Identification of LPCAT1 as a key biomarker for Crohn's disease based on bioinformatics and machine learnings and experimental verification.

Epithelial-mesenchymal transition (EMT) plays a crucial role in regulating inflammatory responses and fibrosis formation. This study aims to explore the molecular mechanisms of EMT-related genes in Crohn's disease (CD) through bioinformatics methods and identify potential key biomarkers. In our research, we identified differentially expressed genes (DEGs) related to EMT based on the GSE52746 dataset and the gene set in the GeneCards database. Key genes were identified through Lasso-cox and Random Forest and validated using the external dataset GSE10616. Immune infiltration analysis showed that Lysophosphatidylcholine acyltransferase 1 (LPCAT1) was positively correlated with Neutrophils and Macrophages M1. The Gene Set Enrichment Analysis (GSEA) results for LPCAT1 showed associations with celladhesionmolecules and ECM receptor interaction. Additionally, a lncRNA-miRNA-mRNA ceRNA network was constructed. Finally, we validated that knocking down LPCAT1 could inhibit the release of inflammatory factors, EMT, and the elevation of fibrosis indices as well as the activation of NF-κB signaling pathway in LPS-induced HT-29 cells. LPCAT1 plays an important role in the occurrence and development of CD and may become a new biomarker.

SLC7A11-ROS/αKG-AMPK axis regulates liver inflammation through mitophagy and impairs liver fibrosis and NASH progression.

The changes of inflammation and metabolism are two features in nonalcoholic steatohepatitis (NASH). However, how they interact to regulate NASH progression remains largely unknown. Our works have demonstrated the importance of solute carrier family 7 member 11 (SLC7A11) in inflammation and metabolism. Nevertheless, whether SLC7A11 regulates NASH progression through mediating inflammation and metabolism is unclear. In this study, we found that SLC7A11 expression was increased in liver samples from patients with NASH. Upregulated SLC7A11 level was also detected in two murine NASH models. Functional studies showed that SLC7A11 knockdown or knockout had augmented steatohepatitis with suppression of inflammatory markers in mice. However, overexpression of SLC7A11 dramatically alleviated diet-induced NASH pathogenesis. Mechanically, SLC7A11 decreased reactive oxygen species (ROS) level and promoted α-ketoglutarate (αKG)/prolyl hydroxylase (PHD) activity, which activated AMPK pathway. Furthermore, SLC7A11 impaired expression of NLRP3 inflammasome components through AMPK-mitophagy axis. IL-1ß release through NLRP3 inflammasome recruited myeloid cells and promoted hepatic stellate cells (HSCs) activation, which contributed to the progression of liver injury and fibrosis. Anti-IL-1ß and anakinra might attenuate the hepatic inflammatory response evoked by SLC7A11 knockdown. Moreover, the upregulation of SLC7A11 in NASH was contributed by lipid overload-induced JNK-c-Jun pathway. In conclusions, SLC7A11 acts as a protective factor in controlling the development of NASH. Upregulation of SLC7A11 is protective by regulating oxidation, αKG and energy metabolism, decreasing inflammation and fibrosis.

LiverRisk score: An accurate, cost-effective tool to predict fibrosis, liver-related, and diabetes-related mortality in the general population.

BACKGROUND: Noninvasive and early assessment of liver fibrosis is of great significance and is challenging. We aimed to evaluate the predictive performance and cost-effectiveness of the LiverRisk score for liver fibrosis and liver-related and diabetes-related mortality in the general population. METHODS: The general population from the NHANES 2017-March 2020, NHANES 1999-2018, and UK Biobank 2006-2010 were included in the cross-sectional cohort (n = 3,770), along with the NHANES follow-up cohort (n = 25,317) and the UK Biobank follow-up cohort (n = 17,259). The cost-effectiveness analysis was performed using TreeAge Pro software. Liver stiffness measurements ≥10 kPa were defined as compensated advanced chronic liver disease (cACLD). FINDINGS: Compared to conventional scores, the LiverRisk score had significantly better accuracy and calibration in predicting liver fibrosis, with an area under the receiver operating characteristic curve (AUC) of 0.76 (0.72-0.79) for cACLD. According to the updated thresholds of LiverRisk score (6 and 10), we reclassified the population into three groups: low, medium, and high risk. The AUCs of LiverRisk score for predicting liver-related and diabetes-related mortality at 5, 10, and 15 years were all above 0.8, with better performance than the Fibrosis-4 score. Furthermore, compared to the low-risk group, the medium-risk and high-risk groups in the two follow-up cohorts had a significantly higher risk of liver-related and diabetes-related mortality. Finally, the cost-effectiveness analysis showed that the incremental cost-effectiveness ratio for LiverRisk score compared to FIB-4 was USD $18,170 per additional quality-adjusted life-year (QALY) gained, below the willingness-to-pay threshold of $50,000/QALY. CONCLUSIONS: The LiverRisk score is an accurate, cost-effective tool to predict liver fibrosis and liver-related and diabetes-related mortality in the general population. FUNDING: The National Natural Science Foundation of China (nos. 82330060, 92059202, and 92359304); the Key Research and Development Program of Jiangsu Province (BE2023767a); the Fundamental Research Fund of Southeast University (3290002303A2); Changjiang Scholars Talent Cultivation Project of Zhongda Hospital of Southeast University (2023YJXYYRCPY03); and the Research Personnel Cultivation Program of Zhongda Hospital Southeast University (CZXM-GSP-RC125).

