Background Type 2 diabetes mellitus is one of the most prevalent diseases,which imposes a heavy burden on patients' families and the society.Sleep disorders are recognized as risk factors for the development of diabetes,which may affect the onset and development of diabetes through neuro-endocrino-metabolic pathways,so identifying the factors responsible for the sleep quality of diabetic patients is of great importance in improving their sleep quality.Objective To investigate the relationship among fear of disease progression,executive function and sleep quality in patients with type 2 diabetes mellitus,so as to provide references for improvement of sleep quality in patients with type 2 diabetes mellitus.Methods A sample of 197 patients with type 2 diabetes mellitus who were admitted to the Endocrinology Department of the Second Affiliated Hospital of the Air Force Military Medical University from January to May 2023 and met the criteria defined in the Guideline for the Prevention and Treatment of Type 2 Diabetes Mellitus in China(2020 edition)were consecutively selected.All subjects were assessed using Fear of Progression Questionnaire-Short Form(FoP-Q-SF),Behavior Rating Inventory of Executive Function-Adult version(BRIEF-A)and Pittsburgh Sleep Quality Index(PSQI).Then the Process macro for SPSS(Model 4)and Bootstrap technique were applied to examine the mediating effect of executive function on the relationship between fear of disease progression and sleep quality in patients with type 2 diabetes mellitus.Results ①75 patients(38.07%)with type 2 diabetes mellitus were found to have sleep problems.②PSQI score in patients with type 2 diabetes mellitus was positively correlated with FoP-Q-SF score and BRIEF-A score(r=0.159,0.287,P<0.01).③Executive function mediated the relationship between fear of disease progression and sleep quality,the indirect value was 0.076(95%CI:0.022～0.146),accounting for 39.58%of the total effect.Conclusion Sleep disorders are common in patients with type 2 diabetes mellitus,and executive function may play a medicating role in the relationship between fear of disease progression and sleep quality.

Objective:To investigate the effect of the transcription factor TBX1 on the proliferation of colorectal cancer cells and to explore potential molecular mechanisms.Methods:The mRNA and protein levels of TBX1 in colorectal cancer cell lines HCT116, RKO, SW480, HT29, and LOVO were detected by using reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Colorectal cancer cell lines HCT116 and SW480 cells with low TBX1 expression were transfected with either a pcDNA3.1 plasmid containing TBX1 mimics (TBX1 overexpression group) or an empty pcDNA3.1 plasmid (the control group). LOVO cells with high TBX1 expression were transfected with small interfering RNA (siRNA) targeting TBX1 including si-TBX1-8604A, si-TBX1-8604B, and a negative control siRNA (si-NC), which were treated as si-TBX1-8604A group, si-TBX1-8604B group, and si-NC group. qRT-PCR was used to detect the expressions of transcriptional level TBX1 and PARK2, and Western blot was used to detect the protein levels of TBX1, PARK2, and key factors in the MAPK and PI3K signaling pathways. Methyl Thiazolyl Tetrazolium (MTT) assay and cell colony formation assay were used to detect the cell proliferation. Combining literatures and the JASPAR database, 2 binding sites of TBX1 in the PARK2 promoter region were predicted. Chromatin immunoprecipitation assay was employed to verify the binding sites of TBX1 to PARK2 in HCT116 and SW480 cells. Dual luciferase reporter gene assay was used to verify the targeting relationship between TBX1 and PARK2. The expression of TBX1 and PARK2 in colon cancer tissues was analyzed by using the Cancer Genome Atlas (TCGA) database (September 2023).Results:High TBX1 expression in HCT116 and SW480 cells transfected with TBX1 mimics plasmid was confirmed by qRT-PCR and Western blot, while TBX1 expression was successfully knocked down in LOVO cells transfected with siRNA targeting TBX1. MTT assay indicated that the absorbance values for HCT116 cells in TBX1 overexpression group on d1, d3, d5, and d7 after inoculation, and for SW480 cells on d3, d5, and d7 after inoculation were lower than those in the control group, and the differences were statistically significant (all P < 0.01). LOVO cells in the si-TBX1-8604A group and si-TBX1-8604B group exhibited higher absorbance values than the si-NC group on d1, d3, d5, and d7 after inoculation, and the differences were statistically significant (all P < 0.05). Cell colony formation assay revealed that after 14 d, the colony number of HCT116 cells [(387±9) vs. (843±13)] and SW480 cells [(413±9) vs. (931±15)] in TBX1 overexpression group was lower than that in the control group, and the differences were statistically significant (all P < 0.05). The colony number of LOVO cells in the si-TBX1-8604A group and si-TBX1-8604B group was (493±77) and (470±32), respectively, which was higher than that in the si-NC group (349±26), and the differences were statistically significant (all P < 0.05). The protein relative expression levels of p-ERK and p-AKT S473 in HCT116 and SW480 cells in TBX1 overexpression group were lower than those in the control group, while protein relative expression levels of p-ERK and p-AKT S473 in LOVO cells in the si-TBX1-8604A group and si-TBX1-8604B group were higher than those in the si-NC group, and the differences were statistically significant (all P < 0.05). The relative expression level of PARK2 mRNA in HCT116 and SW480 cells (all P < 0.01) and the protein level in the overexpression group were higher than those in the control group. Chromatin immunoprecipitation assay demonstrated that the enrichment times of TBX1 binding to 2 sites of PARK2 intron in HCT116 and SW480 cells in TBX1 overexpression group were higher than that in the control group, and the differences were statistically significant (all P < 0.05). Dual luciferase reporter gene assay showed that the relative luciferase activity of HCT116 and SW480 cells co-transfected with pcDNA3.1 plasmid containing TBX1 mimics and pGL3 plasmid containing PARK2 mimics was higher than that of cells co-transfected with empty pcDNA3.1 and pGL3 plasmids, co-transfected with empty pcDNA3.1 plasmid and pGL3 plasmid containing PARK2 mimics, co-transfected with pcDNA3.1 plasmid containing TBX1 mimics and empty pGL3 plasmid, and the differences were statistically significant (all P < 0.05). Spearman analysis showed that there was a positive correlation between transcriptional level TBX1 and PARK2 in colon cancer tissues (288 cases) in TCGA database ( r = 0.226, P < 0.001); and the relative expression level of PARK2 mRNA in colon cancer tissues (383 cases) was lower than that in normal intestinal tissues (50 cases), and the difference was statistically significant ( P < 0.001). Conclusions:Elevated expression of transcriptional factor TBX1 inhibits the proliferation of colorectal cancer cells, potentially by activating the downstream target gene PARK2 and inhibiting the phosphorylation of ERK and AKT in the MAPK and PI3K signaling pathways, ultimately affecting the activation of these pathways.