Antiplatelet effects of the CEACAM1-derived peptide QDTT.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) restricts platelet activation via platelet collagen receptor GPVI/FcRγ-chain. In this study, screening against collagen-induced platelet aggregation was performed to identify functional CEACAM1 extracellular domain fragments. CEACAM1 fragments, including Ala-substituted peptides, were synthesized. Platelet assays were conducted on healthy donor samples for aggregation, cytotoxicity, adhesion, spreading, and secretion. Mice were used for tail bleeding and FeCl3-induced thrombosis experiments. Clot retraction was assessed using platelet-rich plasma. Extracellular segments of CEACAM1 and A1 domain-derived peptide QDTT were identified, while N, A2, and B domains showed no involvement. QDTT inhibited platelet aggregation. Ala substitution for essential amino acids (Asp139, Thr141, Tyr142, Trp144, and Trp145) in the QDTT sequence abrogated collagen-induced aggregation inhibition. QDTT also suppressed platelet secretion and "inside-out" GP IIb/IIIa activation by convulxin, along with inhibiting PI3K/Akt pathways. QDTT curtailed FeCl3-induced mesenteric thrombosis without significantly prolonging bleeding time, implying the potential of CEACAM1 A1 domain against platelet activation without raising bleeding risk, thus paving the way for novel antiplatelet drugs.

What is the context? The study focuses on Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and its role in platelet activation, particularly through the GPVI/FcRγ-chain pathway.The research aims to identify specific fragments of CEACAM1's extracellular domain that could restrict platelet activation, without increasing bleeding risk.What is new? The researchers identified a peptide called QDTT derived from the A1 domain of CEACAM1's extracellular segment. This peptide demonstrated the ability to inhibit platelet aggregation, secretion, and GP IIb/IIIa activation.The study also revealed that specific amino acids within the QDTT sequence were essential for its inhibitory effects on collagen-induced aggregation.What is the impact? The findings suggest that the A1 domain-derived peptide QDTT from CEACAM1 could serve as a potential basis for developing novel antiplatelet drugs. This peptide effectively limits platelet activation and aggregation without significantly prolonging bleeding time, indicating a promising approach to managing thrombosis and related disorders while minimizing bleeding risks.

Luteolin inhibits GPVI-mediated platelet activation, oxidative stress, and thrombosis.

Introduction: Luteolin inhibits platelet activation and thrombus formation, but the mechanisms are unclear. This study investigated the effects of luteolin on GPVI-mediated platelet activation in vitro and explored the effect of luteolin on thrombosis, coagulation, and platelet production in vivo. Methods: Washed human platelets were used for aggregation, membrane protein expression, ATP, Ca2+, and LDH release, platelet adhesion/spreading, and clot retraction experiments. Washed human platelets were used to detect collagen and convulxin-induced reactive oxygen species production and endogenous antioxidant effects. C57BL/6 male mice were used for ferric chloride-induced mesenteric thrombosis, collagen-epinephrine induced acute pulmonary embolism, tail bleeding, coagulation function, and luteolin toxicity experiments. The interaction between luteolin and GPVI was analyzed using solid phase binding assay and surface plasmon resonance (SPR). Results: Luteolin inhibited collagen- and convulxin-mediated platelet aggregation, adhesion, and release. Luteolin inhibited collagen- and convulxin-induced platelet ROS production and increased platelet endogenous antioxidant capacity. Luteolin reduced convulxin-induced activation of ITAM and MAPK signaling molecules. Molecular docking simulation showed that luteolin forms hydrogen bonds with GPVI. The solid phase binding assay showed that luteolin inhibited the interaction between collagen and GPVI. Surface plasmon resonance showed that luteolin bonded GPVI. Luteolin inhibited integrin αIIbß3-mediated platelet activation. Luteolin inhibited mesenteric artery thrombosis and collagen- adrenergic-induced pulmonary thrombosis in mice. Luteolin decreased oxidative stress in vivo. Luteolin did not affect coagulation, hemostasis, or platelet production in mice. Discussion: Luteolin may be an effective and safe antiplatelet agent target for GPVI. A new mechanism (decreased oxidative stress) for the anti-platelet activity of luteolin has been identified.

A systematic review and meta-analysis of the hyperuricemia risk from certain metals.

