Objective To investigate the effect of fluid flow shear stress(FFSS)on the fluid mechanic threshold of high-mobility group box 1(HMGB1)release by synovial cells and chondrocytes.Moreover,the mechanism of chondro-cyte and synovial cell damage induced by abnormal mechanical force was investigated to provide an experimental basis for exploring the pathogenesis and pathology of temporomandibular joint osteoarthritis.Methods With the approval of the Ethics Committee for Animal Experiments of the hospital,synovial tissue and cartilage tissue blocks were obtained from the knee joints of Sprague-Dawley(SD)rats,and synovial cells and chondrocytes were cultured and digested for subsequent experiments.Synovial cells and chondrocytes of 3-4 generations were acquired,and FFSS was applied to sy-novial and cartilage cells using a fluid shear mechanical device.The cells were divided according to the FFSS values of different sizes.Synovial cells were stimulated for 1 h with 1,3,5,or 10 dyn/cm2 of FFSS,and chondrocytes were stimu-lated for 1 h with 4,8,12,or 16 dyn/cm2 of FFSS.Resting cultures(0 dyn/cm2)were used as the control group.Changes in the morphology of the cells were observed.The expression and distribution of HMGB1 and interleukin-1β(IL-1β)were observed by immunohistochemistry.The expression of HMGB1 and IL-1β in the supernatant was analyzed by ELI-SA.The protein expression levels of intracellular HMGB1 and IL-1β were detected by Western blot.Results With in-creasing FFSS,the synovial cells and chondrocytes gradually swelled and ruptured,and the number of cells decreased.With increasing FFSS,the localizationof HMGB1 and IL-1β gradually shifted from the nucleus to the cytoplasm.In synovial cells,compared with those in the control group,the expression levels of HMGB1 and IL-1β were increased both in the supernatant and cells in the 1,3,5 and 10 dyn/cm2 intervention groups(P＜0.01).In chondrocytes,com-pared with those in the control group,the expression levels of HMGB1 in the supernatant were increased in the 4,12 and 16 dyn/cm2 intervention groups(P＜0.05),and the protein expression levels of HMGB1 were significantly increased(P＜0.01).The expression levels of HMGB1 in the supernatant were significantly increased in the 8 dyn/cm2 intervention groups(P＜0.01);however,the protein expression levels of HMGB1 were significantly decreased.Compared with those in the control group,the expression levels of IL-1β in the supernatant gradually increased in the 4,8,12 and 16 dyn/cm2 intervention groups(P＜0.01).With the exception of those in the 4 dyn/cm2 group,the protein expression levels of IL-1β gradually increased with increasing FFSS(P＜0.05).Conclusion With increasing FFSS,synovial cells and chondro-cytes gradually swelled and burst,and the hydromechanical thresholds of HMGB1 release were 1 dyn/cm2 and 8 dyn/cm2,respectively.Therefore,upon stimulation with a mechanical force,synovial damage was damaged before chondrocytes.

Objective:To investigate the effect and mechanism of circular RNA (cirRNA) on the radiosensitivity of rectal cancer.Methods:The differential circRNAs in radiosensitive and radioresistant rectal cancer tissues (biopsy tissue before radiotherapy and chemotherapy) were detected by gene sequencing, and the effect of circRNAs on the radiosensitivity of colorectal cancer cells was further confirmed in vitro. Results:Through gene sequencing of rectal cancer tissue samples, 64 circRNAs were found to be highly expressed in radiosensitive rectal cancer tissues, and 36 circRNAs were lowly expressed in radiosensitive tissues. Ten differential circRNAs were selected and verified by qRT-PCR, and it was found that circATL2 was highly expressed in radiosensitive rectal cancer tissues. In vitro cell experiment indicated that up-regulation of circATL2 expression could significantly improve the radiosensitivity of rectal cancer. Subsequently, 8 miRNAs lowly expressed in radiosensitive rectal cancer tissues were analyzed. The direct binding relationship between miR-205 and circATL2 was confirmed by dual luciferase reporter assay. The rescue experiment confirmed that circATL2 in rectal cancer regulated the radiosensitivity of rectal cancer through miR-205. Conclusion:circATL2 regulates the radiosensitivity of rectal cancer by binding to miR-205.

