Factors Associated with Acute Pulmonary Embolism in Patients with Hypoxia After off-Pump Coronary Artery Bypass Grafting: A Case-Control Study.

Purpose: This study aims to explore the factors linked to the occurrence of acute pulmonary thromboembolism (PE) within a cohort of patients exhibiting hypoxic saturation (oxygen saturation levels falling below 93%), subsequent to undergoing off-pump coronary artery bypass grafting (OPCABG). Methods: A retrospective case-control study was conducted. A total of 296 patients met the inclusion and exclusion criteria, divided into PE group (100 cases) and non-PE group (196 cases) according to whether they had PE or not. The preoperative and postoperative information of patients were collected and statistically analyzed. Results: The results from a multivariate logistic regression analysis indicated the following factors were independently linked to PE following OPCABG: history of smoking (OR = 3.019, 95% CI, 1.437-6.634, P = 0.004), preoperative arterial oxygen partial pressure ≤78.9 mmHg (OR = 3.686, 95% CI, 1.708-8.220, P = 0.001), presence of postoperative lower extremity deep venous thrombosis (OR = 4.125, 95% CI, 1.886-9.310, P < 0.001), elevated postoperative D-dimer levels >6.76 mg/l (OR = 8.078, 95% CI, 3.749-18.217, P<0.001), postoperative NT-BNP levels (OR = 1.001, 95% CI: 1.000-1.001, P = 0.011), and elevated postoperative pulmonary arterial pressure >33.0 mmHg (OR = 10.743, 95% CI: 3.422-37.203, P < 0.001). The developed nomogram exhibited a high predictive accuracy with an area under the curve of 0.913 (95% CI: 0.878-0.948). Conclusion: When patients have a history of preoperative smoking, decreased preoperative arterial oxygen pressure, postoperative lower limb DVT, increased postoperative pulmonary artery pressure, and elevated postoperative D-Dimer and NT pro-BNP levels, it is recommended to take perioperative preventive measures, timely diagnostic evaluation, and if necessary, anticoagulant treatment. In addition, the results of this study may improve the diagnostic sensitivity of medical staff for postoperative PE in OPCABG, thereby increasing the detection rate and potentially reducing the need for excessive medical imaging procedures.

A network pharmacology approach to decipher the mechanism of total flavonoids from Dracocephalum Moldavica L. in the treatment of cardiovascular diseases.

AIM OF THE STUDY: Cardiovascular disease (CVD) seriously endangers human health and is characterized by high mortality and disability. The effectiveness of Dracocephalum moldavica L. in the treatment of CVD has been proven by clinical practice. However, the mechanism by which DML can treat CVD has not been systematically determined. MATERIALS AND METHODS: The active compounds in DML were screened by literature mining and pharmacokinetic analysis. Cytoscape software was used to construct the target-disease interaction network of DML in the treatment of CVD. Gene ontology and signalling pathway enrichment analyses were performed. The key target pathway network of DML compounds was constructed and verified by pharmacological experiments in vitro. A hydrogen glucose deprivation/reoxygenation model was established in H9c2 cells using hypoxia and glucose deprivation for 9 h combined with reoxygenation for 2 h. The model simulated myocardial ischaemic reperfusion injury to investigate the effects of total flavonoids of Cymbidium on cell viability, myocardial injury markers, oxidative stress levels, and reactive oxygen radical levels. Western blot analysis was used to examine NOX-4, Bcl-2/Bax, and PGC-1α protein expression. RESULTS: Twenty-seven active components were screened, and 59 potential drug targets for the treatment of CVD were obtained. Through the compound-target interaction network and the target-disease interaction network, the key targets and key signalling pathways, such as NOX-4, Bcl-2/Bax and PGC-1α, were obtained. TFDM significantly decreased LDH and MDA levels and the production of ROS and increased SOD activity levels in the context of OGD/R injury. Further studies indicated that NOX-4 and Bax protein levels and the p-P38 MAPK/P38 MAPK andp-Erk1/2/Erk1/2 ratios were suppressed by TFDM. The protein expression of Bcl-2 and PGC-1α was increased by TFDM. CONCLUSIONS: Our results showed that DML had multicomponent, multitarget and multichannel characteristics in the treatment of CVD. The mechanism may be associated with the following signalling pathways: 1) the NOX-4/ROS/p38 MAPK signalling pathway, which inhibits inflammation and reactive oxygen species (ROS) production, and 2) the Bcl-2/Bax and AMPK/SIRT1/PGC-1α signalling pathways, which inhibit apoptosis.

