Multidrug-resistant (MDR) Gram-negative pneumonia is associated with high mortality and substantial healthcare resource utilization. Ceftazidime–avibactam (CAZ-AVI) is an important option, yet real-world experience in Chinese pneumonia cohorts is limited and the associated inpatient costs are seldom reported. This study aimed to describe the clinical response to CAZ-AVI in routine practice, to identify the factors associated with 14-day and with 30-day all-cause mortality separately so as to examine how they differ over time, and to characterize inpatient costs. We retrospectively studied 693 adults with MDR pneumonia who received at least 3 days of CAZ-AVI at eight hospitals in Hubei, China, between August 2022 and August 2025. Factors associated with 14-day and 30-day all-cause mortality were examined by univariable and multivariable logistic regression, with LASSO-penalized regression and cross-validation as a sensitivity analysis. Acute kidney injury (AKI) was recorded as a safety observation, and pneumonia-related inpatient costs were summarized descriptively. The study is reported in line with Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). Overall, 480 patients (69.3

The progression of gastric cancer (GC) is profoundly influenced by extracellular matrix (ECM) remodeling within the tumor microenvironment (TME); however, the compartment-specific roles of key ECM proteins (e.g., epithelium vs. stroma) remain incompletely understood. By integrating multi-omics bulk transcriptomic data with single-cell sequencing data, we observed a bulk-compartment discrepancy for COL4A6: COL4A6 carries an inverse association (OR < 1) in bulk transcriptome-based risk models, whereas its protein is markedly upregulated and predominantly localized to the CAF compartment in clinical specimens. We constructed a Matrisome Risk Score (MRS) model and identified ECM subtypes with distinct prognoses, confirming that the high-matrix subtype (MC1) is closely associated with immunosuppression and chemotherapy resistance. Functional experiments demonstrated that COL4A6 from CAF-enriched fibroblast cultures promotes tumor progression and stromal remodeling by inducing CAF activation (upregulation of α-SMA and FAP, remodeling of stress fibers) and promoting EMT in gastric cancer cells. Collectively, our findings support a compartment-dependent model in which epithelial silencing/loss may bias bulk mRNA associations, whereas CAF-compartment COL4A6 accumulation is a functional driver of GC progression. This highlights CAF-compartment COL4A6 as a potential target for therapies aimed at ECM remodeling within the TME.

The gut microbiota is integral to host physiology, contributing to metabolic homeostasis, epithelial barrier integrity, immune balance, and bidirectional communication along gut–organ axes. Disruption of this ecosystem, commonly referred to as dysbiosis, is increasingly implicated in a wide range of gastrointestinal and extra-intestinal diseases. Rather than reflecting isolated compositional changes, microbiota-related pathology often involves interconnected disturbances in barrier function, microbial metabolism, immune regulation, genotoxicity, inflammatory and oncogenic signaling, and long-range communication with distal organs. However, key challenges remain, particularly in resolving causality, accounting for interindividual heterogeneity, and translating complex microbiome data into robust clinical tools. In this review, we summarize the role of the gut microbiota in maintaining host homeostasis and outline the concept, drivers, and consequences of dysbiosis. We then discuss the major mechanisms through which the gut microbiota contributes to disease development and progression, using colorectal cancer as a representative gastrointestinal example and gut–organ axes as a framework for extra-intestinal disorders. We further highlight current translational advances in microbiota-based biomarkers, dietary modulation, biotic and postbiotic strategies, fecal microbiota transplantation, and emerging precision microbiota therapies. By integrating mechanistic insights with translational perspectives, this review offers an updated framework for interpreting the gut microbiota in health and disease and may help inform the future development of more precise, mechanism-informed diagnostic and therapeutic strategies.