Objective:To investigate the effectiveness of abdominal compression in tumor motion and the target volume, and analyze the suitable margins of planning target volume (PTV) for patients treated with lung-SBRT based on 4DCT.Methods:Patients diagnosed with peripheral pulmonary tumor were enrolled. The patients were divided into the whole group, upper-middle-lobe group (group A) and the lower-lobe group (group B). Each patient underwent 3DCT, 4DCT with abdominal compression (4DCT com) and 4DCT with free breath (4DCT free) scans. The GTVs were delineated and IGTVs on these images. PTV MIP 5 mm, PTV MIP 4 mm, PTV MIP 3 mm were constructed with a 5, 4, 3 mm margin in left-right (LR), anterior-posterior (AP) directions and cranial-caudal (CC) directions. Results:The median motion vector with compression reduced by 30.92% in whole group, increased by 3.42% in group A and reduced by 18.80% in group B, respectively. And there were no significant differences of TMA LR, TMA AP, TMA CC and motion vector by the Wilcoxon test ( P>0.05). The median sizes of IGTV MIP com , IGTV MIP free and IGTV10 com, IGTV10 free were 4.01, 5.36 cm 3and 6.59, 7.65 cm 3, with statistically significant difference ( Z=-3.45, -3.14, P<0.01). The median ratio of DI of IGTV CBCT com in PTV MIP 5 mm, PTV MIP 4 mm and PTV MIP 3 mm≥95% was 100%, 100% and 83.33%, respectively. Conclusions:The patients′ respiratory pattern changed with abdominal compression and abdominal compression is useful in reducing the size of IGTV MIP and IGTV10, which could reduce the target volume and protect the normal tissue. Adding a 4 mm margin to IGTV MIP com based on 4DCT account for respiration in SBRT is a tendency for precise radiotherapy.

Objective:To investigate the application value of 18F-FDG PET-CT combined with MRI in the radiotherapy for esophageal carcinoma by comparing the differences in the gross target volume (GTV), position length delineated on the end expiratory (EE) phase of 4DCT, PET-CT and T 2-weighted MRI (T 2W-MRI). Methods:Twenty-six patients with thoracic esophageal cancer scheduled to receive concurrent chemoradiotherapy sequentially underwent 3DCT, 4DCT, PET-CT and enhanced MRI for thoracic localization. All images were fused with the 3DCT images by deformable registration. GTV CT, GTV 50% GTV PET2.5, GTV MRI and GTV DWI were delineated on 3DCT, the EE phase of 4DCT images, PET-CT with the thresholds of SUV≥2.5, T 2W-MRI and diffusion-weighted images, respectively. Results:GTV PET2.5 was significantly larger than GTV 50% and GTV MRI ( P<0.001 and P=0.008), whereas the volume of GTV MRI was similar to that of GTV 50%( P=0.439). Significant differences were observed between the CI of GTV MRI to GTV 50% and GTV PET2.5 to GTV 50%( P=0.004). The conformity indexes (CIs) of GTV MRI to GTV CT and GTV PET2.5 to GTV CT were statistically significant ( P=0.004 and P=0.039). The CI of GTV MRI to GTV PET2.5 was significantly smaller than that of GTV MRI to GTV 50%, GTV MRI to GTV CT, GTV PET2.5 to GTV 50% and GTV PET2.5 to GTV CT ( P=0.000-0.021). The length of gastroscopy was similar to those of GTV PET2.5 and GTV DWI (both P>0.05), and there was no significant difference in the length between GTV PET2.5 and GTV DWI ( P=0.072). Conclusion:GTV MRI yields significantly different volume and poor spatial matching compared with GTV PET2.5. The application of PET-CT combined with MRI under respiratory gating system in the delineation of GTV should be used with caution in thoracic squamous esophageal cancer. MRI-DWI can replace PET-CT to help determine the upper and lower boundaries of GTV based on CT images.

