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.

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.).

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.

EIF4A3-mediated oncogenic circRNA hsa_circ_0001165 advances esophageal squamous cell carcinoma progression through the miR-381-3p/TNS3 pathway.

Esophageal squamous cell carcinoma (ESCC) remains a major clinical challenge due to its poor prognosis and the scarcity effective therapeutic targets. Circular RNAs (circRNAs) are crucial in cancer progression. In this study, high-throughput sequencing was employed to profile ESCC tissues, revealing that hsa_circ_0001165 is notably elevated in both ESCC tumor samples and cell lines, with its expression is positively associated with patients' TNM staging. Knockdown of hsa_circ_0001165 resulted in reduced malignant biological behavior of ESCC cells in vitro and also inhibited tumor growth in vivo. Mechanism experimental analysis found that hsa_circ_0001165 expression is positively enhanced by eukaryotic translation initiation factor 4A3 (EIF4A3). Hsa_circ_0001165 acts as a miRNA sponge for miR-381-3p, increasing the expression of tensin-3 (TNS3) through a series of related mechanism assays include dual-luciferase reporter gene, RNA Immunoprecipitation and RNA-pulldown. The downregulation in miR-381-3p expression was observed in ESCC tissues, and the cell proliferation, invasion, and migration of ESCC were suppressed. The upregulated expression of hsa_circ_0001165 modulates the miR-381-3p/TNS3 axis and promotes aggressive phenotypes of ESCC. Hsa_circ_0001165 is regarded as a encouraging biomarker and potential therapeutic target for ESCC, presenting innovative options for both diagnostic and treatment approaches.

Injection of carbon dioxide instead of iodinated contrast to display the common bile duct during endoscopic retrograde cholangiopancreatography.

ABSTRACT: Common bile duct (CBD) stones are usually caused by biliary tract infection, biliary stricture, duodenal peripapillary diverticulum, Oddis sphincter dysfunction, and so on. Treatment is preferably with endoscopic retrograde cholangiopancreatography (ERCP), where an iodine-containing contrast agent is injected into the CBD to display the stone under fluoroscopy and then to confirm complete removal of the stone(s). We described a 65-year-old woman with CBD stones who had undergone cardiac pacemaker implantation and was allergic to iodinated contrast media. We performed ERCP + lithotomy + stent implantation under local anesthesia, with injection of carbon dioxide instead of iodinated contrast into the CBD, and successfully visualized the stones under fluoroscopy and then confirmed complete removal of them. The patient was generally in good condition without complications. Thus, we have demonstrated in this case report that carbon dioxide can be used as a safe, economical, and effective alternative to iodinated contrast agent during ERCP.

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.

Therapeutic strategies following endoscopic submucosal dissection for T1a-MM/T1b-SM1 esophageal squamous cell carcinoma: comparisons of long-term outcomes with propensity score-matched analysis.

BACKGROUND: For esophageal squamous cell carcinoma (ESCC) invading the muscularis mucosa (T1a-MM) or upper submucosa (T1b-SM1, up to 200 µm), the curative effectiveness of endoscopic submucosal dissection (ESD) and additional therapeutic strategies remain controversial. The present study aims to investigate the effectiveness of ESD followed by different therapeutic strategies in treating such patients. METHODS: A total of 242 patients with T1a-MM/T1b-SM1 ESCCs were involved. Data on therapeutic outcomes and long-term survivals were collected for analysis. Propensity score-matched analysis was performed to compensate for selection bias between patients with no additional therapy (NAT group) and those with additional therapy (AT group). RESULTS: R0 resection rate was 83.1% and curative resection rate was 78.5%. After a mean follow-up period of 57.8 ± 27.3 months, the cumulative recurrence rate was 7.9%. The 5-year overall survival (OS) and cause-specific survival (CSS) rate was 91.1% and 94.0%. In a matched cohort of 24 pairs, the 5-year OS and CSS rates showed no significant difference between NAT group (82.0% and 87.1%) and AT group (86.0% and 89.9%) (P > 0.05). In the subgroup of patients with noncurative ESD (n = 52), the 5-year OS and CSS rates were significantly higher in surgery group (90.2% and 95.2%) than that in NAT group (50.1% and 59.5%) and chemoradiotherapy group (51.4% and 60.0%) (P < 0.05). CONCLUSIONS: ESD with no additional therapy could achieve favorable long-term outcomes in treating T1a-MM/T1b-SM1 ESCCs. For patients with noncurative ESD, surgery ranks a prime recommendation over CRT.

