Development and Validation of a Comprehensive Analysis of the Competing Endogenous circRNA/miRNA/mRNA Network for the Identification of Immune-Related Targets in Esophageal Squamous Cell Carcinoma.

Immunotherapy for esophageal squamous cell carcinoma (ESCC) exhibits notable variability in efficacy. Concurrently, recent research emphasizes circRNAs' impact on the ESCC tumor microenvironment. To further explore the relationship, we leveraged circRNA, microRNA, and mRNA sequence datasets to construct a comprehensive immune-related circRNA-microRNA-mRNA network, revealing competing endogenous RNA (ceRNA) roles in ESCC. The network comprises 16 circular RNAs, 13 microRNAs, and 1,560 mRNAs. Weighted gene co-expression analysis identified immune-related modules, notably cancer-associated fibroblast (CAF) and myeloid-derived suppressor cell modules, correlating significantly with immune and stemness scores. Among them, the CAF module plays a crucial role in extracellular matrix function and effectively discriminates ESCC patients. Four hub collagen family genes within CAF correlated robustly with CAF, macrophage infiltration, and T-cell exclusion. In-house sequencing and RT-qPCR validated their elevated expression. We also identified CAF module-targeting drugs as potential ESCC treatments. In summary, we established an immune-related circRNA-miRNA-mRNA network that not only illuminates ceRNA functionality but also highlights circRNAs' involvement in the CAF through collagen gene targeting. These findings hold promise to predict ESCC immune landscapes and therapy responses, ultimately aiding in more personalized and effective clinical decision-making.

Burden of digestive system diseases in China and its provinces during 1990-2019: Results of the 2019 Global Disease Burden Study.

BACKGROUND: Evaluating the impact of digestive system diseases is vital for devising effective prevention strategies. However, comprehensive reports on the burden of digestive system diseases in China are lacking. Our study aimed to provide an overview of the burden and trends of digestive system diseases from 1990 to 2019 in China and its provinces. METHODS: This cross-sectional study utilized the Global Disease Burden Study 2019 to estimate the incidence, mortality rate, disability-adjusted life years (DALYs), years of life disability, years of life lost, and changes in the burden of digestive diseases across 31 Chinese provinces from 1990 to 2019. The analysis of disease burden primarily examines the characteristics of sub-disease distribution, time trends, age distribution, and sex distribution. Additionally, we compared provincial age-standardized DALYs for digestive diseases with the expected rates based on the socio-demographic index (SDI). RESULTS: In 2019, there were 499.2 million cases of digestive system diseases in China, resulting in 1,557,310 deaths. Stomach cancer, colon and rectal cancer, and esophageal cancer are the top three diseases associated with mortality and DALY related to digestive system diseases. Meanwhile, cirrhosis and other chronic liver diseases, gastroesophageal reflux disease, and gallbladder and biliary diseases are the top three kinds of diseases with the highest prevalence among digestive system diseases. The risk of gastric cancer sharply increases among men after the age of 40 years, leading to a significant disparity in burden between men and women. As the SDI increased, the DALYs associated with digestive system diseases in China and its provinces showed a downward trend. CONCLUSION: Our study highlights the inverse correlation between DALYs associated with digestive system diseases and the SDI, providing valuable insights that can assist public health officials in the estimation of the disease burden in this area.

Risk and pathologic factors of recurrence after endoscopic resection for superficial esophageal squamous cell carcinoma: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The risk and pathologic factors of recurrence after endoscopic resection (ER) for superficial esophageal squamous cell carcinoma (ESCC) are inconsistent across studies. We evaluated this in a systematic review and meta-analysis. METHODS: The data of recurrence in such patients were extracted from all studies. Risk ratios (RRs) were combined using random-effects meta-analysis to assess pooled recurrence rate and pathologic risk factors. Relapse-free survival was combined using the Kaplan-Meier method to estimate the relationship between various pathologic factors and recurrence time. RESULTS: We identified 26 studies, with a total of 5100 patients and 321 with recurrences (pooled rate, 6.2%). The risk of recurrence was significantly higher in positive vertical margin (RR, 4.51; 95% confidence interval [CI], 2.16-9.44), positive horizontal margin (RR, 2.54; 95% CI, 1.57-4.13), lymphovascular invasion (LVI) (RR, 2.33; 95% CI, 1.75-3.11; P < .001), lymphatic invasion (LI) (RR, 2.24; 95% CI, 1.24-4.06), and tumor invading submucosa of ≤200 µm (SM1) (RR, 1.71; 95% CI, 1.32-2.21, compared to muscularis mucosa). Patients with LI (hazard ratio, 2.47; 95% CI, 1.24-4.90; P = .02) and LVI (HR, 2.36; 95% CI, 2.22-4.59; P = .0006) tended to have earlier recurrence after ER. CONCLUSIONS: The recurrence rate of superficial esophageal squamous cell carcinoma after ER is acceptable. Patients with positive margins, LVI, LI, and SM1 need to pay significant attention to the risk of recurrence. LI and VI should be evaluated separately. (PROSPERO CRD42023406309.).

