Background and purpose:Epithelial ovarian cancer(EOC)has a poor prognosis and is prone to developing resistance to platinum-based chemotherapy.Exosomes are currently believed to be involved in platinum resistance in ovarian cancer.This study explored the role and mechanism of exosomes on platinum resistance of ovarian cancer.Methods:Through ultracentrifugation,exosomes were isolated and analyzed using electron microscopy,particle size studies,and Western blot for detailed exosome analysis.We detected the expression levels of exosomal proteins and related signaling pathways.Exosomal protein expression profile was analyzed by proteomics.Key differential proteins were screened by intersecting with existing drug resistance datasets.Furthermore,patients diagnosed with EOC via pathological analysis at the Fudan University Shanghai Cancer Center from August 2023 to August 2024,who underwent surgery and fulfilled the eligibility requirements,were gathered to examine the link between the expression of interferon-stimulated gene 15(ISG15)in serum exosomes and resistance to platinum medication.The expression levels of related proteins in serum exosomes were quantitatively detected by enzyme-linked immunosorbent assay(ELISA).Receiver operating characteristic(ROC)curve was plotted to explore the predictive value of serum exosomal protein in ovarian cancer resistance.Results:Exosomes derived from platinum-sensitive and drug-resistant ovarian cancer cells were extracted and proteomic analysis was further performed.We identified 9 differential proteins associated with platinum-resistance and found the key molecule interferon-stimulated gene 15(ISG15).Compared with sensitive cells,the expression of ISG15 in exosomes of drug-resistant ovarian cancer cells was significantly upregulated.Exosome tracer tests showed that exosomes were successfully taken up by ovarian cancer receptor cells.After coculture with drug-resistant exosomes,the expression level of ISG15 in ovarian cancer receptor cells was increased.Knockdown ISG15 in EOC cells decreased the expression of ISG15 in exosomes,and incubation of ISG15-knockdown exosomes decreased the cell viability on the condition of platinum drugs,indicating that ISG15 in exosomes regulated platinum resistance of ovarian cancer cells.Moreover,ISG15 could regulate the expression of multidrug resistance protein 1(MDR1)through phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/nuclear factor-kappa-light-chain-enchancer of activated B cells(NF-κB)signaling pathway.This study included a total of 87 patients.Clinical serum samples also showed that the expression of ISG15 in exosomes was higher in platinum-resistant ovarian cancer patients than in sensitive ovarian cancer patients.Using serum exosomal ISG15 as an indicator to distinguish between sensitivity and resistance,the area under ROC curve was 0.779(P＜0.05),cutoffvalue was 27.35ng/mL,sensitivity was 70.2%,and specificity was 76.4%.Conclusion:ISG15 in exosomes can regulate the expression of MDR1 in ovarian cancer cells through PI3K/AKT/NF-κB signaling pathway,and promote platinum resistance in ovarian cancer cells.

