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In this study, the application of bovine serum albumin (BSA) as a carrier to glucose-sensitive materials for the detection of glucose was proposed. Au-CuO bimetallic nanoclusters (Au-CuO/BSA) were prepared using BSA as a template, the new sensing material (Au-CuO/BSA/MWCNTs) was synthesized by mixing with multi-walled carbon nanotubes (MWCNT) and applied to non-enzymatic electrochemical sensors to detect glucose stably and effectively under neutral condition. The scanning electron microscopy was used to investigate the morphology of the synthesized nanocomposite. The electrochemical properties of the sensor were studied by cyclic voltammetry. Glucose detection experiments show that Au-CuO/BSA/MWCNTs/Au electrode has good glucose detection ability, stability, accuracy, repeatability, and high selectivity in neutral environment. Unlike existing glucose-sensitive materials, due to the use of BSA, the composite material is firmly fixed to the electrode surface without a Nafion solution, which reduces the current blocking effect on the modified electrode. The composite materials can be effectively preserved for extremely long periods, higher than 80% activity is maintained at room temperature in a closed environment for 3 to 4 months, due to the special effects of BSA. In addition, the feasibility of using BSA in glucose-sensitive materials is confirmed.

Highlights • Up-regulated SMYD3 correlates with worse prognosis and controls DDP resistance of NSCLC. • ANKHD1 interacts with and is essential for SMYD3-induced DDP resistance. • CDK2 is identified to be a downstream effector of SMYD3-ANKHD1 in NSCLC. • SMYD3-ANKHD1 critically regulates the growth DDP-resistant NSCLC cells in vivo., Background Cisplatin (DDP) remains the backbone of chemotherapy for non-small cell lung cancer (NSCLC), yet its clinical efficacy is limited by DDP resistance. We aim to investigate the role of the SET and MYND domain-containing protein 3 (SMYD3) in DDP resistance of NSCLC. Methods Expression pattern of SMYD3 was determined in NSCLC tissues using qRT-PCR, which also validated its correlation with NSCLC clinicopathological stages. Impacts of SMYD3 on DDP resistance were evaluated by knocking down SMYD3 in DDP-resistant cells and overexpressing it in DDP-sensitive cells, and assessed for several phenotypes: IC50 by MTT, long-term proliferation by colony formation, apoptosis and cell-cycle distribution by flow cytometry. The interaction between Ankyrin Repeat and KH Domain Containing 1 (ANKHD1) and SMYD3 was examined by co-immunoprecipitation and immunofluorescence. The transcriptional regulation of SMYD3 on cyclin-dependent kinase 2 (CDK2) promoter regions was confirmed using chromatin-immunoprecipitation. The in vivo experiments using DDP-resistant cells with altered SMYD3 and ANKHD1 expression were further performed to verify the SMYD3/ANKHD1 axis. Results Highly expressed SMYD3 was observed in NSCLC tissues or cells, acted as a sensitive indicator for NSCLC, correlated with higher TNM stages or resistant to DDP treatment, and shorter overall survival. The promotion of SMYD3 on DDP resistance requires co-regulator, ANKHD1. CDK2 was identified as a downstream effector. In vivo, SMYD3 knockdown inhibited the growth of DDP-resistant NSCLC cells, which was abolished by ANKHD1 overexpression. Conclusions SMYD3 confers NSCLC cells chemoresistance to DDP in an ANKHD1-dependent manner, providing novel therapeutic targets to overcome DDP resistance in NSCLC .