Non-invasive diagnosis of esophageal cancer by a simplified circulating cell-free DNA methylation assay targeting OTOP2 and KCNA3: a double-blinded, multicenter, prospective study.

BACKGROUND: Esophageal cancer (EC) is a highly lethal disease lacking early detection approaches. We previously identified that OTOP2 and KCNA3 were specifically hypermethylated in circulating cell-free DNA from patients with EC. We then developed a blood-based methylation assay targeting OTOP2 and KCNA3 (named "IEsohunter") for esophageal cancer noninvasive detection. This double-blinded, multicenter, prospective study aimed to comprehensively evaluate its clinical diagnostic performance. METHODS: Participants with EC, high-grade intraepithelial neoplasia (HGIN), other malignancies, benign gastrointestinal lesions, or no abnormalities were prospectively enrolled from 5 tertiary referral centers across China. Peripheral blood samples were collected, followed by plasma cell-free DNA methylation analysis using the IEsohunter test based on multiplex quantitative polymerase chain reaction adopting an algorithm-free interpretation strategy. The primary outcome was the diagnostic accuracy of IEsohunter test for EC. RESULTS: We prospectively enrolled 1116 participants, including 334 patients with EC, 71 with HGIN, and 711 controls. The areas under the receiver operating characteristic curves of the IEsohunter test for detecting EC and HGIN were 0.903 (95% CI 0.880-0.927) and 0.727 (95% CI 0.653-0.801), respectively. IEsohunter test showed sensitivities of 78.5% (95% CI 69.1-85.6), 87.3% (95% CI 79.4-92.4), 92.5% (95% CI 85.9-96.2), and 96.9% (95% CI 84.3-99.8) for stage I-IV EC, respectively, with an overall sensitivity of 87.4% (95% CI 83.4-90.6) and specificity of 93.3% (95% CI 91.2-94.9) for EC detection. The IEsohunter test status turned negative (100.0%, 47/47) after surgical resection of EC. CONCLUSIONS: The IEsohunter test showed high diagnostic accuracy for EC detection, indicating that it could potentially serve as a tool for noninvasive early detection and surveillance of EC.

Development of esophagogastroduodenoscopy in China: results from the national census in 2013 and 2020.

Background: Given the significant burden of upper digestive diseases, there has been a substantial increase in the utilization of esophagogastroduodenoscopy (EGD) in China from 2012 to 2019. The objective of this study is to investigate the development, practice, and factors influencing the widespread use of EGD during this period. Methods: Two national censuses were conducted among all hospitals in mainland China that perform gastrointestinal endoscopy. These censuses aimed to extract information on the infrastructure, volume, and quality of EGD. The analysis of potential factors influencing EGD practice was based on real-world data from open access sources. Results: From 2012 to 2019, the number of hospitals performing EGD in mainland China increased from 1,518 to 2,265 (1.49-fold) in tertiary hospitals and from 3,633 to 4,097 (1.12-fold) in secondary hospitals, respectively. The national utilization rate of EGD also increased from 1,643.53 to 2,018.06 per 100,000 inhabitants, indicating a 1.23-fold increase. Regions with more endoscopists per 100,000 inhabitants (OR 9.61, P<0.001), more tertiary hospitals performing EGD per million inhabitants (OR 2.43, P<0.001), higher incidence of esophageal and gastric cancer (OR 2.09, P=0 016), and higher number of hospitals performing EGD per million inhabitants (OR 1.77, P=0.01) tended to provided more numerous and qualitied EGD. And hospital grading, regional GDP, incidence of esophageal and gastric cancer and the volume of EGD were observed as the significantly relevant factors of malignant dictation rate (MDR) (P<0.05), but not the number and educational background of endoscopists. Conclusion: Over the past seven years, China has made significant progress in EGD. However, challenges persist in terms of quality and inequality.