Subject To compare the irradiation-induced injury and clinical efficacy between SIB-IMRT and LB-IMRT for early-stage breast cancer after breast-conserving surgery.Methods:From November 2002 to February 2012, 353 early breast cancer patients who underwent IMRT after breast-preserving surgery at Shandong Cancer Hospital were selected, of whom 218 patients receiving SIB-IMRT and 135 patients receiving LB-IMRT.The prescription dose of the SIB-IMRT group was the ipsilateral breast (PTV b ) 1.8-1.9 Gy, 27-28 times, and concurrent tumor bed (PTV t) 2.15-2.3 Gy, 27-28 times. In the LB-IMRT group, the prescription dose was PTV b 2.0 Gy, 25 times, followed by PTV t boost 2.0 Gy, 5-8 times. Results:The median follow-up time was 92 months. The excellent, good, fair, and poor cosmetic results in the SIB-IMRT and LB-IMRT groups were 10.1% and 12.6%, 85.8% and 80.7%, 3.7% and 5.2%, 0.5%, and 0.7%, respectively ( P=0.731). The 5-year locoregional recurrence rates (LRRs) in the SIB-IMRT and LB-IMRT groups were 3.21% and 5.93% and the 10-year LRRs were 4.13% and 6.67%, respectively ( P=0.209, 0.280). The 3-, 5-, 8-, and 10-year overall survival rate in the SIB-IMRT and LB-IMRT groups were 97.7% and 97.8%, 96.3% and 95.2%, 94.9% and 92.0%, 93.6% and 90.3%, respectively ( P=0.288). The 3-, 5-, 8-, and 10-year disease-free survival in the SIB-IMRT and LB-IMRT groups were 95.4% and 93.8%, 91.8% and 87.7%, 89.9% and 84.1%, 89.0% and 82.1%, respectively ( P=0.160). Conclusion:There is no significant difference in the cosmetic effect, local control rate, and survival rate between SIB-IMRT and LB-IMRT after breast-preserving surgery in patients with early-stage breast cancer. SIB-IMRT is a safe and feasible treatment.

Objective:To assess the feasibility of delayed-enhancement MRI in contouring the lumpectomy cavity (LC) for patients with invisible seroma or a low cavity visualization score (CVS≤2) in the excision cavity after breast-conserving surgery (BCS).Methods:Twenty-six patients with stage T 1-2N 0M 0 who underwent prone radiotherapy after BCS were recruited. The LC delineated on CT simulation images was denoted as LC CT. The LCs delineated on T 2WI, as well as on different delayed phases (2-, 5-and 10-minute) of delayed-enhancement T 1WI were defined as LC T2, LC 2T1, LC 5T1 and LC 10T1, respectively. Subsequently, the volumes and locations of the LCs were compared between CT simulation images and different sequences of MR simulation images using deformable image registration. Results:The volumes of LC T2, LC 2T1, LC 5T1 and LC 10T1 were all larger than that of LC CT. A statistical significance was found between the volume of LC CT and those of LC 2T1 or LC 5T1, respectively (both P<0.05). The conformal index (CI), degree of inclusion (DI), dice similarity coefficient (DSC) and the distance between the center of mass of the targets (COM) of LC CT-LC 10T1 were better than those of LC CT-LC T2, LC CT-LC 2T1 and LC CT-LC 5T1, however, there was no statistical difference among them (all P>0.05). Conclusions:It is feasible to delineate the LC based on prone delayed-enhancement MR simulation images in patients with low CVS after BCS. Meanwhile, the LCs derived from prone delayed-enhancement T 1WI of 10-minute are the most similar with those derived from prone CT simulation scans using titanium clips, regardless of the volumes and locations of LCs.

