Asymmetric dimethylarginine correlates with indicators of prethrombotic state in patients with nonvalvular atrial fibrillation.

OBJECTIVE: The mechanism of asymmetric dimethylarginine (ADMA) in thrombosis in patients with nonvalvular atrial fibrillation (NVAF) is still unclear. Our aim was to investigate the relationship between ADMA and indicators of prethrombotic state in NVAF patients and to analyze the predictive role of ADMA in NVAF thrombosis. METHODS: A total of 192 NVAF patients were continuously selected from January 2023 to October 2023. Plasma ADMA levels were measured by high-performance liquid chromatography. P-selectin (P-sel), von Willebrand factor (vWF), D-dimer (D-D), and plasminogen activator inhibitor-1 (PAI-1) levels were measured by enzyme-linked immunosorbent assay (ELISA). Nitric oxide (NO) levels were measured by the nitrate reductase assay for plasma nitrite/nitrate, then the Griess method (Shanghai Hailian Biotechnology Co., Shanghai, China) was used to calculate plasma NO levels. RESULTS: In our study, ADMA levels were significantly elevated and positively correlated with P-sel, vWF, D-D, and PAI-1, whereas NO levels were significantly negatively correlated with these prethrombotic factors in NVAF. Furthermore, multifactorial logistic regression analysis showed that ADMA and LA diameter were independent predictors of high thrombosis risk (CHA2DS2-VASc ≥2 score) in patients with NVAF. CONCLUSIONS: Our findings suggested that ADMA correlated with the prethrombotic state in NVAF and that reduction of ADMA levels in NVAF patients may be a novel therapeutic strategy for thrombosis risk reduction.

Extensive serum biomarker analysis in the prethrombotic state of recurrent spontaneous abortion.

The prethrombotic state (PTS) is a possible cause of recurrent spontaneous abortion (RSA). The aim of this study was to identify serum biomarkers for the detection of RSA with PTS (PSRSA). A Quantibody array 440 was used to screen novel serum-based biomarkers for PSRSA/NRSA (RSA without PTS). Proteins differentially expressed in PSRSA were analysed using bioinformatics methods and subjected to a customized array and enzyme-linked immunosorbent assay (ELISA) validation. We used receiver operating characteristic to calculate diagnostic accuracy, and machine learning methods to establish a biomarker model for evaluation of the identified targets. 20 targets were selected for validation using a customized array, and seven targets via ELISA. The decision tree model showed that IL-24 was the first node and eotaxin-3 was the second node distinguishing the PSRSA and NRSA groups (an accuracy rate of 100% and an AUC of 1). Epidermal growth factor (EGF) as the node distinguished the PSRSA and NC groups (an accuracy rate of 100% and an AUC of 1). EGF as the node distinguished the NRSA and NC groups (an accuracy rate of 96.5% and an AUC of 0.998). Serum DNAM-1, BAFF, CNTF, LAG-3, IL-24, Eotaxin-3 and EGF represent a panel of promising diagnostic biomarkers to detect the PSRSA.

Silica nanoparticles trigger the vascular endothelial dysfunction and prethrombotic state via miR-451 directly regulating the IL6R signaling pathway.

BACKGROUND: Safety evaluation is a prerequisite for nanomaterials in a wide range of fields, including chemical industries, medicine or food sciences. Previously, we had demonstrated that SiNPs could trigger the thrombotic effects in vivo, but the underlying mechanisms remain unknown. This study was aimed to explore and verify the role of miR-451a on SiNPs-induced vascular endothelial dysfunction and pre-thrombotic state. RESULTS: The color doppler ultrasound results showed that SiNPs had the inhibitory effects on aorta velocity and cardiac output. The histological and ultrastructural analysis manifested that SiNPs could induce the vascular endothelial damage. In addition, the expression level of MDA was elevated while the activity of SOD and GSH-Px were decreased in aortic arch triggered by SiNPs, accompanied with the release of iNOS and decline of eNOS in blood serum. The immunohistochemistry results showed that the positive staining of TF and PECAM-1 were elevated in a dose-dependent manner induced by SiNPs. The activation of coagulation function occurred via shortened TT, PT and APTT while the FIB was elevated markedly induced by SiNPs. Coagulant factors (TF, FXa and vWF) and PLT numbers were increased whereas the levels of anticoagulant factors (ATIII, TFPI and t-PA) were decreased. Microarray analysis showed that the down-regulated miR-451a could target the gene expression of IL6R, which further activated the JAK/STAT signaling pathway triggered by SiNPs. Dual-luciferase reporter gene assay confirmed the directly target relationship between miR-451a and IL6R. Additionally, the chemical mimics of miR-451a led to attenuate the expression of IL6R/STAT/TF signaling pathway in vitro and in vivo induced by SiNPs, while the inhibitor of miR-451a enhanced the activation of IL6R/STAT/TF signaling pathway. CONCLUSIONS: In summary, SiNPs could accelerate the vascular endothelial dysfunction and prethrombotic state via miR-451a negative regulating the IL6R/STAT/TF signaling pathway.

