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Background: Non-magnifying endoscopy with narrow-band imaging (NM-NBI) has been frequently used in routine screening of esophagus squamous cell carcinoma (ESCC). The performance of NBI for screening of early ESCC is, however, significantly affected by operator experience. Artificial intelligence may be a unique approach to compensate for the lack of operator experience., Aim: To construct a computer-aided detection (CAD) system for application in NM-NBI to identify early ESCC and to compare it with our previously reported CAD system with endoscopic white-light imaging (WLI)., Methods: A total of 2167 abnormal NM-NBI images of early ESCC and 2568 normal images were collected from three institutions (Zhongshan Hospital of Fudan University, Xuhui Hospital, and Kiang Wu Hospital) as the training dataset, and 316 pairs of images, each pair including images obtained by WLI and NBI (same part), were collected for validation. Twenty endoscopists participated in this study to review the validation images with or without the assistance of the CAD systems. The diagnostic results of the two CAD systems and improvement in diagnostic efficacy of endoscopists were compared in terms of sensitivity, specificity, accuracy, positive predictive value, and negative predictive value., Results: The area under receiver operating characteristic curve for CAD-NBI was 0.9761. For the validation dataset, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CAD-NBI were 91.0%, 96.7%, 94.3%, 95.3%, and 93.6%, respectively, while those of CAD-WLI were 98.5%, 83.1%, 89.5%, 80.8%, and 98.7%, respectively. CAD-NBI showed superior accuracy and specificity than CAD-WLI ( P = 0.028 and P ≤ 0.001, respectively), while CAD-WLI had higher sensitivity than CAD-NBI ( P = 0.006). By using both CAD-WLI and CAD-NBI, the endoscopists could improve their diagnostic efficacy to the highest level, with accuracy, sensitivity, and specificity of 94.9%, 92.4%, and 96.7%, respectively., Conclusion: The CAD-NBI system for screening early ESCC has higher accuracy and specificity than CAD-WLI. Endoscopists can achieve the best diagnostic efficacy using both CAD-WLI and CAD-NBI., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Histone deacetylase 2 (HDAC2), a member of the Histone deacetylase family, plays a vital role in various carcinomas. In this study, we identified that HDAC2 expression levels are associated with liver metastasis, higher T stages and poor prognosis in colorectal cancer. HDAC2 down-regulation via lentivirus-mediated expression of HDAC2-targeting shRNA reduced the in vitro migration and invasion ability of HCT116 cell as well as their liver metastasis in nude mouse xenografts. Mechanistically, HDAC2 promotes epithelial-mesenchymal transition (EMT) in colorectal cancer cells by combining HDAC1 with EZH2 (a key histone methyltransferase), possibly through the modular scaffold function of a new lncRNA, ENSG00000274093.1. HDAC2 thus appears to promote CRC cell migration and invasion through binding HDAC1 and EZH2 via ENSG00000274093.1., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: The use of a self-expandable metallic stent (SEMS) as a bridge to surgery has increased for patients with obstructing colorectal cancer. However, relatively few reports have compared SEMS as a bridge to elective surgery for acute malignant obstruction of the right-sided colon (MORC) vs. emergency surgery (ES). This study aimed to evaluate the benefits of elective surgery after SEMS placement vs. ES for patients (including stage IV cases) with acute MORC., Methods: Patients with acute MORC who underwent radical resection for a primary tumour from July 2008 to November 2016 at Zhongshan Hospital of Fudan University were retrospectively enrolled. Postoperative short-term outcomes, progression-free survival (PFS), and overall survival (OS) were compared between the SEMS and ES groups., Results: In total, 107 patients with acute MORC (35 in the SEMS group and 72 in the ES group) were included for analysis. The Intensive Care Unit admission rate was lower (11.4% vs. 34.7%, P = 0.011), the incidence of complications was reduced (11.4% vs. 29.2%, P = 0.042), and the postoperative length of hospitalisation was significantly shorter (8.23 ± 6.50 vs. 11.18 ± 6.71 days, P = 0.033) for the SEMS group. Survival curves showed no significant difference in PFS (P = 0.506) or OS (P = 0.989) between groups. Also, there was no significant difference in PFS and OS rates between patients with stage II and III colon cancer. After colectomy for synchronous liver metastases among stage IV patients, the hepatectomy rates for the SEMS and ES groups were 85.7% and 14.3%, respectively (P = 0.029). The hazard ratio for colectomy alone vs. combined resection was 3.258 (95% CI 0.858-12.370; P = 0.041)., Conclusion: Stent placement offers significant advantages in terms of short-term outcomes and comparable prognoses for acute MORC patients. For synchronous liver metastases, SEMS placement better prepares the patient for resection of the primary tumour and liver metastasis, which contribute to improved survival.

Taking the "9.3" military parade in 2015 and two red alerts of heavy air pollution in December of the same year as examples, the characteristics of meteorological factors and pollutant concentration variation were compared. Based on the estimation of pollutant emission reduction under different periods, the WRF-CAMx model was used to evaluate the effect of PM 2.5 pollution improvement. The results showed that the daily average PM 2.5 concentration (19.0 μg·m -3 ) during the parade (from August 20 to September 4) decreased by 60.0% and 48.0%, respectively, in comparison to that before (August 15-19) and after (September 5-15) the parade. The daily average PM 2.5 concentration (232.3 μg·m -3 ) during the first red alert period was higher than that of the second red alert (216.6 μg·m -3 ). The air quality before the second red alert was better than that before the first red alert. The proportion of emission reduction during the parade was generally larger than that during the red alert periods, which provided a controllable and favorable condition for the realization of the "Parade Blue". The PM 2.5 concentration in Beijing decreased by 32.4%, 17.1%, and 22.0% under the control measures during the periods of the "9.3" parade, the first red alert, and second red alert, respectively. The higher proportion of PM 2.5 concentration reduction could be attributed to the more intensive regional emission reduction and the favorable meteorological conditions. The intensity of the pollution reduction, the timing of the implementation of emergency control measures, and meteorological conditions were the most important factors that may have influenced the improvement of pollution.

Background: Peroral endoscopic myotomy (POEM) is a safe and effective approach for achalasia. However, the safety, feasibility, perioperative and long-term efficacy in treating geriatric patients has not been well evaluated., Methods: Data of 2367 patients diagnosed with achalasia and treated with POEM in the Endoscopy Center, Zhongshan Hospital, Fudan University from August 2010 to December 2017 were retrospectively reviewed. Last follow-up was in December 2018. Propensity score matching based on baseline characteristics was used to adjust for confounding. With a caliper of 0.01 in propensity scoring, 139 patients aged ≥ 65 years were matched at a 1:2 ratio with 275 patients aged < 65 years. Perioperative complications and long-term outcomes were compared between the two groups., Results: After propensity score matching, the two groups had similar baseline clinical characteristics and distribution of propensity scores. The mean age was 70.22 years in geriatric patients and 42.02 in younger patients. Technical failure occurred in one geriatric and one non-geriatric patients (p = 0.485). The procedural time in geriatric patients was similar to younger patients [50 (interquartile range (IQR) 36-76) vs. 50 (IQR 36-70) min, p = 0.398]. There were also no significant differences in major perioperative adverse events (2.88% vs. 2.18%, p = 0.663) and hospitalization length (median 3 vs. 3 days, p = 0.488). During a median follow-up period of 41 months (IQR 26-60), mean decrease in Eckardt score and pressure of the LES were 6.63 and 11.9 mmHg in geriatric patients, which were similar to the change in non-geriatric patients (6.49 and 11.6 mmHg, p = 0.652 and 0.872, respectively). Clinical reflux occurred in 23.53% geriatric patients and 21.59% non-geriatric patients (p = 0.724). 5-year success rate of 92.94% was achieved in geriatric patients and 92.61% in younger patients (log-rank p = 0.737)., Conclusions: POEM is a safe and reliable treatment in geriatric achalasia patients with confirmed short-term and long-term efficacy compared with those in non-geriatric patients.

All known riboswitches use their aptamer to senese one metabolite signal and their expression platform to regulate gene expression. Here, we characterize a SAM-I riboswitch (SAM-I Xcc ) from the Xanthomonas campestris that regulates methionine synthesis via the met operon. In vitro and in vivo experiments show that SAM-I Xcc controls the met operon primarily at the translational level in response to cellular S-adenosylmethionine (SAM) levels. Biochemical and genetic data demonstrate that SAM-I Xcc expression platform not only can repress gene expression in response to SAM binding to SAM-I Xcc aptamer but also can sense and bind uncharged initiator Met tRNA, resulting in the sequestering of the anti-Shine-Dalgarno (SD) sequence and freeing the SD for translation initiation. These findings identify a SAM-I riboswitch with a dual functioning expression platform that regulates methionine synthesis through a previously unrecognized mechanism and discover a natural tRNA-sensing RNA element. This SAM-I riboswitch appears to be highly conserved in Xanthomonas species.