Background Neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACR) are the standard treatments for esophageal squamous cell carcinoma (ESCC). However, the 5-year overall survival (OS) rate is still far from satisfactory. In recent years, immune checkpoint inhibitors (ICIs) have shown promising results in the treatment of ESCC. More than 20 phase II clinical trials have been launched to explore combinations of ICIs in the neoadjuvant setting for ESCC. Based on our phase II clinical trial, a two-arm phase III trial was launched in Henan Cancer Hospital. ICIs combined with NAC may usher in a new era and may benefit locally advanced, resectable ESCC patients. Methods A two-arm phase III trial was launched in April 2020 in Henan Cancer Hospital. Patient recruitment will be completed within 18 months. The primary endpoint is event-free survival (EFS). The secondary endpoints include pathologic complete response (pCR), disease-free survival (DFS) rate, overall response rate (ORR), R0 resection rate, major pathologic response (MPR), adverse events (AEs), complication rate and quality of life (QOL). A biobank of pretreatment, resected tumor tissue and paired blood samples will be built for translational research in the future. Discussion This RCT directly compares NAC with neoadjuvant toripalimab plus chemotherapy in terms of EFS for locally advanced ESCC. The results may usher in a new era of resectable ESCC treatment. Trial registration NCT04280822 (https://www.clinicaltrials.gov/ct2/show/NCT04280822). Registered title: "A Phase III, Randomized Controlled Study of Neo-adjuvant Toripalimab (JS001) in Combination with Chemotherapy versus Neo-adjuvant Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma". Version 1.0/Nov. 21, 2019.

OBJECTIVE It is still controversial whether patients with clinical T2N0M0 (cT2N0M0) esophageal cancer are treated with induction therapy. The aim of this study was to determine the effect of induction therapy on cT2N0M0 esophageal cancer. METHODS AND MATERIALS We searched PubMed, Embase, the Cochrane Library, and Medline databases from inception up to May 1, 2017. This meta-analysis was performed to compare odds ratios (OR) for 5-year overall survival (OS), pathologically understaged and overstaged after esophagectomy. RESULTS Eight retrospective studies of 2646 patients were included in the meta-analysis. Data showed that no statistically significant difference in 5-year over survival was observed between induction therapy group and direct operation group. The pooled OR and 95% confidence interval (CI) for 5-year OS were 0.92 (95% CI = 0.72-1.18; P = .52). Whereas, compared with induction therapy group, direct operation group had more pathologically understaged and less overstaged after esophagectomy. CONCLUSIONS Currentclinical staging for T2N0M0 esophageal carcinoma remains inaccurate. In this study, we found that direct operation group had more pathologically understaged and less overstaged after esophagectomy compared with induction therapy group. Induction therapy could degrade the tumor staging but not improve the patient's survival.

Background The aim of this study was to evaluate the outcomes of patients with pathologic T0 esophageal carcinoma after neoadjuvant therapy and surgery. Methods We searched PubMed, Embase, Cochrane Library, and Medline databases from inception up to November 12, 2016. The meta-analysis was performed to compare odds ratios (OR) for overall survival (OS), disease-free survival (DFS), local control (LC), and distant control (DC). Results Eight published studies of 837 patients were included in the meta-analysis. Data showed that the ypT0N1 group was associated with worse outcomes compared with the ypT0N0 group. The pooled OR and 95% confidence interval (CI) for 3-year and 5-year OS were 3.08 [2.07, 4.57] and 4.27 [2.76, 6.59], respectively. Whereas, the pooled OR and 95% CI for 3-year and 5-year DFS were 3.90 [2.08, 7.34] and 5.17 [1.93, 13.87], respectively. The pooled OR and 95% CI for LR and DR were 4.52 [1.72, 11.91] and 2.65 [1.38, 5.09], respectively. Conclusions Remnant lymph node metastases after neoadjuvant therapy and surgery in patients with pathologic T0 esophageal carcinoma portend poor survival, and it is an important prognostic factor.

