Objective To investigate the inhibitory effects of IBI302 on experimental choroidal neovascularization (CNV).Methods Affinity of IBI302 to vascular endothelial growth factor (VEGF) family cytokines (including VEGF-A165,VEGF-A121 and placental growth factor PlGF) and complements (C3b,C4b) was determined by enzyme-linked immunosorbent assay (ELISA).The antagonist effect of IBI302 on VEGF was measured by proliferation,migration and tube formation tests of human umbilical vein endothelial cells (HUVEC).The anti-complement activity of IBI302 was measured by hemolysis test mediated by complement classical pathway and alternative pathway.Rhesus laser-induced CNV model was divided into 5 groups including model control group,bevacizumab group,IBI302 0.25 mg group,IBI302 0.50 mg group and IBI302 1.25 mg group.Fluorescein angiography and optical coherence tomography were performed on these monkeys at 14 and 28 days after drug delivery to observe the fluorescein leakage area and retinal thickness.The aqueous VEGF concentration was measured at 29 days after drug delivery.Results IBI302 showed good affinity to VEGF-A165,VEGF-A121 and PlGF,as well as C3b and C4b.IBI302 significantly inhibited the proliferation,migration and tube formation of HUVEC induced by VEGF-A165.IBI302 inhibited the hemolysis induced by complements obviously.At 14 and 28 days after drug delivery,the area of fluorescein leakage and retinal thickness in IBI302 0.25 mg group,IBI302 0.50 mg group,IBI302 1.25 mg group were reduced.The differences of the area of fluorescein leakage and retinal thickness in three IBI302 groups were not significant (P＞0.05).At 29 days after drug delivery,the VEGF concentration in the aqueous of rhesus monkey in bevacizumab group [(38.644 ± 6.521) pg/ml] was decreased than that in model control group [(94.203± 17.360) pg/ml],the difference was significant (P＜ 0.05).The VEGF concentration in the aqueous of rhesus monkey in three IBI302 groups were less than 31.300 pg/ml.Conclusion IBI302 inhibited experimental CNV through blocking the activity of VEGF and complement.

Objective To evaluate the diagnostic value of endoscopic ultrasonography (EUS) for submucosal tumors in upper gastrointestinal tract, and its influence on choice of endoscopic therapies. Methods A total of 82 submucosal tumors from upper gastrointestinal tract were examined by EUS, and treated by various endoscopic therapeutic techniques including fulguration with high frequency current ( FHFC), endoscopic mucosal resection (EMR) and endoscopic band ligation according to orion, size and property of the lesion. The diagnoses of 58 reseeted samples were determined by routine pathological examination and immunohistochemistry. All patients were followed up with routine endoscopy and EUS. Results FHFC was applied in 26 lesions originated from muscularis mucosa, EMR was used in 17 flat lesions originated from muscularis mucosa, and endoscopic band ligation in 38 lesions from muscularis propria and 1 tumor from muscularis mucosa. The diagnostic accuracy of EUS was 91.4% (53/58). Except for post-operative bleeding in 1 patient, no other complications were observed. A total of 79 cases were followed up for 3-24 months, and no recurrence was found. Conclusion EUS can display the origin and property of submucosal tumors in upper gastrointestinal tract and guide the selection of endoscopic therapy, which is effective and safe in treatment of submucosal tumor in upper gastrointestinal tract.

Objective To investigate the risk factors of standard selectivity biliary cannulation in endoscopic retrograde cholangiopancreatography (ERCP) for patints with choledocholithiasis,and the effect and safety of assistant cannulation methods.Methods The clinical data were retrospectively analyzed in 372 patients,who received ERCP for choledocholithiasis in the Yijishan Hospital of Wannan Medical College from January 2014 to December 2014.The risk factors of standard biliary cannulation were assessed by univariate and multivariate logistic regression analysis.The success rate of assistant biliary cannulation and the incidence of post-ERCP pancreatitis (PEP) of standard biliary cannulation were compared with doubleguide wire technique (DGT) and precut sphincterotomy (PS),which were used when standard biliary cannulation failed.Results The univariate analysis showed that floppy and long duodenal papilla (P=0.000),angulated common bile duct(P=0.013) were related to failure of standard biliary cannulation.Multivariate analysis showed that floppy and long papilla (P=0.000,OR=0.131,95％CI:0.056-0.307),angulated common bile duct (P =0.003,OR =0.378,95 ％ CI:0.197-0.726) were independent risk factors for standard biliary cannulation.The success rate of standard biliary cannulation was 83.3％ (310/372),62 cases undergone DGT or PS after standard biliary cannulation failure,and the total success rate of cannulation was 99.7％ (371/372).There were 29 cases suffered from PEP in 371 successful cases of biliary cannulation,including 18 cases (5.8％,18/310) of standard biliary cannulation,8 cases (16.3％,8/49) of DGT,and 3 cases (25.0％,3/12) of PS.The incidence of PEP by DGT (x2 =5.532,P =0.019) and PS (x2 =6.994,P=0.008) was significantly higher than that of standard biliary cannulation,but there was no statistical difference on the incidence of PEP between DGT and PS (x2 =0.079,P =0.778).Conclusion Floppy and long duodenal papilla and angulated common bile duct could easily induce the failure of standard biliary cannulation in ERCP for patients with choledocholithiasis.DGT and PS are effective assistant cannulation methods when the standard cannulation fails.