Endoscopic submucosal dissection for proximal duodenal subepithelial lesions: a retrospective cohort study.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) has been used to remove subepithelial lesions (SELs) in recent years; however, duodenal ESD is associated with high rates of immediate or delayed bleeding and perforation. Whether ESD can be recommended for the treatment of duodenal SELs remains controversial. Therefore, we evaluated the efficacy and safety of ESD for duodenal SELs. METHODS: We conducted a retrospective cohort study in 62 patients (62 lesions) who underwent ESD for duodenal SELs between January 2012 and December 2020. The therapeutic outcomes from ESD for duodenal SELs and procedure-related complications were analyzed. RESULTS: En bloc resection and complete resection rates associated with duodenal ESD were 90.3% and 100%, respectively; four patients had a positive microscopic margin on pathologic examination. The median procedure time was 45 min (range 20-106 min). During the procedure, two patients received emergency surgery for uncontrolled bleeding and perforation, respectively. After the procedure, delayed bleeding occurred in three patients (4.8%), which was successfully managed by clipping, and delayed perforation occurred in two patients (3.2%) and needed emergency surgery. Risk factors related to complications were analyzed. Lesion size was found to be significantly associated with the complications (P = 0.028). No recurrences were detected, and no distant metastasis was observed in any patient during a median follow-up period of 45.5 months (range, 6-103 months). CONCLUSION: Duodenal ESD is relatively safe and feasible for duodenal SELs, especially for lesions no more than 2 cm in size.

Feasibility and Accuracy of Artificial Intelligence-Assisted Sponge Cytology for Community-Based Esophageal Squamous Cell Carcinoma Screening in China.

INTRODUCTION: Screening is the pivotal strategy to relieve the burden of esophageal squamous cell carcinoma (ESCC) in high-risk areas. The cost, invasiveness, and accessibility of esophagogastroduodenoscopy (EGD) necessitate the development of preliminary screening methods. METHODS: Residents aged 40-85 years were recruited in a high-risk area of ESCC. Esophageal cells were collected using an approved novel capsule sponge, and cytology slides were scanned by a trained artificial intelligence (AI) system before cytologists provided confirmation. Atypical squamous cell or more severe diagnosis was defined as positive cytology. AI-based abnormal cell counts were also reported. EGD was performed subsequently with biopsy as needed. Diagnostic accuracy, adverse events, and acceptability of cytology testing were assessed. Esophageal high-grade lesions (ESCC and high-grade intraepithelial neoplasia) were the primary target lesions. RESULTS: In total, 1,844 participants were enrolled, and 20 (1.1%) high-grade lesions were confirmed by endoscopic biopsy. The AI-assisted cytologist-confirmed cytology showed good diagnostic accuracy, with a sensitivity of 90.0% (95% confidence interval [CI], 76.9%-100.0%), specificity of 93.7% (95% CI, 92.6%-94.8%), and positive predictive value of 13.5% (95% CI, 7.70%-19.3%) for detecting high-grade lesions. The area under the receiver operation characteristics curve was 0.926 (95% CI, 0.850-1.000) and 0.949 (95% CI, 0.890-1.000) for AI-assisted cytologist-confirmed cytology and AI-based abnormal cell count, respectively. The numbers of EGD could be reduced by 92.5% (from 99.2 to 7.4 to detect 1 high-grade lesion) if only cytology-positive participants were referred to endoscopy. No serious adverse events were documented during the cell collection process, and 96.1% participants reported this process as acceptable. DISCUSSION: The AI-assisted sponge cytology is feasible, safe, and acceptable for ESCC screening in community, with high accuracy for detecting esophageal squamous high-grade lesions.

ERCP development in the largest developing country: a national survey from China in 2013.

