Objective To investigate the relationship between tooth loss and the occurrence of esophageal cancer in a natural village in Wenfeng District, Anyang City, Henan Province. Methods A prospective cohort study was conducted to observe the occurrence of tooth loss and esophageal cancer among the asymptomatic residents of the natural village for 16 years from January 2008 to July 2024. Data were analyzed by chi-square test, binary logistic regression, and restricted cubic spline. Results Among the total population of 711 cases, 136 cases were lost to follow-up and 575 cases were included in the final statistics, including 45 cases with esophageal cancer. Significant statistical difference was found between esophageal cancer patients with and without tooth loss (P<0.05). Logistic regression analysis showed that tooth loss was associated with the occurrence of esophageal cancer (OR=3.977, 95%CI: 1.543-10.255). After the adjustment for confounders, tooth loss remained significantly associated with the occurrence of esophageal cancer (OR=3.038, 95%CI: 1.035-8.914). A nonlinear dose-response relationship was observed between the number of teeth lost and the incidence of esophageal cancer. When the number of teeth lost was less than 12, the risk of esophageal cancer increased with the number of teeth lost. When more than 12 teeth were lost, the risk of esophageal cancer decreased as the number of teeth lost increased. Conclusion Tooth loss is a risk factor for the occurrence of esophageal cancer in this natural village. When the number of teeth lost is less than 12, the risk of esophageal cancer increases with the number of teeth lost.

BACKGROUND: Pre-transplant exposure to immune checkpoint inhibitors (ICIs) significantly increases the risk of allograft rejection after liver transplantation (LT); however, whether ICI-related rejection leads to increased graft loss remains controversial. Therefore, this study aimed to investigate the association between ICI-related allograft rejection and perioperative graft loss. METHODS: This was a retrospective analysis of adult liver transplant recipients with early biopsy-proven T-cell-mediated rejection (TCMR) at Liver Transplantation Center of Sun Yat-sen Memorial Hospital from June 2019 to September 2024. The pathological features, clinical characteristics, and perioperative graft survival were analyzed. RESULTS: Twenty-eight patients who underwent early TCMR between June 2019 and September 2024 were included. Based on pre-LT ICI exposure, recipients were categorized into ICI-related TCMR (irTCMR, n = 12) and conventional TCMR (cTCMR, n = 16) groups. Recipients with irTCMR had a higher median Banff rejection activity index (RAI) (6 vs . 5, P = 0.012) and more aggressive tissue damage and inflammation. Recipients with irTCMR showed higher proportion of treatment resistance, achieving a complete resolution rate of only 8/12 compared to 16/16 for cTCMR. Graft loss occurred in 5/12 of irTCMR recipients within 90 days after LT, with no graft loss in cTCMRs recipients. Cox analysis demonstrated that irTCMR with an ICI washout period of <30 days was an independent risk factor for perioperative graft loss (hazard ratio [HR], 6.540; 95% confidence interval [CI], 1.067-40.067, P = 0.042). CONCLUSION IrTCMR is associated with severe pathological features, increased resistance to treatment, and higher graft loss in adult liver transplant recipients.
Humans ; Liver Transplantation/adverse effects* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Graft Rejection/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; T-Lymphocytes/drug effects* ; Graft Survival/immunology* ; Aged

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective:To evaluate the effect of Lactobacillus-derived extracellular vesicles (Lac-EVs) on lipopolysaccharide (LPS)-induced activation of microglia and proteomic analysis.Methods:BV2 microglia obtained from mice with good growth status were divided into 3 groups ( n=12 each) using a random number table method: control group (group C), LPS group (group L) and LPS+ Lac-EVs group (group L+ E). Group C was commonly cultured. Group L was incubated for 24 h with LPS (final concentration 1 μg/ml). Group L+ E was incubated for 24 h with Lac-EVs (final concentration 2.5 μg/ml) after being treated with LPS for 24 h. The expression of CD86 and CD206 was detected using immunofluorescence staining. Cell precipitates were taken from L and L+ E groups, and proteomics were used to screen for differentially expressed proteins between the two groups. The differentially expressed proteins were analyzed by the bioinformatics analysis, and two differentially expressed proteins, apolipoprotein A1 and G protein-coupled receptor kinase 2, were verified by quantitative real-time polymerase chain reaction and Western blot. Results:Compared with group C, the expression of CD86 was significantly up-regulated, and the expression of CD206 was down-regulated in group L ( P<0.05). Compared with group L, the expression of CD86 was significantly down-regulated, and the expression of CD206 was up-regulated in L+ E group ( P<0.05). One hundred and twenty-five differentially expressed proteins were identified using proteomics (FC=2.0, P<0.05), of which the expression of 66 proteins was up-regulated and the expression of 59 proteins was down-regulated. The results of GO analysis indicated that these differentially expressed proteins were mainly involved in biological processes such as endothelial cell proliferation, SDNA damage detection, and lipoprotein transport. The results of KEGG analysis indicated that there were differences in PPAR signaling pathway, endocytosis, metabolic pathway, MAPK signaling pathway, etc. The expression trends of the differentially expressed proteins determined by Western blot and quantitative real-time polymerase chain reaction were consistent with the results of proteomics. Conclusions:Lac-EVs can inhibit LPS-induced microglial polarization toward M1 phenotype, and the mechanism may be related to the up-regulated differential proteins apolipoprotein A1 and G protein-coupled receptor kinase 2.