[Predictive value of von Willebrand factor for venous thromboembolism in critically ill patients based on propensity score matching].

OBJECTIVE: To analyze the predictive value of von Willebrand factor (vWF) for venous thromboembolism (VTE) of patients in intensive care unit (ICU) by using propensity score matching (PSM). METHODS: Patients admitted to ICU of the Second Affiliated Hospital of Kunming Medical University from December 2020 to June 2022 who stayed in ICU for ≥72 hours and underwent daily bedside vascular ultrasound screening were included. Baseline data such as age, gender, primary disease, and chronic comorbidities were collected. Coagulation indexes before admission to ICU and 24 hours and 48 hours after ICU admission were collected, including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), international normalized ratio (INR), fibrinogen (Fib), fibrin monomer (FM), vWF, D-dimer, antithrombin III (ATIII), etc. Patients were divided into VTE group and non-VTE group according to whether they had VTE or not [diagnosis of VTE: patients underwent daily ultrasound screening of bedside blood vessels (both upper and lower limbs, visceral veins), and those suspected of having thrombosis were confirmed by ultrasonographer or pulmonary angiography]. Using PSM analysis method, the VTE group was used as the benchmark to conduct 1 : 1 matching of age, whether there was malignant tumor, whether there was infection, whether there was diabetes, and coagulation indicators before admission to ICU. Finally, the cases with balanced covariates between the two groups were obtained. The risk factors of VTE were analyzed by multivariate Logistic regression analysis. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of vWF in the occurrence of VTE in critically ill patients. RESULTS: A total of 120 patients were enrolled, of which 18 (15.0%) were diagnosed with VTE within 72 hours after admission to ICU, and 102 (85.0%) were not found to have thrombus in ICU. Before PSM, there were significant differences in age, gender, proportion of malignant tumor and infection, and coagulation indexes between VTE group and non-VTE group. After PSM, 14 pairs were successfully matched, and the unbalanced covariables between the two groups reached equilibrium. Multivariate Logistic regression analysis showed that vWF was an independent risk factor for VTE at 48 hours after ICU admission in critically ill patients [odds ratio (OR) = 1.165, 95% confidence interval (95%CI) was 1.000-1.025, P = 0.004]. ROC curve analysis showed that the area under the ROC curve (AUC) of vWF at 48 hours after ICU admission for predicting VTE was 0.782, 95%CI was 0.618-0.945, P = 0.007. When the optimal cut-off value was 312.12%, the sensitivity was 67.7% and the specificity was 93.0. CONCLUSIONS: Dynamic monitoring of vWF is helpful to predict the occurrence of VTE in ICU patients, and vWF at 48 hours after ICU admission has certain value in predicting the occurrence of VTE.

[Analysis of treatment for 360 critically ill pregnant and parturient women in intensive care unit].

OBJECTIVE: To analyze the clinical characteristics and outcomes of critically ill pregnant and parturient women in intensive care unit (ICU), and to provide clinical experience for the subspecialty construction of critical obstetrics. METHODS: The clinical data of critically ill pregnant and parturient women admitted to the department of critical care medicine, the Second Affiliated Hospital of Kunming Medical University from January 2011 to December 2019 were collected. The main reasons for maternal transfer to ICU, the causes of maternal death, and organ support measures, etc. were summarized. RESULTS: A total of 39 567 critically ill pregnant and parturient women were admitted to the department of obstetrics in our hospital, and 360 were transferred to ICU, with an average ICU transfer rate of 0.91%. Since 2016, the number of obstetric admissions, the number of ICU transfers and the ICU transfer rate had increased significantly. The average age of severe maternals admitted to ICU was (30.9±5.7) years old. The average acute physiology and chronic health evaluation II (APACHE II) score was 7 (4, 10). The average length of ICU stay was 1 (1, 2) day. The average ventilator duration was 9.0 (3.0, 17.5) hours. The main delivery mode of pregnant women in ICU was cesarean section (84.72%). Forty-eight patients (13.33%) underwent hysterectomy, of which 42 (87.5%) due to postpartum hemorrhage. The top 3 causes of ICU admission were severe postpartum hemorrhage [36.94% (133/360)], hypertensive disorders of pregnancy [21.67% (78/360)], pregnancy with cardiac disease [15.00% (54/360)]. The leading cause of postpartum hemorrhage in women transferred to ICU was placental abnormality [63.98% (103/161)], followed by uterine atony [28.57% (46/161)]. The average blood loss was (4 019±2 327) mL within 24 hours after delivery, and the number of women who underwent hysterectomy due to postpartum hemorrhage decreased year by year. During the study period, there were 2 maternal deaths, which were indirect obstetric deaths, 3 cases were discharged against-advice (expected death), including 1 indirect death and 2 direct obstetric death; the mortality in ICU was 1.39% (5/360). CONCLUSIONS: The most common reasons for pregnant and parturient women to be admitted to ICU were severe postpartum hemorrhage and hypertensive disorders of pregnancy. The leading cause of postpartum hemorrhage was placental problem. Indirect obstetric deaths exceeded direct obstetric deaths, mainly due to pregnancy complicated with cardiac disease and severe pneumonia. ICU has become an important battlefield for rescuing critically ill maternal and an important guarantee for reducing the maternal mortality.

