The role of activation of the coagulation and fibrinolysis system in the pathogenesis and prognosis of cardiovascular diseases (CVDs) has drawn wide attention. Recently, the D-dimer to fibrinogen ...ratio (DFR) is considered as a useful biomarker for the diagnosis and prognosis of ischemic stroke and pulmonary embolism. However, few studies have explored the relationship between DFR and cardiovascular disease. In our study, patients were divided into 2 groups according to DFR value: the lower group (DFR < 0.52, n = 2123) and the higher group (DFR ≥ 0.52, n = 1073). The primary outcome was all-cause mortality (ACM) and cardiac mortality (CM). The average follow-up time was 37.59 ± 22.24 months. We found that there were significant differences between the 2 groups in term of ACM (2.4% vs 6.6%, P < 0.001) and CM (1.5% vs 4.0%, P < 0.001). Kaplan–Meier analyses showed that elevated DFR had higher incidences of ACM (log rank P < 0.001) and CM (log rank P < 0.001). Multivariate Cox regression analyses showed that DFR was an independent predictor of ACM (HR = 1.743, 95%CI: 1.187-2.559 P = 0.005) and CM (HR = 1.695, 95%CI: 1.033-2.781 P = 0.037). This study indicates that DFR is an independent and novel predictor of long-term ACM and CM in post-PCI patients with CAD.
Monocyte count and serum albumin (Alb) have been proven to be involved in the process of systemic inflammation. Therefore, we investigated the prognostic value of monocyte-to-albumin ratio (MAR) in ...patients who underwent percutaneous coronary intervention (PCI).
We enrolled a total of 3561 patients in the present study from January 2013 to December 2017. They were divided into two groups according to MAR cut-off value (MAR < 0.014, n=2220; MAR ≥ 0.014, n=1119) as evaluated by receiver operating characteristic (ROC) curve. The average follow-up time was 37.59 ± 22.24 months.
The two groups differed significantly in the incidences of all-cause mortality (ACM; P<0.001), cardiac mortality (CM; P<0.001), major adverse cardiovascular events (MACEs; P=0.038), and major adverse cardiovascular and cerebrovascular events (MACCEs; P=0.037). Multivariate Cox regression analyses revealed MAR as an independent prognostic factor for ACM and CM. The incidence of ACM increased by 56.5% (hazard ratio HR = 1.565; 95% confidence interval CI, 1.086-2.256; P=0.016) and that of CM increased by 76.3% (HR = 1.763; 95% CI, 1.106-2.810; P=0.017) in patients in the higher-MAR group. Kaplan-Meier survival analysis suggested that patients with higher MAR tended to have an increased accumulated risk of ACM (Log-rank P<0.001) and CM (Log-rank P<0.001).
The findings of the present study suggested that MAR was a novel independent predictor of long-term mortality in patients who underwent PCI.
Alkaline phosphatase (ALP) and albumin (ALB) have been shown to be associated with coronary artery disease (CAD), and it has been reported that alkaline phosphatase-to-albumin ratio (AAR) is ...associated with the liver damage and poorer prognosis of patients with digestive system malignancy. Moreover, several previous studies showed that there was a higher incidence of malignancy in CAD patients. However, to our knowledge, the relationship between AAR and long-term adverse outcomes in CAD patients after undergoing percutaneous coronary intervention (PCI) has not been investigated. Therefore, we aim to access the relation between AAR and long-term adverse outcomes in post-PCI patients with CAD.
A total of 3378 post-PCI patients with CAD were enrolled in the retrospective Clinical Outcomes and Risk Factors of Patients with Coronary Heart Disease after PCI (CORFCHD-ZZ) study from January 2013 to December 2017. The median duration of follow-up was 37.59 ± 22.24 months. The primary end point was long-term mortality including all-cause mortality (ACM) and cardiac mortality (CM). The secondary end points were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs).
Kaplan-Meier analyses showed that an increased AAR was positively correlated with incidences of long-term ACM (log-rank, P=0.014), CM (log-rank, P=0.011), MACEs (log-rank, P=0.013) and MACCEs (log-rank, P=0.006). Multivariate Cox regression analyses showed that the elevated AAR was an independent predictor of long-term ACM (adjusted HR = 1.488 1.031-2.149, P=0.034), CM (adjusted HR = 1.837 1.141-2.959, P=0.012), MACEs (adjusted HR = 1.257 1.018-1.551, P=0.033) and MACCEs (adjusted HR = 1.237 1.029-1.486, P=0.024).
An elevated AAR is a novel independent predictor of long-term adverse outcomes in CAD patients following PCI.