Aim: To describe the clinical results of combined Ahmed valve implantation and 23-gauge vitrectomy for medically uncontrolled neovascular glaucoma (NVG) secondary to proliferative diabetic retinopathy (PDR)., Methods: The medical records of medically uncontrolled NVG patients with PDR who underwent Ahmed valve implantation and 23-gauge vitrectomy between March 2016 and December 2018 were reviewed. Enrolled patients had at least 6-month follow-up. Panretinal photocoagulation (PRP), anti-vascular endothelial growth factor, surgery and medication history were documented., Results: Eleven eyes of 11 patients were included in our study. The visual acuity improved in 8 eyes and remained unchanged in 3 eyes. The preoperative intraocular pressure (IOP) was significantly decreased at the last follow-up (48.8±4.3 to 17.0±1.5 mm Hg, P <0.001). All eyes needed three topical anti-glaucomatous medications before surgery, but the number was significantly reduced to 0.72±0.19 at the last visit ( P <0.001). Four eyes had choroidal detachment and 3 eyes had minor hyphemia, all of which gradually resolved without treatments in one week., Conclusion: Ahmed glaucoma valve implantation combined with 23-gauge vitrectomy might be a safe and alternative treatment for NVG with PDR., (International Journal of Ophthalmology Press.)

Ethnopharmacological Relevance: Moslae Herba, a common traditional Chinese herb with special flavor, has potential for treating respiratory and gastrointestinal diseases., Aim of This Study: Lung endothelial barrier dysfunction (LEBD) accelerates the pathogenesis of influenza A virus (IAV)-induced secondary acute lung injury. New strategies against LEBD provide benefits in prevention and treatment of IAV. Previous studies showed that flavonoids (MHF), main bioactivity fraction derived from M. Herba, exerted anti-inflammatory and antiviral activities, but the underlying protection of MHF against IAV-induced acute lung injury remained obscure. The present study was to investigate the protection of MHF against IAV-induced LEBD in vivo and in vitro., Materials and Methods: Mice were intranasally challenged with IAV and orally administered with MHF for 5 days. The pulmonary hyperpermeability of infected mice was evaluated by Evans Blue staining and in vivo imaging. Serum levels of inflammatory cytokines and mediators were detected by ELISA assay. The transepithelial electrical resistance (TER) of human pulmonary microvascular endothelial cells (HPMVECs) was measured by using TER meter. The expressions of key proteins in NOX4-mediated NF-κB/MLCK pathways were determined by western blotting., Results: MHF treatment reduced lung index, W/D ratios, and serum levels of inflammatory factors (IL-6, TNF-α, IL-1β, PLA 2 , LBT 4 and ICAM-1) in IAV-infected mice. Evans blue staining and in vivo imaging results revealed that MHF alleviated IAV-induced barrier dysfunction and pulmonary hyperpermeability. Moreover, luteolin and kaempferol, the main activity compounds in MHF, significantly inhibited TNF-α-induced HPMVEC apoptosis, and downregulated NF-κB/MLCK pathway by targeting NOX4., Conclusion: MHF attenuated IAV-induced barrier dysfunction by suppressing NOX4/NF-κB/MLCK pathway and may serve as a potential agent for the prevention of LEBD and IAV., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Two polysaccharides (PRP1 and PRP2) were isolated from Platycodonis Radix. Preliminary structural analysis indicated that PRP1 was composed of glucose, fructose, and arabinose in a molar ratio of 1:1.91:1.59 with a molecular weight of 440 kDa, whereas PRP2 was composed of arabinose, fructose, and galactose in a molar ratio of 1:1.39:1.18 with a molecular weight of 2.85 kDa. Compared with PRP2, PRP1 exerted stronger anticancer activity in vitro. Treatment with 5-30 μg/ml of PRP1 significantly inhibited the proliferation of HepG2 cells in vitro, and oral administration at the doses of 75-300 mg/kg also reduced the tumor growth in vivo. The miRNA expression patterns of human liver cancer cells HepG2 in vivo under PRP1 treatment were established, and microRNA-21 (miR-21) as the onco-miRNA was appreciably downregulated. PRP1 repressed the expression of miR-21, which directly targeted and suppressed PTEN (a negative regulator of the PI3K/Akt signaling cascade), and subsequently upregulated the expression of PTEN but downregulated the PI3K/AKT pathway, thereby promoting liver cancer cell apoptosis. These findings indicated that PRP1 inhibited the proliferation and induced the apoptosis of HepG2 mainly via inactivating the miR-21/PI3K/AKT pathway. Therefore, PRP1 could be used as a food supplement and candidate for the treatment of liver cancer., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2020. Published by Elsevier B.V.)

Objective: To explore the necessity and safety of selective endoscopy to detect gastrointestinal (GI) malignancy during the outbreak of coronavirus disease 2019 (COVID-19). Methods: A retrospective cohort study was carried out to analyze the clinical data of selective endoscopy performed at the Endoscopic Center, Zhongshan Hospital of Fudan University from February 20 to March 6, 2020. Clinical data included epidemiological questionnaire, chief complaints, endoscopic findings and biopsy pathology results, etc. All medical staff had blood test for IgM/IgG antibodies of COVID-19. Patients and their families were followed up by phone to determine whether they were infected with COVID-19. Meanwhile, the clinical data of selective endoscopy during the same period from February 20 to March 6, 2019 were collected as the control group to compare the overall results of endoscopy examinations during the epidemic and the detection rate of GI malignancy. Results: A total of 911 patients underwent endoscopy in the epidemic period group, and a total of 5746 cases in the control group, which was 6.3 times over the epidemic period group. In the epidemic period group, 544 cases received gastroscopy and 367 cases received colonoscopy, while 3433 cases received gastroscopy and 2313 cases received colonoscopy in the control group, which were both 6.3 times of epidemic period group. Gastroscopy revealed that 39 patients (7.2%) were diagnosed with upper GI malignancies in the epidemic period group and 77 patients (2.2%) in the control group with significant difference (χ(2)=40.243, P <0.001). The detection rate of gastric cancer in these two groups was 3.3% ( n =18) and 1.7% ( n =59) respectively with significant difference (χ(2)=6.254, P =0.012). The detection rate of esophageal cancer was 3.7% ( n =20) and 0.5% ( n =18) respectively with significant difference (χ(2)=49.303, P <0.001). Colonoscopy revealed that colorectal cancer was found in 32 cases (8.7%) of the epidemic period group and 88 cases (3.8%) of the control group with significant difference (χ(2)=17.888, P <0.001). During the epidemic period, no infection of medical staff was found through the blood test of IgM/IgG antibodies on COVID-19. No patient and family members were infected with COVID-19 by phone follow-up. Conclusion: Compared with the same period in 2019, the number of selective endoscopy decreases sharply during the epidemic period, while the detection rate of various GI malignant tumors increases significantly, which indicates that patients with high-risk symptoms of GI malignancies should still receive endoscopy as soon as possible. Provided strict adherence to the epidemic prevention standards formulated by the state and professional societies, it is necessary to carry out clinical diagnosis and treatment as soon as possible.

Objective: To evaluate the feasibility and short-term efficacy of a novel and simplified closure method developed by our team for the defect closure after endoscopic full-thickness resection (EFTR) for gastric submucosal tumors (SMT) in the gastric wall. Methods: A prospective single-arm clinical study was used. Inclusion criteria: (1) the lesion was located in the fundus or the greater curvature of the stomach, and was confirmed to originate from the muscularis propria layer; (2) the diameter of the tumor was ≤3.5 cm, and the tumor had no extensive adhesion to the peritoneal tissues and organs in extraperitoneal cavity; (3) the tumor had no malignant features under ultrasound endoscopy; (4) the patient agreed to participate in the study; (5) patients with severe complications were excluded. Based on the above criteria, 20 patients with gastric SMT at the Endoscopy Center of Zhongshan Hospital of Fudan University from January 2015 to March 2018 were enrolled in this study, including 5 males and 15 females with mean age of 61.1 (38 to 70) years. Grasping forceps-assisted endo-loop snare ligation device which is called "Shao-Mai" method was used to close the defect site. All the patients underwent EFTR and "Shao-Mai" method to perform defect closure. After successful tumor resection by EFTR, an endo-loop was anchored onto the edge of the gastric defect with grasping forceps assistance and closed tightly. The observation indicators included tumor size, en bloc resection, operation time, postoperative complications and hospital stay. The follow-up indicators included tumor residual, local recurrence, and metachronous lesions. Results: All the 20 lesions were located in the muscularis propria with a size of 0.5-3.5 (mean 1.4) cm. Three of them were located in the greater curvature of the mid-upper gastric body, 17 were located in the fundus. The endoscopic "Shao-Mai" closure was successfully performed after EFTR in all the 20 cases. Endoscope was used uniquely through the entire process, without laparoscopic assistance. The operative time was 20-100 (mean 43.8) minutes, while the "Shao-Mai" closure procedure took a range of 3-30 (mean 10.1) minutes. The en bloc resection rate was 100%. The pathological diagnosis included 17 gastrointestinal stromal tumors and 3 leiomyomas. No major complications occurred during or after surgery. All the patients were discharged 1-11 (mean 3.1) days after operation. The wounds of all the cases were healed completely six months after operation and only scar was observed without ulcer. No residual lesion, tumor recurrence or metastasis, leakage or fistula of digestive tract were found during the follow-up period of 15-54 (median 41) months. Conclusion: The endoscopic "Shao-Mai" closure method is a simplified novel way, which is feasible, effective, and safe for closing the gastric defect after EFTR.

