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Objective: To screen the different expressed genes between osteosarcoma and normal osteoblasts, and find the key genes for the occurrence and development of osteosarcoma. Methods: The gene expression dataset GSE33382 of normal osteoblasts and osteosarcoma was obtained from Gene Expression Omnibus (GEO) database. The different expressed genes between normal osteoblasts and osteosarcoma were screened by limma package of R language, and the different expressed genes were analyzed by Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The protein interaction network was constructed by the String database, and the network modules in the interaction network were screened by the molecular complex detection (MCODE) plug-in of Cytoscape software. The different expressed genes contained in the first three main modules screened by MCODE were analyzed by gene ontology (GO) using the BiNGO module of Cytoscape software. The MCC algorithm was used to screen the top 10 key genes in the protein interaction network. The gene expression and survival dataset GSE39055 of osteosarcoma was obtained from GEO database, and the survival analysis was performed by Kaplan-Meier method. The data of 48 patients with osteosarcoma treated in the First Affiliated Hospital of Fujian Medical University from January 2005 to December 2015 were selected for verification. The expression of STC2 protein in osteosarcoma was detected by immunohistochemical method, and the survival analysis was carried out combined with the clinical data of the patients. Results: A total of 874 different expressed genes were identified from GSE33382 dataset, including 402 down-regulated genes and 472 up-regulated genes. KEGG enrichment analysis showed that different expressed genes were mainly related to p53 signal pathway, glutathione metabolism, extracellular matrix receptor interaction, cell adhesion molecules, folate tolerance, and cell senescence. The top 10 key genes in the interaction network were GAS6, IL6, RCN1, MXRA8, STC2, EVA1A, PNPLA2, CYR61, SPARCL1 and FSTL3. STC2 was related to the survival rate of patients with osteosarcoma ( P <0.05). The results showed that the expression of STC2 protein was related to tumor size and Enneking stage in 48 cases of osteosarcoma. The median survival time of 25 cases with STC2 high expression was 21.4 months, and that of 23 cases with STC2 low expression was 65.4 months. The survival rate of patients with high expression of STC2 was lower than that of patients with low expression of STC2 ( P <0.05). Conclusions: Bioinformatics analysis can effectively screen the different expressed genes between osteosarcoma and normal osteoblasts. STC2 is one of the important predictors for the prognosis of osteosarcoma.

Objectives: Esophagectomy is associated with significant morbidity and mortality. The authors assessed the relationship between intraoperative fluid (IOF) administration and postoperative pulmonary outcomes in patients undergoing a transthoracic, transhiatal, or tri-incisional esophagectomy., Design: Retrospective cohort study (level 3 evidence)., Setting: Tertiary care referral center., Participants: Patients who underwent esophagectomy from 2007 to 2017., Interventions: The IOF rate (mL/kg/h) was the predictor variable analyzed both as a continuous and binary categorical variable based on median IOF rate for this cohort (11.90 mL/kg/h)., Measurements: Primary outcomes included rates of acute respiratory distress syndrome (ARDS) within ten days after esophagectomy. Secondary outcomes included rates of reintubation, pneumonia, cardiac or renal morbidity, intensive care unit admission, length of stay, procedure-related complications, and mortality. Multivariate regression analysis determined associations between IOF rate and postoperative outcomes. Analysis was adjusted for age, sex, body mass index, procedure type, year, and thoracic epidural use., Main Results: A total of 1,040 patients comprised this cohort. Tri-incisional esophagectomy was associated with a higher hospital mortality rate (7.8%) compared with transthoracic esophagectomy (2.6%, p = 0.03) or transhiatal esophagectomy (0.7%, p = 0.01). Regression analysis revealed a higher IOF rate was associated with greater ARDS within ten days (adjusted odds ratio [OR] = 1.03, p = 0.01). For secondary outcomes, a higher IOF rate was associated with greater hospital mortality (adjusted OR = 1.05, p = 0.002), although no significant association with 30-day hospital mortality was identified., Conclusions: Increased IOF administration during esophagectomy may be associated with worse postoperative pulmonary complications, specifically ARDS. Future well-powered studies are warranted, including randomized, controlled trials comparing liberal versus restrictive