Background and purpose:Epithelial ovarian cancer(EOC)has a poor prognosis and is prone to developing resistance to platinum-based chemotherapy.Exosomes are currently believed to be involved in platinum resistance in ovarian cancer.This study explored the role and mechanism of exosomes on platinum resistance of ovarian cancer.Methods:Through ultracentrifugation,exosomes were isolated and analyzed using electron microscopy,particle size studies,and Western blot for detailed exosome analysis.We detected the expression levels of exosomal proteins and related signaling pathways.Exosomal protein expression profile was analyzed by proteomics.Key differential proteins were screened by intersecting with existing drug resistance datasets.Furthermore,patients diagnosed with EOC via pathological analysis at the Fudan University Shanghai Cancer Center from August 2023 to August 2024,who underwent surgery and fulfilled the eligibility requirements,were gathered to examine the link between the expression of interferon-stimulated gene 15(ISG15)in serum exosomes and resistance to platinum medication.The expression levels of related proteins in serum exosomes were quantitatively detected by enzyme-linked immunosorbent assay(ELISA).Receiver operating characteristic(ROC)curve was plotted to explore the predictive value of serum exosomal protein in ovarian cancer resistance.Results:Exosomes derived from platinum-sensitive and drug-resistant ovarian cancer cells were extracted and proteomic analysis was further performed.We identified 9 differential proteins associated with platinum-resistance and found the key molecule interferon-stimulated gene 15(ISG15).Compared with sensitive cells,the expression of ISG15 in exosomes of drug-resistant ovarian cancer cells was significantly upregulated.Exosome tracer tests showed that exosomes were successfully taken up by ovarian cancer receptor cells.After coculture with drug-resistant exosomes,the expression level of ISG15 in ovarian cancer receptor cells was increased.Knockdown ISG15 in EOC cells decreased the expression of ISG15 in exosomes,and incubation of ISG15-knockdown exosomes decreased the cell viability on the condition of platinum drugs,indicating that ISG15 in exosomes regulated platinum resistance of ovarian cancer cells.Moreover,ISG15 could regulate the expression of multidrug resistance protein 1(MDR1)through phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/nuclear factor-kappa-light-chain-enchancer of activated B cells(NF-κB)signaling pathway.This study included a total of 87 patients.Clinical serum samples also showed that the expression of ISG15 in exosomes was higher in platinum-resistant ovarian cancer patients than in sensitive ovarian cancer patients.Using serum exosomal ISG15 as an indicator to distinguish between sensitivity and resistance,the area under ROC curve was 0.779(P＜0.05),cutoffvalue was 27.35ng/mL,sensitivity was 70.2%,and specificity was 76.4%.Conclusion:ISG15 in exosomes can regulate the expression of MDR1 in ovarian cancer cells through PI3K/AKT/NF-κB signaling pathway,and promote platinum resistance in ovarian cancer cells.

Objective:To construct a feature visualization system utilizing deep learning for superficial esophageal squamous cell carcinoma (SESCC) under magnifying endoscopy with narrow band imaging (ME-NBI) to predict the infiltration depth of SESCC.Methods:The feature visualization system consisted of four models: two for segmenting the intrapapillary capillary loops (IPCL) area and avascular area (AVA) in ME-NBI images of SESCC lesions (models 1 and 2, respectively), one for obtaining the principal component of color (PCC) in ME-NBI images of SESCC lesions (model 3), and another for automatically predicting the depth of SESCC infiltration based on the features extracted from the first three models (model 4). A total of 2 341 ME-NBI images of SESCC lesions from April 2016 to October 2021 were used to develop the feature visualization system, which was divided into 3 datasets: dataset 1 (1 077 ME-NBI images) was used to train and test models 1-3, dataset 2 (1 069 ME-NBI images) was expanded by 20 times through feature combination to generate 21 380 feature synthetic images to train and test model 4, and dataset 3 (195 ME-NBI images), containing 146 ME-NBI images with lesion invasion depth from the epithelium to the upper 1/3 of the submucosa (EP-SM1), and 49 ME-NBI images with lesion invasion depth from the middle 1/3 to the lower 1/3 of the submucosa (SM2-SM3), was used to validate the diagnostic performance of the feature visualization system in predicting the invasion depth of SESCC (EP-SM1/SM2-SM3). In order to evaluate the superiority of the feature visualization system, the prediction results of dataset 3 of the traditional deep learning system (trained directly with ME-NBI images), single-item feature models (single-item IPCL feature model, single-item AVA feature model and single-item PCC feature model) were compared with the prediction results of the feature visualization system. In order to evaluate the clinical utility of the feature visualization system, 4 expert physicians (with more than 10 years of endoscopic operation, expert physician group) and 5 senior physicians (with more than 5 years of endoscopic operation, senior physician group) were invited to participate in the human-computer competition to diagnose dataset 3, and the results were compared with the feature visualization system.Results:The accuracy, sensitivity and specificity of the feature visualization system in predicting the invasion depth of SESCC (EP-SM1/SM2-SM3) were 83.08% (162/195), 82.88% (121/146) and 83.67% (41/49), respectively. The above indicators were 60.00% (117/195), 52.05% (76/146) and 83.67% (41/49) for the traditional deep learning system, 74.87% (146/195), 75.34% (110/146) and 73.47% (36/49) for the single IPCL feature model, 58.97% (115/195), 60.27% (88/146) and 55.10% (27/49) for single AVA feature model, 71.28% (139/195), 71.23% (104/146) and 71.43% (35/49) for single PCC feature model, respectively. The results were 66.67%, 78.22% and 32.24% in senior physician group, and 72.31%, 85.96% and 31.63% in expert physician group, respectively. The accuracy of the feature visualization system in predicting the invasion depth of SESCC was significantly higher than that of the other 6 groups ( P<0.05). The sensitivity of feature visualization system was slightly higher than that of senior physician group ( χ2=1.59, P=0.21) and single-item IPCL feature model ( χ2=2.51, P=0.11), slightly lower than that of expert physician group ( χ2=0.89, P=0.35), and significantly higher than that of three other groups ( P<0.05). The specificity of the feature visualization system was similar to the traditional deep learning system ( χ2=0.00, P=1.00), slightly higher than that of single-item IPCL feature model ( χ2=1.52, P=0.22) and single-item PCC feature model (χ2=2.11, P=0.15), and significantly higher than that of the single AVA feature model ( χ2=9.42, P<0.01), senior physician group ( χ2=44.71, P<0.01) and expert physician group ( χ2=43.57, P<0.01). Conclusion:The developed deep learning-based feature visualization system using ME-NBI shows excellent diagnostic performance in predicting the infiltration depth of SESCC (EP-SM1/SM2-SM3), surpassing the accuracy levels of experienced endoscopists with over 10 years of experience.

Background and purpose:The plasma used for routine coagulation test(CCT)can only reflect a single component at a certain coagulation time point/segment,while thromboelastography(TEG)can depict the overall dynamic process curve of coagulation and fibrinolysis,which can more independently and completely reflect the true state of the blood and can serve as a supplement to coagulation function testing.This study aimed to evaluate the application value of combined coagulation function indexes in monitoring the hypercoagulable state of patients with colorectal cancer after chemotherapy,and to explore the risk factors of thrombosis in patients with colorectal cancer after chemotherapy,so as to provide reference for clinical monitoring of hypercoagulable state.Methods:A total of 160 patients with colorectal cancer from Fudan University Shanghai Cancer Center from June 2021 to June 2023 were selected as the experimental group,and 80 healthy subjects were selected as the control group.Then the experimental group was divided into a group without thrombosis(82 cases)and a group with thrombosis(78 cases)according to whether they had thrombosis or not.The determinations of thromboelastography(TEG)[coagulation reaction time(R),coagulation formation time(K),blood clot formation rate(α-Angle),maximum amplitude(MA)and coagulation index(CI)],conventional coagulation tests(CCT)[activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(Fib),D-dimer(DD),fibrinogen degradation products(FDP)]and platelet count(PLT)were studied among three groups.With or without thrombosis as the criterion of hypercoagulable state,statistically significant indicators were selected to be included in the binary logistic regression analysis,and the receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic efficacy of single and combined detection of the coagulation function indicators for hypercoagulable state in patients with colorectal cancer after chemotherapy.Basic information,tumor stage and Autar score of deep vein thrombosis were collected in 160 patients with colorectal cancer.Logistic regression analysis was performed to explore the risk factors of thrombosis.This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(number:050432-4-2108*).Results:Compared with the control group,the R,TT and PLT of the group with thrombosis were decreased(P＜0.05),while APTT,PT,DD and FDP were increased(P＜0.05).The differences in various indicators between the group with thrombosis and the control group were statistically significant(P＜0.05).Compared with the group without thrombosis,the K in the group with thrombosis decreased(P＜0.05),while Angle,MA,CI,FIB,DD and FDP all increased(P＜0.05).ROC curve analysis showed that in the assessment of hypercoagulable state in patients with colorectal cancer after chemotherapy,the area under curve(AUC)of TEG was 0.756,sensitivity was 67.5%,and specificity was 73.8%.The AUC of CCT was 0.691,sensitivity was 78.8%,and specificity was 56.2%.The combined detection AUC was 0.840,sensitivity was 80.0%,and specificity was 77.5%.In the analysis of risk factors,tumor stage,distant metastasis and Autar score were correlated with thrombus formation in patients with colorectal cancer after chemotherapy(P＜0.05),and the differences of the three risk factors in K,Angle,MA,CI,Fib,DD and FDP were statistically significant(P＜0.05).Conclusion:K,Angle,MA,CI,Fib,DD and FDP are the main indicators to reflect the hypercoagulable state,and the combined detection of TEG and CCT can better reflect the coagulation state of patients with colorectal cancer after chemotherapy.Tumor stage Ⅲ to Ⅳ,distant metastasis and high Autar score are risk factors for thrombosis.The incidence of thrombosis can be reduced by monitoring the relevant coagulation indicators in the high-risk population.