[Bushen Huoxue Fang improves recurrent miscarriage in mice by down-regulating the JAK2/STAT3 pathway].

OBJECTIVE: To investigate the efficacy of Bushen Huoxue Fang (BSHXF, a traditional Chinese medicine formula) for improving recurrent spontaneous abortion (RSA) in mice and the role of tyrosine kinase (JAK2) and transcriptional activator (STAT3) signaling pathway in its therapeutic mechanism. METHODS: Female CBA/J mice were caged with male DBA/2 mice to establish RSA mouse models, which were randomly divided into model group, dydrogesterone group and BSHXF group, with the female mice caged with male BALB/c mice as the control group (n=6). From the first day of pregnancy, the mice were subjected to daily intragastric administration of BSHXF, dydrogesterone, or distilled water (in control and model groups) for 12 days. After the treatments, serum levels of antithrombin III (AT-III), activated protein C (APC), tissue plasminogen activator (t-PA), progesterone, human chorionic gonadotropin (HCG), and estradiol (E2) were detected in each group using ELISA. HE staining was used to observe the morphological changes of the endometrium of the mice. Western blotting was performed to determine the expressions of p-JAK2, p-Stat3 and Bcl-2 in the placenta of the mice. RESULTS: Compared with the control mice, the mouse models of RSA showed a significantly increased embryo loss rate with decreased serum levels of AT-III, T-PA, progesterone, APC and HCG, increased placental expressions of p-JAK2, p-STAT3 and Bax, and decreased expression of Bcl-2 (P < 0.05). Treatments with BSHXF and dydrogesterone both increased serum levels of AT-III, t-PA and HCG in the mouse models; Serum APC level was significantly reduced in BSHXF group and serum progesterone level was significantly increased in dydrogesterone group (P < 0.05). CONCLUSION: BSHXF can improve the prethrombotic state and inhibit cell apoptosis by downregulating the JAK2/STAT3 pathway to increase the pregnancy rate in mouse models of RSA.

[Clinical study on the effect of acupuncture on pregnancy outcome in patients with prethrombotic infertility after repeated implantation failure].

OBJECTIVE: To observe the effect of acupuncture combined with medication on the pregnancy outcome of kidney deficiency and blood stasis type recurrent implantation failure (RIF) in prethrombotic infertility patients. METHODS: A total of 70 RIF patients of kidney deficiency and blood stasis type who were to undergo freeze-thaw embryo transplantation were randomly divided into control and treatment groups, with 35 cases in each group. Patients in the control group were given the basic treatment of artificial periodic freeze-thaw embryo transfer and oral aspirin enteric-coated tablet, 25 mg each time, twice a day, for 3 consecutive menstrual cycles. Patients in the treatment group were treated with acupuncture on the basis of the control group, 30 min each time, 3 times a week, for 3 consecutive menstrual cycles. The clinical pregnancy rate, embryo implantation rate and live birth rate of the two groups were compared. Before treatment and 1 day before transplantation, the scores of kidney deficiency and blood stasis symptom were compared. The blood flow pulse index (PI) and resistance index (RI) of the uterus spiral artery were detected by Doppler ultrasound before treatment and 1 day before transplantation. The endometrial thickness was detected 1 day before transplantation. The contents of plasma D-dimer, serum homocysteine (Hcy) and serum thromboxane B2 (TXB2) were detected. RESULTS: The clinical pregnancy rate, embryo implantation rate and live birth rate in the treatment group were higher than those in the control group (P<0.05). After treatment, the scores of kidney deficiency and blood stasis symptom, the levels of plasma D-dimer, serum Hcy and TXB2, the PI and RI value in both groups were decreased (P<0.05) compared with those before treatment, and the indexes in the treatment group were decreased (P<0.05) more than those in the control group. There was no significant difference in endometrial thickness between the two groups. In the course of treatments, 7 patients in the control group underwent gastric distension pain, poor appetite, constipation, nausea and other gastrointestinal reactions, while only 2 patients in the treatment group had the above discomfort reactions. CONCLUSION: On the basis of medication, acupuncture can reduce the serum TXB2 content in RIF patients in prethrombotic state, improve vascular endothelial function, enhance endometrial tolerance, alleviate the symptoms of kidney deficiency and blood stasis, reduce drug adverse reactions, and ultimately improve the pregnancy outcome and increase the rate of embryo implantation.

