ObjectiveTo investigate the expression levels of vascular endothelial growth factor (VEGF)in knee synovial membranes and synovial fluids whether it could be a marker for progressive osteoarthritis.MethodsKnee synovial membranes and synovial fluids of patients with osteoarthritis who were underwent total knee arthroplaaty or arthroscopy were collected. They were classified into four groups according to the radiographic grading[Kellegren-Lawrence(K-L) grade]. Appoint K-L-0-grade patients who suffered from menisci injuries only served as controls. The levels of VEGF in the synovial fluid were measured by enzymelinked immunosorbent assay(ELISA) and VEGF-secreting cells were identified by immunohistochemistry.ANOVA was used for statistical analysis. ResultsVarious degrees of inflammation could be found in all the samplesevaluated histologically on HE-stained sections. Synovial tissue inflammation presented as synovial lining thickening, and inflammatory cells infiltration. VEGF expressed in the synovium linings and surrounding blood vessels. The VEGF levels in the synovial fluids were increased accordingly with K-L grades, which reached the peak level in the late stage of osteoarthritis. The levels of VEGF in the synovial fluids were significantly higher in patients with osteoarthritis[from (1181±116), (1632±140) to (2252±216) pg/ml]than in those with menisci injury (P＜0.01); The percent ages positive cell in each groups were (5±4)％ , (9±4)％,(16±6)％ and (21±6)％ respectively, there were significantly differences too (P＜0.01). ConclusionVEGF originated from synovial tissue may play a role in the pathogenesis of osteoarthritis. High levels of VEGF in the synovial fluids can be regarded as the marker of active osteoarthritis.

Objective To investigate the effect of carotid artery stenting (CAS) on cognitive function in patients with asymptomatic severe carotid artery stenosis.Methods The patients with asymptomatic severe carotid stenosis (stenosis ≥ 70％) were enrolled in the study.The cognitive function evaluation was performed before CAS,1 and 3 months after procedure respectively with mini-mental status scale (MMSE),digital span (DS),Chinese auditory learning test (CALT),judgment of line orientation test (JLOT),and verbal fluency test (VFT),including attention,memory,visual spatial function,and frontal fluency function.Results A total of 26 patients with asymptomatic severe carotid artery stenosis who performed CAS were enrolled,18 were males and 8 were females (aged 52 to 79 years,mean 64.19 ±6.76 years),and the years of education was 9.84 ± 3.29 years.Eighteen patients had left carotid artery stenosis and 8 had contralateral carotid artery stenosis.CAS was performed successfully in all patients,and no complications occurred.Compared with the CAS before procedure,all the cognitive functions were improved significantly at 1 and 3 months after procedure (all P ＜0.01),however,there was no significant difference between 1 and 3 months after procedure (all P＞ 0.05).Conclusions CAS may improve cognitive function in patients with asymptomatic severe carotid artery stenosis,and it was more obvious in the early postoperative period.

Objective:To explore the status of depression symptoms and related factors of depressive symptoms in middle-aged and elderly disabled people in China and provide references on the preventive cares of depression.Methods:Research data were obtained from the 2018 follow-up data of China Health and Retirement Longitudinal Study(CHARLS).Disabled people were selected as the research object. The scores of center for epidemiological studies depression scale(CES-D) were used to evaluate depressive symptoms. Fourteen variables derived from the 3 dimensions of demographic characteristics, health status, and health related behaviors were utilized in this study.SAS 9.4 were used for descriptive analysis, univariate analysis and Logistic regression analysis.Results:A total of 1 708 middle-aged and elderly disabled people were included, among whom 932(54.5%)were diagnosed with depressive symptoms, and the score of CES-D was (11.45±7.19).Self-rated poor health, self-rated poor memory, life dissatisfaction, physical pain were the risk factors of depressive symptoms ( OR=1.87, 4.22, 1.83, 5.30, 1.75). Male, educational level (middle-high school, high school or above), sleeping duration (6-9 h) were the protective factors of depressive symptoms( OR=0.74, 0.72, 0.10, 0.56). Conclusion:Middle-aged and elderly disabled people in China have a high detection rate of depressive symptoms. Female, lower education background, inadequate amount of sleep, self-rated unsatisfactory healthy, self-rated poor memory, dissatisfaction towards life and suffering from physical pain may be more likely to have depressive symptoms in middle-aged and elderly people with disabilities.