Objective To investigate the safety and efficacy of totally no tube three-port thoracoscopic surgery (TNTT) for thymic tumor via lateral thoracic approach. Methods The clinical data of patients with thymoma admitted to the Department of Thoracic Surgery of the General Hospital of Northern Theater Command from November 2021 to May 2022 were retrospectively analyzed. The patients were divided into a TNTT group and a single utility port video-assisted thoracic surgery (SVATS) group according to different surgical methods. The clinical data were compared between the two groups. Results A total of 111 patients were collected. There were 44 patients in the TNTT group, including 20 males and 24 females, with an average age of 60.11±8.64 years, and 67 patients in the SVATS group, including 30 males and 37 females, with an average age of 62.40±7.92 years. There was no significant difference between the two groups in the baseline data (P>0.05). The postoperative hospital stay and intraoperative blood loss were shorter or less in the TNTT group (P<0.05), and the visual analogue scale score 48 hours after the operation was smaller in the SVATS group (P<0.05). Conclusion TNTT has a good surgical safety, and can shorten postoperative hospital stay, reduce intraoperative blood loss, and has significant advantages in enhanced recovery after surgery, but SVATS can reduce postoperative pain in patients.

Objective     To compare the clinical efficacy and safety of da Vinci robot with totally no tube (TNT) versus subxiphoid video-assisted thymectomy surgery (SVATS) in the treatment of thymic tumors. Methods     From 2019 to 2021, a retrospective analysis was conducted on patients with thymic tumor resection in the Department of Thoracic Surgery, General Hospital of Northern Theater Command. All patients underwent total thymectomy and mediastinal fat removal, and they were divided into a TNT group and a SVATS group according to the operation method. The intraoperative blood loss, conversion rate, postoperative visual analogue score (VAS), postoperative hospital stay time and postoperative complications were compared between the two groups. Results     We finally included 435 patiets. There were 168 patients with 83 males and 85 females at an average age of 61.920±9.210 years in the TNT group and 267 patients with 147 males and 120 females at an average age of 61.460±8.119 years in the SVATS group. There was no death or postoperative myasthenic crisis in both groups. There was no statistical difference in postoperative hospital stay (1.540±0.500 d vs. 3.400±0.561 d, P=0.000), intraoperative blood loss (13.450±5.498 mL vs. 108.610±54.462 mL, P=0.000), postoperative 24 h VAS score (4.960±1.757 points vs. 3.600±1.708 points, P=0.000), or postoperative complication rate (3.0% vs. 11.6%, P=0.001). Conclusion     TNT is a more efficient, safe, and effective surgical approach for treating thymic tumors, which can shorten hospital stay time and reduce postoperative complications. However, SVATS can minimize postoperative pain.