LncRNA MSC-AS1 regulates SNIP1 SUMOylation-mediated EMT by binding to SENP1 to promote intestinal fibrosis in Crohn's disease.

As a common complication of Crohn's disease (CD), the mechanism underlying CD intestinal fibrosis remains unclear. Studies have shown that epithelial-mesenchymal transition (EMT) is a key step in the development of intestinal fibrosis in CD. It is currently known that the long non-coding RNA (lncRNA) MSC-AS1 plays an important role in regulating the secretion of inflammatory mediators and EMT; however, its role in intestinal fibrosis remains unclear. MSC-AS1 was significantly upregulated in the CD intestinal tissue and intestinal tissue of mice treated with 2,4,6-trinitrobenzenesulfonic acid. Downregulation of its expression can inhibit EMT and alleviates intestinal fibrosis by regulating SNIP1. In addition, MSC-AS1 directly interacted with SENP1, blocking the deSUMOylation of SNIP1 and inhibiting its activity. Furthermore, we found that SENP1 enhanced the expression of SNIP1 and reduced intestinal fibrosis. In summary, MSC-AS1 regulates EMT through the SENP1/SNIP1 axis to promote fibrosis, and may be considered a potential molecular target for the treatment of CD and intestinal fibrosis.

Differential diagnosis of post pancreatitis diabetes mellitus based on pancreatic and gut hormone characteristics.

PURPOSE: Distinguishing different types of diabetes is important in directing optimized treatment strategies and correlated epidemiological studies. Through detailed analysis of hormone responses to mixed meal tolerance test (MMTT), we aimed to find representing characteristics of post-acute pancreatitis diabetes mellitus (PPDM-A) and post-chronic pancreatitis diabetes mellitus (PPDM-C). METHODS: Participants with PPDM-A, PPDM-C, type 1 diabetes, type 2 diabetes and normal controls underwent MMTT. Fasting and postprandial responses of serum glucose, C-peptide, insulin, glucagon, pancreatic polypeptide (PP), ghrelin, gastric inhibitory peptide (GIP), glucagon like peptide-1 (GLP-1) and peptide YY (PYY) were detected and compared among different groups. Focused analysis on calculated insulin sensitivity and secretion indices were performed to reason major causes of hyperglycemia in different conditions. RESULTS: Participants with PPDM-A were characterized by increased C-peptide, insulin, glucagon and PP, while decreased ghrelin, GIP and PYY compared with controls. Patients with PPDM-C showed secretion insufficiency of C-peptide, insulin, ghrelin and PYY, higher postprandial responses of glucagon and PP than controls. In particular, both fasting and postprandial levels of ghrelin in PPDM-C were significantly lower than other diabetes groups. PYY responses in patients with PPDM-A and PPDM-C were markedly reduced. Besides, the insulin sensitivity of PPDM-A was decreased, and the insulin secretion for PPDM-C was decreased. CONCLUSIONS: Along with the continuum from acute to chronic pancreatitis, the pathological mechanism of PPDM changes from insulin resistance to insulin deficiency. Insufficient PYY secretion is a promising diagnostic marker for distinguishing PPDM from type 1 and type 2 diabetes. Absent ghrelin secretion to MMTT may help identify PPDM-C.

