ObjectiveTo systematically summarize the dynamic changes, mechanisms of action, and potential clinical translational value of neutrophils during gastric carcinogenesis and progression, thereby providing a reference for understanding the gastric cancer immune microenvironment and exploring therapeutic interventions. MethodRecent basic and clinical studies and relevant reviews were summarized and analyzed, with a focus on the Correa cascade of gastric carcinogenesis, neutrophil functional plasticity, and targeted interventions. ResultsThe Correa cascade of gastric carcinogenesis is typically accompanied by dynamic remodeling of the inflammatory microenvironment and immune cell composition. Neutrophils exhibit characteristic functional changes across the cascade. During chronic non-atrophic gastritis, they predominantly display an inflammatory phenotype and exert dual effects involving antimicrobial defense and mucosal injury. During atrophic gastritis, intestinal metaplasia, and dysplasia, neutrophil infiltration persists, although their functional states remain unclear. At the gastric cancer stage, neutrophils evolve into highly heterogeneous tumor-associated neutrophils (TANs) and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), which contribute to tumor progression, immune evasion, and metastasis through multiple mechanisms involving chemokine axes, immunosuppressive molecules, extracellular matrix remodeling, and neutrophil extracellular traps (NETs). The principal neutrophil-targeted strategies include blocking neutrophil recruitment to the tumor microenvironment, modulating N1/N2 polarization, interfering with NETs formation and function, and alleviating PMN-MDSC-mediated myeloid immunosuppression. These strategies have shown potential to enhance antitumor immunity and improve the efficacy of immune checkpoint inhibitors in preclinical models of gastric cancer; however, no therapy directed solely at neutrophils has yet been approved for clinical use in gastric cancer. ConclusionThe dynamic evolution and marked functional heterogeneity of neutrophils in gastric cancer provide potential targets for combination immunotherapy; nevertheless, clinical translation demands precise subtyping of neutrophils, selective intervention, and prospective validation anchored in the Correa cascade.
Objective To investigate the mechanism of bone morphogenetic protein-4 (BMP4) in promoting the recovery of small intestinal mucosal barrier function during the recovery period of small intestine ischemia-reperfusion (I/R) injury. Methods Twenty-eight C57BL/6J male mice aged 6–8 weeks were randomly selected and assigned to small intestine I/R group (n=24) and sham operation (SO) group (n=4) by random number table method. Small intestine I/R injury models of 24 mice were established, then 4 mice were randomly selected at 6, 12, 24 and 48 h after I/R established modeling and killed to observe the morphological changes of small intestinal mucosa and detect the expression of BMP4 mRNA in the jejunal epithelial cells, the other 8 mice were allocated for the experimental observation at the recovery period of small intestine I/R injury (24 h after I/R was selected as the observation time point of recovery period of small intestine I/R injury according to the pre-experimental results). Twelve mice were randomly divided into I/R-24 h-BMP4 group (recombinant human BMP4 protein was injected intraperitoneally), I/R-24 h-NS (normal saline) group (NS was injected intraperitoneally), and I/R-24 h-blank group (did nothing), 4 mice in each group. Then the small intestinal transmembrane electrical impedance (TER) was measured by Ussing chamber. The expressions of BMP4 protein and tight junction proteins (occludin and ZO-1), Notch signaling pathway proteins (Notch1 and Jagged1), and Smad6 protein were detected by Western blot. Results At 24 h after I/R injury, the injuries of villous epithelium, edema, and a small part of villi were alleviated. The BMP4 mRNA expressions at 6, 12, 24 and 48 h after I/R injury in the small intestinal epithelial cells were increased as compared with the SO group. Compared with the I/R-24 h-NS group and the I/R-24 h-blank group, the TER was increased, and the expression levels of occludin, ZO-1, p-Smad6, Notch1, Jagged1 were increased in the I/R-24 h-BMP4 group. Conclusion From the preliminary results of this study, during recovery period of small intestine I/R injury, the expression of BMP4 in small intestinal epithelial cells is increased, permeability of jejunal mucosal barrier is increased, which might promote the recovery of small intestinal mucosal barrier function by activating the Notch signaling pathway (Notch1 and Jagged1), Smad classic signaling pathway, and promoting the increase of tight junction protein expression (occludin and ZO-1).
In order to meet the requirements in the cooperation and competition experiments for an individual patient in clinical application, two human interactive behavior key-press models based on hidden Markov model (HMM) were proposed. To validate the cooperative and competitive models, a verification experimental task was designed and the data were collected. The correlation of the score and subjects’ participation level has been used to analyze the reasonability verification. Behavior verification was conducted by comparing the statistical difference in response time for subjects between human-human and human-computer experiment. In order to verify the physiological validity of the models, we have utilized the coherence analysis to analyze the deep information of prefrontal brain area. Reasonability verification shows that the correlation coefficient for the training data and the testing data is 0.883 1 and 0.578 6 respectively based on cooperation model, and 0.813 1 and 0.617 8 respectively based on the competition model. The behavioral verification result shows that the cooperation and competition models have an accuracy of 71.43% respectively. The results of physiological validity show that the deep information of prefrontal brain area could been extracted based on the cooperation and competition models, and reveal the consistency of coherence between the double key-press cooperative and competitive experiments, respectively. Above all, the high consistency is obtained between the cooperatio/competition model and the double key-press experiment by the behavioral and physiological evaluation results. Consequently, the cooperation and competition models could be applied to clinical trials.
Under the background of the global COVID-19 pandemic, electronic informed consent (eConsent) utilizes technology to provide a new method and idea for clinical trials. It has the advantages of convenience and efficiency, which greatly improves the efficiency of clinical trials. At present, this concept has not been put forward in China while it has been clarified clearly abroad, and some countries have launched a variety of trials and formulated various regulations to further standardize the eConsent. Based on the current situation of eConsent in China, this study analyzed the design and implementation of eConsent, summarized relevant domestic and foreign laws and regulations, and proposed opportunities and challenges for electronic informed consent as well as the relevant preparations for the implementation of this technology in China.