Heterozygous Spink1 c.194+2T>C mutation promotes chronic pancreatitis after acute attack in mice.

BACKGROUND & AIMS: Mutations in genes, including serine protease inhibitor Kazal-type 1 (SPINK1), influence disease progression following sentinel acute pancreatitis event (SAPE) attacks. SPINK1 c.194+2T > C intron mutation is one of the main mutants of SPINK1，which leads to the impairment of SPINK1 function by causing skipping of exon 3. Research on the pathogenesis of SAPE attacks would contribute to the understanding of the outcomes of acute pancreatitis. Therefore, the aim of the study was to clarify the role of SPINK1 c.194+2T > C mutation in the CP progression after an AP attack. METHODS: SAPE attacks were induced in wildtype and SPINK mutant (Spink1 c.194+2T > C) mice by cerulein injection. The mice were sacrificed at 24 h, 14 d, 28 d, and 42 d post-SAPE. Data-independent acquisition (DIA) proteomic analysis was performed for the identification of differentially expressed protein in the pancreatic tissues. Functional analyses were performed using THP-1 and HPSCs. RESULTS: Following SAPE attack, the Spink1 c.194+2T > C mutant mice exhibited a more severe acute pancreatitis phenotype within 24 h. In the chronic phase, the chronic pancreatitis phenotype was more severe in the Spink1 c.194+2T > C mutant mice after SAPE. Proteomic analysis revealed elevated IL-33 level in Spink1 c.194+2T > C mutant mice. Further in vitro analyses revealed that IL-33 induced M2 polarization of macrophages and activation of pancreatic stellate cells. CONCLUSION: Spink1 c.194+2T > C mutation plays an important role in the prognosis of patients following SAPE. Heterozygous Spink1 c.194+2T > C mutation promotes the development of chronic pancreatitis after an acute attack in mice through elevated IL-33 level and the induction of M2 polarization in coordination with pancreatic stellate cell activation.

Development and status quo of digestive endoscopy in China: An analysis based on the national census in 2013 and 2020.

Background and Objectives: Technique and practice of digestive endoscopy are undergoing speedy development all over the world. This study aimed to evaluate its status quo and development in China. Methods: All hospitals performing digestive endoscopy in mainland China participated in the national census in 2013 and 2020. Retrospective data of hospitals, endoscopists, volumes, and qualities were collected via an online structured questionnaire, and its accuracy and rationality were verified by logical tests and manual reviews. Data from other countries were used to compare with that of China. Results: From 2012 to 2019, the number of hospitals performing digestive endoscopy increased from 6,128 to 7,470 (1.22-fold), in which primary healthcare played a minor role. The median hospitals per 100,000 inhabitants per provincial region increased from 0.49 (IQR, 0.39-0.57) to 0.55 (IQR, 0.49-0.63). The endoscopists increased from 26,203 to 39,638 (1.51-fold), but their average workload even expanded. Overall volume increased from 28.8 million to 44.5 million (1.55-fold), and most types of endoscopic procedures recorded a high growth rate. Contrastingly, the specific utilization rates were low and paled in comparison with some developed countries. Nationwide, regional utilization rates showed a significant correlation with GDP per capita (P <0.001). Overall qualities of digestive endoscopy were excellent, but certain results of quality indicators posed a huge challenge, such as the detection rates of adenoma and early cancers. Conclusions: Impressive progress has been made in digestive endoscopy with rapidly expanding economy in China. However, primary healthcare, utilization rates, and income-related inequality of regional services were needed to be improved to promote public health better.

Association between physical activity and risk of gastroesophageal reflux disease: A systematic review and meta-analysis.