Neutrophils act as both messenger and effector which contributed to the pathogenesis of acute lung injury (ALI). Targeting neutrophils could be a novel strategy for prevention and treatment of ALI. Selaginella uncinata is widely used as an antitussive, antipyretic and anti-inflammatory herb to treat various pulmonary diseases, including lung cancer, asthma, pulmonary fibrosis and pneumonia. However, its effective constituents remain unknown. In the present study, the protective effects of flavonoids from S. uncinata (SUF) and its major compound robustaflavone-4'-dimethyl ether (RDE) against lipopolysaccharide (LPS)-induced ALI were investigated in mice and in neutrophils.The results showed that both SUF and RDE had the same inhibition on LPS-induced lung edema and neutrophil infiltration as well as the increased levels of IL-6, TNF-α, P-selectin and ICAM-1 in serum of LPS-challenged mice. Furthermore, RDE significantly inhibited inducible neutrophil activation in a concentration-dependent manner, and also reduced the levels of intracellular calcium as well as the expressions of CCR2. Rescue experiment showed that RDE suppressed FLT3 and its downstream p-p38 and p-AKT, which could be abolished by FLT3 agonist FLT3L but partly by MAPK agonist PDBu or AKT agonist SC79. Therefore, these results indicated that RDE as the main bioactive compound in SUF alleviated LPS-induced acute lung injury and inhibited neutrophil activation via inhibition of FLT3-mediatied AKT and MAPK pathways., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Papillary thyroid carcinoma (PTC) is the most common subtype of differentiated thyroid cancers in Asian coastal cities, where the patients have increased risk of potentially high or excessive iodine intake. Given the high metastasis and recurrence of patients with BRAF V600E mutation, the mortality rate of thyroid cancer has recently shown an upward trend. A variety of therapies, including surgery, radiotherapy, and chemotherapy, have been used to treat thyroid cancer, but these therapies still have limitations, including postoperative complications, drug resistance, poor efficacy, or serious side effects. Recent studies have shown the potential of active ingredients derived from herbal medicine in inhibiting PTC via various cell signaling pathways. Some plant-derived compounds, such as apigenin, genistein, and curcumin, are also known to prevent and treat PTC. This article summarizes the recent advances in the structure-functional impact of anti-PTC active ingredients and their effects on PTC cells and tumor microenvironments with an emphasis on their challenges from basic research to clinical practice., Competing Interests: The authors declare no conflicts of interests., (Copyright © 2020 Yang Yang et al.)

At present, natural orifice specimen extraction surgery (NOSES) has attracted more and more attention worldwide, because of its great advantages including minimal cutaneous trauma and post-operative pain, fast post-operative recovery, short hospital stay, and positive psychological impact. However, NOSES for the treatment of gastric cancer (GC) is still in its infancy, and there is great potential to improve its theoretical system and clinical practice. Especially, several key points including oncological outcomes, bacteriological concerns, indication selection, and standardized surgical procedures are raised with this innovative technique. Therefore, it is necessary to achieve an international consensus to regulate the implementation of GC-NOSES, which is of great significance for healthy and orderly development of NOSES worldwide., (© The Author(s) 2020. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

Background: The endoscopic resection of gastrointestinal mesenchymal tumors (GIMTs) is widely accepted because of its minimal invasiveness. However, one major concern is the high rate of positive microscopic margins remaining following endoscopic resection, which was thought to be related to a higher risk of recurrence. This study aimed to determine whether positive margins affect the recurrence rate of gastric GIMTs and the factors associated with positive margins., Methods: Patients with gastric GIMTs were recruited retrospectively from January 2008 to December 2013. Clinical and pathological features, endoscopic procedure information, and follow-up data were collected and analyzed., Results: The study included 777 patients. All tumors were removed along with the pseudocapsule without macroscopic residual (ER0), and the median tumor size was 15.2 mm (range 3-100 mm). Pathological evaluation revealed 371(47.7%) GISTs. The rate of microscopic R1 resection rate was 47.0% (443/777). In a stepwise multivariate analysis, a significantly increased incidence of R1 resection was recorded for the GISTs (OR 11.13, 95% CI 3.00-41.37). In a subgroup analysis of GISTs, a univariate analysis revealed that EFTR achieved a higher rate of R0 resection (OR 0.56, 95% CI 0.31-1.00), but it was proven insignificant in a stepwise multivariate analysis. Local recurrence occurred in two patients (0.3%) during a mean follow-up time of 34.2 months. Differences in the recurrence rates between the R0 and R1 groups were statistically insignificant (P = 0.841)., Conclusions: R1 resection for gastric GIMTs is not related to a higher recurrence rate than R0 resection, and ER0 resection is sufficient for gastric GIMTs.

Background and Aims: We aimed to establish a predictive model and develop a simple risk-scoring system (Zhongshan POEM Score) to help clinicians to characterize high-risk patients for clinical failure after peroral endoscopic myotomy (POEM)., Methods: A total of 1538 patients with achalasia treated with POEM with available follow-up data were included in this study and were randomly classified to the training cohort (n = 769) or internal validation cohort (n = 769). A risk-scoring system was developed using multivariate Cox regression analysis in the training cohort. The system was then internally validated by survival analysis in the validation cohort., Results: During a median follow-up time of 42 months, 109 patients had clinical failure. In the training stage, 3 risk factors for clinical failure were weighted with point values: previous treatment (2 points), intraprocedural mucosal injury (2 points for type I and 6 points for type II), and clinical reflux (3 points). The patients were categorized into low-risk and high-risk groups. In the validation stage, Kaplan-Meier curves differed significantly between the 2 groups. Patients in the high-risk group had a significantly higher risk of clinical failure than those in the low-risk group (hazard ratio, 3.99; 95% confidence interval, 2.31-6.91; P < .001). Satisfactory discrimination and calibration were shown., Conclusions: This risk-scoring system demonstrated good performance in predicting clinical failure in patients who underwent POEM., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objective: This research aims to investigate the level of microRNA-1236-3p in breast cancer (BCa) tissues and to further investigate its possible mechanism in the progression of BCa., Patients and Methods: The level of microRNA-1236-3p in BCa tissues and adjacent tissues was detected by quantitative Real-time polymerase chain reaction (qRT-PCR). Regulatory effects of microRNA-1236-3p on cell proliferation and invasion were detected by cell counting kit-8 (CCK-8) and transwell assay. The binding relationship between microRNA-1236-3p and zinc-finger E-box binding homeobox (ZEB1) was examined by the dual-luciferase reporter gene assay. Finally, rescue experiments were conducted to verify the potential role of microRNA-1236-3p/ ZEB1 axis in BCa., Results: MicroRNA-1236-3p was downregulated in BCa tissues relative to adjacent tissues, and the similar trend was shown in BCa cell lines. Overexpression of microRNA-1236-3p in MDA-MB-231 and MCF-7 cells inhibited proliferation and attenuated invasiveness, while knockdown of microRNA-1236-3p had an opposite effect. Dual-luciferase reporter gene assay and qRT-PCR results showed that microRNA-1236-3p could target ZEB1 to degrade it. Overexpression of ZEB1 in BCa cells can partially reverse the effect of overexpressed miR-1236-3p on cell proliferative and invasive abilities., Conclusions: MicroRNA-1236-3p could inhibit the growth and metastasis of BCa cells by inhibiting ZEB1 expression, suggesting that microRNA-1236-3p may be a potential therapeutic target for BCa.

