Proton pump inhibitors alter gut microbiota by promoting oral microbiota translocation: a prospective interventional study.

BACKGROUND: The mechanism by which proton pump inhibitors (PPIs) alter gut microbiota remains to be elucidated. We aimed to learn whether PPI induced gut microbiota alterations by promoting oral microbial translocation. METHODS: Healthy adult volunteers were randomly assigned: PP group (n=8, 40 mg esomeprazole daily for seven days) and PM group (n=8, 40 mg esomeprazole along with chlorhexidine mouthwash after each meal for seven days). Fecal and saliva samples were analysed using 16S ribosomal RNA sequencing. Mouse models were introduced to confirm the findings in vivo, while the effect of pH on oral bacteria proliferation activity was investigated in vitro. RESULTS: Taxon-based analysis indicated that PPI administration increased Streptococcus abundance in gut microbiota (P<0.001), and the increased species of Streptococcus were found to be from the oral site or oral/nasal sites, in which Streptococcus anginosus was identified as the significantly changed species (P<0.004). Microbial source tracker revealed that PPI significantly increased the contribution of oral bacteria to gut microbiota (P=0.026), and no significant difference was found in PM group (P=0.467). Compared to the baseline, there was a 42-fold increase in gut abundance of Streptococcus anginosus in PP group (P=0.002), and the times decreased to 16-fold in PM group (P=0.029). Mouse models showed that combination of PPI and Streptococcus anginosus significantly increased the gut abundance of Streptococcus anginosus compared with using PPI or Streptococcus anginosus only. Furthermore, Streptococcus anginosus cannot survive in vitro at a pH lower than 5. CONCLUSIONS: PPIs altered gut microbiota by promoting oral-originated Streptococcus translocation into gut.

3 L split-dose polyethylene glycol is superior to 2 L polyethylene glycol in colonoscopic bowel preparation in relatively high-BMI (≥ 24 kg/m2) individuals: a multicenter randomized controlled trial.

BACKGROUND: Whether body mass index (BMI) is a risk factor for poor bowel preparation is controversial, and the optimal bowel preparation regimen for people with a high BMI is unclear. METHODS: We prospectively included 710 individuals with high BMIs (≥ 24 kg/m2) who were scheduled to undergo colonoscopy from January to November 2021 at 7 hospitals. Participants were randomly allocated into 3 L split-dose polyethylene glycol (PEG) group (n=353) and 2 L PEG group (n=357). The primary outcome was the rate of adequate bowel preparation, and the secondary outcomes included Boston Bowel Preparation Scale (BBPS) score, polyp detection rate, cecal intubation rate, and adverse reactions during bowel preparation. Furthermore, we did exploratory subgroup analyses for adequate bowel preparation. RESULTS: After enrollment, 15 individuals didn't undergo colonoscopy, finally 345 participants took 3 L split-dose PEG regimen, and 350 participants took 2 L PEG regimen for colonoscopic bowel preparation. 3 L split-dose PEG regimen was superior to 2 L PEG regimen in the rate of adequate bowel preparation (81.2% vs. 74.9%, P = 0.045), BBPS score (6.71±1.15 vs. 6.37±1.31, P < 0.001), and the rate of polyp detection (62.0% vs. 52.9%, P = 0.015). The cecal intubation rate was similar in both groups (99.7%). Regarding adverse reactions, individuals were more likely to feel nausea in the 3 L PEG group (30.9% vs. 19.3%; P = 0.001); however, the degree was mild. In the subgroup analysis for adequate bowel preparation, 3 L split-dose PEG regimen performed better than 2 L PEG regimen in the overweight (BMI 25-29.9 kg/m2 ) (P = 0.006) and individuals with constipation (P = 0.044), while no significant differences were observed in relatively normal (BMI 24-24.9 kg/m2) (P = 0.593) and obese individuals (BMI ≥ 30 kg/m2) (P = 0.715). CONCLUSIONS: 3 L split-dose PEG regimen is superior to 2 L PEG regimen for colonoscopic Bowel Preparation in relatively high-BMI individuals, especially overweight individuals (BMI 25-29.9 kg/m2 ). TRIAL REGISTRATION: This trial was registered in the Chinese Clinical Trials Registry (ChiCTR2000039068). The date of first registration, 15/10/2020, http://www.chictr.org.cn.