Relevant detection indicator of prethrombotic state in patients with primary hypertension.

BACKGROUND: Hypertension is a common chronic disease that affects many people worldwide. Only a few reports related to the exploration of relevant indicators of the prethrombotic state in patients with primary hypertension (PH) in clinical settings were available. AIM: To detect prethrombotic state-related indicators in patients with PH and analyze their differences in different patient populations to provide a laboratory basis for the clinical prevention and control of hypertensive thrombotic diseases. METHODS: The general data of patients with PH who attended the Department of Cardiovascular Medicine, The First Affiliated Hospital of Jiangxi Medical College, from January 2022 to December 2022 were collected retrospectively. The patients were divided into three groups of 40 patients each according to the Grade of PH: Grade 1, Grade 2, and Grade 3 hypertension experimental group. The baseline data of 40 volunteers, who underwent physical examination in our hospital but were not diagnosed with PH during the same period, were included in the control group. The relevant indicators of prethrombotic state of the participants were compared, and mainly included inflammation-related indicators, hemorheology-related indicators, and coagulation function related indicators. The relationship between the aforementioned indicators and the progression of PH was analyzed. RESULTS: No significant differences were observed in age, sex, diabetes mellitus, smoking history, drinking history, body mass index, New York Heart Association functional classification, or the course of hypertension among the four groups (P > 0.05). The expressions of high-sensitivity C-reactive protein (hs-CRP), thrombomodulin (TM), hematocrit (Hct), erythrocyte sedimentation rate (ESR), P-selectin on platelet surface (CD62P), and fibrinogen (FIB) in the control group were < Grade 1 hypertension group < Grade 2 hypertension group < Grade 3 hypertension group, and the expressions of platelet (PLT), activated partial thromboplastin time (APTT), prothrombin (PT), and plasma thrombin time (TT) in the control group was > Grade 1 hypertension group > Grade 2 hypertension group > Grade 3 hypertension group, and the difference was statistically significant (P < 0.05). The results of the multivariate logistic regression model showed that the expression of hs-CRP, TM, Hct, ESR, CD62P, PLT, APTT, PT, TT, and FIB in the included participants was related to the progression of PH. Among these, high expression of hs-CRP, TM, Hct, ESR, CD62P, APTT, PT, and TT, and low expression of PLT and FIB were risk factors for PH (OR > 1, P < 0.05). The results of the receiver operating characteristic curve analysis showed that the area under the curve of hs-CRP, TM, ESR, CD62P, APTT, PT, TT, and FIB for the prediction of PH were > 0.80, and the prediction value was ideal. Linear correlation analysis with bivariate Spearman showed that hs-CRP, TM, Hct, ESR, CD62P, APTT, PT, and TT were positively correlated with each other (r > 0, P < 0.05); PLT and FIB were negatively correlated with hs-CRP, TM, Hct, ESR, CD62P, APTT, PT, and TT (r < 0, P < 0.05); and PLT and FIB were positively correlated (r > 0, P < 0.05). Linear correlation analysis using bivariate Spearman showed that hs-CRP, TM, Hct, ESR, CD62P, and FIB were positively correlated with each other (r > 0, P < 0.05), whereas PLT, APTT, PT, and TT were negatively correlated with hs-CRP, TM, Hct, ESR, CD62P, and FIB (r < 0, P < 0.05). There was a positive correlation between PLT, APTT, PT, and TT (r > 0, P < 0.05). CONCLUSION: The relevant indicators of the prethrombotic state in patients with PH, such as hs-CRP, TM, Hct, ESR, CD62P, PLT, APTT, PT, TT, and FIB, showed differences. High expression of hs-CRP, TM, Hct, ESR, CD62P, and FIB, and low expression of PLT, APTT, PT, and TT are the keys to the occurrence, progression, and thrombotic state of PH. Based on the above serum indicators' expression in patients, targeted interventions can be administered to patients with abnormal expression levels to control the progression of their disease and reduce the risk of developing a prethrombotic state.