There is a lack of effective means for precise drug delivery of gastrointestinal diseases. Herein we report a novel magnetically controlled drug delivering capsule endoscope (MDCE) to achieve precision drug delivery for gastrointestinal diseases. MDCE integrates a drug delivery system into conventional capsule endoscope. It can carry 0.5 ml of liquid medication, which can be sprayed onto the target area using an electric pump upon detecting lesions by convolutional neural network (CNN)-model. Additionally, with the aid of an external magnet, the operator can adjust the posture and drug delivery direction of the capsule endoscope to enhance the accuracy of drug release. This adjustment process is monitored in real-time through the camera at the front of the capsule endoscope. To validate the clinical efficacy of the MDCE, we established porcine intestinal epithelial injury and bleeding models, and we demonstrated that MDCE could accurately deliver drugs under magnetic control through direct visualization. MDCE could significantly reduce injury area by delivering organoids to porcine injury sites after 7 days compared to the control group (48 mm2 vs. 21 mm2, p = 0.018). MDCE could significantly reduce bleeding time by spraying norepinephrine to porcine intestinal bleeding site compared to the control group (731 s vs. 418 s, p = 0.007). These demonstrate that MDCE could actively accurately release drugs under magnetic control through direct visualization in a non-invasive manner. This opens a new chapter for the precision treatment of gastrointestinal diseases and provides a novel approach for oral drug administration for systemic diseases.

Introduction:This cross-sectional study aimed to explore the relationship between Helicobacter pylori (Hp) infection and kidney stone formation in China, given the high incidence of Hp infection and its potential to cause damage to multiple systems. Methods:Conducted at the Department of Health Management of Wuhan Union Hospital, the study included 48,294 hp-negative and 28,455 hp-positive individuals. Hp infection was detected using the 13C urea breath test (13C-UBT), and kidney stones were identified via urinary Doppler ultrasonography. Results:Results showed that Hp-negative (Hp-) individuals had higher levels of blood urea nitrogen (BUN), serum creatinine (Scr), and uric acid compared to Hp-positive (Hp+) individuals, while Hp- patients had lower urine pH (P < 0.001). The prevalence of kidney stones was significantly higher in the Hp+ group. Univariate and multivariate regression analyses indicated that Hp infection is an independent risk factor for kidney stones (OR: 1.275, 95% CI: 1.219-1.333, P < 0.001) after adjusting for confounding factors such as age, body mass index (BMI), blood pressure, and lipid profiles. Conclusion:In conclusion, Helicobacter pylori infection is an independent risk factor for kidney stone development in China.

Objectives: Early-onset colorectal cancer (EO-CRC) is becoming increasingly concerning due to its impact on individuals under 50 years old. We explored the burden of EO-CRC to provide information for planning effective management and prevention strategies. Study design: We conducted secondary analyses to assess the burden of EO-CRC using data from GBD 2021. Methods: The incidence, prevalence, deaths, disability-adjusted life years (DALYs) and their rates across 204 countries and territories were obtained from GBD 2021 database. The estimated annual percentage change (EAPC) calculation was used to assess temporal trends in these metrics. Additionally, we reported the proportion of DALYs attributable to risk factors and projected future disease burden till 2050. Results: The global number of new EO-CRC cases increased from 107,310 in 1990 to 211,890 in 2021. Both agestandardized incidence rate (ASIR) and prevalence rate (ASPR) of EO-CRC showed overall increases over the study period (ASIR: EAPC = 0.96 (0.9-1.02), ASPR: EAPC = 1.5 (1.44-1.55)). However, a decline in ASIR and ASPR was observed in 2020 and 2021. Males consistently showed higher EO-CRC indicators compared to females. Furthermore, projections indicated that deaths and DALYs cases are likely to fluctuate but generally increase by 2050, reaching 85,602 and 4,283,093, respectively. Conclusions: The global impact of EO-CRC has increased significantly from 1990 to 2021, revealing notable variations across SDI regions, countries, age groups, and sexes. Besides, deaths and DALYs are predicted to rise by 2050. These results highlight the importance of implementing measures to address the growing burden of EOCRC globally.

Fucosyltransferase 2 (FUT2) is an enzyme that adds fucose to proteins or lipids via α-1,2-fucosylation in the intestinal mucosa. While FUT2 deficiency is linked to increased susceptibility to inflammatory bowel disease (IBD), its role in colorectal cancer (CRC) is unclear, and the molecular mechanisms involved remain largely unknown. We established an azoxymethane (AOM) and dextran sulfate sodium (DSS) model to induce CRC. FUT2 expression was assessed in human CRC tissues, AOM/DSS-induced mouse models, and CRC cell lines using qRT-PCR, western blotting, and UEA-I staining. FUT2 knockout (FUT2△IEC) mice were treated with AOM/DSS, and FUT2-overexpressing CRC cells were created to evaluate the effects of FUT2 on apoptosis in both in vitro and in vivo settings through Western blot analyses and functional assays. N-glycoproteomics, UEA-I chromatography, and co-immunoprecipitation were utilized to identify regulatory mechanisms and target fucosylated proteins. FUT2 expression and α-1,2-fucosylation were significantly decreased in CRC. FUT2 deficiency worsened AOM/DSS-induced CRC and reduced tumor apoptosis, while FUT2 overexpression induced apoptosis and inhibited proliferation in CRC cells and xenografts. Mechanistically, FUT2 appears to suppress autophagy by impairing lysosomal function and directly targeting and fucosylating LAMP1, contributing to lysosomal dysfunction. Our study reveals a fucosylation-dependent antitumor mechanism of FUT2 in CRC, suggesting potential therapeutic strategies for CRC treatment.