fluid administration in this surgical population., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: A prolonged air leak (PAL) is the most frequent complication after pulmonary resection. This study aimed to assess the safety and efficacy of autologous blood patch pleurodesis (ABPP) to treat PAL., Methods: A prospectively maintained database identified patients with a PAL after pulmonary resection for lung cancer between 2015-2019. In this observational cohort study, clinical data were collected to retrospectively compare patients undergoing ABPP to no ABPP in a propensity-matched analysis. Kaplan Meier estimates and Cox models accounting for inverse probability weighting (IPTW) were used to assess the association of ABPP with each outcome., Results: Of the 740 patients undergoing lung resection, 110 (15%) were identified as having a PAL at postoperative day (POD) 5. There was no difference between baseline characteristics among those undergoing ABPP (n=34) versus no ABPP (n=76). Propensity-weighted analysis did not reveal a significant association of ABPP treatment with in-hospital complication (P=0.18), hospital length of stay (LOS) (P=0.13), or post-discharge complication (P=0.13). However, ABPP treatment was associated with a lower risk of hospital readmission [P=0.02, hazard ratio (HR) 0.16] and reoperation for air leak or empyema (P=0.05, HR 0.11). Although not statistically significant, the mean chest tube (CT) removal of 11 days for the ABPP group was less than the no ABPP group (16 days) (P=0.14, HR 1.5-2). Those treated with ABPP were less likely to be discharged with a CT (ABPP 7/34, 21% vs. no ABPP 40/76, 53%). There was no statistical difference in empyema development between groups (ABPP 0/34, 0% vs. no ABPP 4/76, 5%, P=0.39, HR 0.24)., Conclusions: ABPP administration is safe compared to traditional PAL management. In a retrospective propensity-matched analysis, postoperative patients treated with ABPP required less readmission and reoperation for PAL. Larger powered randomized trials may demonstrate the magnitude of benefit from treatment with ABPP., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-1761). The authors have no conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

Objectives: Neuroendocrine thymic tumours (NETTs) are a distinct subgroup of rare malignancies. An international, multicentre retrospective analysis was used to study the clinicopathological features, current pattern of diagnosis, treatment and outcomes of patients with NETT., Methods: One hundred and forty-six NETT treated from 1989 to 2016 at 21 centres in China, Europe and North America were retrospectively collected and reclassified according to the World Health Organization histological type and International Thymic Malignancy Interest Group (ITMIG)/International Association for Studies in Lung Cancer (IASLC)/Union for International Cancer Control (UICC) staging. Clinicopathological features, diagnostic and therapeutic approaches and outcomes were investigated. Results in the earlier and latter halves of the study period were also compared., Results: The pretreatment work-up relied exclusively on computed tomography in 85.6% (125/146) of cases. Most patients had advanced disease, with 32.2% (47/146) having lymph node involvement. Higher-grade histological type was associated with more advanced disease (P < 0.05). Induction therapies and surgical procedures were used more often in the latter half of the study. However, the complete resection rate remained unchanged, being 71.5% (98/137) in the whole group. Complete resection was associated with significantly longer 5-year overall survival (77.2% vs 51.2%; P < 0.001) than incomplete or no resection. Significant survival differences were seen with the T, N and M categories of ITMIG/IASLC/UICC staging. Poorly differentiated carcinoma, ITMIG/IASLC/UICC stage IIIa or above and incomplete or no resection were independent risk factors for worse survival. No survival difference was noted between the earlier and the latter halves of the study (58.2% vs 71.9%; P = 0.299)., Conclusions: Current management similar to that for thymomas is unsatisfactory in providing disease control or long-term survival for patients with NETT. Specific diagnostic tools and novel therapeutic agents are needed to improve management outcomes of this disease., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Osteosarcoma is the most common primary malignant bone tumor, particularly among children and adolescents, and the prognosis of osteosarcoma patients remains poor. The NADPH oxidase 2 (NOX2) has been found over-expressed in several human cancers, and closely associated with poor prognosis. Meanwhile the role of NOX2 in osteosarcoma patients has not been reported. This study aimed to investigate the clinicopathological