BACKGROUND: Lifestyle plays an important role in preventing and managing gastroesophageal reflux disease (GERD). In response to the conflicting results in previous studies, we performed a systematic review and meta-analysis to investigate this association. METHODS: Relevant studies published until January 2023 were retrieved from 6 databases, and the prevalence of symptomatic gastroesophageal reflux (GER) or GERD was determined from the original studies. A random effects model was employed to meta-analyze the association by computing the pooled relative risk (RR) with 95% confidence intervals (95%CIs). Furthermore, subgroup and dose-response analyses were performed to explore subgroup differences and the association between cumulative physical activity (PA) time and GERD. RESULTS: This meta-analysis included 33 studies comprising 242,850 participants. A significant negative association was observed between PA and the prevalence of symptomatic GER (RR = 0.74, 95%CI: 0.66-0.83; p < 0.01) or GERD (RR = 0.80, 95%CI: 0.76-0.84; p < 0.01), suggesting that engaging in PA might confer a protective benefit against GERD. Subgroup analyses consistently indicated the presence of this association across nearly all subgroups, particularly among the older individuals (RR<40 years:RR≥40 years = 0.85:0.69, p < 0.01) and smokers (RRsmoker:RRnon-smoker = 0.67:0.82, p = 0.03). Furthermore, a dose-response analysis revealed that individuals who engaged in 150 min of PA per week had a 72.09% lower risk of developing GERD. CONCLUSION: Maintaining high levels of PA decreased the risk of GERD, particularly among older adults and smokers. Meeting the recommended PA level of 150 min per week may significantly decrease the prevalence of GERD.

Liquid biopsy of oesophageal squamous cell carcinoma: implications in diagnosis, prognosis, and treatment monitoring.

Oesophageal squamous cell carcinoma (ESCC) is a common malignant tumour of the gastrointestinal tract. Early detection and access to appropriate treatment are crucial for the long-term survival of patients. However, limited diagnostic and monitoring methods are available for identifying early stage ESCC. Endoscopic screening and surgical resection are commonly used to diagnose and treat early ESCC. However, these methods have disadvantages, such as high recurrence, lethality, and mortality rates. Therefore, methods to improve early diagnosis of ESCC and reduce its mortality rate are urgently required. In 1961, Gary et al. proposed a novel liquid biopsy approach for clinical diagnosis. This involved examining exosomes, circulating tumour cells, circulating free DNA, and circulating free RNA in body fluids. The ability of liquid biopsy to obtain samples repeatedly, wide detection range, and fast detection speed make it a feasible option for non-invasive tumour detection. In clinical practice, liquid biopsy technology has gained popularity for early screening, diagnosis, treatment efficacy monitoring, and prognosis assessment. Thus, this is a highly promising examination method. However, there have been no comprehensive reviews on the four factors of liquid biopsy in the context of ESCC. This review aimed to analyse the progress of liquid biopsy research for ESCC, including its classification, components, and potential future applications.

Risk model based on genes regulating the response of tumor cells to T-cell-mediated killing in esophageal squamous cell carcinoma.

Immune checkpoint inhibitors (ICIs) represent a promising therapeutic approach for esophageal squamous cell carcinoma (ESCC). However, the subpopulations of ESCC patients expected to benefit from ICIs have not been clearly defined. The anti-tumor cytotoxic activity of T cells is an important pharmacological mechanism of ICIs. In this study, the prognostic value of the genes regulating tumor cells to T cell-mediated killing (referred to as GRTTKs) in ESCC was explored by using a comprehensive bioinformatics approach. Training and validation datasets were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. A prognostic risk scoring model was developed by integrating prognostic GRTTKs from TCGA and GEO datasets using a ridge regression algorithm. Patients with ESCC were divided into high- and low-risk groups based on eight GRTTKs (EIF4H, CDK2, TCEA1, SPTLC2, TMEM209, RGP1, EIF3D, and CAPZA3) to predict overall survival in the TCGA cohort. Using Kaplan-Meier curves, receiver operating characteristic curves, and C-index analysis, the high reliability of the prognostic risk-scoring model was certified. The model scores served as independent prognostic factors, and combining clinical staging with risk scoring improved the predictive value. Patients in the high-risk group exhibited abundant immune cell infiltration, including immune checkpoint expression, antigen presentation capability, immune cycle gene expression, and high tumor inflammation signature scores. The high-risk group exhibited a greater response to immunotherapy and neoadjuvant chemotherapy than the low-risk group. Drug sensitivity analysis demonstrated lower IC50 for AZD6244 and PD.0332991 in high-risk groups and lower IC50 for cisplatin, ATRA, QS11, and vinorelbine in the low-risk group. Furthermore, the differential expression of GRTTK-related signatures including CDK2, TCEA1, and TMEM209 were verified in ESCC tissues and paracancerous tissues. Overall, the novel GRTTK-based prognostic model can serve as indicators to predict the survival status and immunotherapy response of patients with ESCC, thereby providing guidance for the development of personalized treatment strategies.