AIMS:Understanding the global burden of disease attributable to high body mass index (BMI) is essential for informing public health strategies and interventions to mitigate the impact of obesity-related conditions. METHODS AND RESULTS:The global deaths and disability-adjusted life years (DALYs) caused by high BMI were examined based on age, sex, year, and geographical location as well as socio-demographic index. Globally in 2021, the deaths and DALYs attributable to high BMI have risen 2.54-fold and 2.68-fold for both sexes when compared to 1990. The number of global deaths linked to high BMI has risen for females from 828 147.16 (95% uncertainty interval [UI] 407 103.20-1 302 480.38) in 1990 to 2 013 089.03 (95% UI 979 000.37-3 076 044.71) in 2021, and for males from 631 386.07 (95% UI 315 452.97-988 213.75) in 1990 to 1 695 974.32 (95% UI 861 972.49-2 635 343.31) in 2021. The number of DALYs related to high BMI worldwide has risen for females from 26 097 463.34 (95% UI 11 042 501.33-42 206 794.07) in 1990 to 67 213 785.86 (95% UI 28 417 735.35-105 552 568.89) in 2021, and for males from 21 944 645.99 (95% UI 10 106 039.21-35 110 379.12) in 1990 to 61 306 297.23 (95% UI 27 566 755.49-94 931 874.52) in 2021. However, the age-standardized rate of high-BMI-related deaths for females increased by 4.06% and 15.06% for males between 1990 and 2021, while the age-standardized rate of high-BMI-related DALYs increased by 21.60% for females and 31.22% for males. Across the 21 Global Burden of Disease regions, in 2021, the highest age-standardized rates of high-BMI-related deaths and DALYs were observed in Southern Sub-Saharan Africa (125.12, 95% UI 71.21-183.13) and Oceania (3712.97, 95% UI 1666.49-5765.84), respectively. CONCLUSION:Efforts to promote healthy weight management, lifestyle modifications, and early intervention for obesity-related health complications are essential in reducing the morbidity and mortality associated with obesity and improving overall population health.

Until now, few researches have comprehensive explored the role of immune checkpoints (ICIs) and tumor microenvironment (TME) in gastric cancer (GC) patients based on the genomic data. RNA-sequence data and clinical information were obtained from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) database, GSE84437 and GSE84433. Univariate Cox analysis identified 60 ICIs with prognostic values, and these genes were then subjected to NMF cluster analysis and the GC samples (n = 804) were classified into two distinct subtypes (Cluster 1: n = 583; Cluster 2: n = 221). The Kaplan-Meier curves for OS analysis indicated that C1 predicted a poorer prognosis. The C2 subtype illustrated a relatively better prognosis and characteristics of "hot tumors," including high immune score, overexpression of immune checkpoint molecules, and enriched tumorinfiltrated immune cells, indicating that the NMF clustering in GC was robust and stable. Regarding the patient's heterogeneity, an ICI-score was constructed to quantify the ICI patterns in individual patients. Moreover, the study found that the low ICI-score group contained mostly MSI-low events, and the high ICI-score group contained predominantly MSI-high events. In addition, the ICI-score groups had good responsiveness to CTLA4 and PD-1 based on The Cancer Immunome Atlas (TCIA) database. Our research firstly constructed ICIs signature, as well as identified some hub genes in GC patients.

