OBJECTIVE To analyze the correlation of the peak blood concentration （cmax） of compound sulfamethoxazole （TMP/SMZ） and its metabolite N-acetyl sulfamethoxazole （NSMZ） with clinical efficacy and adverse reactions in critically ill patients. METHODS The data of critically ill patients treated with TMP/SMZ in various ICU of Hainan General Hospital from December 2023 to January 2025 were retrospectively collected. The patients were divided into success group and failure group based on the treatment outcome. Simple linear regression and Spearman correlation analysis were used to analyze the correlation of TMP cmax， SMZ cmax， and NSMZ cmax with clinical efficacy and adverse reactions. The receiver operating characteristic curve （ROC） was used to determine the cutoff values of cmax for predicting the occurrence of adverse reactions. RESULTS Among critically ill patients with an acute physiology and chronic health evaluation Ⅱ （APACHE-Ⅱ） ≥15 points 24 h of check-in at ICU， SMZ cmax of success group was significantly higher than failure group （P＜0.05）. The daily total dose of TMP/SMZ was positively correlated with TMP cmax and SMZ cmax（ P＜0.05）. TMP cmax was significantly correlated with hepatotoxicity and nephrotoxicity， SMZ cmax with hepatotoxicity， and NSMZ cmax with nephrotoxicity （P＜0.05）. The cutoff values of TMP cmax for predicting nephrotoxicity and hepatotoxicity were 7.25 μg/mL and 6.63 μg/mL， respectively. The cutoff value of SMZ cmax for predicting hepatotoxicity was 138.00 μg/mL， and that of NSMZ cmax for predicting nephrotoxicity was 60.76 μg/mL. CONCLUSIONS Among critically ill patients with an APACHE-Ⅱ ≥15 points 24 h of check-in at ICU， SMZ cmax is associated with treatment success. Hepatotoxicity risk significantly increases when TMP cmax ≥6.63 μg/mL or SMZ cmax ≥138.00 μg/mL； nephrotoxicity risk significantly increases when TMP cmax ≥7.25 μg/mL or NSMZ cmax ≥60.76 μg/mL.

OBJECTIVES: To investigate the mechanism of DDX17 for regulating proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) during the development of pulmonary hypertension (PH). METHODS: In murine PASMCs cultured under normoxic or hypoxic conditions, the effects of transfection with si-Ddx17 and insulin treatment, alone or in combination, on cell proliferation and migration were evaluated using Ki-67 immunofluorescence staining, scratch assay and Transwell assay. Western Blotting was performed to detect the changes in protein expression levels of DDX17, 4EBP1, S6, p-4EBP1, and p-S6. In a mouse model of PH induced by intraperitoneal injection of monocrotaline (MCT), the changes in pulmonary vasculature were examined using HE staining following tail vein injection of AD-Ddx17i. RESULTS: The PASMCs in hypoxic culture exhibited significantly enhanced cell proliferation and migration and protein expressions of p-4EBP1 and p-S6, and these changes were obviously reversed by transfection with si-Ddx17. Treatment with insulin significantly attenuated the effect of si-Ddx17 against hypoxic exposure-induced changes in PASMCs. In the mouse model of MCT-induced PH, transfection with AD-Ddx17i obviously alleviated pulmonary vascular stenosis and intimal hyperplasia. CONCLUSIONS The expression of DDX17 is elevated in hypoxia-induced PASMCs and PH mice, and silencing DDX17 significantly inhibits PASMC proliferation and migration in vitro and pulmonary vascular remodeling in PH mice by reducing mTORC1 activity.
Animals ; Cell Proliferation ; Cell Movement ; DEAD-box RNA Helicases/metabolism* ; Myocytes, Smooth Muscle/metabolism* ; Mice ; Pulmonary Artery/cytology* ; Hypertension, Pulmonary/metabolism* ; Mechanistic Target of Rapamycin Complex 1 ; Cells, Cultured ; Muscle, Smooth, Vascular/cytology*

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

ACTH Syndrome, Ectopic ; diagnosis ; epidemiology ; etiology ; metabolism ; Adrenocorticotropic Hormone ; metabolism ; Humans ; Lung Neoplasms ; complications