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 the effects of multimodal imaging on the performance of automatic segmentation of glioblastoma targets for radiotherapy based on a deep learning approach.Methods:The computed tomography (CT) images and the contrast-enhanced T1 weighted (T1C) sequence and the T2 fluid attenuated inversion recovery (T2- FLAIR) sequence of magnetic resonance imaging (MRI) of 30 patients with glioblastoma were collected. The gross tumor volumes (GTV) and their corresponding clinical target volumes CTV1 and CTV2 of the 30 patients were manually delineated according to the criteria of the Radiation Therapy Oncology Group (RTOG). Moreover, four different datasets were designed, namely a unimodal CT dataset (only containing the CT sequences of 30 cases), a multimodal CT-T1C dataset (containing the CT and T1C sequences of 30 cases), a multimodal CT-T2-FLAIR dataset (containing the CT and T2- FLAIR sequences of the 30 cases), and a trimodal CT-MRI dataset (containing the CT, T1C, and T2- FLAIR sequences of 30 cases). For each dataset, the data of 25 cases were used for training the modified 3D U-Net model, while the data of the rest five cases were used for testing. Furthermore, this study evaluated the segmentation performance of the GTV, CTV1, and CTV2 of the testing cases obtained using the 3D U-Net model according to the indices including Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), and relative volume error (RVE).Results:The best automatic segmentation result of GTV were achieved using the CT-MRI dataset. Compared with the segmentation result using the CT dataset (DSC: 0.94 vs. 0.79, HD95: 2.09 mm vs. 12.33 mm, and RVE: 1.16% vs. 20.14%), there were statistically significant differences in DSC ( t=3.78, P<0.05) and HD95 ( t=4.07, P<0.05) obtained using the CT-MRI dataset. Highly consistent automatic segmentation result of CTV1 and CTV2 were also achieved using the CT-MRI dataset (DSC: 0.90 vs. 0.91, HD95: 3.78 mm vs. 2.41 mm, RVE: 3.61% vs. 5.35%). However, compared to the CT dataset, there were no statistically significant differences in DSC and HD95 of CTV1 and CTV2 ( P>0.05). Additionally, the 3D U-Net model yielded some errors in predicting the upper and lower bounds of GTV and the adjacent organs (e.g., the brainstem and eyeball) of CTV2. Conclusions:The modified 3D U-Net model based on the multimodal CT-MRI dataset can achieve better segmentation result of glioblastoma targets and its application potentially benefits clinical practice.

Objective    To summarize the experience of totally thoracoscopic cardiac surgery (TTCS) for atrial septal defect. Methods    Clinical data of 442 patients undergoing TTCS for atrial septal defect from May 2008 to December 2018 in Shanghai Yodak Cardiothoracic Hospital was analyzed retrospectively. There were 149 male and 293 female patients, aged 3-74 (29.1±14.3) years. Surgical procedures were performed through 3 ports at the right chest wall. Results    All the operations were completed successfully. Mean operative time was 1.5-4.6 (2.2±0.3) h. The mean extracorporeal circulation and aortic cross-clamp time was 28-118 (55.9±13.3) min and 8-78 (21.5±10.2) min, respectively. Mechanical ventilation and intensive care unit stay time was 3.5-122.0 (8.1±7.4) h and 13-141 (20.7±10.2) h, respectively. Postoperation drainage volume was 70-1 280 (251.8±131.5) mL. The hospital stay was 4-16 (7.1±1.4) d. Intraoperative and postoperative complications occurred in 15 patients (3.3%). The mean follow-up time was 1-128 (67.6±33.3) months, and during the period, there were 25 patients of atrial fibrillation, 25 patients of mild-moderate tricuspid valve incompetence, 1 patient of moderate tricuspid valve incompetence. There was no reoperation or residual shunt during the period of follow-up. And the heart function was improved. Conclusion    TTCS is a feasible, safe and minimal invasive approach for patients with atrial septal defect and has good short to medium-term outcomes.

Objective    To summarize the experience of totally thoracoscopic cardiac surgery for ventricular septal defect. Methods    Clinical data of 449 patients undergoing totally thoracoscopic cardiac surgery for ventricular septal defect from May 2008 to December 2018 in Shanghai Yodak Cardiothoracic Hospital were analyzed retrospectively. There were 232 male and 217 female patients, aged from 3 to 55 years with a mean age of 17.3±11.2 years. Results    All the operations were completed successfully. Mean operative time was 2.4±0.3 h. The mean extracorporeal circulation time and aortic cross-clamp time was 64.2±11.6 min and 28.4±10.7 min, respectively. Mechanical ventilation time and intensive care unit stay was 6.9±3.8 h and 20.5±5.6 h, respectively. Postoperation drainage quantity was 213.1±117.2 mL. The hospital stay was 6.9±1.3 d. Intraoperative and postoperative complications occurred in 11 patients (2.4%), including 1 patient of intraoperative reoperation, 3 patients of reoperation for bleeding, 3 patients of the incision infection, 2 patients of small residual shunt, 1 patient of right femoral artery incision stenosis complicated by thromboembolism and 1 patient of right pleural cavity pneumothorax. The mean follow-up time was 72.2±33.9 months. During the period, there was no reoperation, but 2 patients of ventricular septal defect small residual shunt, 1 patient of mild-moderate mitral valve and 1 patient of mild-moderate aortic valve incompetence, respectively. During the period, heart function of the patients was NYHAⅠ-Ⅱ. Conclusion    Totally thoracoscopic cardiac surgery for ventricular septal defect is a safe and effective treatment, with few serious complications, fast recovery for patients and good short to medium-term outcomes.