Helicobacter pylori (H. pylori) infection is critical in the development and occurrence of gastric cancer. H. pylori secretes gamma-glutamyl transferase (GGT), which affects energy metabolism and histone methylation in mesenchymal stem cells. However, its effect on human gastric epithelial cells remains unclear. This study aimed to investigate the effects of GGT on energy metabolism and histone methylation in gastric epithelial cells and determine its role in the development and progression of H. pylori-induced gastric cancer. A GGT knockout H. pylori strain and mouse gastric cancer model were constructed, and alpha-ketoglutarate (α-KG) was added. The underlying mechanism was investigated using proteomics, immunohistochemistry, Western blotting, and other experimental assays. H. pylori can colonize the host’s stomach and destroy the gastric epithelium. GGT secreted by H. pylori decreased the concentration of glutamine in the stomach and increased H3K9me3 and H3K27me3 expression, which promoted the proliferation and migration of gastric epithelial cells. Additionally, α-KG reversed this effect. GGT increased the tumorigenic ability of nude mice. GGT, secreted by H. pylori, promoted the expression of ribosomal protein L15 (RPL15), while GGT knockout and supplementation with α-KG and trimethylation inhibitors reduced RPL15 expression and Wnt signaling pathway expression. H. pylori secreted GGT decreased the expression of glutamine and α-KG in gastric epithelial cells, increased the expression of histones H3K9me3 and H3K27me3, and activated the Wnt signaling pathway through RPL15 expression, ultimately changing the biological characteristics of the gastric epithelium and promoting the occurrence of gastric cancer. Altered energy metabolism and histone hypermethylation are important factors involved in this process.

Background Liver cancer is a significant fi cant contributor to the global disease burden, of which hepatoblastomas are the most common liver tumors in children, with 90% of cases occurring within the fi rst 5 years of life. It is important for pediatricians and subspecialists in pediatric gastroenterology and hepatology to have knowledge of the epidemiology and incidence trends of pediatric hepatic cancer, despite its rarity. In the present study, we fi rst provide estimates of the incidence and mortality burden of hepatoblastoma and liver cancer from 2000 to 2021 in the childhood and adolescence. Methods Liver cancer burden and its attributable risk factors were estimated using data from the Global Burden of Disease Study (GBD) 2021. Percentage change was estimated to show the trend of liver cancer estimates from 2000 to 2021. The age-standardized rate (ASR) and estimated annual percentage change (EAPC) were utilized for measuring hepatoblastomas incidence and deaths rate trends. In accordance with the GBD framework, 95% uncertainty intervals (UIs) for all estimates by averaging the data from 1000 draws, with the lower and upper bounds of the 95% UIs. Findings Globally, from 2000 to 2021 in the age 5-19 - 19 years group, the incidence cases and deaths cases due to liver cancer decreased from 2449.2 (95% UI: 2235.9-2689.8) - 2689.8) to 1692.9 (95% UI: 1482.0-1992.5) - 1992.5) and 2248.5 (95% UI: 2053.7-2474.9) - 2474.9) to 1516.6 (95% UI: 1322.1-1797.9), - 1797.9), respectively. Meanwhile, from 2000 to 2021 in the age 20-24 - 24 years group, the incidence cases and deaths cases due to liver cancer decreased from 1453.5 (95% UI: 1327.8-1609.4) - 1609.4) to 1285.1 (95% UI: 1159.2-1447.2) - 1447.2) and 1432.3 (95% UI: 1307.6-1585.7) - 1585.7) to 1195.5 (95% UI: 1066.1-1355.2), - 1355.2), respectively. In addition, the prevalence of liver cancer decreased from 41.9% (95% UI: 18.7%-64.7%) - 64.7%) to 26.4% (95% UI: 14.2%-39.1%) - 39.1%) in the age 5-19 - 19 years group, and 46.6% (95% UI: 42.8%-51.5%) - 51.5%) to 36.5% (95% UI: 33.1%-40.9%) - 40.9%) in the age 20-24 - 24 years. From 2000 to 2021, in the age group of 5-19 - 19 years, the proportion of liver cancer incidence due to hepatitis B has decreased from 42.2% to 37.9%, while the proportion due to hepatitis C has increased from 1.1% to 1.6%. Additionally, there has been an increase in the proportion of NASH-induced liver cancer incidence from 5.2% to 9.4%, and alcohol use induced liver cancer incidence has also increased from 0.5% to 0.7% over the same period. Globally, from 2000 to 2021, the incidence cases and deaths cases due to hepatoblastoma decreased from 6131.8 (95% UI: 5234.8-6961.9) - 6961.9) to 4045.6 (95% UI: 3250-4995.8) - 4995.8) and 4059.2 (95% UI: 3494.5-4621.2) - 4621.2) to 2416 (95% UI: 1940.2-3022.5), - 3022.5), respectively. There was some variation in age-related sex-specific fi c patterns, the highest number of hepatoblastoma incidence cases occurred in children between 2 and 4 years old and females in the age range of 12 months to 9 years had a higher number of new cases. Importantly, the incidence of hepatoblastoma was started to increase sharply after the age of 1 month. Interpretation The results of the present study are significant fi cant for liver health policy and practice in childhood and adolescence. Differentiated intervention and outreach strategies based on age and gender would be necessary to reduce the impact of liver cancer. Early screening and interventions for hepatoblastoma is important especially in the population of under 9 years old.

