obtained by deforming and accumulating ten-phase doses of 4D-CT images on the end-expiration phase image.The dosimetric differences of planning target volume and normal liver were compared among Dose-3D,Dose-4D,Dose-EI and Dose-EE.Results The D99 and D95of planning target volume (PTV) in Dose-3D were higher than those of Dose-4D,Dose-Fl and Dose EE (x2 =32.75,26.31,P ＜ 0.05).The conformal index (CI) and homogeneity index (HI) in Dose-3D were better than those of Dose-4D,Dose-E1 and Dose-EE,in which CI decreased from 0.78 to0.63,0.60 and 0.57,while HI increased from 0.08 to 0.15,0.16 and 0.19 (x2 =37.80,31.86,P ＜0.05).No statistically significant differences were found in dosimetric indices of PTV between Dose-4D and Dose EI,Dose-EE,and between Dose-El and Dose-EE (P ＞ 0.05).The mean dose (D),V5,V10,V20,V30 and V40 of normal liver were similar among four dose distributions (P ＞ 0.05).Conclusions More objective and precise dose distribution for target volume and normal liver could be obtained by applying both 4D-CT and deformable registration,which is beneficial to accurately predicting the dosevolume indices of radiation-induced liver injury and offering more reliable evidence of escalation for target dose.

Objective To study the feasibility of defining the internal gross tumor volume (IGTV) of hepatocellular carcinoma applying the enhanced four-dimensional computed tomography (4DCT) images with deformable registration technology.Methods Ten HCC patients who accepted radiation therapy were selected in this study.The 4DCT in free breathing,non-enhanced 3DCT and arterial phase enhanced 3DCT in end inspiration breath holding associated with active breathing coordinator were acquired sequentially.4DCT were sorted into ten series CT images according to breath phase,and named CT00,CT10..…CT90.Gross tumor volume (GTV) were contoured on different CT series and the IGTV1 was merged by ten phases GTVs of 4DCT.The GTV of enhanced 3DCT was registered to different CT series of 4DCT and the IGTVDR was obtained by merging the GTVs after deformable registration.The target volumes differences were compared by paired t-test.Results The edge of tumor was difficult to define on 4DCT and non-enhanced 3DCT images.The enhanced 3DCT image showed clearer tumor edge,and the GTV increased by mean 37.99％ compared to GTV on 4DCT different series images and non-enhanced 3DCT image (P =0.002).The GTV after deformable registration on 4DCT different phase images increased by mean 36.34％ (P =0.011),which were similar to GTV on enhanced 3DCT image (P =0.632).The IGTVDR increased by 19.91％ (P =0.017),compared to IGTV1.Conclusions The contrast-enhanced 4DCT image which was obtained by combining enhanced 3DCT and 4DCT images with deformable registration technology could raise the position precision of the HCC IGTV effectively.

OBJECTIVETo compare the methods of delineating the whole breast target volume based on surface marks, palpation and glandular tissue on CT images, and to explore the contouring criteria after breast-conserving surgery.

METHODSIn 15 patients with breast cancer after breast-conserving surgery, the whole breast target was delineated in 3D CT simulation images each by three different methods. The target volume delineated according to anatomical marks were named CTVan, according to breast palpation named CTVpa, and according to glandular mammary tissue showing by CT images named CTVgl. The volumes of CTVan, CTVpa and CTVgl, and the degree of inclusion (DI) and conformal index (CI) between the targets were measured.

RESULTSThe mean volumes of CTVan, CTVpa and CTVgl were (792.23 ± 282.25) cm(3), (618.33 ± 295.90) cm(3) and (196.83 ± 117.62) cm(3), respectively. The differences among the three methods were statistically significant (P < 0.001). The difference between CTVan and CTVpa had no statistical significance (P = 0.08), and both the differences between CTVan and CTVgl, and between CTVpa and CTVgl had statistical significance (both P < 0.001). The CI between CTVan and CTVpa (0.644 ± 0.122) was significantly larger than the CI between CTVan and CTVgl (0.264 ± 0.108), and the CI between CTVpa and CTVgl (0.328 ± 0.115)(P < 0.001). The DI of CTVan to CTVpa was 0.709 ± 0.144,DI of CTVgl to CTVan was 0.994 ± 0.005 and DI of CTVgl to CTVpa was 0.989 ± 0.008. The differences of inner, outer, upper and lower boundaries of CTVpa and CTVan were (3.35 ± 7.23) mm, (5.57 ± 13.37) mm, (1.75 ± 11.62) mm, and (11.25 ± 4.07)mm, respectively. The cranial and medial boundaries had a negative correlation with CTVpa (P < 0.05 for all).

CONCLUSIONSThe differences among the three methods in the delineation of whole breast target volume are statistically significant. The target volume delineated according to the glandular mammary tissue displayed by CT scan is significantly smaller than that by the other two methods. Combination of breast palpation and anatomical marks may be helpful in delineating the whole breast target volume is relatively reasonable at present.

Breast ; pathology ; Breast Neoplasms ; diagnostic imaging ; Female ; Humans ; Imaging, Three-Dimensional ; Mastectomy, Segmental ; Palpation ; Tomography, X-Ray Computed