Clinical Comparison of the "Windowing" Technique and the "Open Book" Technique in Schatzker Type II Tibial Plateau Fracture.

OBJECTIVE: Surgical treatment for Schatzker type II tibial plateau fractures remains challenging and requires high-quality research. The aim of the study is to compare the "windowing" and "open book" techniques for the treatment of Schatzker type II tibial plateau fractures. METHODS: In this prospective study, all patients with Schatzker type II tibial plateau fractures between January 2014 and December 2017 were managed by open reduction and internal fixation using an anterolateral incision approach. "Windowing" group included 78 patients (53 men and 25 women), with an average age of 57.7 ± 13.5 years, who underwent the "windowing" technique, in which the procedure was performed through a small cortical window against the depressed zone of the lateral plateau. The "open book" group included 80 patients (56 men and 24 women), with an average age of 54.8 ± 12.4 years, who underwent the technique. The clinical outcomes included the Rasmussen classification of knee function and grading of post-traumatic arthritis. The radiographic outcome (x-ray and computed tomography [CT]) was the reduction quality of the lateral plateau based on the modified Rasmussen radiological assessment. The patient-reported outcome was visual analogue scale (VAS) scores. RESULTS: The mean follow-up time for the158 patients was 32 months (range, 24-42 months). The time elapsed from injury to surgery in "windowing" group and "open book" group were 3.7 ± 1.2 (range, 1-10 days) and 3.5 ± 1.4 days (range, 1-11 days), respectively, with no significant difference between the groups (P > 0.05). The operation times did not differ significantly between the "windowing" group (61.0 ± 8.3 min, range, 45-120 min) and the "open book" group (61.2 ± 10.4 min, range, 40-123 min) (P > 0.05). After surgery, CT revealed five (6.4%) and 15 (18.8%) cases of articular depression in the "windowing" and "open book" groups, respectively. Significant differences were observed in the articular depression of tibial plateau fractures between the groups (P < 0.05). However, condylar widening or valgus/varus did not differ significantly between the groups. Furthermore, no significant differences in knee function were observed during follow-up (P > 0.05). VAS scores were similar between the groups at 24 months after surgery (P > 0.05). There were significant differences in the number of severe post-traumatic arthritis (grades 2 and 3) cases between the groups (P < 0.05). CONCLUSIONS: The "windowing" and "open book" techniques are both effective for the treatment of Schatzker type II tibial plateau fractures. However, the "windowing" technique provides better reduction quality, leading to a satisfactory prognosis.

[Mortality Risk Factors for Inpatients with Ischemic Heart Disease Complicated with Gastrointestinal Bleeding].

OBJECTIVE: To investigate the risk factors of in-hospital mortality in patients with combined ischemic heart disease (IHD) and gastrointestinal bleeding (GIB). METHODS: Patients who were hospitalized and received treatment for IHD combined with GIB at West China Hospital, Sichuan University between Jan. 2015 and Jan. 2018 were included in the study. Information concerning their baseline data, comorbidities, history of anticoagulant and antiplatelet medication, laboratory data on admission, and in-hospital treatments was collected. In-hospital death of all causes was taken as the primary endpoint event of the study, and multivariate logistic regression analysis was conducted to identify the independent risk factors of mortality during their hospital stay for this specific type of patients. Then, receiver operating characteristic ( ROC) curve was drawn and the area under curve ( AUC) was calculated accordingly. RESULTS: A total of 395 patients met the enrollment criteria and were included in the study. Among them, 342 patients were discharged after their condition improved, and 53 patients died during hospitalization. Analysis of the cause of death revealed that cardiogenic death was the leading cause of death (54.7%), which was followed by infection-caused death (24.5%). Logistic regression analysis revealed that patients with ST-segment elevation myocardial infarction (STEMI) had a 2.527-fold risk of mortality compared with patients with non-acute coronary syndrome (odds ratio [ OR]=2.527, 95% confidence interval [ CI]: 1.152-8.277, P=0.043), and patients with comorbidity of chronic renal disease (CKD) had a 2.89-fold risk of mortality ( OR=2.89, 95% CI:1.187-7.037, P=0.019). It was also shown the higher level of WBC count ( OR=1.123, 95% CI: 1.057-1.193, P<0.001) and lower hemoglobin ( OR=1.014, 95% CI: 1.003-1.025, P=0.013) on admission were related to in-hospital mortality. On the other hand, endoscopy ( OR=0.305, 95% CI: 0.103-0.881, P=0.029) was identified as a protective factor in hospital treatment that decreased the risk of in-hospital mortality. ROC curve was drawn by combining the aforementioned variables to predict in-hospital mortality, which had an AUC of 0.79. CONCLUSION: The actual type of IHD being STEMI, the patient's condition being complicated with chronic kidney disease, and having high white blood cells and low hemoglobin levels upon admission were considered independent risk factors for in-hospital death outcome of IHD patients complicated with GIB, while undergoing endoscopy during hospitalization was considered as a protective factor.