Background: Endoscopic full-thickness resection (EFTR) provides a significant advancement to the treatment of gastrointestinal submucosal tumors (SMTs). However, technological challenges, particularly in the gastric fundus, hinder its wider application. Here, we investigated the efficacy of a simple traction method that used dental floss and a hemoclip (DFC) to facilitate EFTR., Methods: Between July 2014 and December 2016, we retrospectively reviewed data from all patients with SMTs in the gastric fundus originating from the muscularis propria layer that were treated by EFTR at Zhongshan Hospital of Fudan University. Baseline characteristics and clinical outcomes, including procedure time and complications rate, were compared between groups of patients receiving DFC-EFTR and conventional EFTR., Results: A total of 192 patients were included in our analysis (64 in the DFC-EFTR group and 128 in the conventional EFTR group). Baseline characteristics for the two groups were similar. The mean time for DFC-EFTR and conventional EFTR was 44.2 ± 24.4 and 54.2 ± 33.2 min, respectively (P = 0.034). Although no serious adverse events presented in any of our cases, post-EFTR electrocoagulation syndrome (PEECS), as a minor complication, was less frequent in the DFC-EFTR group (3.1% vs. 12.5%, P = 0.036). Univariate and multivariate analysis identified that DFC, when used in EFTR, played a significant role in reducing procedure time and the rate of PEECS. The mean procedure time was significantly shorter in the DFC-EFTR group for lesions over 1.0 cm (P = 0.005), when the lesions were located in the greater curvature of the gastric fundus (P = 0.025) or when the lesions presented with intraluminal growth (P = 0.032). Moreover, when EFTR was carried out by experts, the mean procedure time was 20.4% shorter in the DFC-EFTR group (P = 0.038)., Conclusions: This study indicated that DFC-EFTR for SMTs in the gastric fundus resulted in a shorter procedure time and reduced the risk of PEECS, a minor complication.

Background and Aims: Few artificial intelligence-based technologies have been developed to improve the efficiency of screening for esophageal squamous cell carcinoma (ESCC). Here, we developed and validated a novel system of computer-aided detection (CAD) using a deep neural network (DNN) to localize and identify early ESCC under conventional endoscopic white-light imaging., Methods: We collected 2428 (1332 abnormal, 1096 normal) esophagoscopic images from 746 patients to set up a novel DNN-CAD system in 2 centers and prepared a validation dataset containing 187 images from 52 patients. Sixteen endoscopists (senior, mid-level, and junior) were asked to review the images of the validation set. The diagnostic results, including accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were compared between the DNN-CAD system and endoscopists., Results: The receiver operating characteristic curve for DNN-CAD showed that the area under the curve was >96%. For the validation dataset, DNN-CAD had a sensitivity, specificity, accuracy, PPV, and NPV of 97.8%, 85.4%, 91.4%, 86.4%, and 97.6%, respectively. The senior group achieved an average diagnostic accuracy of 88.8%, whereas the junior group had a lower value of 77.2%. After referring to the results of DNN-CAD, the average diagnostic ability of the endoscopists improved, especially in terms of sensitivity (74.2% vs 89.2%), accuracy (81.7% vs 91.1%), and NPV (79.3% vs 90.4%)., Conclusions: The novel DNN-CAD system used for screening of early ESCC has high accuracy and sensitivity, and can help endoscopists to detect lesions previously ignored under white-light imaging., (Copyright © 2019 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Gastric small submucosal tumors (SMTs) are becoming increasingly common. However, the fundus of stomach is regarded as a difficult area for endoscopic resection (ER). In this study, we investigated the efficacy, safety, and long-term outcomes of ER for small SMTs of the gastric fundus in a large series of patients, research that was previously lacking., Methods: 537 consecutive patients with SMTs no more than 20 mm in diameter, occurring in the gastric fundus and originating from the muscularis propria layer, which were treated with endoscopic submucosal excavation or endoscopic full-thickness resection (EFTR) were included in this retrospective study at Zhongshan Hospital of Fudan University from January 2013 to September 2016. Clinicopathological, endoscopic, and follow-up data were collected and analyzed., Results: En bloc resection was achieved in 100% of patients, and complete resection was achieved for 530 (98.7%) lesions. Although the total rate of complications was 9.3%, few serious adverse events occurred in only three (0.6%) patients, including major pneumoperitoneum, major hydrothorax, and bleeding. Unlike lager tumor sizes and longer procedure times, endoscopist experience had a positive impact on decreasing the likelihood of complications. Based on statistical analysis, tumors with greater size near the cardia, which were treated by EFTR, were the significant contributors to longer operative times. A median follow-up of 32 months was available, and all patients were free from local recurrence or distant metastasis during the study period., Conclusions: Although the gastric fundus presents technical difficulties, ER is effective for the resection of small gastric SMTs with a high complete resection rate and rare serious adverse events.

In August 2018, The Chinese Consensus on Endoscopic Diagnosis and Management of Gastrointestinal Submucosal Tumors, which was formulated by the Surgical Group of Chinese Society of Digestive Endoscopology, the Chinese Physicians Association Endoscopy Branch Digestive Endoscopy Professional Committee, the Gastrointestinal Surgery Group of Chinese Society of Surgery, was published in Chinese Journal of Gastrointestinal Surgery. This consensus is the first guideline in the area of gastrointestinal submucosal tumors (SMTs) in China, and it proposed the diagnosis and management procedure of SMTs from the endoscopists' viewpoint. This consensus presents case selection principles and technical principles of endoscopic treatment of SMTs. For and the indication and contraindication of endoscopic treatment of SMTs, it is suggested that clinician choose optimal procedure according to disease's characteristics and techniques of the clinician. In this review, the key contents of consensus are interpreted in detail. The application of endoscopic snare resection, endoscopic submucosal excavation, endoscopic full-thickness resection and submucosal tunneling endoscopic resection at different SMTs was summarized. At the same time, the controversies in endoscopic diagnosis and management of the SMTs, such as biopsy, indication of endoscopic treatment and new techniques of endoscopic therapy, were analyzed.

Objective: To evaluate the clinical value of dual channel dual curved endoscope in the endoscopic submucosal dissection (ESD) for gastric angle mucosal lesions. Methods: A descriptive cohort study was carried out. Clinicopathological data of 20 cases with gastric angle mucosal lesions undergoing ESD by dual channel dual curved endoscope in our center from October 2016 to August 2018 were collected and analyzed retrospectively. Inclusion criteria: (1) the lesion was located in the gastric angle confirmed by gastroscopy before ESD. (2) CT examination showed no distant metastasis. (3) pathological biopsy confirmed precancerous lesion or early cancerous lesion without submucosal invasion. (4) the whole operation was performed by the same endoscopist with ESD experience of about 2000 cases. Patients with previous ESD history of gastric angle and other serious diseases were excluded. The dual channel dual curved endoscopy (Olympus, GIF-2TQ260M) and other conventional endoscopic surgical instruments were used in all the cases. Complete tumor resection rate, pathological results, intraoperative and postoperative complications, operation time and hospitalization time were observed. Follow - up parameters included residual tumor, local recurrence and heterogeneous lesion. Results: Of 20 patients, 14 were male and 6 were female with an average of 55.6 years (range, 37 to 75). All the tumors located in gastric angle. Specimen size ranged from 1.2 to 5.5 (average 2.9) cm. Operation time ranged from 50 to 120 (average 85.8) minutes. Hospital stay ranged from 3 to 7 (average 5.1) days. The en bloc excision was performed successfully in all 20 cases. There was no perforation or bleeding during or after operation. Pathological results showed curative or nearly curative resection stage in all the cases. No tumor residual or recurrence was found during follow-up for 8 to 30 (average 18.5) months. Conclusion: Dual channel dual curved endoscope can provide good vision and easy control in removing the lesion completely and avoiding complications during the ESD procedure in gastric angle mucosal lesions with good long-term efficacy.

Endoscopic submucosal dissection (ESD) is the gold standard technique for performing en bloc resection of large superficial tumors in the upper and lower gastrointestinal tract. It has not started in China until early 2006, when it was introduced at Endoscopy Center of Zhongshan Hospital. However, ESD is technically more difficult and can result in more complications, limiting its development in China. At present, reports about ESD training system in China are still not available. Therefore, our center continuously explored and gradually established structured training courses relied on the live pig model. Between 2009 and 2013, we held 23 hands-on ESD training workshops with 550 endoscopists. Questionnaires were distributed via e-mail, and there were 460 participants performing ESD in a step-up approach on the live pigs. More than one half of trainees could perform ESD with en bloc resection in the imaginary "lesion" of colon and stomach, and there were higher rates of hemorrhage and perforation occurring in colorectal ESD as compared to gastric ESD. After graduating from our hands-on workshop, up to over 90% of participants started ESD practice in their home hospitals. It was mostly provided by high-grade hospitals (IIIA) which played a major role as tertiary referral centers, covering almost all provinces and major cities in China. The training on live pig model revealed to be safe and effective as a prior step to its application in humans. It may enable novice endoscopists to acquire ESD skills and start performing ESD as soon as possible. The role of adequate training is of course to influence the spread of this technique and promote ESD development around China.