Resection is one of the most important treatments for esophageal squamous cell carcinoma, and routine postoperative follow-up is an effective method for early detection and treatment of recurrent metastases, which can improve patients' quality of life and prognosis. This consensus aims to provide a reference for colleagues responsible for postoperative follow-up of esophageal squamous cell carcinoma patients in China, and further improve the standardization of the diagnosis and treatment of esophageal squamous cell carcinoma.

Objective:To develop an artificial intelligence-based system for measuring the size of gastrointestinal lesions under white light endoscopy in real time.Methods:The system consisted of 3 models. Model 1 was used to identify the biopsy forceps and mark the contour of the forceps in continuous pictures of the video. The results of model 1 were submitted to model 2 and classified into open and closed forceps. And model 3 was used to identify the lesions and mark the boundary of lesions in real time. Then the length of the lesions was compared with the contour of the forceps to calculate the size of lesions. Dataset 1 consisted of 4 835 images collected retrospectively from January 1, 2017 to November 30, 2019 in Renmin Hospital of Wuhan University, which were used for model training and validation. Dataset 2 consisted of images collected prospectively from December 1, 2019 to June 4, 2020 at the Endoscopy Center of Renmin Hospital of Wuhan University, which were used to test the ability of the model to segment the boundary of the biopsy forceps and lesions. Dataset 3 consisted of 302 images of 151 simulated lesions, each of which included one image of a larger tilt angle (45° from the vertical line of the lesion) and one image of a smaller tilt angle (10° from the vertical line of the lesion) to test the ability of the model to measure the lesion size with the biopsy forceps in different states. Dataset 4 was a video test set, which consisted of prospectively collected videos taken from the Endoscopy Center of Renmin Hospital of Wuhan University from August 5, 2019 to September 4, 2020. The accuracy of model 1 in identifying the presence or absence of biopsy forceps, model 2 in classifying the status of biopsy forceps (open or closed) and model 3 in identifying the presence or absence of lesions were observed with the results of endoscopist review or endoscopic surgery pathology as the gold standard. Intersection over union (IoU) was used to evaluate the segmentation effect of biopsy forceps in model 1 and lesion segmentation effect in model 3, and the absolute error and relative error were used to evaluate the ability of the system to measure lesion size.Results:(1)A total of 1 252 images were included in dataset 2, including 821 images of forceps (401 images of open forceps and 420 images of closed forceps), 431 images of non-forceps, 640 images of lesions and 612 images of non-lesions. Model 1 judged 433 images of non-forceps (430 images were accurate) and 819 images of forceps (818 images were accurate), and the accuracy was 99.68% (1 248/1 252). Based on the data of 818 images of forceps to evaluate the accuracy of model 1 on judging the segmentation effect of biopsy forceps lobe, the mean IoU was 0.91 (95% CI: 0.90-0.92). The classification accuracy of model 2 was evaluated by using 818 forceps pictures accurately judged by model 1. Model 2 judged 384 open forceps pictures (382 accurate) and 434 closed forceps pictures (416 accurate), and the classification accuracy of model 2 was 97.56% (798/818). Model 3 judged 654 images containing lesions (626 images were accurate) and 598 images of non-lesions (584 images were accurate), and the accuracy was 96.65% (1 210/1 252). Based on 626 images of lesions accurately judged by model 3, the mean IoU was 0.86 (95% CI: 0.85-0.87). (2) In dataset 3, the mean absolute error of systematic lesion size measurement was 0.17 mm (95% CI: 0.08-0.28 mm) and the mean relative error was 3.77% (95% CI: 0.00%-10.85%) when the tilt angle of biopsy forceps was small. The mean absolute error of systematic lesion size measurement was 0.17 mm (95% CI: 0.09-0.26 mm) and the mean relative error was 4.02% (95% CI: 2.90%-5.14%) when the biopsy forceps was tilted at a large angle. (3) In dataset 4, a total of 780 images of 59 endoscopic examination videos of 59 patients were included. The mean absolute error of systematic lesion size measurement was 0.24 mm (95% CI: 0.00-0.67 mm), and the mean relative error was 9.74% (95% CI: 0.00%-29.83%). Conclusion:The system could measure the size of endoscopic gastrointestinal lesions accurately and may improve the accuracy of endoscopists.

