Previous studies have shown that gastrointestinal microbiome is associated with the development of esophageal cancer, but the relationship and molecular mechanism between esophageal microbiota and the early development of esophageal cancer remain unclear. Here, we found that Lactobacillus, Escherichia‐Shigella, Rikenellaceae‐RC9‐gut‐group, Morganella, and Fusobacterium were more abundant in early‐stage esophageal cancer (EEC) tissues compared with normal esophageal tissues. The abundance of bacteria such as Prevotella, Fusobacterium, Porphyromonas, Actinobacillus, and Neisseria in advanced esophageal cancer (AEC) was higher than that in EEC. Then, we further verified that Fusobacterium nucleatum (Fn) was enriched in EEC tissues and that its abundance increased with the progression of esophageal cancer by FISH and RT‐PCR. Next, we demonstrated that Fn promoted the proliferation of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. Finally, we confirmed that Fn promoted ESCC proliferation by upregulating the expression of interleukin (IL)‐32/proteinase 3 (PRTN3) and then activating the PI3K/AKT signaling pathway. In conclusion, Fn promoted the early development of ESCC by upregulating the expression of IL‐32/PRTN3 and thereby activating the PI3K/AKT signaling pathway. A better understanding of the molecular mechanism of Fn in early esophageal cancer may contribute to the development of early screening markers to diagnose ESCC and provide new targets for treatment.

Approximately 50% of the patients with ulcerative colitis (UC) are primarily nonresponsive to anti‐tumor necrosis factor (TNF) therapy or lose their responsiveness over time. The gut microbiota plays an important role in the resistance of UC to anti‐TNF therapy; however, the underlying mechanism remains unknown. Here, it is found that the transplantation of gut fecal microbiota from patients with UC alters the diversity of the gut microbiota in dextran sulfate sodium‐induced colitis mice and may affect the therapeutic responsiveness of mice to infliximab. Furthermore, the abundances of Romboutsia and Fusobacterium increase in the tissues of patients with UC who do not respond to anti‐TNF therapy. Differentially abundant metabolites are mainly enriched in nicotinate and nicotinamide metabolism in NCM460 cells after Fusobacterium nucleatum infection. Mechanistically, F. nucleatum promotes the nicotinamide adenine dinucleotide (NAD⁺) salvage pathway by upregulating NAMPT expression, which subsequently leads to the activation of the p38 mitogen‐activated protein kinase (MAPK) signaling pathway and promotes the secretion of inflammatory factors, ultimately inhibiting the therapeutic response to anti‐TNF drugs. These findings demonstrate that the gut microbiota can influence the response to anti‐TNF therapy in patients with UC and highlight the therapeutic potential of targeting F. nucleatum and its associated pathways for preventing and treating drug resistance in UC.

Background: Timely diagnosis of ischemic stroke (IS) in the acute phase is extremely vital to achieve proper treatment and good prognosis. In this study, we developed a novel prediction model based on the easily obtained information at initial inspection to assist in the early identification of IS.Methods: A total of 627 patients with IS and other intracranial hemorrhagic diseases from March 2017 to June 2018 were retrospectively enrolled in the derivation cohort. Based on their demographic information and initial laboratory examination results, the prediction model was constructed. The least absolute shrinkage and selection operator algorithm was used to select the important variables to form a laboratory panel. Combined with the demographic variables, multivariate logistic regression was performed for modeling, and the model was encapsulated within a visual and operable smartphone application. The performance of the model was evaluated on an independent validation cohort, formed by 304 prospectively enrolled patients from June 2018 to May 2019, by means of the area under the curve (AUC) and calibration.Results: The prediction model showed good discrimination (AUC = 0.916, cut-off = 0.577), calibration, and clinical availability. The performance was reconfirmed in the more complex emergency department. It was encapsulated as the Stroke Diagnosis Aid app for smartphones. The user can obtain the identification result by entering the values of the variables in the graphical user interface of the application.Conclusion: The prediction model based on laboratory and demographic variables could serve as a favorable supplementary tool to facilitate complex, time-critical acute stroke identification.

Colitis-associated cancer (CAC) is a serious complication of inflammatory bowel disease (IBD). Recent evidence has indicated that Fusobacterium nucleatum (F. nucleatum) may promote intestinal inflammation and carcinogenesis. However, the effects of F. nucleatum on the cancerous transformation of IBD, along with its underlying mechanisms, remain poorly understood. Our findings revealed that F. nucleatum was enriched in 57.1% of CAC tissues, which was higher than that in ulcerative colitis (UC, 53.0%), Crohn’s disease (CD, 55.6%), and colorectal cancer (CRC, 53.7%) tissues. Furthermore, we demonstrated that F. nucleatum modulated nicotinamide (NAM) metabolism to promote the proliferation of CAC. Mechanistically, F. nucleatum upregulated NNMT to increase PARP1 expression, thereby activating MAPK signalling pathway. These findings provide insight into F. nucleatum-induced metabolic dysregulation and inflammatory cancer development and may propose novel intervention strategies for the prevention and treatment of microbial-associated inflammatory carcinogenesis.