[Risk Factors for Adverse Outcomes in the Elderly Inpatients with Gastrointestinal Bleeding].

OBJECTIVE: To explore the factors affecting the adverse prognosis of elderly inpatients with gastrointestinal bleeding (GIB). METHODS: We retrospectively analyzed the clinical data of elderly patients aged 60 and over admitted with GIB to the Department of Gastroenterology, West China Hospital, Sichuan University between January 2016 and January 2021. The adverse outcome was defined as admission to the intensive care unit and/or in-hospital death during the patient's stay at the hospital. Univariate and multivariate logistic regression analyses were done to identify the risk factors associated with the adverse outcome of the elderly. RESULTS: A total of 885 elderly patients (median age: 72.00 years, 517 males and 368 females) with GIB were enrolled, including 436 cases of upper GIB (UGIB) and 449 cases of lower GIB (LGIB). The overall rate of adverse outcome was 13.22% (117/885), which was significantly higher in the UGIB patients than that in the LGIB patients ( P<0.001). Univariate logistic regression identified UGIB ( P<0.001), shock index>1 ( P<0.001), hemoglobin ( P<0.001), blood urea nitrogen ( P<0.001), creatinine ( P<0.001), and international normalized ratio (INR) ( P<0.001) on admission, as well as erythrocyte transfusion ( P<0.001), fresh frozen plasma (FFP) transfusion ( P<0.001), and platelet transfusion ( P<0.001) were associated with adverse outcome. Multivariate logistic analysis showed that UGIB ( P<0.001), shock index >1 on admission ( P=0.001), higher INR on admission ( P=0.015) and FFP transfusion during hospitalization ( P<0.001) were independent risk factors for adverse outcome of elderly patients with GIB. Further analysis showed that INR>1.5 on admission significantly increased the risks of adverse outcome ( P<0.001). CONCLUSION: Elderly patients with UGIB exhibited worse prognosis than those with LGIB. After adjusting for age and the location of bleeding, shock index>1, INR>1.5 on admission and FFP transfusion were considered independent risk factors for the adverse outcome of elderly inpatients with GIB.

Percutaneous posteroanterior screw fixation for Haraguchi type 1 posterior malleolar fracture in tri-malleolar fracture: Operative technique and randomized clinical results.

PURPOSE: The study described a novel surgical treatment of Haraguchi type 1 posterior malleolar fracture in tri-malleolar fracture and patient outcomes at intermediate period follow-up. METHODS: All patients from January 2015 to December 2017 with tri-malleolar fracture of which posterior malleolar fractures were Haraguchi type 1, were surgically treated in this prospective study. Lateral and medial malleolar fractures were managed by open reduction and internal fixation through dual incision approaches. 36 cases of Haraguchi type 1 posterior malleolar fractures were randomly performed by percutaneous posteroanterior screw fixation with the aid of medial exposure (group 1). And 40 cases were performed by percutaneous anteroposterior screw fixation (group 2). Clinical outcomes, radiographic outcomes and patient-reported outcomes were recorded. RESULTS: Seventy-six patients with mean follow-up of 30 months were included. There were no significant differences in the mean operation time (81.0 ± 11.3 vs. 77.2 ± 12.4), ankle function at different periods of follow-up, range of motions and visual analog scale (VAS) at 24 months between the two groups (p > 0.05). However, the rate of severe post-traumatic arthritis (Grade 2 and 3) and the rate of step-off rather than gap in radiological evaluation were lower in group 1 than that in group 2 (p < 0.05). CONCLUSION: Using our surgical technique, more patients had good outcome with a lower rate of severe post-traumatic arthritis, compared with the group of percutaneous anteroposterior screw fixation. Percutaneous posteroanterior screw fixation can be a convenient and reliable alternative in treating Haraguchi type 1 posterior malleolar fracture.

