[Construction and validation of a predictive model for early occurrence of lower extremity deep venous thrombosis in ICU patients with sepsis].

OBJECTIVE: To investigate the risk factors of lower extremity deep venous thrombosis (LEDVT) in patients with sepsis during hospitalization in intensive care unit (ICU), and to construct a nomogram prediction model of LEDVT in sepsis patients in the ICU based on the critical care scores combined with inflammatory markers, and to validate its effectiveness in early prediction. METHODS: 726 sepsis patients admitted to the ICU of the Affiliated Hospital of Jining Medical University from January 2015 to December 2021 were retrospectively included as the training set to construct the prediction model. In addition, 213 sepsis patients admitted to the ICU of the Affiliated Hospital of Jining Medical University from January 2022 to June 2023 were retrospectively included as the validation set to verify the performance of the prediction model. Clinical data of patients were collected, such as demographic information, vital signs at the time of admission to the ICU, underlying diseases, past history, various types of scores within 24 hours of admission to the ICU, the first laboratory indexes of admission to the ICU, lower extremity venous ultrasound results, treatment, and prognostic indexes. Lasso regression analysis was used to screen the influencing factors for the occurrence of LEDVT in sepsis patients, and the results of Logistic regression analysis were synthesized to construct a nomogram model. The nomogram model was evaluated by receiver operator characteristic curve (ROC curve), calibration curve, clinical impact curve (CIC) and decision curve analysis (DCA). RESULTS: The incidence of LEDVT after ICU admission was 21.5% (156/726) in the training set of sepsis patients and 21.6% (46/213) in the validation set of sepsis patients. The baseline data of patients in both training and validation sets were comparable. Lasso regression analysis showed that seven independent variables were screened from 67 parameters to be associated with the occurrence of LEDVT in patients with sepsis. Logistic regression analysis showed that the age [odds ratio (OR) = 1.03, 95% confidence interval (95%CI) was 1.01 to 1.04, P < 0.001], body mass index (BMI: OR = 1.05, 95%CI was 1.01 to 1.09, P = 0.009), venous thromboembolism (VTE) score (OR = 1.20, 95%CI was 1.11 to 1.29, P < 0.001), activated partial thromboplastin time (APTT: OR = 0.98, 95%CI was 0.97 to 0.99, P = 0.009), D-dimer (OR = 1.03, 95%CI was 1.01 to 1.04, P < 0.001), skin or soft-tissue infection (OR = 2.53, 95%CI was 1.29 to 4.98, P = 0.007), and femoral venous cannulation (OR = 3.72, 95%CI was 2.50 to 5.54, P < 0.001) were the independent influences on the occurrence of LEDVT in patients with sepsis. The nomogram model was constructed by combining the above variables, and the ROC curve analysis showed that the area under the curve (AUC) of the nomogram model for predicting the occurrence of LEDVT in patients with sepsis was 0.793 (95%CI was 0.746 to 0.841), and the AUC in the validation set was 0.844 (95%CI was 0.786 to 0.901). The calibration curve showed that its predicted probability was in good agreement with the actual probabilities were in good agreement, and both CIC and DCA curves suggested a favorable net clinical benefit. CONCLUSIONS: The nomogram model based on the critical illness scores combined with inflammatory markers can be used for early prediction of LEDVT in ICU sepsis patients, which helps clinicians to identify the risk factors for LEDVT in sepsis patients earlier, so as to achieve early treatment.

Clinical significance of miRNA-195 expression in patients with laryngeal carcinoma.

PURPOSE: This study aimed to investigate the expression pattern of microRNA (miRNA)-195 in laryngeal carcinoma and analyze the relationships of miRNA-195 expression with clinicopathological features and prognosis. METHODS: The expression levels of miRNA-195 in pathological cancer tissue and tumor-adjacent normal tissue of 182 patients with laryngeal carcinoma were measured by reverse transcription-polymerase chain reaction (RT-PCR), and the relationships of relative expression levels of miRNA-195 with clinicopathological features and prognosis of patients with laryngeal carcinoma were analyzed. The invasive ability of cells was measured by Transwell chamber test. Cell proliferation in vitro was determined using 3-(4,5)-dimethylthiahiazo-(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) method. RESULTS: The expression level of miRNA-195 in laryngeal carcinoma tissue was lower than that in tumor-adjacent normal tissue (p<0.05). In vitro growth, migration and invasion ability of laryngeal carcinoma cells with lower expression level of miRNA-195 were distinctly higher than those of normal tissue cells. The expression levels of miRNA-195 were not significantly correlated with gender, age, grade of differentiation and tumor site (p>0.05), but were closely correlated with lymph node metastasis and clinical staging (p<0.05). The 5-year survival rate, median survival and progression-free survival in patients with high expression levels of miRNA-195 were significantly better than those in patients with low expression levels of miRNA-195 (78 vs. 39%, 57 months vs. 39 months, 40 months vs. 27 months, p<0.05). CONCLUSION: These findings indicated that expression of miRNA-195 in laryngeal carcinoma tissue is down-regulated, and the low expression of miRNA-195 may be related to invasion and metastasis of laryngeal carcinoma, which indicates poor prognosis of patients. MiRNA-195 may serve as a potential molecular target for the treatment and prognosis evaluation of laryngeal carcinoma.

Induction of apoptosis in hepatocellular carcinoma Smmc-7721 cells by vitamin K(2) is associated with p53 and independent of the intrinsic apoptotic pathway.

Vitamin K(2) (VK(2)) can exert cell growth inhibitory effects in various human cancer cells. In this study, we investigated the cell growth inhibitory effects of VK(2) in hepatocellular carcinoma Smmc-7721 cells and the mechanisms involved. We found that VK(2)-inhibited cell proliferation in Smmc-7721 cells in a dose-dependent manner, and the IC50 of VK(2) in Smmc-7721 cells was 9.73 microM at 24 h. The data from flow cytometric analyses, DNA fragmentation assays, and caspase 3 activity assays revealed that apoptosis was the determining factor in VK(2) activity. Furthermore, a significant increase in p53 phosphorylation and protein level was exhibited in apoptotic cells treated with VK(2), although there were no changes in p53 mRNA expression. Bax expression was unaffected by VK(2) in Smmc-7721 cells. In addition, our study showed that caspase 3 was activated by caspase 8, not caspase 9, in Smmc-7721 cells treated with VK(2). In summary, these data suggested that VK(2) can inhibit the growth of Smmc-7721 cells by induction of apoptosis involving caspase 8 activation and p53. This apoptotic process was not mediated by the intrinsic apoptotic pathway.