and prognostic significance of NOX2 in osteosarcoma patients., Methods: Immunohistochemistry (IHC), western blot (WB) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to detect the expression of NOX2 in 55 primary osteosarcoma specimens and in 20 non-neoplastic bone tissue specimens. The correlations between NOX2 expression and clinicopathological parameters were analysed by using the χ2 test or Fisher's exact test. Disease free survival and overall survival of osteosarcoma patients were assessed by using the Kaplan-Meier method and Cox proportional hazards model., Results: NOX2 was over-expressed significantly in osteosarcoma compared with that in non-neoplastic bone tissue, and correlated with progression free survival (P < 0.001) and overall survival (P < 0.001). The over-expression of NOX2 was associated with tumor size (P < 0.001), tumor location (P < 0.001). The Cox analysed shown that the over-expression of NOX2 was predicted to be worse PFS (hazard ratio (HR) = 4.10, P = 0.004) and OS (hazard ratio (HR) = 3.50, P = 0.010) time in osteosarcoma patients., Conclusions: The results of our study suggest that the over-expression of NOX2 is related to adverse clinical outcome, and can be viewed as an independent prognostic marker in osteosarcoma. Further research is required to verify the predictive value of NOX2 in osteosarcoma patients., Competing Interests: Declaration of Competing Interest None of the authors have any conflict of interest., (Copyright © 2020 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Epiphrenic diverticulum is a rare and benign condition with significant surgical morbidity and evolving surgical management. The objective of this study was to analyze short-term clinical outcomes after surgery for epiphrenic diverticula. We conducted a retrospective cohort study in a single tertiary care center of all patients who underwent treatment for epiphrenic esophageal diverticula from June 1990 to December 2016. Data collection included demographics, operative details and short-term outcomes (esophageal leak, other complications, 30-day mortality). In addition, all preoperative imaging was reviewed by an esophageal radiologist in order to describe epiphrenic diverticula characteristics in a uniform and blinded manner. Of the 94 patients in the study, 84 patients were managed with an open surgical approach and 10 with minimally invasive techniques. Median size of diverticula was 5.5 cm and mean height above gastroesophageal junction was 4 cm. A myotomy was completed in 95% of patients and a fundoplication in 58%. The MIS group had a shorter length of stay (4 vs 6 days). Overall complication rate was 27% with an esophageal leak rate of 7% with 60% grade I leaks that sealed with conservative management. Complete resection of the diverticulum, closure of the muscle over the resection, contralateral myotomy, and consideration for partial fundoplication are common strategies utilized to surgically treat patients with epiphrenic diverticulum. Minimally invasive approaches are increasingly utilized., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Patient-reported reflux is among the most common symptoms after esophagectomy. This study aimed to determine predictors of patient-reported reflux and to ascertain whether a preserved pylorus would protect patients from symptomatic reflux., Methods: A prospective clinical study recorded patient-reported reflux after esophagectomy from August 2015 to July 2018. Eligible patients were at least 6 months from creation of a traditional posterior mediastinal gastric conduit, had completed at least 1 reflux questionnaire, and had the pylorus treated either temporarily (≥100 IU Botox [onabotulinumtoxinA]) or permanently (pyloromyotomy or pyloroplasty)., Results: Of the 110 patients meeting inclusion criteria, the median age was 65 years, and 88 of the 110 (80%) were male. Botox was used in 15 (14%) patients, pyloromyotomy in 88 (80%), and pyloroplasty in 7 (6%). A thoracic anastomosis was performed in 78 (71%) patients, and a cervical anastomosis was performed in 32 (29%). Esophagectomy was performed for malignant disease in 105 of 110 (95%), and 78 of 110 (71%) patients were treated with perioperative chemoradiation. Multivariable linear regression analysis revealed that patient-reported reflux was significantly worse in patients with shorter gastric conduit lengths (P = .02) and in patients who did not undergo perioperative chemoradiation (P = .01). No significant difference was found between patients treated with pyloric drainage and those treated with Botox., Conclusions: The absence of perioperative chemoradiation therapy and a shorter gastric conduit were predictors of patient-reported reflux after esophagectomy. Although few patients had Botox, preservation of the pylorus did not appear to