Objective:To observe and describe the clinicopathologic manifestations of acute kidney injury (AKI) caused by immune checkpoint inhibitors (ICIs).Methods:The clinicopathologic manifestations of patients diagnosed as AKI related to ICIs in Ningbo LiHuili Hospital during the period between December 2020 to December 2021 were retrospectively analyzed, including the primary tumor disease, renal pathological features, renal function progression and therapeutic effects.Results:A total of 6 patients were enrolled, all of whom were male, aged (62±11) years old. The median time from the application of ICIs to the onset of AKI was 46 d (ranging from 31 to 95 d). The median of the peak serum creatinine was 311 (205 to 1 053) μmol/L, and 1 patient received hemodialysis treatment. Six patients received renal biopsy, among which 4 cases were acute tubulointerstitial nephritis, 1 case of tubulointerstitial nephritis with both acute and chronic changes, 1 case of chronic tubulointerstitial nephritis. Of the 6 patients, 5 received glucocorticoid therapy, and 2 of the patients completely recovered, while 3 partially recovered. One patient didn′t use glucocorticoid, but his renal function was partially restored after stopping ICIs.Conclusions:AKI caused by ICIs is mainly manifested by acute tubulointerstitial nephritis. Glucocorticoid has some therapeutic effects on AKI caused by ICIs and may be an effective treatment.

Objective To propose a treatment planning optimization algorithm which can make full use of OAR dose distribution prediction meanwhile improving the output planning quality as much as possible.Methods We had reformulated an FMO function under the guidance of dose distribution prediction and also integrated equivalent uniform dose (gEUD) based on the consideration of prediction uncertainty,for providing optimal solution.Performance of the method was evaluated by comparing the optimized IMRT plan quality of 8 cervical cancers in the term of DVH curves,dose distribution and dosimetric endpoints with the original ones.Results The proposed method had a feasible,fast solution.Compared with original plan,its output plan had better plan quality in better dose homogeneity,less hot spot and further dose sparing for OARs.V30,V45 of rectum was decreased by (6.60±3.53)％ and (17.03±7.44)％,respectively,with the statistically significant difference (t=-4.954,-6.055,P＜0.05).V30,V45 of bladder was decreased by (14.74 ± 5.61) ％ and (14.99 ± 4.53) ％,respectively,with the statistically significant difference (t=-6.945,-8.759,P＜0.05).Conclusions We have successfully developed a predicted dose distribution and equivalent uniform dose-based planning optimization method,which is able to make good use of 3D dose prediction and ensure the output plan quality for intensity modulated radiation therapy.

Objective To establish a three-dimensional (3D) dose prediction model,which can predict multiple organs simultaneously in a single model and automatically learn the effect of the geometric anatomical structure on dose distribution.Methods Clinical radiotherapy plans of patients diagnosed with the same type of tumors were collected and retrospectively analyzed.For every plan,each organs at risk (OAR) voxel was regarded as the study sample and its deposited dose was considered as the dosimetric feature.A regularized multi-task learning method than could learn the relationship among different tasks was employed to establish the relationship matrix among tasks and the correlation between geometric structure and dose distribution among organs.In this experiment,the spinal cord,brainstem and bilateral parotids involved in the intensity-modulated radiotherapy (IMRT) plan of 15 nasopharyngeal cancer patients were utilized to establish the multi-organ prediction model.The relative percentage error between the predicted dose of voxel and the clinical planning dose was calculated to assess the feasibility of the model.Results Ten cases receiving IMRT plans were utilized as the training data,and the remaining five cases were used as the test data.The test results demonstrated a higher prediction accuracy and less data demand.And the average voxel dose errors among the spinal cord,brainstem and the left and right parotids were (2.01±0.02)％,(2.65± 0.02) ％,(2.45± 0.02) ％ and (2.55± 0.02) ％,respectively.Conclusion The proposed model can accurately predict the dose of multiple organs in a single model and avoid the establishment of multiple single-organ prediction models,laying a solid foundation for patient-specific plan quality control and knowledge-based treatment planning.

