Deep learning assists detection of esophageal cancer and precursor lesions in a prospective, randomized controlled study.

Endoscopy is the primary modality for detecting asymptomatic esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Improving detection rate remains challenging. We developed a system based on deep convolutional neural networks (CNNs) for detecting esophageal cancer and precancerous lesions [high-risk esophageal lesions (HrELs)] and validated its efficacy in improving HrEL detection rate in clinical practice (trial registration ChiCTR2100044126 at www.chictr.org.cn). Between April 2021 and March 2022, 3117 patients ≥50 years old were consecutively recruited from Taizhou Hospital, Zhejiang Province, and randomly assigned 1:1 to an experimental group (CNN-assisted endoscopy) or a control group (unassisted endoscopy) based on block randomization. The primary endpoint was the HrEL detection rate. In the intention-to-treat population, the HrEL detection rate [28 of 1556 (1.8%)] was significantly higher in the experimental group than in the control group [14 of 1561 (0.9%), P = 0.029], and the experimental group detection rate was twice that of the control group. Similar findings were observed between the experimental and control groups [28 of 1524 (1.9%) versus 13 of 1534 (0.9%), respectively; P = 0.021]. The system's sensitivity, specificity, and accuracy for detecting HrELs were 89.7, 98.5, and 98.2%, respectively. No adverse events occurred. The proposed system thus improved HrEL detection rate during endoscopy and was safe. Deep learning assistance may enhance early diagnosis and treatment of esophageal cancer and may become a useful tool for esophageal cancer screening.

Developing a Prognostic Model for Primary Biliary Cholangitis Based on a Random Survival Forest Model.

Background: Primary biliary cholangitis (PBC) is a rare autoimmune liver disease with few effective treatments and a poor prognosis, and its incidence is on the rise. There is an urgent need for more targeted treatment strategies to accurately identify high-risk patients. The use of stochastic survival forest models in machine learning is an innovative approach to constructing a prognostic model for PBC that can improve the prognosis by identifying high-risk patients for targeted treatment. Method: Based on the inclusion and exclusion criteria, the clinical data and follow-up data of patients diagnosed with PBC-associated cirrhosis between January 2011 and December 2021 at Taizhou Hospital of Zhejiang Province were retrospectively collected and analyzed. Data analyses and random survival forest model construction were based on the R language. Result: Through a Cox univariate regression analysis of 90 included samples and 46 variables, 17 variables with p-values <0.1 were selected for initial model construction. The out-of-bag (OOB) performance error was 0.2094, and K-fold cross-validation yielded an internal validation C-index of 0.8182. Through model selection, cholinesterase, bile acid, the white blood cell count, total bilirubin, and albumin were chosen for the final predictive model, with a final OOB performance error of 0.2002 and C-index of 0.7805. Using the final model, patients were stratified into high- and low-risk groups, which showed significant differences with a P value <0.0001. The area under the curve was used to evaluate the predictive ability for patients in the first, third, and fifth years, with respective results of 0.9595, 0.8898, and 0.9088. Conclusion: The present study constructed a prognostic model for PBC-associated cirrhosis patients using a random survival forest model, which accurately stratified patients into low- and high-risk groups. Treatment strategies can thus be more targeted, leading to improved outcomes for high-risk patients.

Role of ferroptosis in colorectal cancer.

Colorectal cancer (CRC) is the second deadliest cancer and the third-most common malignancy in the world. Surgery, chemotherapy, and targeted therapy have been widely used to treat CRC, but some patients still develop resistance to these treatments. Ferroptosis is a novel non-apoptotic form of cell death. It is an iron-dependent non-apoptotic cell death characterized by the accumulation of lipid reactive oxygen species and has been suggested to play a role in reversing resistance to anticancer drugs. This review summarizes recent advances in the prognostic role of ferroptosis in CRC and the mechanism of action in CRC.

The Feasibility of Applying Artificial Intelligence to Gastrointestinal Endoscopy to Improve the Detection Rate of Early Gastric Cancer Screening.