affect patient-reported reflux. Further objective studies are needed to confirm these findings., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Osteosarcoma is a malignant bone tumor with extremely high invasion, metastasis and mortality. The prognosis of patients with osteosarcoma remains poor. The ErbB receptor family was found to be overexpressed in human cancers and associated with poor prognosis. However, the role of ErbB receptor family in osteosarcoma has not been fully understood. The present study aimed to investigate the clinicopathological and prognostic significances of ErbB receptors in primary osteosarcoma. Western blot (WB), reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization (FISH) were used to detect the protein and gene expression of ErbB receptors in 60 primary osteosarcoma specimens and 30 non-neoplastic bone tissues. WB and RT-qPCR analyses showed that the protein and mRNA expression levels of EGFR, ErbB3 and ErbB4 in osteosarcoma specimens were significantly higher than those in non-neoplastic bone tissues. Seventeen (28.33%), 15 (25.00%) and 15 (25.00%) osteosarcoma specimens presented with amplification of EGFR, ErbB3 and ErbB4 gene, respectively, which were significantly higher compared with non-neoplastic bone tissues. The amplification of ErbB3 and ErbB4 in osteosarcoma was associated with advanced surgical stage. The amplification of EGFR, ErbB3, ErbB4 and the co-amplification of EGFR-ErbB3, EGFR-ErbB4, ErbB3-ErbB4 was linked with poor response to chemotherapy and distant metastasis. The amplification of EGFR, ErbB3 and ErbB4, as well as their co-amplification demonstrated independent prognostic values for reduced survival time of osteosarcoma patients and may serve as potential therapeutic targets for osteosarcoma patients in the future.

According to the educational regulations in Taiwan, students are required to learn English when they are at the first grade of elementary school. However, not all the students have an appropriate environment to practice English, especially, for those students whose school is not located in the city. Thus, their English abilities in speaking, reading, and listening are poor. An intelligent tutoring system is used to help the students improve their English capabilities. This paper aims to provide a convenient tutoring environment, where teachers and students do not need to prepare a lot of teaching aids. They can teach and learn English whenever in the environment. Also, it proposes a method to verify the intelligent tutoring system using Petri nets. We have built the intelligent tutoring system based on Augmented Reality (AR), Text-to-Speech (TTS), and Speech Recognition (SR). This intelligent tutoring system is divided into two parts: one for teachers and the other for students. The experimental results have indicated that using Petri nets can help users verify the intelligent tutoring system for better learning performance and operate it correctly.

Objective: To determine the impact of histology on pathologic response, survival outcomes, and recurrence patterns in patients with esophageal cancer (EC) who received neoadjuvant chemoradiotherapy (CRT)., Summary of Background Data: There is a paucity of data regarding comparative outcomes after neoadjuvant CRT between esophageal squamous cell carcinoma (SCC) and adenocarcinoma., Methods: Between 2002 and 2015, 895 EC patients who underwent neoadjuvant CRT followed by esophagectomy at 3 academic institutions were retrospectively reviewed, including 207 patients with SCC (23.1%) and 688 patients with adenocarcinoma (76.9%). Pathologic response, survival, recurrence pattern, and potential prognostic factors were compared., Results: Pathologic complete response (pCR) rate was significantly higher for SCC compared with adenocarcinoma (44.9% vs 25.9%, P < 0.001). After a median follow-up of 52.9 months, 71 patients (34.3%) with SCC versus 297 patients (43.2%) with adenocarcinoma had recurrent disease (P = 0.023). For patients who achieved a pCR, no significant differences were found in recurrence pattern, sites, or survival end-points between the 2 histology groups. For non-pCR patients, the SCC group demonstrated significantly higher regional and supraclavicular recurrence rates but a lower hematogenous metastasis rate than adenocarcinoma patients, whereas the adenocarcinoma patients had a more favorable locoregional failure-free survival (P = 0.005) and worse distant metastasis-free survival (P = 0.024). No differences were found in overall survival (P = 0.772) or recurrence-free survival (P = 0.696) between groups., Conclusions: SCC was associated with a significantly higher pCR rate than adenocarcinoma. Recurrence pattern and survival outcomes were significantly different between the 2 histology subtypes in non-pCR patients.