Prospects of polyglycolic acid sheets for the treatment of esophageal stricture after esophageal endoscopic submucosal dissection.

Esophageal cancer is the seventh most common type of cancer and the sixth leading cause of cancer -related mortality worldwide. Endoscopic submucosal dissection (ESD) is widely used for the resection of early esophageal cancer. However, post-ESD esophageal stricture is a common long-term complication, which requires attention. Patients with post-ESD esophageal stricture often experience dysphagia and require multiple dilatations, which greatly affects their quality of life and increases healthcare costs. Therefore, to manage post-ESD esophageal stricture, researchers are actively exploring various strategies, such as pharmaceutical interventions, endoscopic balloon dilation, and esophageal stenting. Although steroids-based therapy has achieved some success, steroids can lead to complications such as osteoporosis and infection. Meanwhile, endoscopic balloon dilatation is effective in the short term, but is prone to recurrence and perforation. Additionally, esophageal stenting can alleviate the stricture, but is associated with discomfort during stenting and the complication of easy displacement also present challenges. Tissue engineering has evolved rapidly in recent years, and hydrogel materials have good biodegradability and biocompatibility. A novel type of polyglycolic acid (PGA) sheets has been found to be effective in preventing esophageal stricture after ESD, with the advantages of a simple operation and low complication rate. PGA membranes act as a biophysical barrier to cover the wound as well as facilitate the delivery of medications to promote wound repair and healing. However, there is still a lack of multicenter, large-sample randomized controlled clinical studies focused on the treatment of post-ESD esophageal strictures with PGA membrane, which will be a promising direction for future advancements in this field.

A novel upregulated hsa_circ_0032746 regulates the oncogenesis of esophageal squamous cell carcinoma by regulating miR-4270/MCM3 axis.

INTRODUCTION: Circular RNAs (CircRNA) have emerged as an interest of research in recent years due to its regulatory role in various kinds of cancers of human body. Esophageal squamous cell carcinoma (ESCC) is one of the major disease subtype in Asian countries, including China. CircRNAs are formed by back-splicing covalently joined 3'- and 5'- ends rather than canonical splicing and are found to have binding affinity with miRNAs that conjointly contribute to oncogenesis. MATERIALS AND METHODS: 4 pairs of normal, cancer adjacent tissues and cancer tissues were analyzed by high-throughput RNA sequencing and 84 differentially upregulated circRNAs were detected in cancer tissues. hsa_circ_0032746 was silenced by siRNA and lentivirus and then further proliferation, migration and invasion were performed by CCK-8 and transwell assays. Bioinformatic analysis  predicted binding affinity of circRNA/miRNA/mRNA axis. RESULTS: After qPCR validation, we selected a novel upregulated hsa_circ_0032746 to explore its biogenetic functions which showed high expression in cancer tissues but not in cancer adjacent tissues. The clinicopathological relation of hsa_circ_0032746 showed positive correlation with the tumor location (P = 0.026) and gender (P = 0.05). We also predicted that hsa_circ_0032746 could sponge with microRNA. Bioinformatic analysis predicted 11 microRNA response element (MRE) sequences of hsa_circ_0032746 and dual luciferase reporter assay confirmed binding affinity with miR4270 evidencing further study of circRNA/miRNA role. The knockdown of hsa_circ_0032746 by siRNA and lentivirus demonstrated that proliferation, invasion and migration of ESCC were inhibited in vitro and vivo experiments. Bioinformatic analysis further predicted MCM3 as a target of miR-4270 and was found upregulated in ESCC upon validation. miR4270 mimic decreased the level of hsa_circ_0032746 and MCM3 while further rescue experiments demonstrated that hsa_circ_0032746 was dependent on miR4270/MCM3 axis on the development process of ESCC. CONCLUSION: We revealed for the first time that circ_0032746/mir4270/MCM3 contributes in proliferation, migration and invasion of ESCC and could have potential prognostic and therapeutic significance.

Digital cholangioscopy-assisted, direct visualization-guided, radiation-free, endoscopic retrograde intervention for cholelithiasis: technical feasibility, efficacy, and safety.