A pan-cancer analysis of the oncogenic role of Golgi transport 1B in human tumors.

Background: Owing to the aggressiveness and treatment-refractory nature of cancer, ideal candidates for early diagnosis and treatment are needed. Golgi transport 1B (GOLT1B) has been associated with cellular malignant behaviors and immune responses in colorectal and lung cancer, but a systematic pan-cancer analysis on GOLT1B has not been conducted. Methods: The expression status and clinical association of GOLT1B in The Cancer Genome Atlas (TCGA) were analyzed. Genetic and methylation alterations in GOLT1B were explored. The relationship between GOLT1B and immune cell infiltration was also investigated. Genes related to GOLT1B expression were selected and analyzed. Results: GOLT1B was highly expressed in most tumors, and there was a positive correlation between GOLT1B expression and clinical pathological parameters. High expression levels of GOLT1B have been associated with poor prognosis of most cancers. Copy number amplification was the primary type of GOLT1B genetic alterations, which was related to the prognosis of pan-cancer cases. There were different levels of GOLT1B promoter methylation across cancer types. The methylation level of the probe cg07371838 and cg25816357 was closely associated with prognosis in diverse cancers. There was also a positive correlation between GOLT1B genetic alterations and CD4+ T lymphocytes, especially the Th2 subset, as well as between GOLT1B expression and the estimated infiltration value of cancer-associated fibroblasts. Serine/threonine kinase receptor-associated protein (STRAP), integrator complex subunit 13 (INTS13), and ethanolamine kinase 1 (ETNK1) were the most relevant genes for GOLT1B expression, and their interactions with GOLT1B were involved in regulating the transforming growth factor (TGF)-ß receptor signaling pathway and epithelial-mesenchymal transition (EMT). Conclusions: This pan-cancer analysis provided a comprehensive understanding of the oncogenic role of GOLT1B, highlighting a potential mechanism whereby GOLT1B influences the tumor microenvironment, as well as cancer immunotherapy.

Development, quality, and influencing factors of colonoscopy in China: results from the national census in 2013 and 2020.

Background and Aim: With the increasing burden of colorectal cancer (CRC), the practice of colonoscopy is gaining attention worldwide. However, it exhibits distinct trends between developing and developed countries. This study aims to explore its development and identify influencing factors in China. Methods: The Chinese Digestive Endoscopy Censuses were conducted twice in mainland China under the supervision of health authorities. Information regarding the practice of colonoscopy was collected through a structured online questionnaire. The authenticity of the data was evaluated through logical tests, and a random selection of endoscopic reports underwent manual validation by Quality Control Centers. Potential factors associated with colonoscopy were analyzed using real-world information. Results: From 2012 to 2019, the number of hospitals that performed colonoscopy increased from 3,210 to 6,325 (1.97-fold), and the volume increased from 5.83 to 12.92 million (2.21-fold). The utilization rate rose from 436.0 to 914.8 per 100,000 inhabitants (2.10-fold). However, there was an exacerbation of regional inequality in the adequacy of colonoscopy. Regions with higher incidence of CRC, higher gross domestic product per capita, more average numbers of endoscopists and tertiary hospitals tended to provide more accessible colonoscopy (P<0.001). Nationwide, the cecal intubation rate improved from 83.9% to 94.4% and the unadjusted adenoma detection rate (ADR) improved from 16.3% to 18.1%. Overall, hospital grading, educational background of endoscopists, economic income, and colonoscopy volume were observed as the significantly positive factors affecting ADR (P<0.05), but not the incidence of CRC or the number of endoscopists. Conclusions: Tremendous progress in colonoscopy has been made in China, but some issues needed timely reflection. Our findings provide timely evidence for better colonoscopy strategies and measures, such as quality control and medical education of endoscopists.