Objective: To explore the effect of intensive care on the comfort of patients after pacemaker implantation. Methods: 36 patients admitted from January 2016 to May 2017 were selected as routine care group, and 38 patients admitted from June 2017 to October 2018 were selected as cluster care group. Routine care was given in the postoperative routine care group, and intensive care was given in the intensive care group until the day before the postoperative discharge. The changes in comfort score, anxiety score, and lumbar and back pain score of the two groups were recorded and compared on the day before the surgery and the day before discharge. Results: There were no statistically significant differences in comfort score, lumbar and back pain score and SAS score between the intensive care group and the preoperative conventional care group (all P > 0.05). Postoperative comfort score (43.71±3.29, 73.27±4.37), lumbar and back pain score (4.31±1.07, 1.56±1.04) and SAS score (53.49±6.18, 38.29±7.35) in the intensive care group were significantly better than those in the conventional care group, with statistically significant differences (t=8.478, 3.218, 6.293, all P < 0.05). Conclusion The application of bundles of care after pacemaker implantation can effectively improve patients′ body discomfort, cardiac rehabilitation effect and quality of life, which is worthy of clinical promotion.

Objective To prospectively study the clinical diversity of the middle and lower segment of stage of esophageal cancer patients who accepted the thoracoscopic combined with laparoscopic esophagectomy ( TLE) between Mongolian and Han nationalities in Inner Mongolia , to further clarity the feasibility of TLE.Methods 92 consecutive cases of middle and lower segment of stage of esophageal cancer patients of Mongolian and Han were selected,and the patients accepted the TLE ,including 41 cases of Mongolian and 51 cases of Han.The postoperative pain was evaluated with the visual analog scale (VAS) at 1-14d after operation,and the postoperative complication , the hospitalization of postoperation and the postoperative pathological situation were compared .Results Compared with the Han patients,the postoperative pain of Mongolian significantly reduced ,duration of postoperative of pain significantly shorter in the 1-5 d after surgery(P <0.05).Mongolian patients turned to mild pain in the second day of the postoperative period,and Han turned to mild pain in the fourth day after surgery .The postoperative pain in the 6-14 d after surgery of the Mongolian was not significantly different from Han (P >0.05).The Mongolian had lower incidence rate of postoperative complication compared with Han (9.8% vs.27.5%,χ2 =4.522,P <0.05).For example,the incidence rates of respiratory complications in Mongolian patients ,such as pulmonary infection,atelectasis and the occurrence of pleural effusion that need to be treated were significantly lower than those in Han (7.3% vs. 23.5%,2.4% vs.15.7%,4.9% vs.19.6%,P <0.05).There was no statistically significant difference in the incidence of other complications(P >0.05).The postoperative hospitalization of Mongolian was significantly shorter than that of Han[(11.9 ±1.2) d vs.(15.5 ±1.0) d,t =-15.811,P <0.05].No significant difference in the total number of cases of lymph node dissection ,the abdominal lymph node dissection and the chest lymph node dissection . The number of the regional lymph nodes metastasis of Mongolian was higher than that of Han [(3.9 ±0.7) vs. (1.8 ±0.7),t =13.460,P <0.05],most of which were poorly differentiated (6 /25/10 vs 20 /20 /11,χ2 =7.139, P <0.05).Meanwhile,the incidence rates of cancer embolus in the vasculature and nerve invasion of Mongolian were higher than those of Han(75.6% vs.47.1%,70.7% vs.17.6%,χ2 =7.706,26.418,all P <0.05).Conclusion The Mongolian were more easily tolerant to the TLE,which has the advantages of reducing pain ,trauma,rapid recovery, satisfactory curative effect and the lesser postoperative complications .The degree of the malignancy of esophageal cancer of Mongolian was higher than Han .Mongolian who suffered from esophageal cancer needed earlier discovery , earlier treatment and further research of the causes of difference .