Objective: To explore clinical features and prognosis factors of surgical complications after intersphincteric resection (ISR) for low rectal cancer following neoadjuvant chemoradiotherapy. Methods: The clinical data of 132 patients with low rectal cancer who underwent ISR following neoadjuvant chemoradiotherapy from September 2010 to June 2017 at Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University were retrospectively reviewed. There were 100 males and 32 females, with the age of (52.9±11.4) years and distance to anal verge of 3.9 cm. Records of perioperative complication (POC) within 30 days after surgery, anastomotic leakage (AL), and anastomotic stenosis (AS) were analyzed. POC was recorded according to the Clavien-Dindo classification. AL was graded by ISREC system and classified into the early AL within 30 days after surgery and delayed AL beyond 30 days. AS was defined as narrowing of the bowel lumen at the anastomosis that prevented passage through a colonoscope with a 12 mm diameter. According to the shape of narrowing, AS was recorded as the stenosis in situ or stenosis with long-segment bowel above. Univariate and multivariate analysis were used to identify risk factors of anastomotic complications. Results: Among the 132 patients, full-dose radiotherapy and diverting stoma were performed in 128 (97.0%) patients, respectively. In entire cohort, AL was found in 41 (31.1%) patients, including 32 patients with clinical leakage (24.2%). The median time for diagnosis of AL was 37 days (2 to 214 days) after surgery. There were 25 patients (18.9%) who were diagnosed with delayed AL beyond 30 days. Chronic presacral sinus formation was detected in 22 of 129 (17.1%) patients at 12 months from surgery. Among the 128 eligible patients, 36 (28.1%) were diagnosed as AS, including 24 (18.8%) patients with stenosis in situ and 12 (9.4%) patients with bowel stenosis above. After a median follow-up of 26 months, 7(5.3%) patients received permanent colostomy and the other 20(15.2%) patients retained a persistent ileostomy, owing to anastomotic complications. Results of multivariate analysis showed that radiation colitis was an independent prognosis factor of AL after ISR (OR=5.04, 95% CI: 2.05 to 12.43, P=0.000); male gender (OR=5.19, 95% CI: 1.24 to 21.75, P=0.024) and AL (OR=8.49, 95% CI: 3.32 to 21.70, P=0.000) were independent prognosis factors of AS after ISR. Conclusions Surgical complications are common after ISR for low rectal cancer patients with neoadjuvant chemoradiotherapy. A high rate of AL is observed after long-term follow-up, which is associated with AS. Increasing awareness of anastomotic complications after ISR should be raised, especially for male patients with radiation colitis.

Objective:To establish a correlation model between MRI and CT images to generate synthetic-CT (sCT) of head and neck cancer during MRI-guided radiotherapy by using generative adversarial networks (GAN).Methods:Images and IMRT plans of 45 patients with nasopharyngeal carcinoma were collected before treatment. Firstly, the MRI (T1) and CT images were preprocessed, including rigid registration, clipping, background removal and data enhancement, etc. Secondly, the cases were trained by GAN, of which 30 cases were randomly selected and put into the network as training set images for modeling and learning, and the other 15 cases were used for testing. The image quality of predicted sCT and real CT were statistically compared, and the dose distribution recalculated upon predicted sCT was statistically compared with that of real planned dose distribution.Results:The mean absolute error of the predicted sCT of the testing set was (79.15±11.37) HU, and the SSIM value was 0.83±0.03. The MAE values of dose distribution difference at different regional levels were less than 1% compared to the prescription dose. The gamma passing rate of the sCT dose distribution was higher than 92% and 98% under the 2mm/2% and 3mm/3% criteria.Conclusions:We have successfully proposed and realized the generation of sCT for head and neck cancer using GAN, which lays a foundation for the implementation of MRI-guided radiotherapy. The comparison of image quality and dosimetry shows the feasibility and accuracy of this method.