BACKGROUND: Nonradiation, digital cholangioscope (DCS)-assisted endoscopic intervention for cholelithiasis has not been widely performed. For this study, we aimed to report the feasibility, efficacy, and safety of an established DCS-guided lithotomy procedure. METHODS: Data relating to biliary exploration, stone clearance, adverse events, and follow-up were obtained from 289 patients. The choledocholithiasis-related outcomes via the DCS-guided procedure were subsequently compared to those via conventional endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: Biliary access was achieved in 285 patients. The technical success rate for the exploration of the common bile duct, the cystic stump, the hilar ducts, and secondary radicals was 100%. Moreover, the success rates were 98.4%, 61.7%, and 20.7%, for the exploration of the cystic duct, complete cystic duct, and gallbladder, respectively. Suspicious or confirmed suppurative cholecystitis, cholesterol polyps, and hyperplastic polyps were detected in 42, 23, and 5 patients, respectively. Stone clearance was achieved in one session in 285 (100%), 11 (100%), 13 (100%), 7 (100%), 6 (100%), and 3 (14.3%) patients with choledocholithiasis and hepatolithiasis, cystic duct stump stones, nondiffuse located intrahepatic lithiasis, a single cystic duct stone, a single gallbladder stone, and diffuse located intrahepatic lithiasis, respectively. Complete stone clearance for diffuse intrahepatic lithiasis was achieved in 19 (90.5%) patients, and fractioned re-lithotomy was performed in 16 (76.2%) patients. One patient developed mild acute cholangitis, and 12 developed mild pancreatitis. Stones recurred in one patient. Compared with conventional ERCP, DCS-guided lithotomy has the advantages of clearing difficult-to-treat choledocholithiasis and revealing concomitant biliary lesions, and this technique has fewer complications and a decreased risk of stone recurrence. CONCLUSIONS: The technical profile, efficacy, and safety of nonradiation-guided and DCS-guided lithotomy are shown in this study. We provide a feasible modality for the endoscopic removal of cholelithiasis.

Diverticular peroral endoscopic myotomy (D-POEM) for symptomatic oesophageal diverticulum: a multicentre cohort study with a minimum follow-up of 3 years.

OBJECTIVE: To evaluate the medium- and long-term outcomes of diverticular peroral endoscopic myotomy (D-POEM) for symptomatic oesophageal diverticulum. METHODS: Consecutive patients with symptomatic oesophageal diverticulum who underwent D-POEM from 1st May 2016 to 1st April 2020 in 6 centres were extracted and researched. Symptoms assessed by the modified Eckardt score were registered pre- and post-D-POEM at 1, 6, 12, 24 and 36 months. RESULTS: A total of 34 patients with Zenker's diverticulum (ZD, n = 12), mid-oesophageal diverticulum (MED, n = 12), and epiphrenic diverticulum (ED, n = 10) were included. Complete septotomy was achieved in a mean of 39.15 min, with 100% technical success. No severe intraoperative or postoperative complications were observed. Five patients exhibited subcutaneous emphysema, while 1 had mucosal injury. The mean Eckardt score was 8.59 preoperatively and 2.56 at 1 month, 2.09 at 6 months, 2.21 at 12 months, 2.15 at 24 months, and 2.21 at 36 months postoperatively. The total clinical success rates at 1, 6, 12, 24 and 36 months postoperatively were 97.1%, 97.1%, 94.1%, 91.2%, and 88.2%, respectively. With a median follow-up of 47.2 months, four patients suffered symptom relapse, with a total clinical success rate of 88.2%. A long disease duration, a high Eckardt score, and coexistence of achalasia were identified as risk factors for symptomatic recurrence by multivariable Cox analysis. CONCLUSIONS: D-POEM is an effective and durable treatment for patients with symptomatic oesophageal diverticulum.

Interleukin-21 modulates balance between regulatory T cells and T-helper 17 cells in chronic hepatitis B virus infection.

