Blood Urea Nitrogen and In-Hospital Mortality in Critically Ill Patients with Cardiogenic Shock: Analysis of the MIMIC-III Database.

The association between blood urea nitrogen (BUN) and prognosis has been the focus of recent research. Therefore, the objective of this study was to investigate the association between BUN and hospital mortality in critically ill patients with cardiogenic shock (CS). This was a retrospective cohort study, in which data were obtained from the Medical Information Mart for Intensive Care III V1.4 database. Data from 697 patients with CS were analyzed. Logistic regression and subgroup analyses were used to assess the association between BUN and hospital mortality in patients with CS. The average age of the 697 participants was 71.14 years, and approximately 42.18% were men. In the multivariate logistic regression model, after adjusting for age, sex, diabetes, cardiac arrhythmias, urine output, simplified acute physiology score II, sequential organ failure assessment, creatinine, anion gap, and heart rate, high BUN demonstrated strong associations with increased in-hospital mortality (per standard deviation increase: odds ratio [OR] 1.47, 95% confidence interval [CI] 1.13-1.92). A similar result was observed in BUN tertile groups (BUN 23-37 mg/dL versus 6-22 mg/dL: OR [95% CI], 1.42 [0.86-2.34]; BUN 38-165 mg/dL versus 6-22 mg/dL: OR [95% CI], 1.99 [1.10-3.62]; P trend 0.0272). Subgroup analysis did not reveal any significant interactions among various subgroups, and higher BUN was associated with adverse clinical outcomes in patients with CS.

Salvianolic acid a inhibits platelet activation and aggregation in patients with type 2 diabetes mellitus.

BACKGROUND: Platelets in patients with type 2 diabetes mellitus (DM2) are characterized by increased activation and aggregation, which tends to be associated with a high morbidity and mortality due to cardiovascular disease (CVD). Moreover, a large proportion of DM2 patients show an inadequate response to standard antiplatelet treatments, contributing to recurrent cardiovascular events. In our previous study, we indicated that Salvianolic acid A (SAA) presents an antiplatelet effect in healthy volunteers. However, whether it can inhibit "activated platelets" with a pathologic status has not been explored. Therefore, this study was designed to investigate the antiplatelet effect of SAA and its diabetic complication-related difference in DM2. METHODS: Forty patients diagnosed with DM2 from January 2018 to April 2018 were recruited. Fibrinogen-binding (PAC-1) and P-selectin (CD62p) flow cytometry reagents were measured under resting and stimulated conditions by flow cytometry, while agonist-induced platelet aggregation was conducted by light transmission aggregometry. Before all these measurements were conducted, all platelet samples were preincubated with a vehicle or SAA for 10 min. Additionally, the diabetic complication-related difference in the antiplatelet effect of SAA was further studied in enrolled patients. RESULTS: The expressions of PAC-1 and CD62p were elevated in DM2, as well as the maximal platelet aggregation. In addition, SAA decreased the expressions of PAC-1 and CD62p, which were enhanced by ADP and thrombin (all P < 0.01). It also reduced the platelet aggregation induced by ADP (P < 0.001) and thrombin (P < 0.05). Comparing the antiplatelet effect of SAA on DM2, with and without diabetic complications, no statistically significant difference was found (all P > 0.05). CONCLUSIONS: The present study demonstrated that SAA can inhibit platelet activation and aggregation in patients with DM2, and the inhibition did not abate for the existence of diabetic complications.

Association between Triglyceride-Glucose Index and Type 2 Diabetes Mellitus in the Japanese Population: A Secondary Analysis of a Retrospective Cohort Study.

Triglyceride-glucose index (TyG index) is associated with type 2 diabetes mellitus (T2DM), but research on this relationship is limited in Japan. The purpose of this study was to evaluate the correlation between TyG index and the risk of T2DM in the Japanese population. Here, 12732 participants were selected from the NAGALA study (NAfld in the Gifu Area, Longitudinal Analysis) conducted between 2004 and 2015 for a retrospective cohort analysis. The association between TyG index and T2DM was assessed using the Cox proportional-hazard model. Subgroup analyses were conducted according to age, sex, smoking status, alcohol consumption, waist circumference, BMI, and follow-up duration. The formula for TyG index was expressed as ln [fasting triglyceride level (mg/dL) × fasting plasma glucose level (mg/dL)/2]. After follow-up, 150 (1.18%) patients developed T2DM. After adjusting for potential confounders, a linear relationship was observed between TyG and the risk of T2DM. After adjusting for age, sex, BMI, waist circumference, HDL-cholesterol, total cholesterol, systolic blood pressure, regular exercise, smoking status, and alcohol consumption, TyG index, as a continuous variable, was associated with an increased risk of T2DM (adjusted hazard ratio (aHR), 1.79; 95% confidence interval (95% CI), 1.25-2.57). Compared with the first quartile of TyG index, subjects in the fourth quartile were 2.33-fold more likely to develop T2DM (aHR 2.33, 95% CI 1.09-4.96; P for trend 0.0224). Subgroup analyses showed that the association between TyG index and incident T2DM stably existed in different subgroups according to the variables tested. Therefore, TyG index was linearly related to the risk of incident T2DM in the Japanese population and may be used as a monitoring tool.