A network pharmacology approach to decipher the total flavonoid extract of Dracocephalum Moldavica L. in the treatment of cerebral ischemia- reperfusion injury.

BACKGROUND AND OBJECTIVE: Cerebral ischemia-reperfusion injury (CIRI) is a major injury that seriously endangers human health and is characterized by high mortality and high disability. The total flavonoid extract of Dracocephalum moldavica L.(TFDM) in the treatment of CIRI has been proved by clinical practice. But the mechanism for the treatment of CIRI by TFDM has not been systematically revealed. STUDY DESIGN AND METHODS: The active compounds contained in TFDM were screened by literature mining and pharmacokinetic parameters, and the targets related to CIRI were collected by searching Drugbank, Genecards and OMIM databases. Cytoscape software was used to construct the protein interaction network of TFDM for the prevention and treatment of CIRI. Geneontology and signal pathway enrichment were analyzed. The key target pathway network of TFDM compounds was constructed and verified by pharmacological experiment in vitro. RESULTS: 21 active components were screened, 158 potential drug targets for the prevention and treatment of CIRI were obtained, 53 main targets were further screened in the protein-protein interaction network, and 106 signal pathways, 76 biological processes, 26 cell components and 50 molecular functions were enriched (P<0.05). Through the compound-target-pathway network, the key compounds that play a role in the prevention and treatment of CIRI, such as acacetin, apigenin and other flavonoids, as well as the corresponding key targets and key signal pathways, such as AKT1, SRC and EGFR were obtained. TFDM significantly decreased LDH, MDA levels and increased the NO activity levels in CIRI. Further studies have shown that TFDM increases the number of SRC proteins, and TFDM also increases p-AKT/ AKT. Molecular docking results showed that acacetin-7-O (- 6''-acetyl) -glucopyranoside, acacetin7-O-ß-D-glucopyranoside, apigenin-7-O-ß-D-galactoside respectively had good affinity for SRC protein. Acacetin-7-O (- 6''-acetyl) -glucopyranoside,acacetin-7-O-ß-D-glucuronide, acacetin7-O-ß-D-glucopyranoside had good affinity for AKT1 protein, respectively. CONCLUSION: Our research showed that TFDM had the characteristics of multi-component, multi-target and multi-channel in the treatment of CIRI. The potential mechanism may be associated with the following signaling pathways:1) the signaling pathways of VEGF/SRC, which promote angiogenesis, 2) the signaling pathways of PI3K/AKT, which inhibit apoptosis, and 3) acacetin-7-O (- 6''-acetyl) -glucopyranoside is expected to be used as a candidate monomer component for natural drugs for further development.

A population-based study on the prevalence of gestational diabetes mellitus in association with temperature in Taiwan.

BACKGROUND: Previous studies showing seasonal clustering of gestational diabetes mellitus (GDM) were conducted in the temperate or frigid zones and mostly included pregnant Caucasian women. This study aims to investigate the association of ambient temperature with prevalence of GDM in Taiwan, a sub-tropic country. METHODS: This population-based cohort study comprised women (n = 371,131) who gave births between 2013 and 2014; of which, 43,538 (11.7%) were diagnosed with GDM. The mean daily temperature and difference in temperature within a day was calculated over a 35-day period prior to GDM diagnosis or the first day of the 27th gestational week (for non-GDM subjects). Multiple logistic regression models with generalized estimation equation were performed to estimate the adjusted odds ratio (aOR) and 95% confidence interval (CI) of GDM in association with temperature. RESULTS: After controlling for potential confounders, summer and fall were associated with higher risk of GDM diagnosis, with aOR [95% CI] of 1.05 [1.04-1.07] and 1.04 [1.02-1.06] in reference to winter. Additionally, an increase of 1 °C from 14 °C to 27 °C was associated with an aOR of 1.03 [1.02-1.03]. The aOR greatly increased to 1.54 [1.48-1.60] after 28 °C. An increase of 1 °C difference within a day was associated with a reduced aOR at 0.90 [0.87-0.92]. CONCLUSION: A higher prevalence of GDM was associated with a higher daily temperature, but with a smaller difference in temperature within a day.