Abstract Background The burden of gastric cancer (GC) should be further clarified worldwide, and helped us to understand the current situation of GC. Methods In the present study, we estimated disability-adjusted life-years (DALYs) and mortality rates attributable to several major GC risk factors, including smoking, dietary risk, and behavioral risk. In addition, we evaluated the incidence rate and trends of incidence-based mortality (IBM) due to GC in the United States (US) during 1992–2018. Results Globally, GC incidences increased from 883,395 in 1990 to 1,269,805 in 2019 while GC-associated mortality increased from 788,316 in 1990 to 957,185 in 2019. In 2019, the age-standardized rate (ASR) of GC exhibited variations around the world, with Mongolia having the highest observed ASR (43.7 per 100,000), followed by Bolivia (34 per 100,000) and China (30.6 per 100,000). A negative association was found among estimated annual percentage change (EAPC) and ASR (age-standardized incidence rate (ASIR): r = − 0.28, p < 0.001; age-standardized death rate (ASDR): r = − 0.19, p = 0.005). There were 74,966 incidences of GC and 69,374 GC-related deaths recorded between 1992 and 2018. The significant decrease in GC incidences as well as decreasing trends in IBM of GC were first detected in 1994. The GC IBM significantly increased at a rate of 35%/y from 1992 to 1994 (95% CI 21.2% to 50.4%/y), and then begun to decrease at a rate of − 1.4%/y from 1994 to 2018 (95% CI − 1.6% to − 1.2%/y). Conclusion These findings mirror the global disease burden of GC and are important for development of targeted prevention strategies.

Background: Recent studies have shown that young patients with gastric cancer are at a more advanced stage and have poor survival, but the cause is still unclear. The prognosis of gastric cancer is closely related to LNM, but the relationship between age and LNM in early gastric cancer (EGC) is currently unclear. Therefore, we aimed to study the relationship between age and the risk of LNM in EGC. Materials and Methods: We screened out patients with EGC who underwent surgery from the SEER research database from 1975 to 2016, and retrospectively analyzed the proportion of LNM in different age groups. We grouped age into 18-39, 40-49, 50-59, 60-69, 70-79, and ≥ 80 years old, and used univariate analysis and multivariate logistic regression to analyze the correlation between age and LNM. Results: We included 9231 patients with EGC, with LNM rates of 20.3%, 23.3%, 21.0%, 19.8%, 18.1%, and 13.2% in the age groups of 18-39 years old (2.3%), 40-49 (6.1%), 50-59 years old (15.7%), 60-69 years old (24.8%), 70-79 years old (27.2%) and ≥80 years old (23.9%), respectively. We found that when older than 39 years old, the risk of LNM and postoperative survival time of EGC patients decrease (p<0.001). Multivariate analysis results showed that age, tumor size, the number of retrieved lymph nodes (rN), tumor grade, and tumor location were related to LNM. Conclusions: This study found that age in patients with EGC was inversely related to the risk of LNM, and positively correlated with postoperative survival. For older patients with EGC, endoscopic treatment is more appropriate. For young patients with EGC, LNM should be considered when choosing endoscopic treatment.