BACKGROUND: Chronic HBV infection is always accompanied by differences in the balance between regulatory T cells (Tregs) and T-helper 17 (Th17) cells in infection phases. IL-21 plays an important role in the progression of chronic HBV infection. Thus, the aim of our study was to investigate the role of the regulatory function of IL-21 in maintaining the balance between Tregs and Th17 cells in chronic HBV infection. METHODS: Twenty-five chronic HBV-infected patients in the immune-tolerant (IT) phase and 23 chronic hepatitis B (CHB) patients were recruited in this study. Cytokines production was measured by ELISA. The mRNA expression levels were determined by qPCR. CD4+T cells were stimulated with or without IL-21. Tregs and Th17 cells were measured by flow cytometry. pSTAT3 and STAT3 expression was assessed by Western blotting. RESULTS: The concentration of IL-21 in the serum of CHB were significantly higher than that in the serum from IT patients, and IL-21 and IL-21R levels in the PBMCs from CHB were higher than those from IT patients. IL-21 promoted Th17 cells differentiation and function but inhibited Treg cells differentiation and function by activating STAT3 signaling pathways, upregulating RORγt expression, downregulating Foxp3 expression, by increasing IL-17and IL-22 secretion, and decreasing TGF-ß secretion in chronic HBV infection. The proportion of Tregs and TGF-ß concentrations in CHB was significantly lower than that in IT patients. Furthermore, the percentage of Th17 cells and the IL-17 concentration in CHB was markedly higher than that in IT patients, causing a reduction in the Tregs/Th17 ratio in CHB patients. CONCLUSIONS: Our results suggest that IL-21 may contribute to inflammation in chronic HBV infection by modulating the balance between Treg and Th17 cells.

Analysis of white-light imaging-based features predictive for determination of lesion depths of superficial flat esophageal squamous cell carcinoma: a retrospective multicenter study from China.

OBJECTIVES: Endoscopic diagnosis of invasion depth of superficial esophageal squamous cell carcinoma (SESCC) by white-light imaging (WLI) modality remains difficult. This study aims to clarify WLI-based features which are predictive for invasion depth of SESCC. METHODS: A two-phase study was performed by enrolling 1288 patients with 1396 SESCC lesions. Endoscopic appearances, clinical characteristics and post-operative pathological outcomes were collected and reviewed. The association between lesion features and invasion depth were analyzed. A predictive nomogram was constructed for prediction of invasion depth. RESULTS: Among 1396 lesions in derivation and validation cohort, 1139 (81.6%), 194 (13.9%) and 63 (4.5%) lesions were diagnosed as lesions confined into the intraepithelium or the lamina propria mucosa (T1a-EP/LPM), lesions invading the muscularis mucosa (T1a-MM) or superficial submucosa (T1b-SM1) and tumor with moderate invasion into the submucosa or deeper submucosal invasion (≥ T1b-SM2), respectively. Lesion length > 2 cm (p < 0.001), wider circumferential extension (p < 0.001, 0.002 and 0.048 for > 3/4, 1/2-3/4 and 1/4-1/2 circumferential extension, respectively), surface unevenness (p < 0.001 for both type 0-IIa/0-IIc lesions and mixed type lesions), spontaneous bleeding (p < 0.001), granularity (p < 0.001) and nodules (p < 0.001) were identified as significant factors predictive for lesion depth. A nomogram based on these factors was constructed and the values of area under the Receiver Operating Characteristics curve were 0.89 and 0.90 in the internal and external patient cohort. CONCLUSIONS: Our study provides six WLI-based morphological features predicting for lesion depth of SESCC. Our findings will make endoscopic evaluation of invasion depth for SESCC more convenient by assessing these profiles.

Comparison between ESD and RFA in patients with total or near-total circumferential early esophageal squamous cell neoplasia.

BACKGROUND: Patients with early esophageal squamous cell neoplasias (ESCNs) that are totally or nearly totally circumferential face challenges in their clinical work. Endoscopic submucosal dissection (ESD) frequently leads to esophageal strictures. Endoscopic radiofrequency ablation (RFA), which stands out for its simplicity of use and low rate of stenosis, is a rapidly evolving therapeutic strategy for early ESCNs. We contrast ESD with RFA in order to find which method is best for the treatment of a wide range of esophageal diseases. METHODS: Patients who had flat-type, early, large ESCNs (extending more than 3/4 of the esophageal circumference) treated endoscopically were enrolled retrospectively. The primary outcome measurements were adverse events and local control of the neoplastic lesion. RESULTS: A total of 105 patients received treatment; 60 had ESD and 45 received RFA. Despite the patients receiving RFA typically having larger tumors (14.27 vs. 5.70 cm, P < 0.05), the local control of the neoplastic lesion and procedure-related complications were comparable between the ESD and RFA groups. A considerably higher risk of esophageal stenosis was observed in patients with extensive lesions in the ESD group compared to the RFA group (60% vs. 31%; P < 0.05), and the rate of refractory stricture is also higher than that of the RFA. CONCLUSION: Both RFA and ESD are effective in treating large, flat, early ESCNs; however, ESD is more likely to cause side effects, such as esophageal stricture, particularly in lesions that are larger than 3/4 of the diameter. Before RFA, a more precise and thorough pretreatment examination should be performed. A more accurate pretreatment evaluation will be an important development direction for early esophageal cancer in future. After surgery, a strict routine review is crucial.