Convolutional neural networks in the field of artificial intelligence show great potential in image recognition. It assisted endoscopy to improve the detection rate of early gastric cancer. The 5-year survival rate for advanced gastric cancer is less than 30%, while the 5-year survival rate for early gastric cancer is more than 90%. Therefore, earlier screening for gastric cancer can lead to a better prognosis. However, the detection rate of early gastric cancer in China has been extremely low due to many factors, such as the presence of gastric cancer without obvious symptoms, difficulty identifying lesions by the naked eye, and a lack of experience among endoscopists. The introduction of artificial intelligence can help mitigate these shortcomings and greatly improve the accuracy of screening. According to relevant reports, the sensitivity and accuracy of artificial intelligence trained on deep cirrocumulus neural networks are better than those of endoscopists, and evaluations also take less time, which can greatly reduce the burden on endoscopists. In addition, artificial intelligence can also perform real-time detection and feedback on the inspection process of the endoscopist to standardize the operation of the endoscopist. AI has also shown great potential in training novice endoscopists. With the maturity of AI technology, AI has the ability to improve the detection rate of early gastric cancer in China and reduce the death rate of gastric cancer related diseases in China.

Cost-effective low-coverage whole-genome sequencing assay for the risk stratification of gastric cancer.

BACKGROUND: Gastric cancer (GC), a multifactorial disease, is caused by pathogens, such as Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV), and genetic components. AIM: To investigate microbiomes and host genome instability by cost-effective, low-coverage whole-genome sequencing, as biomarkers for GC subtyping. METHODS: Samples from 40 GC patients were collected from Taizhou Hospital, Zhejiang Province, affiliated with Wenzhou Medical University. DNA from the samples was subjected to low-coverage whole-genome sequencing with a median genome coverage of 1.86 × (range: 1.03 × to 3.17 ×) by Illumina × 10, followed by copy number analyses using a customized bioinformatics workflow ultrasensitive chromosomal aneuploidy detector. RESULTS: Of the 40 GC samples, 20 (50%) were found to be enriched with microbiomes. EBV DNA was detected in 5 GC patients (12.5%). H. pylori DNA was found in 15 (37.5%) patients. The other 20 (50%) patients were found to have relatively higher genomic instability. Copy number amplifications of the oncogenes, ERBB2 and KRAS, were found in 9 (22.5%) and 7 (17.5%) of the GC samples, respectively. EBV enrichment was found to be associated with tumors in the gastric cardia and fundus. H. pylori enrichment was found to be associated with tumors in the pylorus and antrum. Tumors with elevated genomic instability showed no localization and could be observed in any location. Additionally, H. pylori-enriched GC was found to be associated with the Borrmann type II/III and gastritis history. EBV-enriched GC was not associated with gastritis. No statistically significant correlation was observed between genomic instability and gastritis. Furthermore, these three different molecular subtypes showed distinct survival outcomes (P = 0.019). EBV-positive tumors had the best prognosis, whereas patients with high genomic instability (CIN+) showed the worst survival. Patients with H. pylori infection showed intermediate prognosis compared with the other two subtypes. CONCLUSION: Thus, using low-coverage whole-genome sequencing, GC can be classified into three categories based on disease etiology; this classification may prove useful for GC diagnosis and precision medicine.

Optimization of Minimum Segment Width Parameter in the Intensity-Modulated Radiotherapy Plan for Esophageal Cancer.

PURPOSE: This study was designed to explore the optimal minimum segment width (MSW) in the intensity-modulated radiotherapy (IMRT) plan for esophageal cancer. PATIENTS AND METHODS: The imaging data of 20 esophageal cancer patients were selected for this study. Four IMRT plans were designed for each patient with MSWs of 0.5, 1.0, 1.5, and 2.0 cm. The conformity index (CI) and homogeneity index (HI) of the planning target volumes (PTV), organs at risk (OARs), control points (CP), monitor units (MU), plan delivery time (DT), and gamma passing rates (GPR) were collected and compared to appraise the treatment plan quality and delivery efficiency. RESULTS: Lower-MSW plans had larger CI and smaller HI values, and lower dose parameters of OARs and PTVs. The HI, CI, and dose parameter of OARs in the 0.5 and 1.0 cm MSW groups were similar and much better than those of the 1.5 and 2.0 cm MSW groups. Meanwhile, the plan in the 0.5 cm MSW group had significantly higher MUs, CPs, and DTs, and a significantly lower relative dose of GPR with a 3% dose difference and 3 mm distance to agreement criteria than the other three groups. CONCLUSION: The 0.5 and 1 cm MSW groups had better dosimetric parameters and IMRT plan quality than the other groups. However, plans with 0.5 cm MSW had worse delivery accuracy and efficiency than the other three groups. Thus, MSW of 1.0 cm was the optimal choice to ensure good quality, delivery accuracy, and treatment efficiency in IMRT plans for esophageal cancer.