BACKGROUND AND AIMS: The ERCP volume in developed countries has decreased recently, whereas the ERCP trend is unknown in developing countries. This study aimed to evaluate the ERCP development in China between 2006 and 2012. METHODS: All hospitals performing ERCP in mainland China in 2012 participated in an online survey. Data on ERCP infrastructure, volume, indication, and adverse events were collected and compared with those in a previous national survey and in developed countries. RESULTS: From 2006 to 2012 the number of hospitals performing ERCP in China increased from 470 to 1156. The total ERCP volume increased from 63,787 to 195,643, of which >95% were therapeutic. The ERCP rate in China (14.4 per 100,000 inhabitants) in 2012 was still much lower than that in developed countries. There was significant imbalance between different regions (1.3-99.1 per 100,000 inhabitants). The median ERCP volume per hospital decreased from 80 (interquartile range [IQR], 31-150) in 2006 to 52 (IQR, 20-146) in 2012. The median volume of the 686 hospitals that started ERCP after 2006 was 31.5 (IQR, 11-82). The post-ERCP adverse event rate in 2012 was comparable between hospitals in terms of volume (≥500 or <500 per year: 5.8% vs 5.6%) and practice durations (starting ERCP before or after 2006: 5.5% vs 5.6%). CONCLUSIONS: ERCP has developed considerably in China in recent years. Despite low annual volume, the hospitals starting ERCP after 2006 have acceptable adverse event rates and will be promising and important sources of ERCP development in China.

Correlation of Surface Toll-Like Receptor 9 Expression with IL-17 Production in Neutrophils during Septic Peritonitis in Mice Induced by E. coli.

IL-17 is a proinflammatory cytokine produced by various immune cells. Polymorphonuclear neutrophils (PMNs) are the first line of defense in bacterial infection and express surface Toll-like receptor 9 (sTLR9). To study the relationship of sTLR9 and IL-17 in PMNs during bacterial infection, we infected mice with E. coli intraperitoneally to establish a septic peritonitis model for studying the PMNs response in peritoneal cavity. We found that PMNs and some of "giant cells" were massively accumulated in the peritoneal cavity of mice with fatal septic peritonitis induced by E. coli. Kinetically, the CD11b(+) PMNs were increased from 20-40% at 18 hours to >80% at 72 hours after infection. After E. coli infection, sTLR9 expression on CD11b(+) and CD11b(-) PMNs and macrophages in the PLCs were increased at early stage and deceased at late stage; IL-17 expression was also increased in CD11b(+) PMNs, CD11b(-) PMNs, macrophages, and CD3(+) T cells. Using experiments of in vitro blockage, qRT-PCR and cell sorting, we confirmed that PMNs in the PLCs did increase their IL-17 expression during E. coli infection. Interestingly, sTLR9(-)CD11b(+)Ly6G(+) PMNs, not sTLR9(+)CD11b(+)Ly6G(+) PMNs, were found to be able to increase their IL-17 expression. Together, the data may help understand novel roles of PMNs in septic peritonitis.

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.

Dysregulated inclusion of BOLA3 exon 3 promoted by HNRNPC accelerates the progression of esophageal squamous cell carcinoma.

Dysregulated RNA splicing events produce transcripts that facilitate esophageal squamous cell carcinoma (ESCC) progression, but how this splicing process is abnormally regulated remains elusive. Here, we unveiled a novel alternative splicing axis of BOLA3 transcripts and its regulator HNRNPC in ESCC. The long-form BOLA3 (BOLA3-L) containing exon 3 exhibited high expression levels in ESCC and was associated with poor prognosis. Functional assays demonstrated the protumorigenic function of BOLA3-L in ESCC cells. Additionally, HNRNPC bound to BOLA3 mRNA and promoted BOLA3 exon 3 inclusion forming BOLA3-L. High HNRNPC expression was positively correlated with the presence of BOLA3-L and associated with an unfavorable prognosis. HNRNPC knockdown effectively suppressed the malignant biological behavior of ESCC cells, which were significantly rescued by BOLA3-L overexpression. Moreover, BOLA3-L played a significant role in mitochondrial structural and functional stability. E2F7 acted as a key transcription factor that promoted the upregulation of HNRNPC and inclusion of BOLA3 exon 3. Our findings provided novel insights into how alternative splicing contributes to ESCC progression.

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.

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.

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.

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.