The relationship between exposure to certain metals and the risk of hyperuricemia (HUA) has biological plausibility, yet prior studies have presented inconsistent findings. We aim to clarify the relationship between exposure to certain metals and HUA using a systematic review and meta-analysis approach. We searched the Web of Science, Embase, MEDLINE, Pubmed, Corchrane and China National Knowledge Infrastructure databases from inception through December, 2021 in order to identify studies that assessed the relationships between metals and the risk of HUA. Data were pooled by random-effects models and expressed as pooled odds ratios (OR) and 95% confidence intervals (CIs). The risk of bias was assessed using a tool from Agency for Healthcare Research and Quality (AHRQ). Twenty eligible articles (nineteen cross-sectional studies and one cohort) were included in our analysis, involving 63,283 participants in total. The studies showed that arsenic (pooled OR = 1.702, 95% CI: 1.44, 2.011; n = 6, I2 = 29.5%), calcium (pooled OR = 1.765, 1.111, 2.804; 4, 82.3%), cadmium (pooled OR = 1.199,1.020, 1.410; 11, 38.5%) and lead (pooled OR = 1.564,1.205, 2.030; 11, 72.9%) exposure were, all linked to an increased risk of HUA. Exposure to molybdenum (pooled OR = 0.804, 0.724, 0.975, 3, 0%) was linked to a decreased risk of HUA, however. Exposure to arsenic, calcium, cadmium and lead is associated with an increased risk of HUA. Molybdenum exposure was associated with a decreased prevalence of HUA; however, aluminum, cobalt, copper, iron, magnesium, manganese, mercury, selenium, thallium and zinc are not associated with HUA risk. Further experimental studies are warranted to decipher the mechanisms by which exposure to the above metals affect HUA risk. The findings reinforced the importance of metals in the HUA risk, and provided a reference for legislation to prevent HUA and protect people's health.

Effect of Evodiamine on Collagen-Induced Platelet Activation and Thrombosis.

Evodia rutaecarpa has multiple pharmacological effects and is widely used in the prevention and treatment of migraine, diabetes, cardiovascular disease, cancer, and other chronic diseases; however, the pharmacological effects of its active compound evodiamine (Evo) have not been thoroughly investigated. The purpose of this study was to investigate the effects of Evo on antiplatelet activation and thrombosis. We discovered that Evo effectively inhibited collagen-induced platelet activation but had no effect on platelet aggregation caused by activators such as thrombin, ADP, and U46619. Second, we found that Evo effectively inhibited the release of platelet granules induced by collagen. Finally, evodiamine inhibits the transduction of the SFKs/Syk/Akt/PLCγ2 activation pathway in platelets. According to in vivo studies, Evo significantly prolonged the mesenteric thromboembolism induced by ferric chloride and had no discernible effect on the coagulation function of mice. In conclusion, the antiplatelet and thrombotic effects of Evo discovered in this study provide an experimental basis for the investigation of the pharmacological mechanisms of Evo and the development of antiplatelet drugs.

Applying a Psychological Nursing Care Quality Evaluation Index in hospitalized patients: A pilot study.

Psychological problems have become a significant public health problem. Appropriate mental health care is crucial in promoting patient care quality. This study aimed to test the feasibility of a Psychological Nursing Quality Evaluation Index in hospitalized patients. This is a pilot study with patients hospitalized with myocardial infarction from July to September 2020 in China. The researchers used an observational approach to examine nurses' psychological health care performance based on the Psychological Nursing Quality Evaluation Index. The results indicated high compliance rates of nurses' psychological care performance, which provides references for evaluating and monitoring inpatient psychological nursing care.

Experimental Study on the Effect of Allogeneic Endothelial Progenitor Cells on Wound Healing in Diabetic Mice.

Endothelial progenitor cells (EPCs) are involved in the neovascularization in traumatic and ischemic sites, but EPCs are "detained" in bone marrow under diabetic conditions, which results in reduction of the number of EPCs and their biological activity in peripheral blood. Based on our previous study to mobilize autologous bone marrow EPCs by administering AMD3100+G-CSF to realize the optimal effect, our present study is aimed at exploring the effects of transplanting EPCs locally in a wound model of diabetic mice. First, we prepared and identified EPCs, and the biological functions and molecular characteristics were compared between EPCs from DB/+ and DB/DB mice. Then, we performed full-thickness skin resection in DB/DB mice and tested the effect of local transplantation of EPCs on skin wound healing. The wound healing process was recorded using digital photographs. The animals were sacrificed on postoperative days 7, 14, and 17 for histological and molecular analysis. Our results showed that DB/+ EPCs were biologically more active than those of DB/DB EPCs. When compared with the control group, local transplantation of EPCs accelerated wound healing in DB/DB mice by promoting wound granulation tissue formation, angiogenesis, and collagen fiber deposition, but there was no significant difference in wound healing between DB/+ EPCs and DB/DB EPCs transplanted into the wound. Furthermore, local transplantation of EPCs promoted the expression of SDF-1, CXCR4, and VEGF. We speculated that EPC transplantation may promote wound healing through the SDF-1/CXCR4 axis. This point is worth exploring further. Present data are of considerable significance because they raise the possibility of promoting wound healing by isolating autologous EPCs from the patient, which provides a new approach for the clinical treatment of diabetic wounds in the future.