Objective: Synchronous multiple primary early esophageal cancers (SMPEEC) are rare and aggressive. Early detection of esophageal cancer can improve survival rate. Endoscopic submucosal dissection (ESD) is a minimally invasive endoscopic treatment of early esophageal cancers. However, ESD for SMPEEC is little known. We aimed to clarify the clinical outcomes of simultaneous ESD treating SMPEEC. Methods: We retrospectively reviewed the medical data of 34 patients, who underwent ESD for SMPEEC at Endoscopy Center of Zhongshan Hospital, Fudan University, between May 2013 and December 2014. The data of lesion size, histopathology, en bloc resection, curative resection, complication, and tumor local recurrence were analyzed. Results: Among 34 patients, 67 lesions were removed simultaneously in 33 cases; 2 lesions were removed in 2 operations for 1 case. For the simultaneous resection, the en bloc rate was 97.01% (65/67) and the curative resection rate was 92.54% (62/67). Postoperative stricture occurred in two cases and delayed bleeding occurred in one case. There was one local recurrence, no metastasis or procedure-related death. Conclusions: Simultaneous ESD as a treatment for SMPEEC is technically feasible, benefited from reducing hospitalization time and medical expenses. For the cases with risk factors of complications, simultaneous ESD needs to be avoided.

The aim of the present study was to identify the functional role of galectin-3 (Gal-3) in lipopolysaccharide (LPS)-induced injury in ATDC5 cells and to explore the probable molecular mechanisms. Here, we identified that LPS is sufficient to enhance the expression of Gal-3 in ATDC5 cells. In addition, repression of Gal-3 obviously impeded LPS-stimulated inflammation damage as exemplified by a reduction in the release of inflammatory mediators interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, as well as the production of nitric oxide and prostaglandin E2 (PGE2) concomitant with the downregulation of matrix metalloproteinases (MMP)-13 and MMP-3 expression in ATDC5 cells after LPS administration. Moreover, ablation of Gal-3 dramatically augmented cell ability and attenuated cell apoptosis accompanied by an increase in the expression of antiapoptotic protein Bcl-2 and a decrease in the expression of proapoptotic protein Bax and caspase-3 in ATDC5 cells subjected with LPS. Importantly, we observed that forced expression of TLR4 or blocked PPAR-γ with the antagonist GW9662 effectively abolished Gal-3 inhibition-mediated anti-inflammatory and antiapoptosis effects triggered by LPS. Mechanistically, depletion of Gal-3 prevents the NF-κB signaling pathway. Taken together, these findings indicated that the absence of Gal-3 exerted chondroprotective properties dependent on TLR4 and PPAR-γ-mediated NF-κB signaling, indicating that Gal-3 functions as a protector in the development and progression of osteoarthritis., (© 2018 Wiley Periodicals, Inc.)

Background: Achalasia is a motility disorder of unknown etiology. Previous studies supported the hypothesis that autoimmune-mediated inflammatory responses produce inhibitory neuronal degeneration. This study was designed to explore the role of mast cells in achalasia., Methods: We collected information from 116 patients with achalasia who underwent peroral endoscopic myotomy between December 2016 and May 2017. Lower esophageal sphincter (LES) muscle biopsy was performed in all patients with achalasia, as well as 20 control subjects. The number of mast cells, interstitial cells of Cajal (ICCs), nNOS-positive cells, and S-100-positive cells in the LES were evaluated by immunohistochemistry. Pathological and clinical data were compared between groups., Key Results: Compared with controls, the LES of patients with achalasia had significantly fewer ICCs, nNOS-positive cells, and S-100-positive cells and a higher number of mast cells (all P < 0.001). Furthermore, the increased mast cell infiltration was significantly associated with decreased ICCs, nNOS-positive cells, and S-100-positive cells in patients with achalasia (all P < 0.05). Clinically, the number of strongly positive mast cells was highest in patients with type I achalasia and lowest in those with type III achalasia (P < 0.001). In addition, patients with a history of autoimmune disease or viral infection had greater mast cell infiltration in the LES muscle (P = 0.040)., Conclusions & Inferences: In patients with achalasia, mast cell infiltration in the LES muscle is increased, in association with loss of ICCs and neuronal degeneration. Mast cells may thereby play a crucial role in the development of achalasia., (© 2019 John Wiley & Sons Ltd.)

Objective: To evaluate the safety and efficacy of dental floss traction-assisted endoscopic submucosal dissection (DFS-ESD) for rectal neuroendocrine neoplasm (NEN). Methods: A retrospective cohort study was performed. Clinical data of rectal NEN patients undergoing ESD at Endoscopy Center of Zhongshan Hospital, Fudan University from January 2016 to December 2017 were retrospectively analyzed. Inclusion criteria: 1) age of 18 to 80 years old; 2) maximal diameter of lesions <1.5 cm; 3) tumor locating in the submucosa without invasion into the muscularis propria; 4) no enlarged lymph nodes around bowel and in abdominal cavity; 5) ESD requested actively by patients. A total of 37 patients were enrolled, including 23 male and 14 female cases with mean age of (56.0±11.3) years. All the lesions were single tumor of stage T1, and the mean size was 0.8±0.2(0.5-1.2) cm. Postoperative pathology revealed all samples as neuroendocrine tumors (NET). Seventeen patients received DFS-ESD treatment (DFS-ESD group) and 20 patient received conventional ESD treatment (conventional ESD group). In DFS-ESD group, after the mucosa was partly incised along the marker dots, the endoscopy was extracted, and the dental floss was tied to one arm of the metallic clip. When the endoscope was reinserted, the hemoclip was attached onto the incised mucosa; another hemoclip was attached onto normal mucosa opposite to the lesion in the same way. The submucosa was clearly exposed with the traction of dental floss and the resection could proceed. The conventional ESD group received the traditional ESD operation procedure. The operation time, modified operation time (remaining time after excluding the assembly time of dental floss traction in DFS-ESD group), en bloc resection rate, R0 resection rate, morbidity of operative complication, recurrence and metastasis were compared between two groups. Results: The average tumor size was (0.8±0.2) cm in DFS-ESD group and (0.7±0.2) cm in conventional ESD group ( t =0.425, P =0.673). According to postoperative pathological grading of rectal neuroendocrine neoplasm, 13 were G1 and 4 were G2 in DFS-ESD group, while 17 cases were G1 and 3 cases were G2 in conventional ESD group without significant difference ( P =0.680). There were no significant differences in baseline data between in the two groups (all P> 0.05). All the basal resection margins were negative, the en bloc resection rate was 100% and the R0 resection rate was 100%. Pathological results showed tumor tissue close to the burning margin in 5 cases of conventional ESD group and in 2 cases of DFS-ESD group ( P =0.416). The operation time was (17.9±6.6) minutes in conventional ESD group and (14.7±3.3) minutes in DFS-ESD group ( t =1.776, P =0.084). The modified operation time of DFS-ESD group was (11.9±2.8) minutes, which was significantly shorter than (17.9±6.6) minutes in conventional ESD group ( t= 3.425, P =0.002). The hospital stay was (2.3±0.6) days and (2.0±0.5) days in conventional ESD group and DFS-ESD group, respectively, without significant difference ( t =1.436, P =0.160). No patient was transferred to surgery, and no delayed bleeding or perforation occurred in either group. There was no recurrence or primary tumor-related death, and all the patients recovered well during a follow-up period of 14(1-24) months. Conclusion: Dental floss traction-assisted ESD for rectal neuroendocrine neoplasm can simplify operation and ensure negative basal margin.

Background: Hepatocellular carcinoma (HCC) is frequently associated with metabolism dysfunction. Increasing evidence has demonstrated the crucial role of lipid metabolism in HCC progression. The function of apolipoprotein F (ApoF), a lipid transfer inhibitor protein, in HCC is incompletely understood. We aimed to evaluate the functional role of ApoF in HCC in this study., Methods: We used quantitative reverse-transcription polymerase chain reaction (qRT-PCR) to detect ApoF mRNA expression in HCC tissues and hepatoma cell lines (SMMC-7721, HepG2, and Huh7). Immunohistochemistry was performed to detect the expression of ApoF in HCC tissues. The associations between ApoF expression and clinicopathological features as well as HCC prognosis were analyzed. The effect of ApoF on cellular proliferation and growth of SMMC-7721 and Huh7 cells was examined in vitro and in vivo ., Results: ApoF expression was significantly down-regulated at both mRNA and protein levels in HCC tissues as compared with adjacent tissues. In SMMC-7721 and Huh7 HCC cells, ApoF overexpression inhibited cell proliferation and migration. In a xenograft nude mouse model, ApoF overexpression effectively controlled HCC growth. Kaplan-Meier analysis results showed that the recurrence-free survival rate of HCC patients with low ApoF expression was significantly lower than that of other HCC patients. Low ApoF expression was associated with several clinicopathological features such as liver cirrhosis, Barcelona Clinic Liver Cancer stage and tumor-node-metastasis stage., Conclusions: ApoF expression was down-regulated in HCC, which was associated with low recurrence-free survival rate. ApoF may serve as a tumor suppressor in HCC and be a potential application for the treatment of this disease., (© The Author(s) 2019. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