Genome-wide methylation profiling identified methylated KCNA3 and OTOP2 as promising diagnostic markers for esophageal squamous cell carcinoma.

BACKGROUND: Early detection of esophageal squamous cell carcinoma (ESCC) can considerably improve the prognosis of patients. Aberrant cell-free DNA (cfDNA) methylation signatures are a promising tool for detecting ESCC. However, available markers based on cell-free DNA methylation are still inadequate. This study aimed to identify ESCC-specific cfDNA methylation markers and evaluate the diagnostic performance in the early detection of ESCC. METHODS: We performed whole-genome bisulfite sequencing (WGBS) for 24 ESCC tissues and their normal adjacent tissues. Based on the WGBS data, we identified 21,469,837 eligible CpG sites (CpGs). By integrating several methylation datasets, we identified several promising ESCC-specific cell-free DNA methylation markers. Finally, we developed a dual-marker panel based on methylated KCNA3 and OTOP2, and then, we evaluated its performance in our training and validation cohorts. RESULTS: The ESCC diagnostic model constructed based on KCNA3 and OTOP2 had an AUC of 0.91 [95% CI: 0.85-0.95], and an optimal sensitivity and specificity of 84.91% and 94.32%, respectively, in the training cohort. In the independent validation cohort, the AUC was 0.88 [95% CI: 0.83-0.92], along with an optimal sensitivity of 81.5% and specificity of 92.9%. The model sensitivity for stage I-II ESCC was 78.4%, which was slightly lower than the sensitivity of the model (85.7%) for stage III-IV ESCC. CONCLUSIONS: The dual-target panel based on cfDNA showed excellent performance for detecting ESCC and might be an alternative strategy for screening ESCC.

Construction and results of a comprehensive index for gastrointestinal health monitoring in China: a nationwide study.

Background: The disease burden of gastrointestinal disease (GD) in China is high, with significant variation across provinces. A comprehensive agreed set of indicators could guide rational resource allocation to support better GD outcomes. Methods: This study collected data from multiple sources, including national surveillance, surveys, registration systems, and scientific research. Literature reviews and Delphi methods were used to obtain monitoring indicators; the analytic hierarchy process was used to determine indicator weights. Findings: The China Gastrointestinal Health Index (GHI) system consisted of four dimensions and 46 indicators. The weight of the four dimensions from high to low included the prevalence of gastrointestinal non-neoplastic diseases and gastrointestinal neoplasms (GN) (0.3246), clinical treatment of GD (0.2884), prevention and control of risk factors (0.2606), and exposure to risk factors (0.1264). The highest indicator weight of GHI rank was the successful smoking cessation rate (0.1253), followed by the 5-year survival rate of GN (0.0905), and the examination rate of diagnostic oesophagogastroduodenoscopy (0.0661). The overall GHI for China in 2019 was 49.89, varying from 39.19 to 76.13 across all sub-regions. The top five sub-regions in the total GHI score were in the eastern region. Interpretation: GHI is the first system designed to monitor gastrointestinal health systematically. In the future, data from sub-regions of China should be used to test and improve the GHI system for its impact. Funding: This research was supported by the National Health Commission of China, the First Affiliated Hospital of Naval Medical University (2019YXK006), and the Science and Technology Commission of Shanghai Municipality (21Y31900100).

Setting 6-Minute Minimal Examination Time Improves the Detection of Focal Upper Gastrointestinal Tract Lesions During Endoscopy: A Multicenter Prospective Study.