Effectiveness and safety of over-the-scope clip in closing perforations after duodenal surgery.

BACKGROUND: Endoscopic resection of duodenal subepithelial lesions (SELs) is a difficult procedure with a high risk of perforation. At present, dealing with perforation after endoscopic resection of duodenal SELs is still considered a great challenge. AIM: To evaluate the effectiveness and safety of an over-the-scope clip (OTSC) in the treatment of perforation post-endoscopic resection of duodenal SELs. METHODS: From May 2015 to November 2019, 18 patients with perforation following endoscopic resection of duodenal SELs were treated with OTSCs. Data comprising the rate of complete resection, closure of intraprocedural perforation, delayed bleeding, delayed perforation, and postoperative infection were extracted. RESULTS: The rate of complete removal of duodenal SELs and successful closure of the perforation was 100%. The median perforation size was 1 cm in diameter. Seventeen patients had minor intraoperative bleeding, while the remaining 1 patient had considerable amount of bleeding during the procedure. Seven patients had postoperative abdominal infections, of which 1 patient developed an abscess in the right iliac fossa and another patient developed septic shock. All 18 patients recovered and were discharged. No delayed bleeding or perforation was reported. The mean time taken to resume normal diet after the procedure was 6.5 d. The mean postoperative hospital stay was 9.5 d. No residual or recurrent lesions were detected during the follow-up period (15-66 mo). CONCLUSION: Closing a perforation after endoscopic resection of duodenal SELs with OTSCs seems to be an effective and reasonably safe therapeutic method.

The Immunomodulatory Properties of Mesenchymal Stem Cells Play a Critical Role in Inducing Immune Tolerance after Liver Transplantation.

Although liver transplantation is considered to be the best choice for patients with end-stage liver diseases, postoperative immune rejection still cannot be overlooked. Patients with liver transplantation have to take immunosuppressive drugs for a long time or even their entire lives, in which heavy economic burden and side effects caused by the drugs have become the major impediment for liver transplantation. There is a growing body of evidences indicating that mesenchymal stem cell (MSC) transplantation, a promising tool in regenerative medicine, can be used as an effective way to induce immune tolerance after liver transplantation based on their huge expansion potential and unique immunomodulatory properties. MSCs have been reported to inhibit innate immunity and adaptive immunity to induce a tolerogenic microenvironment. In in vitro studies, transplanted MSCs show plasticity in immune regulation by altering their viability, migration, differentiation, and secretion in the interactions with the surrounding host microenvironment. In this review, we aim to provide an overview of the current understanding of immunomodulatory properties of MSCs in liver transplantation, to elucidate the potential mechanisms behind MSCs regulating immune response, especially in vivo and the influence of the microenvironment, and ultimately to discuss the feasible strategies to improve the clinical prognosis of liver transplantation. Only after exhaustive understanding of potential mechanisms of the MSC immunomodulation can we improve the safety and effectiveness of MSC treatment and achieve better therapeutic effects.

Retraction of "Nanostructured Lipid Carriers Delivering Sorafenib to Enhance Immunotherapy Induced by Doxorubicin for Effective Esophagus Cancer Therapy".

[This retracts the article DOI: 10.1021/acsomega.0c02072.].

Use of Artificial Intelligence to Improve the Quality Control of Gastrointestinal Endoscopy.