Background and Aims: According to guidelines, endoscopic resection should only be performed for patients whose early gastric cancer invasion depth is within the mucosa or submucosa of the stomach regardless of lymph node involvement. The accurate prediction of invasion depth based on endoscopic images is crucial for screening patients for endoscopic resection. We constructed a convolutional neural network computer-aided detection (CNN-CAD) system based on endoscopic images to determine invasion depth and screen patients for endoscopic resection., Methods: Endoscopic images of gastric cancer tumors were obtained from the Endoscopy Center of Zhongshan Hospital. An artificial intelligence-based CNN-CAD system was developed through transfer learning leveraging a state-of-the-art pretrained CNN architecture, ResNet50. A total of 790 images served as a development dataset and another 203 images as a test dataset. We used the CNN-CAD system to determine the invasion depth of gastric cancer and evaluated the system's classification accuracy by calculating its sensitivity, specificity, and area under the receiver operating characteristic curve., Results: The area under the receiver operating characteristic curve for the CNN-CAD system was .94 (95% confidence interval [CI], .90-.97). At a threshold value of .5, sensitivity was 76.47%, and specificity 95.56%. Overall accuracy was 89.16%. Positive and negative predictive values were 89.66% and 88.97%, respectively. The CNN-CAD system achieved significantly higher accuracy (by 17.25%; 95% CI, 11.63-22.59) and specificity (by 32.21%; 95% CI, 26.78-37.44) than human endoscopists., Conclusions: We constructed a CNN-CAD system to determine the invasion depth of gastric cancer with high accuracy and specificity. This system distinguished early gastric cancer from deeper submucosal invasion and minimized overestimation of invasion depth, which could reduce unnecessary gastrectomy., (Copyright © 2019 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Osteosarcoma (OS) is the most common primary bone malignancy. It predominantly occurs in adolescents, but can develop at any age. The age at diagnosis is a prognostic factor of OS, but the molecular basis of this remains unknown. The current study aimed to identify age‑induced differentially expressed genes (DEGs) and potential molecular mechanisms that contribute to the different outcomes of patients with OS. Microarray data (GSE39058 and GSE39040) obtained from the Gene Expression Omnibus database and used to analyze age‑induced DEGs to reveal molecular mechanism of OS among different age groups (<20 and >20 years old). Differentially expressed mRNAs (DEMs) were divided into up and downregulated DEMs (according to the expression fold change), then Gene Ontology function enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed. Furthermore, the interactions among proteins encoded by DEMs were integrated with prediction for microRNA‑mRNA interactions to construct a regulatory network. The key subnetwork was extracted and Kaplan‑Meier survival analysis for a key microRNA was performed. DEMs within the subnetwork were predominantly involved in 'ubiquitin protein ligase binding', 'response to growth factor', 'regulation of type I interferon production', 'response to decreased oxygen levels', 'voltage‑gated potassium channel complex', 'synapse part', 'regulation of stem cell proliferation'. In summary, integrated bioinformatics was applied to analyze the potential molecular mechanisms leading to different outcomes of patients with OS among different age groups. The hub genes within the key subnetwork may have crucial roles in the different outcomes associated with age and require further analysis.

Background and Aims: Mucosal injury (MI) is one of the most common perioperative adverse events of per-oral endoscopic myotomy (POEM). Severe undertreated MI may lead to contamination of the tunnel and even mediastinitis. This study explored the characteristics, predictors, and management approaches of intraoperative MI., Methods: A retrospective review of the prospectively collected database at a large tertiary referral endoscopy unit was conducted for all patients undergoing POEM between August 2010 and March 2016. MI was graded according to the difficulty of repair (I, easy to repair; II, difficult to repair). The primary outcomes were the incidence and predictors of intraoperative MI. Secondary outcomes were MI details and the corresponding treatment., Results: POEM was successfully performed in 1912 patients. A total of 338 patients experienced 387 MIs, for an overall frequency of 17.7% (338/1912). Type II MI was rare, with a frequency of 1.7% (39/1912). Major adverse events were more common in patients with MI than in those without MI (6.2% vs 2.5%, P < .001). On multivariable analysis, MI was independently associated with previous Heller myotomy (odds ratio [OR], 2.094; P = .026), previous POEM (OR, 2.441; P = .033), submucosal fibrosis (OR, 4.530; P < .001), mucosal edema (OR, 1.834; P = .001), and tunnel length ≥13 cm (OR, 2.699; P < .001). Previous POEM (OR, 5.005; P = .030) and submucosal fibrosis (OR, 12.074; P < .001) were significant predictors of type II MI. POEM experience >1 year was a protective factor for MI (OR, .614; P = .042) and type II MI (OR, .297; P = .042)., Conclusions: MI during POEM is common, but type II injury is rare. Previous POEM and submucosal fibrosis were significant predictors of type II mucosal injury. POEM experience after the learning curve reduces the risk of MI., (Copyright © 2019 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Osteosarcoma is the most common bone tumor that occurs in children., Methods: To identify co-expression modules and pathways correlated with osteosarcoma and its clinical characteristics, we performed weighted gene co-expression network analysis (WGCNA) on RNA-seq data of osteosarcoma with 52 samples. Then we performed pathway enrichment analysis on genes from significant modules., Results: A total of 5471 genes were included in WGCNA, and 16 modules were identified. Module-trait analysis identified that a module involved in microtubule bundle formation, drug metabolism-cytochrome P450, and IL-17 signaling pathway was negatively correlated with osteosarcoma and positively correlated with metastasis; a module involved in DNA replication was positively correlated with osteosarcoma; a module involved in cell junction was positively correlated with metastasis; and a module involved in heparin binding negatively correlated with osteosarcoma. Moreover, expression levels in four of the top ten differentially expressed genes were validated in another independent dataset., Conclusions: Our analysis might provide insight for molecular mechanisms of osteosarcoma.

Background: Endoscopic full-thickness resection (EFTR) derived from endoscopic submucosal dissection has gradually been accepted and even promoted for the treatment of submucosal tumors (SMTs) originating from the muscularis propria (MP) layer. However, there are some difficulties when EFTR is used to treat MP lesions in the gastric fundus. This study intends to explore whether EFTR can be made simpler, safer, and more effective with the traction assistance of dental floss., Methods: The clinical data of patients (trial group) with lesions in the MP layer in the gastric fundus undergoing EFTR with traction assistance of dental floss at Zhongshan Hospital, in 2016, were reviewed retrospectively. The control group was matched with the trial group according to tumor size. The differences in tumor resection time, patient hospitalization time, and complication rate were evaluated., Results: There was no significant difference in the average age of the two groups, each of which comprised 24 cases (58.7 ± 11.8 years versus 56.6 ± 7.9 years, t = 0.663, P = .511). However, there was a statistically significant difference in the operative time between the two groups (10.8 ± 2.8 minutes versus 19.0 ± 4.7 minutes, t = 7.298, P < .05). There was no statistically significant difference in the length of the postoperative hospital stay (3.2 ± 0.5 days versus 3.2 ± 0.5 days, t = 0.291, P = .772). In the trial group, there were 19 cases of gastrointestinal stromal tumors (group 1) and 5 cases of leiomyoma. The control group had similar results. Neither group experienced postoperative delayed bleeding, perforation, or other complications., Conclusions: When EFTR is used to treat SMTs originating from the MP in the gastric fundus, dental floss traction assistance can relieve the tumor boundary to simplify the surgical procedure and save the operation time.

Background: According to the Japanese Esophageal Society (JES) guidelines, early esophageal squamous cell carcinoma (SCC) involving the muscularis mucosae (M3) or upper submucosal (SM1) layers are relative indications for endoscopic submucosal dissection (ESD). Additional esophagectomy or chemoradiotherapy is recommended for patients with relative indications after evaluation. However, elderly patients (≥ 60 years) with relative indications in China often refuse additional treatment because of the debilitating side effects. The aim of this study was to evaluate the long-term outcomes of elderly patients with relative indications who did not undergo additional treatment after ESD., Methods: Data from elderly patients with relative indications who underwent ESD for early esophageal SCC between January 2008 and December 2013 were reviewed retrospectively. Stricture and recurrence, and 5-year progression-free survival (PFS) and overall survival rates were compared with patients with absolute indications for ESD., Results: 158 elderly patients were included and analyzed (89 in the absolute indications group and 69 in the relative indications group). The baseline characteristics were balanced between the two groups. During 56 months (range 1 - 108) of follow-up, the postoperative stricture rates were similar in the absolute and relative indications groups (21.3 % vs. 31.9 %; P  = 0.13). The hazard ratio (HR) for PFS in the absolute vs. the relative indications groups was 1.025 (95 % confidence interval [CI] 0.36 - 2.95; P  = 0.96). The 5-year PFS rates were 90.5 % (95 %CI 83.44 - 97.56) and 90.8 % (95 %CI 83.74 - 97.86) for the absolute and relative indications groups, respectively. The HR for overall survival in the absolute vs. the relative indications groups was 0.564 (95 %CI 0.13 - 2.52; P  = 0.45). The 5-year overall survival rates were 96.6 % (95 %CI 92.88 - 100) and 95.6 % (95 %CI 90.70 - 100) for the absolute and relative indications groups, respectively., Conclusions: Based on this study, regular follow-up without additional treatment may be considered as another choice for elderly patients with early esophageal SCC and relative indications after ESD., Competing Interests: None., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: With the improvement of endoscopic diagnosis, the discovery rate of the synchronous multiple primary early cancers in esophagus and stomach is gradually increased, while the traditional surgery bringing serious damages. Endoscopic submucosal dissection (ESD) has become the first treatment option of early cancer in the digestive tract partly. This study intends to explore the feasibility, safety, and effectiveness of ESD in the treatment of the synchronous multiple early gastric cancer or precancerous lesions in the esophagus and stomach., Methods: From January 2008 to December 2016, data of 12 patients with early esophageal cancer and early gastric cancer treated by ESD in the Endoscopy Center of Zhongshan Hospital, Fudan University were reviewed. We analyzed the patient's history, the size of esophageal and gastric lesions, pathological results, the results of complete or curative resection, and so on., Results: Among the 12 patients described in this study, all were diagnosed with synchronous multiple primary early cancers in the esophagus and stomach. Lesions were removed by ESD in 10 cases at the same time and were removed by stage in 2 cases. The complete resection rate was 100% (24/24), and the curative resection rate was 100% (24/24). Postoperative esophageal stricture occurred in 2 cases, which improved after dilation. Median follow-up time was 30 (8-115) months, when 9 patients survived and 3 patients died. However, the cause of death was not associated with treatment of this disease., Conclusion: ESD is a minimally invasive endoscopic surgery, which can be used as a method of treating synchronous multiple primary early cancers in the esophagus and stomach.