Background: Postoperative chylothorax can be managed by any or all of observation, parenteral nutrition, surgical duct ligation, pleurodesis, or thoracic duct embolization. The objective of this study was to determine the efficacy of standard therapies, such as surgical duct ligation and observation, compared with newer treatment methods (thoracic duct embolization)., Methods: A prospectively maintained database at a single institution was used to identify and review patients with postoperative chylothorax from 2008 to 2015., Results: Postoperative chylothorax occurred in 97 patients, including 54 men (56%). The median age was 61 years (range, 24 to 87 years). Thoracic duct leak followed esophagectomy in 46 patients (47%), pulmonary resection in 30 (31%), mediastinal mass resection in 7 (8%), and after other procedures in 15. Of 28 medically observed patients achieving resolution without intervention, the median peak chest tube output in 24 hours was 725 mL compared with 1,910 mL in the group that required intervention (p = 0.0001). Thoracic duct ligation was successful in 44 of 52 patients that proceeded to the operating room (85%). Of the 40 patients undergoing diagnostic lymphangiography, a leak was identified in 34 (85%), but the cisterna chyli could only be cannulated in 19 (48%) and was subsequently successful in 15 (38%)., Conclusions: Patients with chylous chest tube outputs of 1,100 mL or more in 24 hours postoperatively should be considered for intervention. Intention-to-treat analysis shows surgical duct ligation is more effective than thoracic duct embolization, with the ability to cannulate the cisterna chyli being the limiting factor. Lymphangiography may help determine which patients are better treated with ligation or embolization., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: We aimed to compare long-term survival and quality of life (QOL) outcomes after bilobectomy and lobectomy for non-small cell lung cancer patients., Methods: A cohort of 951 consecutive patients was identified from a single treatment institution, of whom 128 underwent bilobectomy and 823, lobectomy. Propensity score matching (1:3) was applied to balance known confounders between the two surgical groups and resulted in 512 patients (matched cohort). Unmatched and matched analyses were performed to compare clinical outcomes between the two groups, including operative mortality rate, morbidity rate, long-term survival, overall QOL, and specific symptoms., Results: Operative mortality was higher in the bilobectomy group than in the lobectomy group (2.3% versus 0.5%, p = 0.022). Morbidity rates did not differ significantly between the two groups in either unmatched or matched cohort. In the unmatched analysis, the overall survival (OS [p = 0.003]) and disease-free survival (DFS [p = 0.003]) were significantly lower in the bilobectomy group; whereas in the matched analysis, no significant difference was found in either OS (p = 0.473) or DFS (p = 0.387). Using multivariate analysis, the operation type was not found to be a significant factor for either OS (hazard ratio 1.18; 95% confidence interval: 0.91 to 1.52; p = 0.22) or DFS (hazard ratio 1.22; 95% confidence interval: 0.95 to 1.58; p = 0.13). Patients who underwent bilobectomy appeared to have similar measures of QOL as lobectomy patients, except for coughing and dyspnea., Conclusions: Our findings indicate that patients with non-small cell lung cancer treated with bilobectomy had similar morbidity, OS, DFS, and overall QOL as patients treated with lobectomy, but had higher mortality by matched analysis., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)