With the rapid development of science and technology, artificial intelligence (AI) systems are becoming ubiquitous, and their utility in gastroenteroscopy is beginning to be recognized. Digestive endoscopy is a conventional and reliable method of examining and diagnosing digestive tract diseases. However, with the increase in the number and types of endoscopy, problems such as a lack of skilled endoscopists and difference in the professional skill of doctors with different degrees of experience have become increasingly apparent. Most studies thus far have focused on using computers to detect and diagnose lesions, but improving the quality of endoscopic examination process itself is the basis for improving the detection rate and correctly diagnosing diseases. In the present study, we mainly reviewed the role of AI in monitoring systems, mainly through the endoscopic examination time, reducing the blind spot rate, improving the success rate for detecting high-risk lesions, evaluating intestinal preparation, increasing the detection rate of polyps, automatically collecting maps and writing reports. AI can even perform quality control evaluations for endoscopists, improve the detection rate of endoscopic lesions and reduce the burden on endoscopists.

Liver injury in COVID-19: Detection, pathogenesis, and treatment.

In the early December 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 was first reported in Wuhan, China, followed by an outbreak that spread around the world. Numerous studies have shown that liver injury is common in patients with coronavirus disease 2019 (COVID-19), and may aggravate the severity of the disease. However, the exact cause and specific mechanism of COVID-associated liver injury needs to be elucidated further. In this review, we present an analysis of the clinical features, potential mechanisms, and treatment strategies for liver injury associated with COVID-19. We hope that this review would benefit clinicians in devising better strategies for management of such patients.

Electrocardiogram Characteristics of Different Motor Types of Parkinson's Disease.

AIM: This study aims to investigate the electrocardiogram characteristics of the different motor types of Parkinson's disease. METHODS: The data on 118 patients with Parkinson's disease (PD), who were initially diagnosed in the Outpatient and Inpatient Department, was collected. Among these 118 PD patients, 74 patients were assigned to the PIGD group, while 44 patients were assigned to the TD group, and their clinical features were analyzed, which included age, course, disease classification, and electrocardiogram parameters (PR, QRS, QT interval, and QTC). RESULTS: The QT interval in PD patients was positively correlated with the course of the disease and Hoehn-Yahr stage, and the QT interval in the PIGD group was longer than that in the TD group. CONCLUSION: A prolonged QT interval may indicate a longer disease period and a more severe disease condition.

miR-1249-5p regulates the osteogenic differentiation of ADSCs by targeting PDX1.

BACKGROUND: Osteoporosis (OP) is an age-related systemic bone disease. MicroRNAs (miRNAs) are involved in the regulation of osteogenic differentiation. The purpose of this study was to explore the role and mechanism of miR-1249-5p for promoting osteogenic differentiation of adipose-derived stem cells (ADSCs). METHODS: GSE74209 dataset was retrieved from NCBI Gene Expression Omnibus (GEO) database and performed bioinformatic analyses. OP tissue and healthy control tissues were obtained and used for RT-PCR analyses. ADSCs were incubated with miR-1249-5p mimic, inhibitor and corresponding negative control (NC), alkaline phosphatase (ALP) staining, and Alizarin Red Staining (ARS) were then performed to assess the role of miR-1249-5p for osteogenesis of ADSCs. Targetscan online website and dual-luciferase reporter assay were performed to verify that the 3'-UTR of PDX1 mRNA is a direct target of miR-1249-5p. RT-PCR and western blot were also performed to identify the mechanism of miR-1249-5p for osteogenesis of ADSCs. RESULTS: A total of 170 differentially expressed miRNAs were selected, among which, 75 miRNAs were downregulated and 95 miRNAs were upregulated. Moreover, miR-1249-5p was decreased in OP patients, while showed a gradual increase with the extension of induction time. miR-1249-5p mimic significantly increased osteogenic differentiation capacity and p-PI3K and p-Akt protein levels. Luciferase activity in ADSCs co-transfected of miR-1249-5p mimic with PDX1-WT reporter plasmids was remarkably decreased, but there was no obvious change in miR-1249-5p mimic with PDX1-MUT reporter plasmids co-transfection group. Overexpression PDX1 could partially reverse the promotion effects of miR-1249-5p on osteogenesis of ADSCs. CONCLUSION: In conclusion, miR-1249-5p promotes osteogenic differentiation of ADSCs by targeting PDX1 through the PI3K/Akt signaling pathway.