Background and Aims: Per-oral endoscopic myotomy (POEM) has received wide acceptance as a highly effective and safe treatment for esophageal achalasia. Short-term and small-scale studies are ample, but long-term large-scale studies are few. The aim of the study was to systematically analyze our long-term results of POEM, with particular emphasis on POEM failures and associated risk factors., Methods: In this single-center study, consecutive patients treated with POEM between August 2010 and December 2012 were included. The Kaplan-Meier survival function was used to estimate clinical success rate at each year. The Cox proportional hazards model was used to analyze risk factors related to recurrence., Results: A total of 564 patients were included. Major perioperative adverse events occurred in 36 patients (6.4%). After a median follow-up of 49 months (range, 3-68), the Eckardt score and lower esophageal sphincter (LES) pressure were significantly decreased (median Eckardt score, 8 to 2 [P < .05]; median LES pressure, 29.7 mm Hg to 11.9 mm Hg [P < .05]). Fifteen failures occurred within 3 months, 23 between 3 months and 3 years, and 10 after 3 years. The estimated clinical success rates at 1, 2, 3, 4, and 5 years were 94.2%, 92.2%, 91.1%, 88.6%, and 87.1%, respectively. Multivariate Cox regression revealed long disease duration (≥10 years) and history of prior interventions to be risk factors for recurrence. Clinical reflux occurred in 37.3% of patients (155/ 416)., Conclusions: POEM is a highly safe and effective treatment for esophageal achalasia with favorable long-term outcomes., (Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: The aging of Chinese society has increased interest in improving the health-related quality of life (HRQoL) of the elderly, including their oral health-related quality of life (OHRQoL). This study aims to evaluate the OHRQoL of elders living in Sichuan Province (China) and to explore the explanatory factors of their OHRQoL., Methods: A cross-sectional study conducted in 2016 in the Sichuan Province analyzed data from 744 elders, aged 65 to 74 years (mean age 69.3, 51.3% female). Clinical examinations and questionnaires were completed to collect information on the participants' socio-demographic characteristics, health-related behaviors, dental status, subjective health conditions and General Oral Health Assessment Index (GOHAI) score., Results: The mean GOHAI score was 48.23 (SD 7.62), and the median score was 49. After adjustment for age and gender, the multiple linear regression analysis showed that participants who were female, had fair or poor self-rated oral health, decayed, missing and filled teeth (DMFT) score ≥ 20, fair or poor self-rated general health, and ≥ 2 teeth with root caries had worse OHRQoL, and participants who were edentulous had better OHRQoL (F = 29.58, p < 0.001)., Conclusion: The OHRQoL of the elders living in Sichuan Province was relatively good. The explanatory variables were gender; self-rated oral health; DMFT score; self-rated general health; number of natural teeth; and number of teeth with root caries. More attention should be paid to caries status and retention of healthy teeth to improve the OHRQoL of elders in Sichuan Province, preserving a healthy mouth contributes to better OHRQoL.

Background and Aims: The colorectal endoscopic submucosal dissection (ESD) remains technically challenging, especially for older patients who frequently encounter complex chronic diseases and have a loose colon. However, only limited number of studies are available for the safety of ESD in older patients with especially large laterally spreading tumors. Therefore, in this retrospective study, we compared the outcomes of ESD for laterally spreading tumors (LST) ≥3cm(cm) in older patients to that in younger patients., Methods: Consecutive patients with LSTs 3cm or larger were enrolled for from May 2010-2016. These patients were divided into two groups: the younger group (<65years) and the older group (≥65years). The clinicopathologic findings and the outcomes of ESD procedures were compared between the two groups., Results: A total of 70 patients in the younger group and 73 patients in the older group were treated by ESD for colorectal LSTs larger than 3cm. No significant differences were observed in the gender ratio, tumor morphological type, tumor location, and tumor size between the two groups. The en bloc resection rates were 85.7 and 89.0%, respectively, without a significant difference. The procedural time was similar between the younger and older patients (71.8±34.7min vs. 70.6±29.5min). The duration of hospital stay was not significantly different between the two groups (4.1±2.2days vs. 4.4±2.5days). No significant differences were observed between the two groups with respect to ESD-related complications including delayed bleeding, perforation, and stricture., Conclusions: ESD appears to be an effective and safe method for LSTs larger than 3cm in older patients., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Peroral endoscopic myotomy (POEM) is a minimally invasive yet challenging procedure for achalasia. Additional technological innovations and improvements are important for simplifying the procedure., Methods: We report the successful use of a modified POEM procedure, which utilized a "Push and Pull" technique, on a patient with achalasia., Results: Our modifications resulted in a short operation time of only 35 min. No complications arose during or after the procedure, up to a follow-up period of 6 months, and symptoms were significantly and quickly improved., Conclusions: This modified procedure shortens operation time and lowers the difficulty of the operation, while leaving the safety and efficacy uncompromised.

Background: Colorectal carcinomas (CRCs) arise from premalignant precursors in an adenoma-carcinoma sequence, in which adenoma with high-grade dysplasia (HGD) and early-stage carcinoma are defined as advanced neoplasia. A limited number of studies have evaluated the long-term outcomes of endoscopic submucosal dissection (ESD) for advanced colorectal neoplasia. This study aimed to assess the efficacy and safety of ESD for advanced colorectal neoplasia as well as the long-term outcomes, including local recurrence and metastasis., Methods: We analyzed data collected from 610 consecutive patients with 616 advanced colorectal neoplasia lesions treated with ESD between January 2007 and December 2013. Clinical, endoscopic, and histological data were collected over a median follow-up period of 58 months to determine tumor stage and type, resection status, complications, tumor recurrence, and distant metastasis., Results: The overall rates of en bloc resection, histological complete resection, and major complications were 94.3%, 89.4%, and 2.3%, respectively. Hybrid ESD was an independent factor of piecemeal resection. Tumor location in the colon was associated with increased risk of ESD-related complications. During the follow-up period, all patients remained free of metastasis. However, local recurrence occurred in 4 patients (0.8%); piecemeal resection was a risk factor., Conclusions: ESD is effective and safe for resection of advanced colorectal neoplasia, with a high en bloc resection rate and favorable long-term outcomes. ESD is indicated for the treatment of HGD and early-stage CRC to obtain curative resection and reduce local recurrence rate.