INTRODUCTION: Positive correlation between examination time and neoplasm detection using esophagogastroduodenoscopy (EGD) has been described by observational studies, but the effect of setting minimal examination time still requires investigation. METHODS: This prospective, 2-stage, interventional study was conducted in 7 tertiary hospitals in China, enrolling consecutive patients undergoing intravenously sedated diagnostic EGDs. In stage I, the baseline examination time was collected without informing the endoscopists. In stage II, the minimal examination time was set for the same endoscopist according to the median examination time of normal EGDs in stage I. The primary outcome was the focal lesion detection rate (FDR), defined as the proportion of subjects with at least one focal lesion among all subjects. RESULTS: A total of 847 and 1,079 EGDs performed by 21 endoscopists were included in stages I and II, respectively. In stage II, the minimal examination time was set as 6 minutes, and the median time for normal EGD increased from 5.8 to 6.3 minutes ( P < 0.001). Between the 2 stages, the FDR was significantly improved (33.6% vs 39.3%, P = 0.011), and the effect of the intervention was significant (odds ratio, 1.25; 95% confidence interval, 1.03-1.52; P = 0.022) even after adjusting for subjects' age, smoking status, endoscopists' baseline examination time, and working experience. The detection rate of high-risk lesions (neoplastic lesions and advanced atrophic gastritis) was also significantly higher in stage II (3.3% vs 5.4%, P = 0.029). In the endoscopist-level analysis, all practitioners reached a median examination time of 6 minutes, and the coefficients of variation of FDR (36.9%-26.2%) and examination time (19.6%-6.9%) decreased in stage II. DISCUSSION: Setting a 6-minute minimal examination time significantly improved the detection of focal lesions during EGDs and has the potential to be implemented for quality improvement.

EUS development in China: Results from national surveys in 2013 and 2020.

Background and Objectives: EUS has recently gained attraction in mainland China. This study aimed to evaluate the development of EUS from results of two national surveys. Methods: EUS-related information, including infrastructure, personnel, volume, and quality indicator, was extracted from the Chinese Digestive Endoscopy Census. Data from 2012 and 2019 were compared, and differences among various hospitals and regions were analyzed. The EUS rates (EUS annual volume per 100,000 inhabitants) between China and developed countries were also compared. Results: The number of hospitals performing EUS in mainland China increased from 531 to 1236 (2.33-fold), and 4025 endoscopists performed EUS in 2019. The volumes of all EUS and interventional EUS increased from 207,166 to 464,182 (2.24-fold) and 10,737 to 15,334 (1.43-fold), respectively. The EUS rate in China was lower than that in developed countries but showed a higher growth rate. EUS rate varied substantially among different provincial regions (in 2019: 4.9-152.0 per 100,000 inhabitants) and showed significant positive association with gross domestic product per capita (in 2019: r = 0.559, P = 0.001). The EUS-FNA-positive rate in 2019 was comparable between hospitals in terms of annual volume (≥50 or < 50: 79.9% vs. 71.6%, P = 0.704) and practice duration (starting EUS-FNA before or after 2012: 78.7% vs. 72.6%, P = 0.565). Conclusion: EUS has developed considerably in China in recent years but still needs substantial improvement. More resources are in demand for hospitals in less-developed regions and with low EUS volume.

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.

Identification of novel factors that affect the onset of idiopathic chronic pancreatitis: The role for microRNA-323b-5p.

BACKGROUND: The c.194+2 T>C variant of serine protease inhibitor Kazal type 1 (SPINK1) is a known genetic risk factor found in Chinese patients with idiopathic chronic pancreatitis (ICP), but the early-onset mechanisms of ICP are still unclear. METHODS: Complementary experimental approaches were used to pursue other potential pathologies in the present study. The serum level of SPINK1 of ICP patients in the Han population in China was detected and verified by an enzyme-linked immunosorbent assay. Next, differentially expressed proteins and microRNAs from plasma samples of early-onset and late-onset ICP patients were screened by proteomic analysis and microarray, respectively. RESULTS: Combined with these advanced methods, the data strongly suggest that the regulatory effects of microRNAs were involved in the early-onset mechanism of the ICP by in vitro experiments. There was no significant difference in the plasma SPINK1 expression between the early-onset ICP and the late-onset patients. However, the expression of plasma glutathione peroxidase (GPx3) in early-onset ICP patients was markedly lower than that in late-onset ICP patients, although the level of hsa-miR-323b-5p was lower in late-onset patients compared to the early-onset ICP group. In vitro experiments confirmed that hsa-miR-323b-5p could increase apoptosis in caerulein-treated pancreatic acinar cells and inhibit the expression of GPx3. CONCLUSIONS: The up-regulated hsa-miR-323b-5p might play a crucial role in the early-onset mechanisms of ICP by diminishing the antioxidant activity through the down-regulation of GPx3.