CXCL8 as a Potential Biomarker for Crohn's Disease is Associated with Immune Infiltration and RNA Methylation.

TRP channels have an important role in regulating the function of gastrointestinal epithelial cells. The aim of this study was to investigate the molecular mechanisms of genes associated with TRP channels in Crohn's disease (CD) by bioinformatics approach and to identify potential key biomarkers. In our study, we identified TRP channel-related differentially expressed genes (DEGs) based on the GSE95095 dataset and the TRP channel-related gene set from the GeneCards database. Hub genes (CXCL8, HIF1A, NGF, JUN, IL1A) were identified by the PPI network and validated by the external GSE52746 dataset. Immune infiltration analysis revealed that CXCL8 was significantly correlated with B cells memory, NK cells activated, Mast cells resting, Mast cells activated, and Neutrophils. GSEA of CXCL8 results showed inositol phosphate metabolism, RNA polymerase, propanoate metabolism, MAPK signaling pathway, base excision repair, and Calcium signaling pathway. In addition, we constructed a lncRNA-miRNA-mRNA ceRNA network and a drug-gene interaction network. Finally, we performed in vitro experiments to verify that LPS induced CXCL8 expression in HT-29 cells and that knockdown of CXCL8 inhibited the inflammatory stimulatory effects of LPS. This study reveals that CXCL8 plays an important role in the pathogenesis of Crohn's disease and is expected to be a novel biomarker.

Nomogram model predicting the overall survival for patients with primary gastric mucosa-associated lymphoid tissue lymphoma.

BACKGROUND: Increasingly extranodal marginal B-cell lymphoma of mucosa-associated lymphoid tissue, known as mucosa-associated lymphoid tissue (MALT) lymphoma, is a type of non-Hodgkin's lymphoma. The prognosis of primary gastric MALT (GML) patients can be affected by many factors. Clinical risk factors, including age, type of therapy, sex, stage and family hematologic malignancy history, also have significant effects on the development of the disease. The available data are mainly focused on epidemiology; in contrast, few studies have investigated the prognostic variables for overall survival (OS) in patients with primary GML. Based on the realities above, we searched a large amount of data on patients diagnosed with primary GML in the Surveillance, Epidemiology and End Results (SEER) database. The aim was to develop and verify a survival nomogram model that can predict the overall survival prognosis of primary GML by combining prognostic and determinant variables. AIM: To create an effective survival nomogram for patients with primary gastric GML. METHODS: All data of patients with primary GML from 2004 to 2015 were collected from the SEER database. The primary endpoint was OS. Based on the LASSO and COX regression, we created and further verified the accuracy and effectiveness of the survival nomogram model by the concordance index (C-index), calibration curve and time-dependent receiver operating characteristic (td-ROC) curves. RESULTS: A total of 2604 patients diagnosed with primary GML were selected for this study. A total of 1823 and 781 people were randomly distributed into the training and testing sets at a ratio of 7:3. The median follow-up of all patients was 71 mo, and the 3- and 5-year OS rates were 87.2% and 79.8%, respectively. Age, sex, race, Ann Arbor stage and radiation were independent risk factors for OS of primary GML (all P < 0.05). The C-index values of the nomogram were 0.751 (95%CI: 0.729-0.773) and 0.718 (95%CI: 0.680-0.757) in the training and testing cohorts, respectively, showing the good discrimination ability of the nomogram model. Td-ROC curves and calibration plots also indicated satisfactory predictive power and good agreement of the model. Overall, the nomogram shows favorable performance in discriminating and predicting the OS of patients with primary GML. CONCLUSION: A nomogram was developed and validated to have good survival predictive performance based on five clinical independent risk factors for OS for patients with primary GML. Nomograms are a low-cost and convenient clinical tool in assessing individualized prognosis and treatment for patients with primary GML.

To Establish an Early Prediction Model for Acute Respiratory Distress Syndrome in Severe Acute Pancreatitis Using Machine Learning Algorithm.