[A method of primary cell culture of rat pulmonary artery smooth muscle cells and effects of platelet-derived growth factor induced proliferation and migration].

OBJECTIVE: To establish an easy, not depending on advanced laboratory apparatus method to isolate and culture rat pulmonary artery smooth muscle cells (PASMCs), and to explore the effects of platelet-derived growth factor (PDGF) on cell proliferation and migration. METHODS: The right ventricle was perfused with the mixture of iron, agarose, and the PASMCs and iron could adhere to agarose. The iron-con-taining tissue would move to side of the tube next to the magnet and could be digested by collagenase I. By the method, vessel-containing tissue could be attained. With 3-4 weeks' purification, the PASMCs could be obtained. The PASMCs morphology was observed by an inverted micro-scope, and identified by immunocytochemistry and immunofluorescence. The effects of PDGF on cell proliferation and migration was detected by MTT assay and scratch wound assay. RESULTS: 14 days、21 days and primary culture after isolation, the PASMCs was identified, and the re-sult showed that isolation and primary culture of the cells were PASMCs. Compared with the cells with no stimulation, the proliferation of PASMCs exposed to PDGF was increased significantly(P<0.05), and scratch wound assay demonstrated that PDGF induced the significant increase of migration of PASMCs. CONCLUSIONS: This method to isolate and culture rat PASMCs is simple, not depending on advanced laborato-ry. PDGF can promote the proliferation and migration of PASMCs.

Platelet-mediated mesenchymal stem cells homing to the lung reduces monocrotaline-induced rat pulmonary hypertension.

Bone marrow mesenchymal stem cell (BM-MSC) transplantation has been suggested to be a promising method for the treatment of pulmonary arterial hypertension (PAH), a fatal disease currently without effective preventive/therapeutic strategies. However, the detailed mechanisms underlying BM-MSC therapy are largely unknown. We designed the present study to test the hypothesis that circulating platelets facilitate BM-MSC homing to the lung vasculature in a rat model of PAH induced by monocrotalin (MCT). A single subcutaneous administration of MCT induced a marked rise in right ventricular systolic pressure (RVSP) and the weight ratio of right to left ventricle plus septum (RV/LV+S) 3 weeks after injection. The injection of MSCs via tail vein 3 days after MCT significantly reduced the increase of RVSP and RV/LV+S. The fluorescence-labeled MSCs injected into the PAH rat circulation were found mostly distributed in the lungs, particularly on the pulmonary vascular wall, whereas cell homing was abolished by an anti-P-selectin antibody and the GPIIb/IIIa inhibitor tirofiban. Furthermore, using an in vitro flow chamber, we demonstrated that MSC adhesion to the major extracellular matrix collagen was facilitated by platelets and their P-selectin and GPIIb/IIIa. Therefore, the current study suggested that platelet-mediated MSC homing prevented the aggravation of MCT-induced rat PAH, via P-selectin and GPIIb/IIIa-mediated mechanisms.

Systemic evaluation of platelet and leukocyte activation and interaction in a rat model of pulmonary arterial hypertension.

OBJECTIVES: Thrombosis and inflammation are associated with the pathogenesis of pulmonary arterial hypertension (PAH). However, there are no solid data supporting the involvement of platelet and leukocyte activation and interaction in PAH. The present study thus investigated the activation and interaction of circulating platelets and leukocytes in a rat model of monocrotaline (MCT)-induced pulmonary hypertension. METHODS: Mean pulmonary arterial pressure (mPAP) was monitored in rats (n = 24) before and 2, 3 and 7 weeks after MCT (60 mg/kg)injection. In parallel, activation of circulating platelets and leukocytes and platelet-leukocyte aggregates were measured by whole-blood flow cytometry. RESULTS: Two weeks after MCT injection, mPAP had increased significantly, i.e. from 11.25 ± 0.92 mm Hg at baseline to 15.71 ± 1.66 mm Hg (p < 0.05), and it had increased even further at week 7 (26.83 ± 3.29 mm Hg; p < 0.01). Fibrinogen binding of circulating platelets had increased from the basal level of 1.45 ± 0.61 to 4.08 ± 1.59% 3 weeks after MCT injection (p < 0.01). Platelet responsiveness to ADP was also significantly enhanced. CD11b expression of circulating neutrophils was elevated; i.e. mean fluorescence intensity increased from 1.67 ± 0.38 before MCT injection to 2.37 ± 0.31 3 weeks after MCT injection (p < 0.01), and N-formyl-methionyl-leucyl-phenylalanine (1 × 10⁻7M) stimulation induced more marked elevation of neutrophil CD11b expression in MCT-treated animals. Circulating platelet-neutrophil aggregates were already increased 2 weeks after MCT treatment (14.93 ± 4.22%; p < 0.01) compared to baseline (6.01 ± 2.91%) and remained elevated at 3 weeks (15.19 ± 4.78%; p < 0.01). CONCLUSIONS: MCT-induced PAH in rats is associated with increased platelet and leukocyte activation and platelet-leukocyte interaction in vivo, which may play an important role in the pathogenesis of PAH.