Background and Aims: Endoscopic submucosal dissection (ESD) of colorectal submucosal tumors (SMTs) is becoming increasingly common; however, there have been few large consecutive studies analyzing its therapeutic efficacy and safety. The aim of this study was to evaluate the efficacy, safety, and long-term outcomes of ESD for colorectal SMTs., Methods: This retrospective study included 412 consecutive patients with colorectal SMTs who underwent ESD at the Zhongshan Hospital of Fudan University from January 2008 to July 2014. Tumor histopathology, completeness of resection, adverse events, tumor recurrence, and distant metastasis were analyzed., Results: Complete resection was achieved for 358 lesions (86.9%). Thirteen patients had serious adverse events (3.2%) including bleeding and perforation, and 28 patients (6.8%) had post-ESD electrocoagulation syndrome (PEECS). Because more ESDs for colorectal SMTs were performed by endoscopists, the rate of complete resection increased (78.5% vs 88.5%), and the rate of serious adverse events decreased (9.2% vs 2.0%). SMTs in the colon increased the risk of incomplete resection (19.6% vs 11.3%), serious adverse events (8.7% vs 1.6%), and PEECS (16.3% vs 4.1%). SMTs originating from the muscularis propria and sized ≥20 mm increased the rate of PEECS (22.7% vs 5.9% and 31.3% vs 5.8%, respectively)., Conclusion: ESD is effective for resection of colorectal SMTs and rarely causes serious adverse events. Tumor location and the experience of endoscopists influence the complete resection rate and the development of serious adverse events. ESD is feasible for large tumors and tumors in the muscularis propria, but this is associated with relatively high risks of adverse events., (Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Submucosal tunneling endoscopic resection (STER) is regarded as a promising method for resection of submucosal tumors (SMTs); however, little is known about a comprehensive comparison of STER and thoracoscopic enucleation (TE). The aim of this study was to compare the clinical outcomes of STER and TE for large symptomatic SMTs in the esophagus and esophagogastric junction, as well as to analyze the factors that affect the feasibility and safety of STER., Study Design: We enrolled 166 patients with large symptomatic SMTs in the esophagus and esophagogastric junction from September 2011 to March 2016 in this retrospective study. The clinicopathologic features and treatment results were collected and analyzed., Results: En bloc resection was achieved in 84.6% of the patients in the STER group and 86.7% of the patients in the TE group (p = 0.708). Notably, the procedure time and hospital stay in the STER group were considerably shorter than those in the TE group. Tumor transverse diameter is a significant risk factor for piecemeal resection, adverse events, and technical difficulties. No recurrence or metastasis was found during a mean follow-up period of more than 2 years., Conclusions: Submucosal tunneling endoscopic resection is effective and safe for large SMTs in the esophagus and esophagogastric junction. This procedure has the advantage of being more minimally invasive with a shorter procedure time and hospital stay compared with TE. Submucosal tunneling endoscopic resection for tumors with a transverse diameter ≥3.5 cm and an irregular shape is associated with relatively high risk for piecemeal resection, adverse events, and technical difficulties., (Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Human Nestin (hNestin) has been found to express in melanoma, and its expression is positively correlated with the advanced stage of melanoma. However, the precise role of hNestin in the development of melanoma has not been fully understood. The present study aimed to explore the role of hNestin in the proliferation and invasion of melanoma cells. The lentivirus vector carrying a short hairpin RNAs (shRNAs) targeting hNestin (hNestin-shRNA-LV) was stably infected into human melanoma cells UACC903, which expressed high levels of hNestin. The effects of hNestin knockdown on the proliferation, apoptosis, migration of melanoma cells and the related signaling pathways were investigated by immunofluorence, Western blotting and reverse transcription polymerase chain reaction (RT-PCR), respectively. The results showed that hNestin was expressed in most melanoma specimens and the melanoma cells studied. Knockdown of hNestin expression significantly inhibited the proliferation of melanoma cells, blocked the formation of cell colony, arrested cell cycle at G 1 /S stage and suppressed the activation of Akt and GSK3β. hNestin-silent cells also showed a sheet-like appearance with tight cell-cell adhesion, decreased membrane expression of N-cadherin and β-catenin, and attenuated migration. Furthermore, hNestin silence resulted in the inhibition of tumor growth in vivo. Our study indicates that hNestin knockdown suppresses the proliferation of melanoma cells, which might be through affecting Akt-GSK3β-Rb pathway-mediated G 1 /S arrest, and hNestin silence inhibits the migration by selectively modulating the expression of cell adhesion molecules in the process of epithelial-mesenchymal transition.

Background: Additional surgery is recommended when early colorectal cancer (ECRC) is resected by non-curative endoscopic submucosal dissection (ESD) and there is significant risk of lymph node metastasis (LNM). The aim of this study was to investigate the efficacy and safety of additional surgery after non-curative ESD for ECRC and evaluate long-term outcomes., Methods: Patients with ECRC who underwent ESD and additional surgery between July 2007 and November 2013 were identified. Histology and patient data were collected during an average period of more than 5 years to determine tumor stage and type, resection status, complications, tumor recurrence, and distant metastasis., Results: Fifty-one patients who underwent additional surgery were eligible for analysis. Overall, regional LNM was detected in 5 patients (9.8%) and presence of lymphovascular infiltration was a significant risk factor. Surgery-related complications occurred in 3 patients (5.9%). During a median follow-up period of 59 months, no metastasis or local recurrence was observed. Three patients died of other diseases and no CRC-related deaths took place., Conclusions: Additional surgery after non-curative ESD for ECRC is effective and safe and should be encouraged to foster curative treatment and better long-term outcomes.

The molecular mechanisms underlying colorectal cancer (CRC) development remain elusive. In this study, we examined the miRNA and mRNA expressions in the adenoma-carcinoma sequence (ACS), a critical neoplastic progression in CRC development. We found that miR-137 was down-regulated in all adenoma and carcinoma tissues. Low miR-137 levels were correlated negatively with tumor progression and metastasis. Then we identified the inhibition effect of the miR-137 in CRC development, both in CRC cell lines and mouse models. MiR-137 was shown to control CRC cell proliferation, colony formation, migration and invasion and to control tumor growth and metastasis. We further confirmed the negative association between miR-137 and c-Met expression and thus validated this important oncogene as the target of miR-137 in CRC. In addition, we found a DNA methyl-CpG-binding protein, Mecp2, was up-regulated in ACS tissues via mRNA sequencing. Further experiment showed that miR-137 expression in CRC was subjected to epigenetic regulation mediated by Mecp2. We also confirmed c-Met expression can be up-regulated by silencing of miR-137 and suppressed by coexpression of Mecp2 and miR-137. These findings highlight the critical role of miR-137-c-Met nexus in CRC development and reveal Mecp2-regulated epigenetic silence causes the downregulation of miR-137 in colorectal adenoma and carcinoma.

Ethnopharmacological Relevance: Selaginella uncinata (Desv.) Spring, known as "Cuiyuncao", is a perennial herb widely distributed in the Southeast Asian countries. In the folk medicine, the local minority commonly use it to treat cough and asthma for centuries., Aim of the Study: This study was carried out to investigate the protective mechanisms of total flavonoids from S. uncinata (SUF) on airway hyperresponsiveness, cytokine release and bitter taste receptors (T2Rs) signaling with emphasis on inflammatory responses in a rat model of ovalbumin (OVA)-induced asthma., Materials and Methods: Rats were sensitized and challenged with OVA to induce typical asthmatic reactions. Pathological changes of lung tissue were examined by HE staining. The serum levels of T cell-associated cytokines (IFN-γ, IL-4, IL-5 and IL-13), total IgE and OVA-specific IgE were determined by enzyme-linked immunosorbent assay (ELISA). Gene expressions of T2R10, IP3R1 and Orai1 in lung tissue were assayed by fluorescence quantitative real-time polymerase chain reaction (FQ-PCR) while protein expressions of NFAT1 and c-Myc were assayed by western blot analysis. The activation of SUF was investigated on tansgentic T2R10-GFP HEK293 cells., Results: SUF treatment attenuated airway hyperresponsiveness and goblet cell hyperplasia compared with OVA-challenged asthmatic rats. The serum levels of IL-4, IL-5 and IL-13 as well as total and OVA-specific IgE were decreased while serum IFN-γ was increased in SUF-treated rats. SUF treatment significantly up-regulated T2R10 gene expression, down-regulated IP3R1 and Orai1 gene expression. SUF further suppressed eotaxin, NFAT1 and c-Myc protein expression in lung tissues of OVA-challenged rats., Conclusions: These results imply that SUF exerts anti-inflammatory function through the T2R10/IP3R1/NFAT1 dependent signaling pathway, and may warrant further evaluation as a possible agent for the treatment of asthma., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Aim: To evaluate the advantage of canaloplasty compared to trabeculectomy for patients with open angle glaucoma., Methods: Potentially relevant studies were systematically searched using various databases from inception until December 2015. The outcome analyses performed automatically using Revman 5.3 included intraocular pressure reduction (IOPR), postoperative success rate, anti-glaucoma medications reduction and the incidence of adverse events., Results: We included four qualified studies incorporating a total of 215 eyes for quantitative synthesis. The weighted mean difference (WMD) of IOPR between canaloplasty and trabeculectomy from baseline to 12mo was -2.33 (95%CI: -4.00, -0.66). There was not significant improvement in the complete or qualified success rate (OR: 0.58, 95%CI: 0.26, 1.31; OR: 0.50, 95%CI: 0.10, 2.44, respectively). Similarly, no statistically significance was observed in anti-glaucoma mediations reduction (WMD: -0.54, 95%CI: -1.18, 0.09). Sensitivity analysis of the primary outcome estimate confirmed the stability of the Meta-analysis result., Conclusion: Trabeculectomy seems to be more effective in lowering IOP up to 12mo when comparing with canaloplasty. Canaloplasty does not seem to be inferior to trabeculectomy considering the postoperative success rate or the number of postoperative anti-glaucoma medications. Meanwhile, it has an advantage of less bleb related complications.