[Effects of swimming training on blood pressure and prethrombotic state molecules in hypertensive rats].

Objective: To observe the effects of 10-week swimming training on blood pressure and prethrombotic state in spontaneously hypertensive rats (SHR). Methods: Eighteen 10-week-old male SHR were randomly divided into control group (8 rats) and training group (10 rats). The SHR training group underwent weightless swimming training for 10 weeks, five times a week, 60 minutes a time, and blood pressure was measured every two weeks. The platelet aggregation rate, von willebrand factor(vWF), tissue plasminogen activator(t-PA), plasminogen activator inhibitor -1(PAI-1) in plasma were measured after 10 weeks of training. Results: Compared with the control group, blood pressure in SHR training group was decreased significantly(P＜0. 05) after 4-week of swimming training, and blood pressure, platelet aggregation rate, plasma vWF level, PAI-1 activity were decreased significantly(P＜0. 01), while plasma t-PA activity was increased significantly (P＜0. 01) after 10-week of swimming training. Conclusion: Suitable swimming training will effectively reduce the blood pressure of SHR and has a significant effect if persisting in training for 4 weeks, and it also can improve pre-thrombotic state, prevent hypertensive thrombotic complications significantly in SHR.

The efficacy and safety of multiple-dose intravenous tranexamic acid in reducing perioperative blood loss in patients with thoracolumbar burst fracture.

OBJECTIVE: To evaluate the efficacy and safety of tranexamic acid (TXA) for single-segment thoracolumbar burst fracture without neurologic injury underwent pedicle screw fixation via Wiltse approach. PATIENTS AND METHODS: We identified 264 patients with single-segment thoracolumbar burst fracture without neurologic injury underwent pedicle screw fixation via Wiltse approach (January 2016-June 2019) at a single center. The cohort was separated into three groups. Group A received 20 mg/kg TXA at 5 min before skin incision and 16 h after first dose; Group B received 20 mg/kg TXA at 5 min before skin incision; Group C received NS at each same time point. The outcomes were evaluated by hidden blood loss (HBL), total blood loss (TBL), intraoperative blood loss (IBL), transfusion rate, maximum hemoglobin (Hb) drop, prethrombotic state molecular markers, liver and renal function, coagulation function, inflammatory factor and adverse events. RESULTS: The HBL, TBL and maximum Hb drop were significantly lower in Group A than those of Group B and Group C, while the difference between Group B and Group C was statistically significant. The IBL was significantly lower in Group A and Group B than that of Group C. However, there was no significantly difference among the three groups in live and renal function, coagulation function, prethrombotic state molecular markers, transfusion rate and complications during the perioperative period. There was significantly lower level of interleukin-6 (IL-6) in Group A than Group C at the day after surgery, and lower level of C-reactive protein (CRP) at the third day after surgery. CONCLUSIONS: Intravenous TXA used in the treatment of thoracolumbar burst fracture underwent pedicle screw fixation via Wiltse approach is effective and safe in decreasing perioperative blood loss. The two-dose TXA regimen can further reduce blood loss and alleviate post-operative inflammation response, without affecting prethrombotic state molecular marks and without increasing the risk of complications.

Endometrial receptivity and conception outcome among women with light menstrual bleeding of unidentified etiology.

OBJECTIVE: To investigate endometrial receptivity (ER), conception outcome, and other factors among women with light menstrual bleeding of unidentified etiology. METHODS: A prospective study was undertaken at a center in China. Between January 1, 2011, and December 31, 2014, women meeting the inclusion criteria (aged 20-35 years, without any history of pregnancy, desire to conceive, follicle-stimulating hormone <10 IU on second or third day of cycle, and regular menstrual periods) were enrolled. Participants with a menstrual blood volume of 5-20 mL formed the study group; others were in the control group. ER measures were obtained by transvaginal Doppler ultrasonography. Serum estradiol and progesterone levels were measured and items of prethrombotic state were screened in mid-luteal phase. Participants were followed up for 1 year to establish conception outcome. RESULTS: The ER (Salle) score was significantly lower in the study group (n=110) than in the control group (n=330; 9.41 ± 3.02 vs 15.67 ± 2.63, P<0.001). The natural rate of conception within 1 year was lower (60.0% [63/105] vs 72.1% [230/319], P=0.020), and the spontaneous abortion rate in early pregnancy was higher (34.4% [21/61] vs 18.1% [41/227], P=0.006) in the study group than in the control group. CONCLUSION: Women with light menstrual bleeding of unidentified etiology had an increased prevalence of low ER and poor conception outcome.