Objective:To compare the accuracy and generalized robustness of three predictive models of knowledge-based treatment strategies for radiotherapy for optimized model selection.Methods:The clinical radiotherapy plans of 45 prostate cancer (PC) cases and 25 nasopharyngeal cancer (NPC) cases were collected, and analyzed using three models (Z, L and S model), proposed by Zhu et al, Appenzoller et al and Shiraishi et al, respectively, to predict the dose-volume histogram (DVH) of bladder and rectum on PC cases and that of left and right parotid on NPC cases. The prediction error was measured by the difference of area under the predicted DVH and the clinical DVH curves (|V (pre_DVH)-V (clin_DVH)|), where a smaller prediction error implies a greater prediction accuracy. The accuracies of these three models were compared on the single organ at risk (OAR), and the generalized robustness of models was evaluated and compared by calculating the standard deviation of the prediction accuracy on different OAR. Results:For bladder and rectum, the prediction error of L model (0.114 and 0.163, respectively) was significantly higher than those values of Z and S models (≤0.071, P<0.05); for left parotid gland, the predicted error of S model (0.033) did not present significant difference from those values of Z and L models (≤0.025, P>0.05); for right parotid gland, S model (0.033) demonstrated significantly higher prediction error than those of Z and L models (≤0.028, P<0.05). Regarding different OAR, S model showed a lower standard deviation of prediction accuracy when comparing to Z and L models (0.016, 0.018 and 0.060, respectively). Conclusions:In the prediction of DVH in bladder and rectum of PC, Z and S models were more accurate than L model. In contrast, Z and L models demonstrated higher accuracy than S model in the prediction of left and right parotid glands of NPC. In respect to different OAR, the generalized robustness of S model was superior than the other two models.

Objective:To explore clinical factors of poor prognosis in patients with anti-melanoma differentiation-associated gene 5 andtibody positive dermatomyositis (MDA5-DM).Methods:One hundred and twenty-six enrolled adults with MDA5-DM were divided into the survival group and the deceased group according to the outcomes. Survival time, clinical manifestations, laboratory tests, pulmonary function tests, myositis antibodies and treatments were collected for statistical analysis. Serum concentrations of IL-15, HMGB1, and sCD163 were measured by ELISA in MDA5-DM patients and healthy controls. Mann-Whitney U nonparametric test and Student′s t-test were used to compare the continuous variables between the two groups, and χ2 or Fisher′s exact test were used for comparison of categorical variables. Cox regression analysis was used to assess the survival predictors in MDA5-DM patients. The cumulative survival rate was calculated by Kaplan-Meier curve analysis, and Log-rank tests were used to examine differences in survival curves. P<0.05 was considered statistically significant. Results:Cox multivariate regression analysis revealed that age > 57 years [ HR (95% CI)=3.05 (1.20, 7.80), P=0.020], RP-ILD [ HR (95% CI)=25.07 (5.42, 115.98), P<0.001], and levels of anti-Ro52 antibody [ HR (95% CI)=3.41 (1.36, 8.53), P=0.009] were important prognostic factors independent of multiple clinical parameters. The ELISA test results showed that the levels of serum IL-15[0.91 (0.66, 2.00)pg/ml vs. 0.51(0.39, 0.72)pg/ml, Z=-4.57, P<0.001] and HMGB1 [230.53(90.40, 394.31)ng/ml vs. 32.66 (17.82, 46.21)ng/ml, Z=-6.52, P<0.001] in MDA5-DM patients were significantly higher than those in healthy controls, but there were no significant differences in the level of serum IL-15 [1.21(0.63, 2.12)pg/ml vs. 0.91(0.68, 1.66)pg/ml, Z=-0.30, P=0.766], HMGB1[267.61(167.03, 444.23)ng/ml vs. 228.35(74.74, 344.32)ng/ml, Z=0.82, P=0.413], and sCD163 [112.70(93.45, 148.51)ng/ml vs. 132.72(96.79, 203.18)ng/ml, Z=-0.62, P=0.536] between the survival group and the deceased group. Conclusion:Older age, RP-ILD, and high levels of anti-Ro52 antibody significantly increase the risk of death in MDA5-DM patients. Intensive follow-up of patients with the above factors in the early stages may help to improve the prognosis.