PKMYT1: A Potential Target for CCNE1 Amplificated Colorectal Tumors.

Colorectal cancer is a malignant tumor with higher morbidity and mortality. The purpose of this study is to investigate whether inhibition of Protein Kinase, Membrane Associated Tyrosine/Threonine 1 (PKMYT1) affects tumor cell proliferation, survival and migration in colon tumors with high Cyclin E1 (CCNE1) expression. PcDNA3.1-CCNE1 vector and si-PKMYT1 were transfected in SW480 cells by Lipofectamine 2000. Q-PCR and western blot assay were processed to detect the expression. Transwell assay and Edu assay were undertaken to verify the migration and proliferation. CCNE1 promotes the proliferation and migration of SW480. Silencing of PKMYT1 inhibited the proliferation of tumor cells. Silencing the expression of PKMYT1 under the premise of overexpression of CCNE1, the level of Cyclin Dependent Kinase 1 (CDK1)-PT14 was reduced, indicating that the cell cycle was blocked. The expression of γH2AX increased significantly, indicating that the DDR pathway of tumor cells was activated and DNA damage accumulated. The results of immunofluorescence microscopy showed significantly increased expression of DNA damage-associated marker (γH2AX: H2AX Variant Histone). In CCNE1 amplificated colorectal tumor cells, knockdown of PKMYT1 reduced cells in S phase, inhibited cell proliferation and promoted cell apoptosis, confirming that PKMYT1 was a potential therapeutic target for colorectal tumor. This study may verify a potential therapeutic target and provide a new idea for the treatment of colorectal cancer in the future.

Diagnostic value of a new axial loading MRI device in patients with suspected lumbar spinal stenosis.

OBJECTIVES: This study was carried out to investigate a new device for axial loading MRI (alMRI) in the diagnosis of lumbar spinal stenosis (LSS). METHODS: A total of 87 patients with suspected LSS sequentially underwent conventional MRI and alMRI using a new device with pneumatic shoulder-hip compression mode. Four quantitative parameters of dural sac cross-sectional area (DSCA), sagittal vertebral canal diameter (SVCD), disc height (DH), and ligamentum flavum thickness (LFT) at L3-4, L4-5, and L5-S1 in both examinations were measured and compared. Eight qualitative indicators were compared as valuable diagnostic information. Image quality, examinee comfort, test-retest repeatability, and observer reliability were also assessed. RESULTS: Using the new device, all 87 patients successfully completed alMRI with no statistically significant differences in image quality and examinee comfort from conventional MRI. Statistically significant changes were observed in DSCA, SVCD, DH, and LFT after loading (p < 0.01). SVCD, DH, LFT, and DSCA changes were all positively correlated (r = 0.80, 0.72, 0.37, p < 0.01). Eight qualitative indicators increased from 501 to 669 after axial loading, for a total increase of 168 (33.5%). Nineteen patients (21.8%, 19/87) developed absolute stenosis after axial loading and 10 of them (11.5%, 10/87) also had a significant reduction in DSCA (> 15 mm2). The test-retest repeatability and observer reliability were good to excellent. CONCLUSION: The new device is stable for performing alMRI and can exacerbate the severity of spinal stenosis, providing more valuable information for diagnosing LSS and reducing missed diagnoses. KEY POINTS: • The new axial loading MRI (alMRI) device could detect a higher frequency of patients with lumbar spinal stenosis (LSS). • The new device with pneumatic shoulder-hip compression mode was used to investigate its applicability in alMRI and diagnostic value for LSS. • The new device is stable for performing alMRI and can provide more valuable information for diagnosing LSS.

Investigation of Statin Medication Use in Elderly Patients with Cardiovascular Disease on Regular Physical Examination and the Relationship with Glucolipid Metabolism and Adverse Cardiovascular Prognosis.

Our purpose of this study was to investigate the use of statins in elderly patients with cardiovascular diseases during regular physical examination and to analyze the relationship between statins and glucose and lipid metabolism and adverse cardiovascular prognosis. From January 2019 to December 2021, 2121 elderly patients with cardiovascular disease underwent regular physical examination as the study subjects to investigate the use and intensity of statins. The patients were divided into the dosing group (n = 1848) and the nondosing group (n = 273) according to whether they were taking statins or not. The cardiac function, glucose and lipid metabolism indexes, and cardiovascular adverse events were compared between the two groups. Statin use in elderly patients with cardiovascular disease was 87.13% (1848/2121). The intensity of statin use decreased with age (P < 0.05); the left ventricular ejection fraction (LVEF) was greater in the medicated group than in the nonmedicated group, and the left ventricular end-diastolic internal diameter (LVDd) and left ventricular end-systolic internal diameter (LVDs) were smaller than in the nonmedicated group (P < 0.05). The total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and fasting blood glucose (FBG) levels were lower in the medicated group than in the nonmedicated group, the high-density lipoprotein cholesterol (HDL-C) levels were higher than in the nonmedicated group, and the glycated hemoglobin (HbA1c) values were lower than in the nonmedicated group (P < 0.05). The overall incidence of cardiovascular adverse events in the medicated group was lower than that in the nonmedicated group (P < 0.05). Statin use was higher in elderly patients with cardiovascular disease; the intensity of drug use decreased with age. The patients' cardiac function, glucose metabolism, and prognosis were significantly improved after statin treatment.