Clinical value of combined detection of thrombus precursor protein and P-selectin in the diagnosis of acute coronary syndrome / Valor clínico de la detección combinada de proteína precursora de trombo y selectina P en el diagnóstico del síndrome coronario agudo

Abstract Acute coronary syndrome (ACS), including acute myocardial infarction (AMI) and unstable angina (UA), is the most threatening and lethal form of coronary heart disease. ACS has an abrupt onset and rapid development, which may lead to fatal conditions at any time. Thus, it is never too early to detect and diagnose patients with ACS. The objective of this work was to explore the significance of the combined detection of plasma thrombus precursor protein (TpP) and serum P-selectin (Ps), in the detection and diagnosis of patients with early ACS. A total of 126 subjects were included in the study, 64 ACS patients, 30 individuals with stable angina (SA) and 32 healthy persons who were selected as the control groups. There were no differences in gender, age, ethnicity, or blood glucolipid levels among the groups. Enzyme linked immunosorbent assay (Elisa) was used to quantitatively determine the plasma levels of TpP and Ps. The levels of the two biomarkers in the case group were significantly higher than those in the control groups. Among the ACS patients, the levels of TpP and Ps were higher in AMI patients than in the UA patients. In addition, there was no significant differences in the levels of Ps between SA patients and healthy persons. In conclusion, plasma TpP and serum Ps are remarkably increased in patients with ACS. Therefore, TpP and Ps may serve as ACS indicators, and their measurement may provide a support for an early clinical identification of ACS.

Resumen El síndrome coronario agudo (SCA), que incluye el infarto agudo de miocardio (IAM) y la angina inestable (AI), es la forma más amenazante y letal de enfermedad coronaria. El SCA tiene un inicio abrupto y un desarrollo rápido, lo que puede conducir a condiciones fatales en cualquier momento. Por lo tanto, nunca es demasiado pronto para detectar y diagnosticar pacientes con SCA. El objetivo de este trabajo fue explorar la importancia de la detección combinada de la proteína precursora de trombos plasmáticos (TpP) y la selectina P sérica (Ps), en la detección y diagnóstico de pacientes con SCA precoz. Se incluyeron en el estudio un total de 126 sujetos, 64 pacientes con SCA, 30 individuos con angina estable (AE) y 32 personas sanas que fueron seleccionadas como grupos de control. No hubo diferencias en el género, la edad, el origen étnico o los niveles de glucolípidos en sangre entre los grupos. Se usó el ensayo inmunoabsorbente ligado a enzimas (Elisa) para determinar cuantitativamente los niveles plasmáticos de TpP y Ps. Los niveles de los dos biomarcadores en el grupo de casos (SCA) fueron significativamente más altos que los de los grupos de control. Entre los pacientes con SCA, los niveles de TpP y Ps fueron más altos en los pacientes con IAM que en los pacientes con AI. Además, no hubo diferencias significativas en los niveles de Ps entre pacientes con SA y personas sanas. En conclusión, la TpP plasmática y la Ps sérica están notablemente aumentadas en pacientes con SCA. Por lo tanto, TpP y Ps pueden servir como indicadores de SCA y su medición puede proporcionar un apoyo para una identificación clínica temprana de SCA.

Prethrombotic state and cardiac events in patients with coronary heart disease during noncardiac surgery.

This study aimed to investigate the significance of the prethrombotic state (PTS) and 4 plasma markers in predicting perisurgical adverse cardiac events in patients with coronary heart disease (CHD) undergoing abdominal surgery. Perioperative adverse effects were recorded in 128 consecutive patients with CHD undergoing elective abdominal surgery. Plasma d-dimer, P-selectin, von Willebrand factor (VWF), and thrombus precursor protein were measured before and after the surgery. Patients with abnormal values in one or more of the 4 PTS markers were identified as having PTS, and data were analyzed by univariate and multivariate logistic regression. Abnormal presurgery levels of the 4 markers were found more frequently in those with adverse perioperative cardiac events than in those without. Multivariate analysis showed the odds ratios for adverse cardiac events to be 64.3 (PTS, P < .001), 25.7 (VWF, P = .003), and 23.5 (P-selectin, P = .04). Preoperative PTS is an independent risk factor for perioperative events in patients with CHD undergoing noncardiac surgery.