Background Liver cancer is a significant contributor to the global disease burden, of which hepatoblastomas are the most common liver tumors in children, with 90% of cases occurring within the first 5 years of life. It is important for pediatricians and subspecialists in pediatric gastroenterology and hepatology to have knowledge of the epidemiology and incidence trends of pediatric hepatic cancer, despite its rarity. In the present study, we first provide estimates of the incidence and mortality burden of hepatoblastoma and liver cancer from 2000 to 2021 in the childhood and adolescence. Methods Liver cancer burden and its attributable risk factors were estimated using data from the Global Burden of Disease Study (GBD) 2021. Percentage change was estimated to show the trend of liver cancer estimates from 2000 to 2021. The age-standardized rate (ASR) and estimated annual percentage change (EAPC) were utilized for measuring hepatoblastomas incidence and deaths rate trends. In accordance with the GBD framework, 95% uncertainty intervals (UIs) for all estimates by averaging the data from 1000 draws, with the lower and upper bounds of the 95% UIs. Findings Globally, from 2000 to 2021 in the age 5–19 years group, the incidence cases and deaths cases due to liver cancer decreased from 2449.2 (95% UI: 2235.9–2689.8) to 1692.9 (95% UI: 1482.0–1992.5) and 2248.5 (95% UI: 2053.7–2474.9) to 1516.6 (95% UI: 1322.1–1797.9), respectively. Meanwhile, from 2000 to 2021 in the age 20–24 years group, the incidence cases and deaths cases due to liver cancer decreased from 1453.5 (95% UI: 1327.8–1609.4) to 1285.1 (95% UI: 1159.2–1447.2) and 1432.3 (95% UI: 1307.6–1585.7) to 1195.5 (95% UI: 1066.1–1355.2), respectively. In addition, the prevalence of liver cancer decreased from 41.9% (95% UI: 18.7%–64.7%) to 26.4% (95% UI: 14.2%–39.1%) in the age 5–19 years group, and 46.6% (95% UI: 42.8%–51.5%) to 36.5% (95% UI: 33.1%–40.9%) in the age 20–24 years. From 2000 to 2021, in the age group of 5–19 years, the proportion of liver cancer incidence due to hepatitis B has decreased from 42.2% to 37.9%, while the proportion due to hepatitis C has increased from 1.1% to 1.6%. Additionally, there has been an increase in the proportion of NASH-induced liver cancer incidence from 5.2% to 9.4%, and alcohol use induced liver cancer incidence has also increased from 0.5% to 0.7% over the same period. Globally, from 2000 to 2021, the incidence cases and deaths cases due to hepatoblastoma decreased from 6131.8 (95% UI: 5234.8–6961.9) to 4045.6 (95% UI: 3250–4995.8) and 4059.2 (95% UI: 3494.5–4621.2) to 2416 (95% UI: 1940.2–3022.5), respectively. There was some variation in age-related sex-specific patterns, the highest number of hepatoblastoma incidence cases occurred in children between 2 and 4 years old and females in the age range of 12 months to 9 years had a higher number of new cases. Importantly, the incidence of hepatoblastoma was started to increase sharply after the age of 1 month. Interpretation The results of the present study are significant for liver health policy and practice in childhood and adolescence. Differentiated intervention and outreach strategies based on age and gender would be necessary to reduce the impact of liver cancer. Early screening and interventions for hepatoblastoma is important especially in the population of under 9 years old. Funding This study was supported by the National Key R&D Program of China (grant numbers 2023YFC2307000), National Natural Science Foundation of China [grant numbers 82170571 and 81974068], China Postdoctoral Science Foundation (grant numbers 2023M741283).