Objective To investigate the difference of target volumes and dosimetric parameters between supine and prone positions for external-beam partial breast irradiation (EB-PBI) after breastconserving surgery (BCS).Methods Thirty breast cancer patients with T1N0M0 stage who underwent three-dimensional conformal radiation therapy (3D-CRT) EB-PBI after BCS were enrolled from July 2016 to April 2017.Supine and prone scan sets were acquired during free breathing for all patients.Target volumes and organs at risk (OARs) including heart,ipsilateral lung and bilateral breast were contoured by the same radiation oncologist.The tumor bed (TB) was determined based on surgical clips.The clinical target volume (CTV) consisted of the TB plus 1.0 cm margin and the planning target volume (PTV) was CTV plus 0.5 cm.Dosimetric parameters for target volumes and OARs were compared between supine and prone positions.Results The median volumes of the TB,the CTV and the PTV in supine were 14.40 cm3,57.35 cm3,108.85 cm3 and 14.10 cm3,62.60 cm3,113.70 cm3 for prone positions,respectively.The CTV and PTV in prone position were significantly greater than those in supine position,respectively (Z=-3.01,-2.87,P ＜0.05),but the TBs were not statistically different (P ＞0.05).The median homogeneity indexs (HI) in supine position was less than those in prone position (Z =-3.137,P ＜0.05),while the mean conformal indexs (CI) was increased with prone positioning (t =9.034,P ＜ 0.05).The mean dose (D) to the heart in the supine position was significantly lower than that in prone (0.34 and 1.19 Gy,Z =-4.12,P ＜0.05).The D to the ipsilateral lung in the prone position was significantly lower than that in supine (1.59 and 1.72 Gy,Z =-2.18,P ＜ 0.05).There was not significantly statistical difference for the D to the ipsilateral breast between two positionings (10.01 and 10.40 Gy,P ＞0.05).Conclusions It was feasible to carry out 3D-CRT EB-PBI in prone position in free breathing for Chinese breast cancer patient,with primary advantages of better CI and the significantly lower radiation dose to the ipsilateral lung.

Objective To detect the changes of heart volume during concurrent chemoradiotherapy for esophageal cancer based on repeated enhanced 4DCT.Methods Patients with squamous cell esophageal cancer underwent repeated enhanced 4DCT and 3DCT scans before and after 10,20 and 30 fractions of radiotherapy,respectively.The heart was contoured on 3DCT,end expiratory (EE) and maximum intensity projection (MIP) of 4DCTimages.The changes in theheart volume,blood pressure.and heart rate were statistically compared at different time points.Results A total of forty-six patients completed 4 fractions of 3DCT and enhanced 4DCT scans.Compared with the initial values,the heart volume was significantly decreased by 3.27％,4.45％ and 4.52％ after 10 fractions of radiotherapy,and reduced by 6.05％,5.64％ and 4.51％ following 20 fractions of radiotherapy on 3DCT,EE and MIP,respectively (P=0.000-0.027).The heart volume after 30 fractions of radiotherapy did not significantly differ from the initial volume (P＞ 0.05).After radiotherapy,there was a significant decrease inboth systolic and diastolic blood pressure (P =0.000 and P =0.009) and a significant ‖ increase in the heart rate (P=0.0 0 1) compared with those measured before radiotherapy.Conclusions Enhanced 4DCT scan can clearly reflect the changes of heart volume throughout concurrent chemoradiotherapy.The heart volume starts to shrink during the early stage of radiotherapy and continue to decrease until the middleand late-stage,whereas it restores to the initial volume after radiotherapy.Simultaneously,blood pressure declines and heart rate is accelerated during radiotherapy.