Mental distress and influencing factors in nurses caring for patients with COVID-19.

BACKGROUND: Nurses are experiencing tremendous stress during the new coronavirus disease 2019 (COVID-19) pandemic, especially intensive care nurses. The pandemic of the disease is a tragedy, which may leave a catastrophic psychological imprint on nurses. Understanding nurses' mental distress can help when implementing interventions to mitigate psychological injuries to nurses. AIMS AND OBJECTIVES: To quantify the severity of nurses' post-traumatic stress disorder (PTSD) symptoms and stress and explore the influencing factors of their psychological health when caring for patients with COVID-19. DESIGN: A cross-sectional survey. METHODS: The PTSD Checklist-Civilian and the Perceived Stress Scale were administered from 11 to 18 March 2020, to 90 nurses selected from another city to go and help an intensive care unit (ICU) in Wuhan, China. These nurses were selected because of their high levels of clinical performance and resilience status. RESULTS: Nurses' average PTSD score was 24.62 ± 6.68, and five (5.6%) of the nurses reported a clinically significant level of PTSD symptoms (>38 points). Nurses' perceived stress averaged 19.33 ± 7, and 20 nurses (22.22%) scored positively >25 points. Nurses' stress and PTSD symptoms were positively correlated (P < .01). Major stress sources included working in an isolated environment, concerns about personal protective equipment shortage and usage, physical and emotional exhaustion, intensive workload, fear of being infected, and insufficient work experiences with COVID-19. CONCLUSIONS: This study showed that even relatively highly resilient nurses experienced some degree of mental distress, including PTSD symptoms and perceived stress. Our findings highlight the importance of helping nurses cultivate resilience and reduce stress. RELEVANCE TO CLINICAL PRACTICE: Recommendations for practice include providing adequate training and orientation before assigning nurses to ICU to help, offering disaster-emergency-preparedness training to keep nurses prepared, providing caring and authentic nursing leadership, offering ongoing psychological support to frontline nurses.

Current State and Influencing Factors of Nurse Resilience and Perceived Job-Related Stressors.

BACKGROUND: Resilience is a characteristic and skill that nurses can learn. This study examined the current state and influencing factors of nurse resilience and nurse perceived job-related stressors. METHOD: This cross-sectional survey study was conducted at a university-affiliated hospital in China between May and August 2018. The Connor-Davidson Resilience Scale was used to measure nurse resilience. RESULTS: A total of 2,981 nurses participated in the study, with an average resilience score of 61.35 ± 13.12. Nurse resilience was significantly correlated with age, years of employment, clinical rank, and education (p < .05). Main job-related stressors included frequent inspections and examinations, heavy workload, mandatory overtime, and low wages. CONCLUSION: The participants had resilience scores that were lower than in the general public in the United States and China, as well as in nurses in developed countries. This study indicated a need for hospital leaders to find ways to reduce nurse work-related stress. Building nurse resilience should be an important focus for leaders. [J Contin Educ Nurs. 2020;51(3):132-137.].

Comparison of Ticagrelor and Clopidogrel for Patients Undergoing Emergency Percutaneous Coronary Intervention.