Nanostructured Lipid Carriers Delivering Sorafenib to Enhance Immunotherapy Induced by Doxorubicin for Effective Esophagus Cancer Therapy.

The tumor microenvironment (TME) plays a significant role in weakening the effect of cancer immunotherapy, which calls for the remodeling of TME. Herein, we fabricated a nanostructured lipid carrier (NLC) to codeliver doxorubicin (Dox) and sorafenib (Sfn) as a drug delivery system (NLC/D-S). The Sfn was expected to regulate the TME of esophagus cancer. As a result, the immune response induced by Dox-related immunogenicity cell death could be fully realized. Our results demonstrated that Sfn was able to remodel the TME through downregulation of regulatory T cells (Treg), activation of effector T cells, and relieving of PD-1 expression, which achieved synergistic effect on the inhibition of primary tumor but also subsequent strong immune response on the regeneration of distant tumor.

Neutrophil-lymphocyte ratio as an early predictor for patients with acute paraquat poisoning: A retrospective analysis.

This retrospective study aimed to investigate whether the neutrophil-lymphocyte ratio (NLR) can be used as an early predictor of 90-day survival in patients with acute paraquat (PQ) poisoning.This study enrolled 105 patients with acute PQ poisoning admitted from May 2012 to May 2018. Kaplan-Meier curve, receiver operating characteristic curve, and Cox proportional hazards regression analyses were used to investigate the predictive value of NLR for 90-day survival of patients with acute PQ poisoning.The 90-day survival rate was 40.95% (43/105). Survivors had lower NLR (P <.001), which was an independent predictor of 90-day survival according to the Cox proportional hazard regression analyses. The area under the NLR curve was 0.842 (95% CI: 0.767-0.917, P <.001) in predicting 90-day survival.Our findings showed that low NLR was a valuable early predictor of 90-day survival in patients with acute PQ poisoning.

Monocytes as an Early Predictor for Patients with Acute Paraquat Poisoning: A Retrospective Analysis.

BACKGROUND: The predictive values of monocytes in the prognosis of patients with acute paraquat (PQ) poisoning are unclear. This retrospective study investigated the predictive values of monocytes in the prognosis of patients with acute PQ poisoning. METHODS: Adult patients who suffered from acute PQ poisoning in the emergency care unit of Cangzhou Central Hospital from May 2012 to December 2018 were enrolled. The patients were divided into groups, namely, survival and nonsurvival, according to a 90-day prognosis. Moreover, correlation, logistic regression, receiver-operator characteristic (ROC), and Kaplan-Meier curve analyses were applied to evaluate the monocyte values used to predict the prognosis of patients with acute PQ poisoning. RESULT: Among the 109 patients, 45 survived within 90 days after the poisoning, resulting in a 41.28% survival rate. The monocyte count of the nonsurvivors was significantly higher than that of the survivors (P< 0.001). Correlation analysis showed that monocyte count positively correlated with plasma PQ concentration (r= 0.413; P< 0.001) and negatively correlated with survival time (r= 0.512; P< 0.001) and 90-day survival (r= 0.503; P< 0.001). Logistic regression analysis showed that elevated monocytes were the independent risk factors for the 90-day survival. The area under the ROC curve of the monocyte count used to predict the 90-day survival was 0.826 (95% CI: 0.751-0.904), the optimal cut-off was 0.51×109/L, sensitivity was 73.4%, and specificity was 86.7%. CONCLUSION: This study demonstrated that elevated monocyte count is a useful early predictor of 90-day survival in patients with acute PQ poisoning. However, further studies are warranted to draw firm conclusions.

Proton pump inhibitor use does not increase dementia and Alzheimer's disease risk: An updated meta-analysis of published studies involving 642305 patients.