Objective: To evaluated the unplanned coverage dose to the internal mammary chain (IMC) in patient treated with postmastectomy radiotherapy (PMRT). Methods: One hundred and thirty eight patients with breast cancer receiving radiotherapy (RT) in our hospital were retrospectively analyzed. Patients were divided into three groups: three-dimensional conformal radiotherapy (3D-CRT) group, forward intensity-modulated radiotherapy (F-IMRT) group and inverse IMRT (I-IMRT) group. The IMC were contoured according to Radiation Therapy Oncology Group (RTOG) consensus, and were not include into the planning target volume (PTV). The incidental irradiation dose to IMC among the three groups and the first three intercostal spaces IMC (ICS-IMC 1-3) were all compared, and explored the relationship between the mean doses (Dmean) of IMC and the OARs (ipsilateral lung and heart). Results: The dose delivered to IMC showed no difference in CRT, F-IMRT and I-IMRT(33.80 Gy, 29.65 Gy and 32.95 Gy). And 10.42%, 2.04%, and 9.76% patients achieved ≥45 Gy when treated with CRT, F-IMRT and I-IMRT. For the IMC dose in the first three intercostal spaces (ICS1-3), there was no difference to the three treatment plannings. The Dmean, V₂₀, V₃₀, V₄₀ and V₅₀ of the ICS-IMC2 and ICS-IMC3 were all obviously superior than ICS-IMC1 for all these three plannings. Moderate positive correlation was founded between Dmean for IMC and Dmean for heart for left breast cancer patients underwent CRT (r=0.338, P=0.01). Whereas for F-IMRT and I-IMRT groups, positive correlation were founded between Dmean for IMC and Dmean and V₂₀ for ipsilateral lung for all patients (F-IMRT: r=0.366, P=0.010; r=0.318, P=0.026; I-IMRT: r=0.427, P=0.005; r=0.411, P=0.008). Conclusions In 3D-CRT, F-IMRT and I-IMRT planning methods, partial patients get IMC irradiated doses that could achieve therapeutic doses. Compared with 3D-CRT, F-IMRT and I-IMRT further reduced the dose of irradiated organs. However, there is no difference in the dose coverage of IMC for the three planned approaches when the IMC made an unplanned target.

Objective: To explore the differences and correlation between the target volumes based on deformation registration (DIR) using preoperative prone diagnostic magnetic resonance (MR) imaging and postoperative prone computed tomography (CT) simulation imaging for patients undergoing breast-conserving surgery (BCS). Methods: Eighteen breast cancer patients suitable for external-beam partial breast irradiation (EB-PBI) after BCS were enrolled. Preoperative prone diagnostic MR and postoperative prone CT scan sets were acquired during free breathing for all patients. The gross tumor volume (GTV) delineated on the preoperative diagnostic MR images was defined as GTV_MRI, the clinical target volumes (CTV_{MRI+ 1} and CTV_{MRI+ 2})were defined as 10 and 20 mm margins around the GTV_MRI, and the planning target volume (PTV_{MRI+ 1} and PTV_{MRI+ 2}) were defined as 15 and 25 mm margins around the GTV_MRI, respectively. Tumor bed (TB) delineated on the postoperative prone CT simulation images acquired during free breathing was defined as GTV_TB, CTV and PTV were defined as 10 and 15 mm margins around the GTV_TB, respectively. The target volume of the whole breast contoured on the MR and CT images were defined as CTV_Breast-MRI and CTV_Breast-CI, respectively. The MR and CT images were registered deformably in MIM software system. Results: The GTV_TB, CTV_TB and PTV_TB were significantly greater than GTV_MRI, GTV_{MRI+ 1} and PTV_{MRI+ 1}, respectively (Z=-3.593, -3.593, -2.983, P<0.05). Meanwhile, the CTV_TB and PTV_TB were significantly less than the CTV_{MRI+ 2} and PTV_{MRI+ 2}, respectively(Z=-2.722, -2.853, P<0.05). The conformal index (CI) and degree of inclusion (DI) of GTV_TB-GTV_MRI, GTV_TB-CTV_{MRI+ 1}, CTV_TB-GTV_MRI and CTV_TB-GTV_{MRI+ 1} based on center-coincidence of the compared targets were better than those based on DIR of the thorax(Z=-3.724、-3.724、-2.591、-3.593, P<0.05; Z=-3.724、-3.724、-3.201、-3.724, P<0.05). Conclusions For the patients enrolled for prone EB-PBI, target volumes delineated on the preoperative prone MR images were significantly smaller compared to that on the postoperative prone CT images, but a statistically significant positive correlation was found between the MR and CT target volumes. There were still relatively poor spatial overlap whether for the whole breast or the targets between the preoperative prone diagnostic MR images and the postoperative prone simulation CT images based on DIR. Therefore, it is infeasible to guide postoperative EB-PBI target delineation using the preoperative prone diagnostic MR images.