[Quantitative and functional changes of circulating endothelial progenitor cells in dogs with dehydromonocrotaline-induced pulmonary artery hypertension].

OBJECTIVE: To determine the quantitive and functional changes of circulating endothelial progenitor cells (EPCs) in dogs with dehydromonocrotaline-induced pulmonary artery hypertension (PAH). METHODS: Dehydromonocrotaline was injected into the canine right ventricle to induce pulmonary hypertension. Circulating EPCs were enumerated as AC+(113), KDR+ cells by fluorescence-activated cell sorter using counting beads, and the number and activity of EPCs after in vitro expansion were determined by acLDL uptake/lectin staining assay and in vitro tubule forming assay. RESULTS: Nine of the 10 beagles survived after dehydromonocrotaline injection. Six weeks later, mean pulmonary artery pressure increased from (11.3 +/- 2.0) mm Hg (1 mm Hg = 0.133 kPa) to (20.2 +/- 1.6) mm Hg (t =10.307, P < 0.01), and the AC+(133) and KDR+ cells decreased from (632.8 +/- 42.8) cells/ml to (206.1 +/- 26.8) cells/ml (t = 25.361, P < 0.01). UEA- I and DiLDL positive cells deceased from (41 +/- 6) EPCs/ x 200 field to (22 +/- 6) EPCs/ x 200 field (t = 6.510, P < 0.01). In addition, in vasculogenesis assay, PAH EPCs formed less quantitative (11.2 +/- 2.8 vs 21.1 +/- 2.8 tubules/ x 200 field, respectively, t = 7. 583, P <0. 01) and less qualitive tubules than baseline EPCs. CONCLUSION: The number and vessel forming ability of EPCs are impaired in this canine model of dehydromonocrotaline-induced pulmonary hypertension.

Differences in blood pressure readings between supine and sitting positions in hypertensive patients.

OBJECTIVE: The objective of this study was to investigate the impact of postures on blood pressure (BP) readings in patients with hypertension. METHODS AND RESULTS: BP was measured in 1,487 hypertensive patients in sitting and supine positions. The systolic (SBP) and diastolic (DBP) BP in supine position was 2.9 +/- 7.8mmHg and 0.9 +/- 5.4 mmHg higher, respectively, than in the sitting position (P <0.001). The greatest difference between supine and sitting SBP was found in those aged between 30 and 39 years (3.6 +/- 6.8 mmHg), and in those who were older than 80 years (5.3 +/- 7.9 mmHg).A greater difference between the supine and sitting DBP was identified in the groups > 60-years of age. Multivariate regression analysis showed that age and sex were independent predictors for the increment of BP in the supine position. CONCLUSION: There is a significant difference between supine and sitting SBP and DBP, with age and sex being the most important predicting factors.

[Effects of angiotensin converting enzyme inhibitor on the expression of angiotensin converting enzyme 2 in atrium of patients with atrial fibrillation].

OBJECTIVE: To investigate the expression of angiotensin converting enzyme 2 (ACE2) and the changes treated with angiotensin converting enzyme inhibitor (ACEI), and its signal transduction pathway. METHODS: Atrial tissues were obtained from 47 patients with RHD undergoing cardiac surgery. The mRNA of ACE2 and ACE were semi-qualified by RT-PCR and normalized to the gene beta-actin. Western blot analysis was employed to examine the expressions of ACE2, ACE, ERK1/2 and phosphorylated ERK (pERK1/2). The atrial tissue angiotensin II (Ang II) content was determined by radioimmunoassay detection. RESULTS: The expression of ACE2 was significantly decreased (P < 0.05), the expression of ACE and pERK1/2 were significantly increased (P < 0.05), and the level of atrial tissue Ang II was significantly increased in patients with chronic atrial fibrillation group (CAF) compared with sinus rhythm group (SR) (P < 0.05). Compared with CAF patients treated without ACEI, the expression of ACE2 significantly increased (P < 0.01), and the relative activity of ERK1/2 significantly decreased (P < 0.05), whereas the expression of ACE and the level of atrial tissue Ang II remained unchanged in CAF patients treated with ACEI. CONCLUSIONS: The study suggested that the dysequilibrium of ACE/ACE2 might play an important role in the process of atrial fibrillation, which may be related to the activation of ERK1/2 pathway. The clinical effect of long-term treatment of ACEI maybe associated with elevated ACE2 expression but not ACE expression.