[lncRNA-HOTAIR inhibits the proliferation of H9c2 rat cardiomyocytes induced by lipopolysaccharide and promotes inflammation through targeting negative regulation of miR-1-3p].

Objective To investigate whether long non-coding RNA-HOX transcript antisense intergenic RNA (lncRNA-HOTAIR) regulates the inflammatory response of sepsis by targeting microRNA miR-1-3p. Methods 0.5 µg/mL lipopolysaccharide (LPS) was used to induce cardiomyocytes of H9c2 rats to establish a septic cardiomyocyte injury model. H9c2 cells were divided into control group, LPS group, and LPS combined with HOTAIR small interfering RNA negative control (si-NC) group, LPS combined with HOTAIR small interfering RNA (si-HOTAIR) group, LPS combined with miR-1-3p negative control (miR-NC) group, LPS combined with miR-1-3p group, LPS combined with si-HOTAIR and miR-1-3p inhibitor negative (anti-miR-NC) group, and LPS combined with siHOTAIR and anti-miR-1-3p group. Real-time quantitative PCR was used to determine the expression of HOTAIR and miR-1-3p, CCK-8 assay was used to detect cell proliferation, and Western blotting was used to analyze antigen KI-67 (ki67), P21, B-cell lymphoma 2 (Bcl2), Bcl2-related X protein (BAX) protein expression. Flow cytometry was performed to evaluate cell apoptosis. ELISA was used to determine the inflammatory factor interleukin 6(IL-6) and tumor necrosis factor-α (TNF-α) levels. The dual luciferase report experiment analyzes the targeting relationship between HOTAIR and miR-1-3p. Results The expression of HOTAIR in H9c2 cells of the LPS group was higher than that of the control group, and the expression of miR-1-3p was lower than that of the control group. Compared with the LPS combined with si-NC group, the LPS combined with si-HOTAIR treated H9c2 cell proliferation activity, presenting increased ki67 and Bcl2 expression, as well as decreased level of P21 expression, apoptosis rate, BAX expression, IL-6 and TNF-α. HOTAIR targets and regulates the expression of miR-1-3p. Compared with the LPS combined miR-1-3p group, the proliferation activity, ki67, Bcl2 expression of H9c2 cells increased in the LPS combined miR-NC group, and the P21 expression, apoptosis rate, BAX expression, IL-6, and TNF-α levels decreased. Compared with the LPS combined with si-HOTAIR and anti-miR-NC group, the H9c2 cell proliferation activity in the LPS combined with siHOTAIR and anti-miR-1-3p group descended, and the expression of ki67 and Bcl2 decreased, while the expression of P21, BAX, apoptosis, IL-6 and TNF-α levels increased. Conclusion HOTAIR negatively regulates the expression of miR-1-3p, inhibits LPS-induced cardiomyocyte H9c2 proliferation, and induces cell apoptosis and inflammation.

Swertianolin ameliorates immune dysfunction in sepsis via blocking the immunosuppressive function of myeloid- derived suppressor cells.