"Candidatus Liberibacter asiaticus" Secretes Nonclassically Secreted Proteins That Suppress Host Hypersensitive Cell Death and Induce Expression of Plant Pathogenesis-Related Proteins.

Although emerging evidence indicates that bacteria extracellularly export many cytoplasmic proteins referred to as non-classically secreted proteins (ncSecPs) for their own benefit, the mechanisms and functional significance of the ncSecPs in extracellular milieu remain elusive. "Candidatus Liberibacter asiaticus" (CLas) is a fastidious Gram-negative bacterium that causes Huanglongbing (HLB), the most globally devastating citrus disease. In this study, using the SecretomeP program coupled with an Escherichia coli alkaline phosphatase assay, we identified 27 ncSecPs from the CLas genome. Further, we demonstrated that 10 of these exhibited significantly higher levels of gene expression in citrus than in psyllid hosts, and particularly suppressed hypersensitive response (HR)-based cell death and H2O2 overaccumulation in Nicotiana benthamiana, indicating their opposing effects on early plant defenses. However, these proteins also dramatically enhanced the gene expression of pathogenesis-related 1 protein (PR-1), PR-2, and PR-5, essential components of plant defense mechanisms. Additional experiments disclosed that the increased expression of these PR genes, in particular PR-1 and PR-5, could negatively regulate HR-based cell death development and H2O2 accumulation. Remarkably, CLas infection clearly induced gene expression of PR-1, PR-2, and PR-5 in both HLB-tolerant and HLB-susceptible species of citrus plants. Taken together, we hypothesized that CLas has evolved an arsenal of ncSecPs that function cooperatively to overwhelm the early plant defenses by inducing host PR genes.IMPORTANCE In this study, we present a combined computational and experimental methodology that allows a rapid and efficient identification of the ncSecPs from bacteria, in particular the unculturable bacteria like CLas. Meanwhile, the study determined that a number of CLas ncSecPs suppressed HR-based cell death, and thus indicated a novel role for the bacterial ncSecPs in extracellular milieu. More importantly, these ncSecPs were found to suppress cell death presumably by utilizing host PR proteins. The data overall provide a novel clue to understand the CLas pathogenesis and also suggest a new way by which phytopathogens manipulate host cellular machinery to establish infection.

A Sec-Dependent Secretory Protein of the Huanglongbing-Associated Pathogen Suppresses Hypersensitive Cell Death in Nicotiana benthamiana.

"Candidatus Liberibacter asiaticus" (CLas) is a phloem-restricted Gram-negative bacterium that is the causal agent of citrus huanglongbing (HLB). In this study, we identified a CLas-encoded Sec-dependent secretory protein CLIBASIA_04405 that could contribute to the pathogenicity of this bacterium. The gene expression level of CLIBASIA_04405 was significantly higher in citrus than in psyllids. Transient overexpression of the mature CLIBASIA_04405 protein (m4405) in Nicotiana benthamiana leaves could suppress hypersensitive response (HR)-based cell death and H2O2 accumulation triggered by the mouse BAX and the Phytophthora infestans INF1. An alanine-substitution mutagenesis assay revealed the essential of amino acid clusters EKR45-47 and DE64-65 in cell death suppression. Challenge inoculation of the transgenic N. benthamiana-expressing m4405 with Pseudomonas syringae DC3000ΔhopQ1-1 demonstrated the greatly reduced bacterial proliferation. Remarkably, transcriptome profiling and RT-qPCR analysis disclosed that the gene expression of six small heat shock proteins (sHSPs), a set of plant defense regulators, were significantly elevated in the transgenic m4405 lines compared with those in wild-type N. benthamiana. In addition, the transgenic m4405 lines displayed phenotypes of dwarfism and leaf deformation. Altogether, these data indicated that m4405 was a virulence factor of CLas.