Background: Over the last few decades, the annual global incidence of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) has steadily increased. Because of the complex and inconsistent treatment of GEP-NETs, the prognosis of patients with GEP-NETs is still difficult to assess. The study aimed to construct and validate the nomograms included treatment data for prediction overall survival (OS) in GEP-NETs patients. Methods: GEP-NETs patients determined from the Surveillance, Epidemiology, and End Results (SEER)-13 registry database (1992–2018) and with additional treatment data from the SEER-18 registry database (1975–2016). In order to select independent prognostic factors that contribute significantly to patient survival and can be included in the nomogram, multivariate Cox regression analysis was performed using the minimum value of Akaike information criterion (AIC) and we analyzed the relationship of variables with OS by calculating hazard ratios (HRs) and 95% CIs. In addition, we also comprehensively compared the nomogram using to predict OS with the current 7th American Joint Committee on Cancer (AJCC) staging system. Results: From 2004 to 2015, a total of 42 662 patients at diagnosis years with GEP-NETs were determined from the SEER database. The results indicated that the increasing incidence of GEP-NETs per year and the highest incidence is in patients aged 50–54. After removing cases lacking adequate clinicopathologic characteristics, the remaining eligible patients (n=7564) were randomly divided into training (3782 patients) and testing sets (3782 patients). In the univariate analysis, sex, age, race, tumour location, SEER historic stage, pathology type, TNM, stage, surgery, radiation, chemotherapy, and CS tumour size were found to be significantly related to OS. Ultimately, the key factors for predicting OS were determined, involving sex, age, race, tumour location, SEER historic stage, M, N, grade, surgery, radiation, and chemotherapy. For internal validation, the C-index of the nomogram used to estimate OS in the training set was 0.816 (0.804–0.828). For external validation, the concordance index (C-index) of the nomogram used to predict OS was 0.822 (0.812–0.832). In the training and testing sets, our nomogram produced minimum AIC values and C-index of OS compared with AJCC stage. Decision curve analysis (DCA) indicated that the nomogram was better than the AJCC staging system because more clinical net benefits were obtained within a wider threshold probability range. Conclusion: A nomogram combined treatment data may be better discrimination in predicting overall survival than AJCC staging system. The authors highly recommend to use their nomogram to evaluate individual risks based on different clinical features of GEP-NETs, which can improve the diagnosis and treatment outcomes of GEP-NETs patients and improve their quality of life.

Background It has previously been observed that the prognostic value of tumor size varied according to different stages patients enrolled in gastric cancer. We aimed to investigate the influence of T stage on the prognostic and predicting value of tumor size. Material and methods A total of 13,585 patients with stage I–III gastric cancer were selected from the Surveillance, Epidemiology, and End Results Program (SEER) database. Univariate and multivariate cox regression analysis stratified by T stage were performed. C-index and time-dependent receiver operating characteristic curve (ROC) curve were applied to assess discrimination ability of tumor size and other factors. Nomograms were constructed to further assess the performance of tumor size in a specific model. Calibration ability, discrimination ability, reclassification ability and clinical benefits were executed to judge the performance of models. Results Stratified analyses according to T stage illustrated that with the increase of T stage, the effect of tumor size on overall survival (OS) and cancer-specific survival (CSS) significantly decreased. Moreover, tumor size showed superior discrimination ability in T1 gastric cancer, outperformed other prognostic factors in predicting both CSS (C-index: 0.666, AUC: 0.687) and OS (C-index: 0.635, AUC: 0.660). The cox regression model included tumor size showed better performance than the model excluded tumor size in every aspect. Conclusion T stage had a negative impact on the predicting value of tumor size. Tumor size showed significant prognostic value in T1 gastric cancer, which may be effective in clinical practice.

Our previous study showed that fucosyltransferase 2 (Fut2) deficiency is closely related to colitis. Colitis increases the risk for the development of colorectal cancer (CRC). This study aimed to investigate the effect and underlying mechanism of action of Fut2 in CRC. Intestinal epithelium-specific Fut2 knockout (Fut2△IEC) mice were used in this study. CRC was induced using azoxymethane (AOM) and dextran sulfate sodium (DSS). Immunofluorescence was used to examine the fucosylation levels. Proteomics and N-glycoproteomics analyses, Ulex Europaeus Agglutinin I (UEA-I) affinity chromatography, immunoprecipitation, and rescue assay were used to investigate the mechanism of Fut2 in CRC. The expression of Fut2 and α-1,2-fucosylation was lower in colorectal tumor tissues than in the adjacent normal tissues of AOM/DSS-induced CRC mice. More colorectal tumors were detected in Fut2△IEC mice than in control mice, and significant downregulation of melanoma cell adhesion molecule (MCAM) fucosylation was detected in the colorectal tumor tissues of Fut2△IEC mice. Overexpression of Fut2 inhibited cell proliferation, invasion and tumor metastasis in vivo and in vitro in SW480 and HCT116 cells. Moreover, fucosylation of MCAM may be a mediator of Fut2 in CRC. Peracetylated 2-F-Fuc, a fucosyltransferase inhibitor, repressed fucosylation modification of MCAM and reversed the inhibitory effects of Fut2 overexpression on SW480 cell proliferation, migration, and invasion. Our results indicate that Fut2 deficiency in the intestinal epithelium promotes CRC by downregulating the fucosylation of MCAM. The regulation of fucosylation may be an potential therapy for CRC, especially in patients with Fut2 gene defects.