Adolescence is a critical neurodevelopmental period for both excitatory and inhibitory (E/I) neurotransmission and often witnesses the typical onsets of schizophrenia. One possibility is that ...disruptions in adolescent neurodevelopmental processes may produce schizophrenia-like behavioral and neurobiological abnormalities. We previously reported that subchronic treatment of adolescent animals with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 induced cognitive deficits and reduced interneuron densities in rat medial prefrontal cortex, and these changes persisted one week after MK-801 exposure. However, it remains unclear how this treatment may affect E/I balance in hippocampus, which has long been associated with the pathophysiology of schizophrenia. Here, we examined hippocampal E/I biomarkers in adolescent rats treated with MK-801 (0.2 mg/kg, i.p., 14 days) and found increases in the ratio of the expression levels of vesicular glutamate transporter-1 (VGluT1) and vesicular gamma-aminobutyric acid (GABA) transporter (VGAT) 24 h and 7 days after MK-801 exposure. Interestingly, the increased VGluT1/VGAT ratio at the two time points was driven by upregulated VGluT1 expression and downregulated VGAT expression, respectively. The decrease in VGAT expression persisted 14 days after MK-801 exposure and recovered two weeks later. No alterations in hippocampal interneuron densities were observed. Behaviorally, the treatment decreased prepulse inhibition at 24 h but not 14 days, after MK-801 exposure. Taken together, these results demonstrate that subchronic NMDA receptor blockade during adolescence induces long-term, but not permanent, E/I imbalance in the rat hippocampus, which could be attributed to the dysregulation of glutamatergic transmission in the short term and of GABAergic transmission in the long term.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Two new dinuclear lanthanide complexes based on bis-(o-vanillin) schiff base ligand and β-diketone coligand display magnetocaloric effect with −ΔSm = 18.95(2) J kg−1 K−1 for ΔH = 7 T at 2 K and slow ...relaxation of magnetization with energy barrier of 0.73(1) K, respectively.
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Two new dinuclear lanthanide complexes, namely, Ln2L(dbm)4·2CH3OH (Ln = Gd (1) and Dy (2), H2L = N,N′-bis(3-methoxysalicylidene)-1,3-diamino-2-propanol, Hdbm = 1,3-diphenyl-1,3-propanedione) have been synthesized and characterized by elemental analyses, single crystal X-ray diffraction and magnetic measurements. The studies of single crystal X-ray diffraction analysis demonstrate that both 1 and 2 are isostructural with a Ln2 core. Magnetic investigations reveal the presence of a weak antiferromagnetic interaction in 1 and 2, respectively, of which 1 displays magnetocaloric effect with a large magnetic entropy change (−ΔSm = 18.95(2) J kg−1 K−1 for ΔH = 7 T at 2 K), while 2 exhibits slow relaxation of magnetization with the anisotropy energy barrier ΔE/kB = 0.73(1) K.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Objective
In the present study, we aimed to establish a novel score to predict long-term mortality of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients who underwent ...percutaneous coronary intervention (PCI).
Methods
A total of 2,174 NSTE-ACS patients from the CORFCHD-ZZ study were enrolled as the derivation cohort. The validation cohort including 1,808 NSTE-ACS patients were from the CORFCHD-PCI study. Receiver operating characteristic analysis and area under the curve (AUC) evaluation were used to select the candidate variables. The model performance was validated internally and externally. The primary outcome was cardiac mortality (CM). We also explored the model performance for all-cause mortality (ACM).
Results
Initially, 28 risk factors were selected and ranked according to their AUC values. Finally, we selected age, N-terminal pro-B-type natriuretic peptide, and creatinine to develop a novel prediction model named “ABC” model. The ABC model had a high discriminatory ability for both CM (C-index: 0.774,
p <
0.001) and ACM (C-index: 0.758,
p <
0.001) in the derivation cohort. In the validation cohort, the C-index of CM was 0.802 (
p <
0.001) and that of ACM was 0.797 (
p <
0.001), which suggested good discrimination. In addition, this model had adequate calibration in both the derivation and validation cohorts. Furthermore, the ABC score outperformed the GRACE score to predict mortality in NSTE-ACS patients who underwent PCI.
Conclusion
In the present study, we developed and validated a novel model to predict mortality in patients with NSTE-ACS who underwent PCI. This model can be used as a credible tool for risk assessment and management of NSTE-ACS after PCI.
It has been confirmed that the triglyceride to high-density lipoprotein cholesterol ratio (THR) is associated with insulin resistance and metabolic syndrome. However, to the best of our knowledge, ...only a few studies with small sample sizes have investigated the relationship between THR and coronary artery disease (CAD). Therefore, we aimed to assess the correlation between the THR and long-term mortality in patients with CAD after undergoing percutaneous coronary intervention (PCI) in our study that enrolled a large number of patients.
A total of 3269 post-PCI patients with CAD were enrolled in the CORFCHD-ZZ study from January 2013 to December 2017. The mean follow-up time was 37.59 ± 22.24 months. Patients were divided into two groups according to their THR value: the lower group (THR < 2.84, n = 1232) and the higher group (THR ≥ 2.84, n = 2037). The primary endpoint was long-term mortality, including all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs).
In our study, ACM occurred in 124 patients: 30 (2.4%) in the lower group and 94 (4.6%) in the higher group (P = 0.002). MACEs occurred in 362 patients: 111 (9.0%) in the lower group and 251 (12.3%) in the higher group (P = 0.003). The number of MACCEs was 482: 152 (12.3%) in the lower group and 320 (15.7%) in the higher group (P = 0.008). Heart failure occurred in 514 patients: 89 (7.2%) in the lower group and 425 (20.9%) in the higher group (P < 0.001). Kaplan-Meier analyses showed that elevated THR was significantly related to long-term ACM (log-rank, P = 0.044) and the occurrence of heart failure (log-rank, P < 0.001). Multivariate Cox regression analyses showed that the THR was an independent predictor of long-term ACM (adjusted HR = 2.042 1.264-3.300, P = 0.004) and heart failure (adjusted HR = 1.700 1.347-2.147, P < 0.001).