Genome-wide identification of the Sec-dependent secretory protease genes in Erwinia amylovora and analysis of their expression during infection of immature pear fruit.

The general secretory (Sec) pathway represents a common mechanism by which bacteria secrete proteins, including virulence factors, into the extracytoplasmic milieu. However, there is little information about this system, as well as its associated secretory proteins, in relation to the fire blight pathogen Erwinia amylovora. In this study, data mining revealed that E. amylovora harbors all of the essential components of the Sec system. Based on this information, we identified putative Sec-dependent secretory proteases in E. amylovora on a genome-wide scale. Using the programs SignalP, LipoP, and Phobius, a total of 15 putative proteases were predicted to contain the N-terminal signal peptides (SPs) that might link them to the Sec-dependent pathway. The activities of the predicted SPs were further validated using an Escherichia coli-based alkaline phosphatase (PhoA) gene fusion system that confirmed their extracytoplasmic property. Transcriptional analyses showed that the expression of 11 of the 15 extracytoplasmic protease genes increased significantly when E. amylovora was used to inoculate immature pears, suggesting their potential roles in plant infection. The results of this study support the suggestion that E. amylovora might employ the Sec system to secrete a suite of proteases to enable successful infection of plants, and shed new light on the interaction of E. amylovora with host plants.

The impact of albumin infusion on the risk of rebleeding and in-hospital mortality in cirrhotic patients admitted for acute gastrointestinal bleeding: a retrospective study of a single institute.

BACKGROUND: To investigate the effect of albumin infusion on cirrhotic patients admitted for acute gastrointestinal bleeding. METHODS: Medical records of cirrhotic patients who admitted due to acute gastrointestinal bleeding through January 2009 to December 2018 were reviewed. Clinical data and the total amount of albumin and red blood cell used during hospitalization were recorded. For patients with rebleeding, the amount of albumin and red blood cell used before rebleeding was also documented. The primary outcome was the occurrence of rebleeding, and the second outcome was in-hospital mortality. Univariate and multivariate logistic analysis was performed to identify risk factors associated with rebleeding and in-hospital mortality. RESULTS: A total of 1503 cirrhotic patients were included in the analysis. There were 146 episodes of in-patient rebleeding occurred, while 81 patients died. Overall, more red blood cells and albumin were prescribed to patients who suffered rebleeding. In terms of the amount before rebleeding, the red blood cell was higher in patients with rebleeding, but the albumin infusion was similar. In the multivariate model, the albumin infusion before rebleeding was an independent risk factor associated with rebleeding (adjusted OR for ≤40 g vs 0 g, 0.469 [0.269-0.793], p = 0.006; adjusted OR for > 40 g vs 0 g, 0.272 [0.115-0.576], p = 0.001). In Child-Pugh C class patients, the use of albumin more than 40 g during hospitalization associated with a lower risk of in-patient mortality (adjusted OR for > 40 g vs 0 g, 0.136 [0.019-0.741], p = 0.031). CONCLUSIONS: Albumin infusion was associated with a lower risk of rebleeding and in-hospital deaths in cirrhosis admitted for acute gastrointestinal bleeding.

NtRBP45, a nuclear RNA-binding protein of Nicotiana tabacum, facilitates post-transcriptional gene silencing.

The tobacco RBP45 is a nuclear RNA binding protein (RBP). In this study, we identified that the gene expression of NtRBP45 was significantly up-regulated upon the Tobacco mosaic virus infection and the central region of the protein accounted for its nuclear localization. In particular, using a green fluorescent protein-based transient suppression assay, we uncovered that the transiently overexpressed NtRBP45 was able to enhance local post-transcriptional gene silencing (PTGS), facilitate siRNA accumulation, and compromise the RNA silencing suppression mediated by Tomato aspermy virus 2b protein. Deletion mutagenesis showed that both the N- and C-terminal regions of NtRBP45 were necessary for enhancing PTGS. The data overall indicated a novel RNA silencing factor that might participate in antiviral defense.

Development and validation of a model to determine risk of refractory benign esophageal strictures.