BACKGROUND: We compared treatments with the antiplatelets ticagrelor and clopidogrel used in patients with acute myocardial infarction (AMI) during the perioperative period for emergency percutaneous coronary intervention (PCI). METHODS: A total of 120 patients were selected and randomly divided into control and observation groups (60 patients in each) from 2014-2016 at The Affiliated Hospital of Qingdao University. The patients in the control group received 300 mg clopidogrel and 300 mg aspirin for oral administration, while those in the observation group were given 180 mg ticagrelor and 300 mg aspirin orally prior to the PCI. During the operation, heparinization and a tirofiban micro-pump were used continuously. RESULTS: Coronary artery and peripheral venous blood were extracted from each patient to obtain various parameters of thrombelastogram (TEG), and the maximum platelet aggregation rates in order to compare antiplatelet effects. Major adverse cardiac events (MACE) were recorded during the following 6-month follow-up. Analysis of the data showed no differences in terms of the time span between medication intake and stent implantation, or the dosage of heparin and tirofiban used between the two groups. Before stent implantation, and 24 and 48 h after the procedure the average R and K values of TEG in coronary artery blood and peripheral venous blood samples in the observation group were longer than those in the control group, while the α angle, MA, CI, MARAA and MARADP values were lower (P<0.05). CONCLUSION: Ticagrelor can improve antiplatelet treatment for patients with AMI during the perioperative period of emergency PCI.

Novel hydroxybutyl chitosan nanoparticles for siRNA delivery targeting tissue factor inhibits proliferation and induces apoptosis in human vascular smooth muscle cells.

Chitosan, a polysaccharide isolated from shrimp and other crustacean shells, has been widely investigated for DNA and siRNA delivery. Despite substantial effort having been made to improve chitosan as a non­viral gene delivery vector, the application is severely limited by its poor solubility under physiological conditions. Hydroxybutyl chitosan (HBC), a modified chitosan, is soluble under neutral conditions. Tissue factor (TF) is involved in the pathogenesis of cardiovascular diseases by promoting thrombus formation and inducing the migration and proliferation of vascular smooth muscle cells. Targeting TF is an attractive therapeutic strategy for cardiovascular diseases. In the present study, the use of HBC for the transfer of TF­siRNAs into human umbilical vein smooth muscle cells (HUVSMCs) was investigated, and the effects of TF knockdown on cell proliferation and apoptosis were examined. HBC/siRNA nanoparticles were produced by mixing HBC and siRNA solutions with the assistance of tripolyphosphate buffer. The transfection efficiency with these nanoparticles was 74±2.5%, which was determined using a fluorescence­labeled siRNA under fluorescence microscopy. The delivery of HBC/TF­siRNA resulted in reductions in the production of cellular and soluble TF protein in HUVMSCs, which were measured using western blotting and enzyme­linked immunosorbent assay, respectively. TF knockdown led to inhibited cell proliferation, as assessed using a Cell Counting Kit­8 assay, and increased cell apoptosis, determined using Annexin V­fluorescein isothiocyanate staining. These findings suggested that HBC may be a promising vector for siRNA delivery, and that in vivo HBC/siRNA nanoparticle delivery targeting TF may be a potential option for the treatment of cardiovascular diseases, which warrants further investigation.

Percutaneous extraction of leads from coronary sinus vein and branch by modified techniques.

BACKGROUND: Cardiac resynchronization therapy (CRT) device and coronary sinus (CS) lead extraction are required due to the occurrence of systemic infection, malfunction, or upgrade. Relevant research of CS lead extraction is rare, especially in developing countries because of the high cost and lack of specialized tools. We aimed to evaluate percutaneous extraction of CS leads by modified conventional techniques. METHODS: Of 200 patients referred for lead extraction from January 2007 to June 2011, 24 (12.0%) involved CS leads (24 CS leads). We prospectively analyzed clinical characteristics, optimized extraction techniques and feasibility of extraction. RESULTS: Complete procedural success was achieved in 23 patients (95.8%), and the clinical success in 24 patients (100.0%). The leading indication for CS lead extraction was infection (66.7%). Mean implant duration was (29.5 ± 20.2) months (range, 3 - 78 months). Sixteen CS leads (66.6%) were removed with locking stylets plus manual traction by superior transvenous approach. Mechanical dilatation and counter-traction was required to free fibrotic adhesions and extract 4 CS leads (16.7%), which had longer implant duration than other leads ((62.5 ± 12.3) vs. (22.9 ± 14.1) months, P < 0.05). Another 4 CS (16.7%) leads were removed by modified and innovative snare techniques from femoral vein approach. Median extraction time was 11 minutes (range, 3 - 61 minutes) per CS lead, which had significant correlation with implant duration (r = 0.8, P < 0.001). Sixteen patients (66.6%) were reimplanted with new devices at a median of 7.5 days after extraction. Median followed-up was 23.5 months (range, 8 - 61 months), three patients died due to sudden cardiac death (26 months), heart failure (45 and 57 months, respectively). CONCLUSION: The modified procedure was proved to be practical for percutaneous extraction of CS leads, especially in developing countries lacking expensive powered sheaths.