OBJECTIVE: To develop binary and quaternary classification prediction models in patients with severe acute pancreatitis (SAP) using machine learning methods, so that doctors can evaluate the risk of patients with acute respiratory distress syndrome (ARDS) and severe ARDS at an early stage. METHODS: A retrospective study was conducted on SAP patients hospitalized in our hospital from August 2017 to August 2022. Logical Regression (LR), Random Forest (RF), Support Vector Machine (SVM), Decision Tree (DT), and eXtreme Gradient Boosting (XGB) were used to build the binary classification prediction model of ARDS. Shapley Additive explanations (SHAP) values were used to interpret the machine learning model, and the model was optimized according to the interpretability results of SHAP values. Combined with the optimized characteristic variables, four-class classification models, including RF, SVM, DT, XGB, and Artificial Neural Network (ANN), were constructed to predict mild, moderate, and severe ARDS, and the prediction effects of each model were compared. RESULTS: The XGB model showed the best effect (AUC = 0.84) in the prediction of binary classification (ARDS or non-ARDS). According to SHAP values, the prediction model of ARDS severity was constructed with four characteristic variables (PaO2/FiO2, APACHE II, SOFA, AMY). Among them, the overall prediction accuracy of ANN is 86%, which is the best. CONCLUSIONS: Machine learning has a good effect in predicting the occurrence and severity of ARDS in SAP patients. It can also provide a valuable tool for doctors to make clinical decisions.

LINC01116 modulates EMT process via binding with AGO1 mRNA in oesophageal squamous cell carcinoma.

Recent researches have uncovered that long non-coding RNAs (lncRNAs) are closely correlated with the development of different diseases, while biological functions and hidden molecular mechanisms of antisense lncRNAs in oesophageal squamous cell carcinoma (OSCC) remain unclear. Here, we identified upregulation of LINC01116 in RNA sequencing data, online database, and in OSCC and intraepithelial neoplasia (IEN) specimens. Functionally, LINC01116 facilitates OSCC advancement and metastasis in vitro and vivo. Mechanistically, elevated expression of LINC01116 in OSCC cells other than tumor stroma and cytoplasmic enables it to activate AGO1 expression via complementary binding with AGO1 mRNA to facilitate EMT process of OSCC.

Machine learning-based automated sponge cytology for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction: a nationwide, multicohort, prospective study.

BACKGROUND: Oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction have a dismal prognosis, and early detection is key to reduce mortality. However, early detection depends on upper gastrointestinal endoscopy, which is not feasible to implement at a population level. We aimed to develop and validate a fully automated machine learning-based prediction tool integrating a minimally invasive sponge cytology test and epidemiological risk factors for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction before endoscopy. METHODS: For this multicohort prospective study, we enrolled participants aged 40-75 years undergoing upper gastrointestinal endoscopy screening at 39 tertiary or secondary hospitals in China for model training and testing, and included community-based screening participants for further validation. All participants underwent questionnaire surveys, sponge cytology testing, and endoscopy in a sequential manner. We trained machine learning models to predict a composite outcome of high-grade lesions, defined as histology-confirmed high-grade intraepithelial neoplasia and carcinoma of the oesophagus and oesophagogastric junction. The predictive features included 105 cytological and 15 epidemiological features. Model performance was primarily measured with the area under the receiver operating characteristic curve (AUROC) and average precision. The performance measures for cytologists with AI assistance was also assessed. FINDINGS: Between Jan 1, 2021, and June 30, 2022, 17 498 eligible participants were involved in model training and validation. In the testing set, the AUROC of the final model was 0·960 (95% CI 0·937 to 0·977) and the average precision was 0·482 (0·470 to 0·494). The model achieved similar performance to consensus of cytologists with AI assistance (AUROC 0·955 [95% CI 0·933 to 0·975]; p=0·749; difference 0·005, 95% CI, -0·011 to 0·020). If the model-defined moderate-risk and high-risk groups were referred for endoscopy, the sensitivity was 94·5% (95% CI 88·8 to 97·5), specificity was 91·9% (91·2 to 92·5), and the predictive positive value was 18·4% (15·6 to 21·6), and 90·3% of endoscopies could be avoided. Further validation in community-based screening showed that the AUROC of the model was 0·964 (95% CI 0·920 to 0·990), and 92·8% of endoscopies could be avoided after risk stratification. INTERPRETATION: We developed a prediction tool with favourable performance for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction. This approach could prevent the need for endoscopy screening in many low-risk individuals and ensure resource optimisation by prioritising high-risk individuals. FUNDING: Science and Technology Commission of Shanghai Municipality.

