Concrete epidemiological evidence has suggested the mutually-contributing effect respectively between nonalcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (T2DM), and periodontitis (PD); however, their shared crosstalk mechanism remains an open issue. The NAFLD, PD, and T2DM-related datasets were obtained from the NCBI GEO repository. Their common differentially expressed genes (DEGs) were identified and the functional enrichment analysis performed by the DAVID platform determined relevant biological processes and pathways. Then, the STRING database established a PPI network of such DEGs and topological analysis through Cytoscape 3.7.1 software along with the machine-learning analysis by the least absolute shrinkage and selection operator (LASSO) algorithm screened out hub characteristic genes. Their efficacy was validated by external datasets using the receiver operating characteristic (ROC) curve, and gene expression and location of the most robust one was determined using single-cell sequencing and immunohistochemical staining. Finally, the promising drugs were predicted through the CTD database, and the CB-DOCK 2 and Pymol platform mimicked molecular docking. Intersection of differentially expressed genes from three datasets identified 25 shared DEGs of the three diseases, which were enriched in MHC II-mediated antigen presenting process. PPI network and LASSO machine-learning analysis determined 4 feature genes, of which the MS4A6A gene mainly expressed by macrophages was the hub gene and key immune cell type. Molecular docking simulation chosen fenretinide as the most promising medicant for MS4A6A⁺ macrophages. MS4A6A⁺ macrophages were suggested to be important immune-related mediators in the progression of NAFLD, PD, and T2DM pathologies.

The Rome IV criteria for functional dyspepsia (FD) has strict requirements for symptom frequency and onset duration, making it difficult for patients to meet these criteria in clinical practice. This study aimed to investigate the impact of relaxing the Rome IV criteria on the diagnosis and symptom pattern of FD. A cross-sectional, multi-center study was conducted involving 2935 consecutive broadly defined FD patients without positive findings on upper gastrointestinal endoscopy or routine examinations. Questionnaires were used to collect demographic and upper gastrointestinal symptom data. Symptom pattern was compared between Rome IV criteria defined FD patients and those defined by relaxed Rome IV criteria. Only 22.2% of broadly defined FD patients rigorously fulfilled Rome IV criteria. No significant difference was found for proportion of patients with dyspeptic symptoms, dysmotility-like symptoms, reflux-like symptoms, as well as severity and onset frequency of dyspeptic symptoms (all P > 0.05), between patients who didn’t fulfill Rome IV criteria for FD solely due to a duration of 3–6 months and Rome IV criteria defined FD patients. Patients with broadly defined postprandial distress syndrome (PDS) who didn’t fulfill Rome IV criteria solely due to a symptom frequency of 1–2 days per week had significantly lower symptom severity (P < 0.001), but similar postprandial symptom characteristics compared to those defined by the Rome IV criteria. A symptom duration criterion of 3 months may be sufficient for diagnosing FD. Reducing the symptom onset frequency to no less than 1 day per week in the Rome IV criteria for PDS does not affect its postprandial symptom characteristics.

Background The Rome IV criteriafor functional dyspepsia (FD) has strict requirements for symptom frequency and onset duration, making it challenging to identify patients with broadly defined FD in clinical practice. This study aimed to investigate the impact of relaxing the Rome IV criteria on the diagnosis and symptom pattern of FD. Methods A cross-sectional, multi-center study was conducted involving 2935 consecutive broadly defined FD patients with no positive findings on upper gastrointestinal endoscopy and routine examinations. Questionnaires were used to collect demographic and upper gastrointestinal symptom data. Symptom pattern was compared between Rome IV criteria defined FD patients and those defined by relaxed Rome IV criteria. Results Only 22.2% of broadly defined FD patients rigorously fulfilled Rome IV criteria. No significant difference was found for proportion of patients with dyspeptic symptoms, dysmotility-like symptoms, reflux-like symptoms, as well as severity and onset frequency of dyspeptic symptoms (all P>0.05), between broadly defined FD who fulfilled Rome IV criteria but had a duration of 3-6 months and Rome IV criteria defined FD. Broadly defined Postprandial Distress Syndrome (PDS) patients who fulfilled the Rome IV criteria but had a symptom frequency of 1-2 days per week had significantly lower symptom severity (P<0.001), but similar postprandial symptom characteristics compared to those defined by the Rome IV criteria. Conclusions A symptom duration criterion of 3 months may be sufficient for diagnosing FD. Reducing the symptom onset frequency to no less than 1 day per week in the Rome IV criteria for PDS does not affect its postprandial symptom characteristics.