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.

Accumulating evidence links m⁶A modification with immune infiltration. However, the correlation and mechanism by which m⁶A modification promotes intestinal immune infiltration in inflammatory bowel disease (IBD) is unknown. Here, genomic information from IBD tissues was integrated to evaluate disease-related m⁶A modification, and the correlation between the m⁶A modification pattern and the immune microenvironment in the intestinal mucosa was explored. Next, we identified hub genes from the key modules of the m⁶Acluster and analyzed the correlation among the hub genes, immune infiltration, and therapy. We found that IGF2BP1 and IGF2BP2 expression was decreased in Crohn’s disease (CD) tissues and that IGF2BP2 was decreased in ulcerative colitis (UC) tissues compared with normal tissues (P < 0.05). m⁶Acluster2, containing higher expressions of IL15, IL16, and IL18, was enriched in M0 macrophage, M1 macrophage, native B cells, memory B cells, and m⁶Acluster1 with high expression of IL8 and was enriched in resting dendritic and plasma cells (P < 0.05). Furthermore, we reveal that expression of m⁶A phenotype-related hub genes (i.e., NUP37, SNRPG, H2AFZ) was increased with a high abundance of M1 macrophages, M0 macrophages, and naive B cells in IBD (P < 0.01). Immune checkpoint expression in the genecluster1 with higher expression of hub genes was increased. The anti-TNF therapeutic response of patients in genecluster1 was more significant, and the therapeutic effect of CD was better than that of UC. These findings indicate that m⁶A modification may affect immune infiltration and therapeutic response in IBD. Assessing the expression of m⁶A phenotype-related hub genes might guide the choice of IBD drugs and improve the prediction of therapeutic response to anti-TNF therapy.

Purpose: The emergence of resistant strains has greatly reduced the eradication rate of H. pylori (HP) in conventional bismuth-containing quadruple therapy. Meanwhile, the new 7-day dual therapy with vonoprazan (VPZ) and amoxicillin (AMO) failed to achieve the expected therapeutic effect in China. Patients and Methods: A total of 256 untreated HP-infected patients are included in this non-inferiority clinical trial. The patients were randomly divided into three groups: 14-day dual therapy group (VPZ 20mg b.i.d + AMO 750mg t.i.d for 14 days, VA14), 14-day modified triple therapy group (VA14 + Jinghua Weikang Capsule 160mg t.i.d, VAC), and conventional bismuth-containing quadruple therapy group for 14 days (BCQ). Eradication rates, drug-related adverse events (AEs), patient compliance, and drug costs were compared among the three groups. Results: The eradication rates in the BCQ, VA14, and VAC were 78.67, 77.33%, and 86.49% by intention-to-treat analysis, respectively, and 96.72%, 90.63%, and 92.75% by pre-protocol or modified intention-to-treat analysis, respectively. VA14 therapy indicated a non-inferiority eradication rate and advanced safety and economics to BCQ therapy. JWC further improved the eradication rate and reduced the incidence of AEs. Conclusion: A modified 14-day dual therapy with VPZ and AMO provides satisfied efficacy as the first-line treatment for HP infection in China.

The tetraspanins (TSPANs) are a family of four-transmembrane proteins with 33 members in mammals. They are variably expressed on the cell surface, various intracellular organelles and vesicles in nearly all cell types. Different from the majority of cell membrane proteins, TSPANs do not have natural ligands. TSPANs typically organize laterally with other membrane proteins to form tetraspanin-enriched microdomains (TEMs) to influence cell adhesion, migration, invasion, survival and induce downstream signaling. Emerging evidence shows that TSPANs can regulate not only cancer cell growth, metastasis, stemness, drug resistance, but also biogenesis of extracellular vesicles (exosomes and migrasomes), and immunomicroenvironment. This review summarizes recent studies that have shown the versatile function of TSPANs in cancer development and progression, or the molecular mechanism of TSPANs. These findings support the potential of TSPANs as novel therapeutic targets against cancer.