Supplemental Digital Content is available in the text, Background: Achalasia is an esophageal motility disorder, of unknown cause, which results in increased lower esophageal sphincter tone and symptoms of difficulty swallowing. Current major therapeutic options include laparoscopic Heller myotomy (LHM) and pneumatic dilation (PD). We undertake a systematic review comparing the efficacy and safety of these 2 treatments in the treatment of esophageal achalasia. Methods: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched for randomized controlled trial investigating LHM versus PD in the treatment of primary achalasia. The primary outcome was symptom remission rates. The Mantel–Haenszel method with fixed-effect or random-effects model was used to calculate relative risks and 95% confidence intervals (CIs). Results: Five studies involving 498 participants were included. The cumulative remission rate was significantly higher with LHM at 3 months and 1 year (short-term), with a risk ratio of 1.16 (95% CI 1.01–1.35, P = 0.04) and 1.14 (95% CI 1.02–1.27, P = 0.02), respectively. There were no significant differences between LHM and PD in 2-year and 5-year remission rate (long-term), with a risk ratio of 1.05 (95% CI 0.91–1.22, P = 0.49) and 1.17 (95% CI 0.84–1.64, P = 0.34), respectively. Rates of major mucosal tears requiring subsequent intervention with LHM were significantly lower than those of esophageal perforation with PD requiring postprocedural medical or surgical therapy, with a risk ratio of 0.25 (95% CI 0.08–0.81, P = 0.02). Postprocedural rates of gastroesophageal reflux, lower esophageal sphincter pressures, and quality of life scores did not differ in trials with sufficient data. Conclusions: There were no significant differences between LHM and PD in 2-year and 5-year remission rate. This study indicates that either treatment can be proposed as initial treatment for achalasia.

AIM: To identify genes potentially involved in Helicobacter pylori (H. pylori)-induced gastric carcinogenesis. METHODS: GES-1 cells were co-cultured with H. pylori strains isolated from patients with gastric carcinoma (GC, n = 10) or chronic gastritis (CG, n = 10) for in vitro proliferation and apoptosis assays to identify the most and least virulent strains. These two strains were cagA-genotyped and used for further in vivo carcinogenic virulence assays by infecting Mongolian gerbils for 52 wk, respectively; a broth free of H. pylori was lavaged as control. Genomic profiles of GES-1 cells co-cultured with the most and least virulent strains were determined by microarray analysis. The most differentially expressed genes were further verified using quantitative real-time polymerase chain reaction in GES-1 cells infected with the most and least virulent strains, and by immunohistochemistry in H. pylori positive CG, precancerous diseases, and GC biopsy specimens in an independent experiment. RESULTS: GC-derived H. pylori strains induced a potent proliferative effect in GES-1 cells in co-culture, whereas CG-derived strains did not. The most (from a GC patient) and least (from a CG patient) virulent strains were cagA-positive and negative, respectively. At week 52, CG, atrophy, metaplasia, dysplasia, and GC were observed in 90.0%, 80.0%, 80.0%, 90%, and 60.0%, respectively, of the animals lavaged with the most virulent strain. However, only mild CG was observed in 90% of the animals lavaged with the least virulent strain. On microarray analysis, 800 differentially expressed genes (49 up- and 751 down-regulated), involving those associated with cell cycle regulation, cell apoptosis, cytoskeleton, immune response, and substance and energy metabolisms, were identified in cells co-cultured with the most virulent strain as compared with those co-cultured with the least virulent strain. The six most differentially expressed genes (with a betweenness centrality of 0.1-0.2) were identified among the significant differential gene profile network, including JUN, KRAS, BRCA1, SMAD2, TRAF1, and HDAC6. Quantitative real-time polymerase chain reaction analyses verified that HDAC6 and TRFA1 mRNA expressions were significantly more up-regulated in GES-1 cells co-cultured with the most virulent strain than in those co-cultured with the least virulent strain. Immunohistochemistry of gastric mucosal specimens from H. pylori-positive patients with CG, intestinal metaplasia (IM), dysplasia, and GC showed that moderately positive and strongly positive HDAC6 expression was detected in 21.7% of CG patients, 30.0% of IM patients, 54.5% of dysplasia patients, and 77.8% of GC patients (P < 0.001). The up-regulation of TRAF1 expressions was detected in 34.8%, 53.3%, 72.7%, and 88.9% specimens of CG, IM, dysplasia, and GC, respectively (P < 0.001). CONCLUSION: The overexpression of HDAC6 and TRAF1 in GES-1 cells co-cultured with the GC-derived strain and in H. pylori-positive dysplasia and GC suggests that HDAC6 and TRAF1 may be involved in H. pylori-induced gastric carcinogenesis.