BACKGROUND: Current research has identified several risk factors for refractory benign esophageal strictures (RBES), but research is scarce on the prediction of RBES in benign esophageal strictures patients. Meanwhile, the long-term outcomes of RBES remain unclear. The aim of this study was to develop and validate a model to determine the progression of RBES in patients with benign esophageal strictures. And we also explored the long-term outcomes and safety in patients with RBES. AIM: To develop and validate a model to determine the progression of RBES in patients with benign esophageal strictures, based on the demographic data and endoscopic findings. METHODS: A total of 507 benign esophageal stricture patients treated by dilation alone or in combination with stenting were retrospectively enrolled between January 2009 and February 2018. The primary outcome was to establish a risk-scoring model predicting RBES in benign esophageal strictures. The secondary outcome was to explore the clinical effectiveness and adverse events in patients with RBES. RESULTS: In the study, age, etiology, and number and length of strictures were the independent risk factors for the refractory performance of benign esophageal strictures. According to risk factors of benign esophageal strictures, a risk-scoring model for predicting RBES in benign esophageal strictures was established: The risk score ranged from 0 to 8 points, and the risk scores were divided into low risk (0-2 points), intermediate risk (3-5 points), and high risk (6-8 points). The proportions of RBES in the corresponding risk categories were 1.0%, 12.2%, and 76.0%, respectively. Among 507 patients, 57 had RBES (39 males; median age, 60 years). The success rate of dilation treatment (51.2%, 21/41) was higher than that of stent placement (37.5%, 6/16). CONCLUSION: In this study, 11.3% (57/507) patients had RBES at our hospital. The risk-scoring model predicting RBES in benign esophageal strictures could predict the long-term outcome of patients with strictures ahead.

The role of endoscopic dilation and stents in refractory benign esophageal strictures: a retrospective analysis.

BACKGROUND: The outcomes of patients with refractory benign esophageal strictures (RBES) are unclear, and the clinical efficacy of dilation versus stent placement is lacking. Our objective was to explore the role of endoscopic dilation and stents placement in the management of RBES. METHODS: RBES patients treated with dilation and stents in our hospital between January 2009 and December 2017 were included in this study. The primary outcomes were to assess clinical effectiveness and adverse events. The secondary outcome was to identify factors that predicted the dysphagia-free period. RESULTS: Among 75 RBES patients (54 male; median age 59 years), 39 (52%), 20 (26.7%), 3 (4%), 10 (13.3%), and 3 (4%), were postsurgical, post-ESD, achalasia of cardia, caustic and mixed etiology, respectively. The median number of endoscopic therapy was 5 times (range 3, 21). Endoscopic therapy was successful in 46 patients (61.3%). Patients treated with dilation showed a higher success rate (70.9%, 39/55) than that treated with stents (35%, 7/20). Fifteen patients died during follow-up. Nineteen patients had adverse events after endoscopic therapy. In total, the mean dysphagia-free period was 3.4 months (95% CI, 2.5-4.3). The patients treated with dilation demonstrated a dysphagia-free period of 3.7 months (95% CI, 2.7-5), while patients treated with stents displayed a dysphagia-free period of 2.3 months (95% CI, 1.5-3). The dysphagia-free period had a linear growth trend over time, with an increase of 12 days per endoscopic therapy. CONCLUSION: The dysphagia-free period increased by 12 days per endoscopic therapy, so the endoscopic therapy tended to be effective in patients with RBES by increasing the dysphagia-free period. However, compared to dilation therapy, stent therapy was not effective in increasing the dysphasia-free period and reducing the times and frequency of dilation. In addition, univariate and multivariate analyses also indicated that etiology may predict the endoscopic therapy outcome. TRIAL REGISTRATION: This study was retrospectively registered and approved by the Ethics Committee of West China Hospital of Sichuan University (IRB number: ChiCTR1800016321 ).

Tunable composites prepared from graphene oxide and zeolitic imidazolate framework-8 for improved selective isolation of hemoglobin.