STAT1/3 and ERK1/2 synergistically regulate cardiac fibrosis induced by high glucose.

BACKGROUND: Hyperglycaemia promotes the proliferation of cardiac fibroblasts (CFs) and collagen synthesis in CFs. However, the molecular mechanism underlying the effects of HG on proliferation and collagen synthesis of CF, is not completely understood. OBJECTIVES: The objectives of the present study were to determine whether the STAT proteins has a functional role in high glucose-induced proliferation of CFs and collagen synthesis in vitro and whether the STAT signaling pathway and MAPK signaling pathway have synergetical effects on high glucose-mediated cardiac fibroblasts proliferation and collagen synthesis. METHODS: Rat CFs were cultured in Dulbecco's modified Eagle's medium, supplemented with 5.5 or 25 mmol/L D-glucose, in the presence of absence of STAT1 inhibitor Fludarabine, STAT3 inhibitor S31-201 and ERK1/2 inhibitor PD98059. Proliferation were measured by the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, the production of Type I and III collagen was evaluated using real-time quantitative RT-PCR and ELISA, and the phosphorylation expression of STAT1 and STAT3 were analyzed by Western blot. RESULTS: High glucose treatment promoted the proliferation of cardiac fibroblasts and collagen types I and III synthesis. High glucose treatment induced STAT1 and STAT3 phosphorylation in cardiac fibroblasts, the mode and level of STAT1 and STAT3 phosphorylation were significantly different. Fludarabine and S31-201 could both inhibited high glucose stimulated proliferation of cardiac fibroblasts and collagen types I and III synthesis with different effects. Combination of Fludarabine and PD98059 or combination of S31-201 and PD98059 both exhibited stronger inhibitions on proliferation of cardiac fibroblasts and collagen types I synthesis, but the effects and functional modes are different. CONCLUSION: Both STAT1 and STAT3 mediate the proliferation of cardiac fibroblasts and collagen synthesis induced by high glucose. STAT1 and STAT3 both have synergetic effects with ERK1/2 on regulating proliferation of cardiac fibroblasts and collagen types I synthesis.

Soluble decoy receptor 3 induces angiogenesis by neutralization of TL1A, a cytokine belonging to tumor necrosis factor superfamily and exhibiting angiostatic action.

TL1A is a member of the tumor necrosis factor superfamily and plays an important role in regulating endothelial cell apoptosis. A previous study shows TL1A is able to interact with death receptor 3 and decoy receptor 3 (DcR3). Here, we demonstrate that DcR3 is able to induce angiogenesis in human umbilical vein endothelial cells (HUVECs). DcR3 promotes HUVEC proliferation and migration and up-regulates matrix metalloproteinase-2 mRNA expression and enzyme activity. Furthermore, DcR3 enhances EC differentiation into cord vascular-like structures in vitro, as well as neovascularization in vivo. The effects of DcR3 on HUVECs are also mimicked by anti-TL1A and antideath receptor 3 antibodies. In contrast, human aortic endothelial cells, which do not express TL1A, are not responsive to DcR3 treatment, including cell proliferation, migration, and angiogenic differentiation. These data demonstrate DcR3 might not only help tumor cells to escape immune surveillance but also induce angiogenesis by blocking TL1A action in endothelial cells. The pathological role of DcR3 in promoting cancer progress raises the possibility to target DcR3 for antiangiogenic therapy in the future.