An increased THR is an independent predictor of long-term ACM and heart failure in post-PCI patients with CAD.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Liquid submerged fermentation is an effective strategy to achieve large-scale production of active ingredients by macrofungi, and controlling mycelium morphology is a key factor restricting the ...development of this technology. Mining for superior morphological regulatory factors and elucidation of their regulatory mechanisms are vital for the further development of macrofungal fermentation technology. In this study, microparticles were used to control the morphology of
Paraisaria dubia
(
P. dubia
) in submerged fermentation, and the underlying regulatory mechanisms were revealed by transcriptomic. The relative frequency of S-type pellet diameter increased significantly from 7.14 to 88.31%, and biomass increased 1.54 times when 15 g/L talc was added. Transcriptome analysis showed that the morphological regulation of filamentous fungi was a complex biological process, which involved signal transduction, mycelium polar growth, cell wall synthesis and cell division, etc. It also showed a positive impact on the basic and secondary metabolism of
P. dubia
. We provided a theoretical basis for controlling the mycelium morphology of
P. dubia
in submerged fermentation, which will promote the development of macrofungal fermentation technology.
Graphical abstract
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This study investigated pharmacokinetics, tissue distribution and excretion of ACT001 in Sprague-Dawley rats. Stability study and metabolism study of ACT001 are conducted. The absolute ...bioavailability of ACT001 is 50.82%. ACT001 has no accumulation effect and displayed wide tissue distribution. ACT001 can be rapidly distributed to tissues after oral administration and can diffuse through the blood-brain barrier. The total cumulative excretion of ACT001 in feces, urine and bile were found to be 0.05, 3.42 and 0.012%, respectively. UPLC/ESI–QTOF–MS coupled with MetaboLynx XS software was utilized to detect the metabolites of ACT001 in vitro. Five metabolites (M1, M2, M3, M4 and M5) were detected. M2 wasn't discovered in human liver microsome samples and bile samples. M1 and M2 weren't discovered in rat plasma and human plasma. M3, M4 and M5 weren't discovered in bile samples. M5 is an active metabolite named micheliolide (MCL). There is no significant difference in half-life, type of identified metabolites and the amount of each metabolites between using rat plasma and human plasma. Owing to the species differences of hepatomicrosome enzymes, significant differences were shown in half-life, type of identified metabolites and the amount of each metabolites between using rat liver microsome and human liver microsome.
•Detailed information of pharmacokinetic data of ACT001 were reported for the first time.•A HPLC-MS/MS method was established to determine the concentration of ACT001.•ACT001 has no accumulation effect and displayed wide tissue distribution.•UPLC/ESI–QTOF–MS coupled with MetaboLynx XS software was utilized to detect metabolites.•The active metabolite MCL, containing a α‑methylene‑γ‑lactone group, was detected.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The aims of this study were to make clear whether miR-21 was dysregulated in hydatidiform mole (HM) tissues and choriocarcinoma (CCA) cells, to elucidate whether aberrant miR-21 expression would ...affect the function of CCA cells, and to find out whether there was a relationship between miR-21 and AKT, PDCD4, and PTEN in CCA cells.
Fresh and formalin-fixed, paraffin-embedded trophoblastic tissues (normal first trimester placentas and HMs) were retrieved from the biobank in the International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University. Choriocarcinoma JAR and JEG-3 cells were cultured. Expression of miR-21 in trophoblast cells and tissues was examined by quantitative real-time polymerase chain reaction. Location and distribution of miR-21 in trophoblast tissues were determinated by in situ hybridization and fluorescent in situ hybridization. The effect of miR-21 on JAR and JEG-3 cells was tested by miR-21 mimics and inhibitor transfection, followed by cell viability assay, flow cytometric analysis, and Transwell analysis. Interaction between miR-21 and its target genes in CCA cells was verified by quantitative real-time polymerase chain reaction, Western blot, and luciferase report system.
We originally found miR-21 was markedly upregulated in HM tissues compared with normal first trimester placentas. The expression of miR-21 was exclusively confined in trophoblastic layers. Furthermore, we discovered miR-21 was significantly increased in JAR and JEG-3 cells compared with normal primary human trophoblastic cells. Moreover, we demonstrated miR-21 could promote proliferation, migration, and invasion of CCA cells. We furthermore proved miR-21 negatively regulated PDCD4 and PTEN in CCA cells and targeted to PDCD4 3'UTR directly. In addition, we confirmed that miR-21 could activate Akt pathway by phosphorylating Akt at Ser 473.
Our results suggested miR-21 was responsible for aggressive phenotype of gestational trophoblastic disease and had the potential diagnostic and therapeutic values for gestational trophoblastic neoplasm.
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