In this study, we studied the long-term proliferation trajectory of myeloid-derived suppressor cells (MDSCs) in murine sepsis model and investigated whether swertianolin could modulate the immunosuppressive function of MDSCs. A murine sepsis model was established by cecal ligation and perforation (CLP), according to the Minimum Quality Threshold in Pre-Clinical Sepsis Studies (MQTiPSS) guidelines. The bone marrow and spleen of the mice were collected at 24 h, 72 h, 7 and 15 d after sepsis induction. The proportions of monocytic-MDSCs (M-MDSCs; CD11b+LY6G-LY6Chi) and granulocytic-MDSCs (G-MDSC, CD11b+ Ly6G+ Ly6Clow) were analyzed by flow cytometry. Then, we have investigated whether swertianolin could modulate the immunosuppressive function of MDSCs in in vitro experiments. G-MDSCs and M-MDSCs increased acutely after sepsis with high levels sustained over a long period of time. G-MDSCs were the main subtype identified in the murine model of sepsis with polymicrobial peritonitis. Furthermore, it was found that swertianolin reduced significantly interleukin-10 (IL-10), nitric oxide (NO), reactive oxygen species (ROS), and arginase production in MDSCs, while reducing MDSC proliferation and promoting MDSC differentiation into dendritic cells. Swertianolin also improved T-cell activity by blocking the immunosuppressive effect of MDSCs. Both subsets of MDSCs significantly increased in the bone marrow and spleen of the mice with sepsis, with G-MDSCs being the main subtype identified. Swertianolin effectively regulated the functions of MDSCs and reduced immune suppression.

Swertiamarin suppresses proliferation, migration, and invasion of hepatocellular carcinoma cells via negative regulation of FRAT1.

Studies have shown that swertiamarin (STM) has multiple biological activities, but its anti-tumour effects and molecular mechanisms are still unclear. The present research aimed to validate the STM's impacts on the proliferation, migration, and invasion of hepatocellular carcinoma (HCC) cells, and to study its potential mechanism. Two HCC cell lines were treated with STM. Tumour growth was observed by the mouse tumour xenografts model. HCC cell lines stably expressing T-cell lymphomas 1 (FRAT1) were generated by lentivirusmediated overexpression. Cell viability, proliferation, migration, and invasion were observed using Cell Counting Kit-8 (CCK8), the xCELLigence Real-Time Cell Analyzer system (RTCA), and transwell analysis, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to observe the expression of FRAT1 and proteins related to the Wnt/ß-catenin signalling pathway. Tumour growth was inhibited by STM in vivo. STM suppressed the proliferation, migration, and invasion of HCC cells. STM negatively regulated FRAT1 expression, whereas overexpressed FRAT1 blocked the anti-tumour function of STM. The results revealed that STM suppressed the FRAT1/Wnt/ß-catenin signalling pathway. The findings of this study provide new insights into investigation of therapeutic strategies against HCC.

Bioinformatics analysis of differentially expressed genes in hepatocellular carcinoma cells exposed to Swertiamarin.

Aim: To explore gene expression profiling in hepatocellular carcinoma (HCC) cells exposed to swertiamarin. Methods: Cell viability, apoptosis and invasion were examined in HepG2 cells after swertiamarin treatment. Tumor growth of SK-Hep-1 cells xenografted in nude mice was monitored after swertiamarin treatment. Total RNA was isolated from HepG2 cells treated with swertiamarin for microarray analysis. The data of microarray were analyzed by bioinformatics. Results: Swertiamarin treatment decreased the viability and invasion while increased the apoptosis of HepG2 cells, and significantly inhibited the growth of SK-Hep-1 cells xenografted in nude mice. Pathway and biological process analysis of differentially expressed genes (DEGs) in swertiamarin treated HepG2 cells showed that PI3k-Akt was the most significant regulated pathway. 47 targets of swertiamarin were predicted by CGBVS while 21 targets were predicted by 3NN. Notably, 8 targets were predicted as the targets of swertiamarin by both programs, including two prominent targets JUN and STAT3. A large range of DEGs induced by swertiamarin could be regulated by JUN and STAT3. Conclusion: Swertiamarin treatment led to significant changes in the expression of a variety of genes that modulate cell survival, cell cycle progression, apoptosis, and invasion. Moreover, most of these genes can be clustered into pathway networks such as PI3K, JUN, STAT3, which are predicted targets of swertiamarin. Further confirmation of these targets will reveal the anti-tumor mechanisms of swertiamarin and facilitate the development of swertiamarin as a novel agent for cancer prevention and treatment.