Recent studies have indicated an increased risk of dementia and Alzheimer's disease (AD) among people who consume proton pump inhibitors (PPIs), but the results of those studies are inconsistent. This meta-analysis aimed to explore the correction risk of dementia and AD among PPI users. The literature search for relevant studies was conducted in PubMed, Web of Science, EMBase and ScienceDirect. Pooled hazard ratio (HR) and 95% confidence intervals (CIs) were used to assess the relationship between the PPIs and risk of dementia and AD. Ten independent studies that involved 642305 participants were included in this meta-analysis. PPI users were unassociated with dementia (HR = 1.04, 95% CI 0.92-1.15; I2 = 95.6%, p < 0.001) and AD (HR = 0.96, 95% CI 0.83-1.09; I2 = 80.7%, p <0 .001). No evidence of publication bias was detected by Begg's and Egger's test. Sensitivity analyses showed no important differences in the estimates of effects. The current evidence indicates that PPI use does not increase dementia and AD risk. The remarkable heterogeneity among the studies warrants a further review of our findings.

Platelet-lymphocyte ratio is not a prognostic predictor for acute paraquat-intoxicated patients: A retrospective analysis.

This study aimed to investigate the prognostic predictive value of the platelet-lymphocyte ratio (PLR) in patients with acute paraquat (PQ) intoxication.A total of 107 patients with acute PQ intoxication via oral ingestion were admitted in Cangzhou Central Hospital from May 2012 to September 2018. Valuable detection indices were screened out by using Cox proportional hazard regression and receiver operating characteristic (ROC) curve analyses, and their diagnostic efficiency was evaluated by using Kaplan-Meier curve.The 90-day mortality was 58.9% (63/107). The Kaplan-Meier curve showed that PLR was not associated with 90-day survival (log-rank test; P = .661). In Cox proportional hazard regression analyses, PLR was not an independent risk factor. Meanwhile, the ROC curves showed that PLR had an AUC value of 0.569 (95% confidence interval: 0.459-0.679, P = .227) in predicting 90-day survival.PLR is not a prognostic predictor for patients with acute PQ intoxication.

MicroRNA-26a inhibits multiple myeloma cell growth by suppressing cyclin-dependent kinase 6 expression.

MicroRNA-26a (miR-26a) has been reported to be involved in the tumorigenesis of several tumors, but its biological function and molecular mechanism in multiple myeloma (MM) are still unknown. In this study, we found that overexpression of miR-26a obviously inhibited MM cell growth, and delayed tumor growth in xenografts. Further studies showed that overexpression of miR-26a induced cell cycle arrest at G0/G1 phase in MM cells. MiR-26a mimic down-regulated the expression levels of CDK6 and E2F1, but up-regulated p53 and p21 expression. In contrast, overexpression of CDK6 decreased the effect of miR-26a mimic on MM cell survival. Moreover, miR-26a targeted CDK6 mRNA and thus suppressed CDK6 protein expression. Overexpression of miR-26a also enhanced the cytotoxic action of doxorubicin against MM. These results demonstrated that miR-26a was involved in the development of MM through regulating CDK6 signaling pathway, and indicated that miR-26a could be as a novel target for anti-tumor therapy in clinic as a single strategy or in combination with other anti-tumor drugs in MM.

Level of uric acid and uric acid/creatinine ratios in correlation with stage of Parkinson disease.

This study aims to investigate relationship between the level of uric acid (UA) and UA/creatinine ratios (UA/Cr) to the stage of Parkinson disease (PD).A total of 120 cases of PD patients who were admitted in our hospital between 2013 and 2015 were enrolled into this study; these 120 cases of PD patients were divided into 3 groups, according to Hoehn-Yahr (H-Y) classification: early stage (1-2 classification), medium stage (2.5-3 classification), and advanced stage (4-5 classification); UA and UA/Cr level in each group was compared. Then, factors including age, gender, dopamine dosage, UA, and UA/Cr levels were analyzed to find the independent predictive factors of PD by logistic regression.UA and UA/Cr levels in the early and medium stage PD patients were significantly higher than in the advanced stage ones. UA and UA/Cr levels in patients with good prognosis were significantly higher than in the poor ones.UA and UA/Cr levels are negatively correlated with the stages of PD and are independent negatively predicting biological indexes of PD incidence and progression.