Artificial intelligence assisted cytological detection for early esophageal squamous epithelial lesions by using low-grade squamous intraepithelial lesion as diagnostic threshold.

BACKGROUND: Manual cytological diagnosis for early esophageal squamous cell carcinoma (early ESCC) and high-grade intraepithelial neoplasia (HGIN) is unsatisfactory. Herein, we have introduced an artificial intelligence (AI)-assisted cytological diagnosis for such lesions. METHODS: Low-grade squamous intraepithelial lesion or worse was set as the diagnostic threshold for AI-assisted diagnosis. The performance of AI-assisted diagnosis was evaluated and compared to that of manual diagnosis. Feasibility in large-scale screening was also assessed. RESULTS: AI-assisted diagnosis for abnormal cells was superior to manual reading by presenting a higher efficiency for each slide (50.9 ± 0.8 s vs 236.8 ± 3.9 s, p = 1.52 × 10-76 ) and a better interobserver agreement (93.27% [95% CI, 92.76%-93.74%] vs 65.29% [95% CI, 64.35%-66.22%], p = 1.03 × 10-84 ). AI-assisted detection showed a higher diagnostic accuracy (96.89% [92.38%-98.57%] vs 72.54% [65.85%-78.35%], p = 1.42 × 10-14 ), sensitivity (99.35% [95.92%-99.97%] vs 68.39% [60.36%-75.48%], p = 7.11 × 10-15 ), and negative predictive value (NPV) (97.06% [82.95%-99.85%] vs 40.96% [30.46%-52.31%], p = 1.42 × 10-14 ). Specificity and positive predictive value (PPV) were not significantly differed. AI-assisted diagnosis demonstrated a smaller proportion of participants of interest (3.73%, [79/2117] vs.12.84% [272/2117], p = 1.59 × 10-58 ), a higher consistence between cytology and endoscopy (40.51% [32/79] vs. 12.13% [33/272], p = 1.54 × 10- 8), specificity (97.74% [96.98%-98.32%] vs 88.52% [87.05%-89.84%], p = 3.19 × 10-58 ), and PPV (40.51% [29.79%-52.15%] vs 12.13% [8.61%-16.75%], p = 1.54 × 10-8 ) in community-based screening. Sensitivity and NPV were not significantly differed. AI-assisted diagnosis as primary screening significantly reduced average cost for detecting positive cases. CONCLUSION: Our study provides a novel cytological method for detecting and screening early ESCC and HGIN.

LncRNA SNHG16 promotes development of oesophageal squamous cell carcinoma by interacting with EIF4A3 and modulating RhoU mRNA stability.

BACKGROUND: Numerous studies have revealed that long noncoding RNAs (lncRNAs) are closely related to the development of many diseases and carcinogenesis. However, their specific biological function and molecular mechanism in oesophageal squamous cell carcinoma (ESCC) remains unclear. METHODS: RNA-Seq was performed to determine the differential expressions of lncRNAs in ESCC, and the level of SNHG16 expression was detected in ESCC and intraepithelial neoplasia (IEN) samples. In vitro and in vivo experiments were performed to explore the role of SNHG16 and the interaction of EIF4A3 and Ras homologue family member U (RhoU) signalling. RESULTS: One hundred and seventy-five upregulated and 134 downregulated lncRNAs were identified by RNA-Seq. SNHG16 was highly expressed in ESCC and intraepithelial neoplasia (IEN) samples, and its expression level was correlated with tumour differentiation and T stage. Overexpression of SNHG16 can facilitate ESCC cell proliferation and metastasis. Mechanistically, we noticed that SNHG16 could bind RNA binding protein (RBP)-eukaryotic translation initiation factor (EIF4A3) and interact with it to form a complex. Importantly, the coalition of SNHG16 and EIF4A3 ultimately regulated Ras homologue family member U (RhoU). SNHG16 modulated RhoU expression by recruiting EIF4A3 to regulate the stability of RhoU mRNA. Knockdown of RhoU further alleviated the effect of the SNHG16 oncogene in ESCC cells. CONCLUSIONS: The newly identified SNHG16-EIF4A3-RhoU signalling pathway directly coordinates the response in ESCC pathogenesis and suggests that SNHG16 is a promising target for potential ESCC treatment.