The authors report on the preparation of composites made from graphene oxide (GO) and zeolitic imidazolate framework-8 (ZIF-GO), with various fractions of GO. GO acts as the template and as a modulator for the surface properties of the composites. It also improves the selective adsorption of specific proteins, i.e. hemoglobin (Hb) in this case. The adsorption capacity for Hb is as high as 436 mg g-1 when using a composite containing 20% of GO as sorbent, and 95% of specific activity is maintained for the Hb recovered. The sorbent is applied to selectively isolate Hb from human whole blood. Graphical abstract Graphene oxide-zeolitic imidazolate framework-8 composites (ZIF-GO) with varying mass ratios of GO were prepared in order to tune surface properties and to improve the adsorption selectivity toward hemoglobin.

[Accuracy of EUS and ME-NBI for Evaluating the Invasion Depth of Early Esophageal Cancer].

OBJECTIVE: To assess the accuracy of endoscopic ultrasound (EUS) and magnifying endoscopy with narrow-band imaging (ME-NBI) in evaluating the invasion depth of early esophageal carcinoma. METHODS: Patients who underwent endoscopic resection for early esophageal cancer from March 2013 to October 2017 were enrolled. The EUS and ME-NBI results were compared with the pathology results. RESULTS: A total of 392 lesions from 333 patients were assessed, including 83 mild and moderate dysplasia, 72 severe dysplasia, 235 squamous cell carcinoma, and 2 adenosquamous carcinoma. About 308 lesions were given EUS only, 7 had ME-NBI only, 77 underwent both EUS and ME-NBI. EUS resulted in a 43.9% accuracy for the 385 lesions, with poor consistency (Kappa=0.1) with the pathology results. But higher accuracy (68.2%) was found for lesions infiltrating into the submucosa of the lesions, compared with 40.5% for lesions contained within the mucosa (P=0.001). ME-NBI resulted in a 72.6% accuracy for the 84 lesions, with a medium consistency (Kappa=0.4). The accuracy for lesions contained within the mucosa was 91.0%, compared with 16.7% for lesions infilrtrating into the submucosa (P=0.001). EUS and ME-NBI for the 77 lesions demonstrated an accuracy of 42.9% for the EUS and 84.3% for the ME-NBI (P=0.001). CONCLUSIONS: ME-NBI has higher accuracy than EUS in evaluating the invasion depth of early esophageal carcinoma.

The oxidation states of DJ-1 dictate the cell fate in response to oxidative stress triggered by 4-hpr: autophagy or apoptosis?

AIM: Chemotherapy-induced reactive oxygen species (ROS) not only contribute to apoptosis, but also trigger autophagy. Since autophagy is reported to protect cancer cells from apoptosis, this weakens the therapeutic effect of chemotherapy. This study aimed at identifying the key molecules that determine the cellular response to ROS and, therefore, provide better strategies to increase chemotherapeutic efficiency. RESULTS: Increasing concentrations of N-(4-hydroxyphenyl) retinamide (4-HPR)-treatment pushed autophagy down to apoptosis in a dose-dependent manner, and 4-HPR-induced ROS contribute to this process. Since we found that ASK1-regulated JNK1 and p38 are responsible for 4-HPR-induced autophagy and apoptosis, respectively, we further utilized co-immunoprecipitation followed by liquid chromatography-tandem mass spectrometry analysis to identify proteins that specifically bind to ASK1 under different oxidative states. Of note, DJ-1, a crucial antioxidant protein, was identified. Interestingly, DJ-1 functions as a redox sensor that senses ROS levels and determines the cellular response to 4-HPR: Under mild oxidative stress, moderate oxidation of DJ-1 is recruited to inhibit the activity of ASK1 and maintain cell viability by activating autophagy; under a lethal level of oxidative stress, excessive oxidized DJ-1 dissociates from ASK1 and activates it, thereby initiating p38 activation and enabling the cells to commit to apoptosis. Moreover, the depletion of DJ-1 increases the sensitivity of tumor cells to 4-HPR both in vitro and in vivo. INNOVATION: Our results reveal that the different oxidation states of DJ-1 function as a cellular redox sensor of ROS caused by 4-HPR and determine the cell fate of autophagy or apoptosis. Moreover, the results suggest that DJ-1 might be a potent therapeutic target for cancer treatment. CONCLUSION: ROS-mediated changes in the oxidation state of DJ-1 are involved in 4-HPR's effect on pushing autophagy down to apoptosis. Consequently, this change mediates ASK1 activation by regulating DJ-1-ASK1 complex formation and determines the cell fate of autophagy or apoptosis.