Slow magnetic relaxation in 8-coordinate Mn(II) compounds.

The design and synthesis of high-spin Mn(II)-based single-molecule magnets (SMMs) have not been well developed to a great extent, as compared with a large number of SMMs based on the other first row transition metal complexes. In light of our success in designing Fe(II), Co(II) and Fe(III)-based SMMs with a high coordination number of 8, it is of great interest to design Mn(II) analogues with such a strategy. In this contribution, four Mn(II) compounds, [MnII(Ln)2](ClO4)2 (1-4) were obtained from reactions of neutral tetradentate ligands, L1-L4, with hydrated MnII(ClO4)2 (L1 = 2,9-bis(carbomethoxy)-1,10-phenanthroline, L2 = 2,9-bis(carbomethoxy)-2,2'-dipyridine, L3 = N2,N9-dibutyl-1,10-phenanthroline-2,9-dicarboxamide, L4 = 6,6'-bis(2-(tert-butyl)-2H-tetrazol-5-yl)-2,2'-bipyridine). Their crystal structures have been determined by X-ray crystallography and it clearly shows that the Mn(II) centers in these compounds have an oversaturated coordination number of 8. Their magnetic properties have been investigated in detail; to our surprise, all of these Mn(II) compounds show interesting slow magnetic relaxation behaviors under an applied direct current field, although they have very small negative D values.

hIMB1636-MMAE, a Novel TROP2-Targeting Antibody-Drug Conjugate Exerting Potent Antitumor Efficacy in Pancreatic Cancer.

Herein, we first prepared a novel anti-TROP2 antibody-drug conjugate (ADC) hIMB1636-MMAE using hIMB1636 antibody chemically coupled to monomethyl auristatin E (MMAE) via a Valine-Citrulline linker and then reported its characteristics and antitumor activity. With a DAR of 3.92, it binds specifically to both recombinant antigen (KD ∼ 0.687 nM) and cancer cells and could be internalized by target cells and selectively kill them with IC50 values at nanomolar/subnanomolar levels by inducing apoptosis and G2/M phase arrest. hIMB1636-MMAE also inhibited cell migration, induced ADCC effects, and had bystander effects. It displayed significant tumor-targeting ability and excellent tumor-suppressive effects in vivo, resulting in 5/8 tumor elimination at 12 mg/kg in the T3M4 xenograft model or complete tumor disappearance at 10 mg/kg in BxPc-3 xenografts in nude mice. Its half-life in mice was about 87 h. These data suggested that hIMB1636-MMAE was a promising candidate for the treatment of pancreatic cancer with TROP2 overexpression.

NOX2 inhibition stabilizes vulnerable plaques by enhancing macrophage efferocytosis via MertK/PI3K/AKT pathway.

NADPH oxidases 2 (NOX2) is the main source of ROS in macrophages, which plays a critical role in the formation of atherosclerosis. However, effects of NOX2 inhibition on established vulnerable plaques and the potential role involved remain unclear. The purpose of this study is to investigate the latent mechanism of NOX2-triggered vulnerable plaque development. We generated a vulnerable carotid plaque model induced by carotid branch ligation and renal artery constriction, combined with a high-fat diet in ApoE-/- mice. NOX2 specific inhibitor, GSK2795039 (10 mg/kg/day by intragastric administration for 8 weeks) significantly prevented vulnerable plaque, evaluated by micro-ultrasound imaging parameters. A profile of less intraplaque hemorrhage detection, increased collagen-lipid ratio, fibrous cap thickness and less necrotic core formation were also found in GSK2795039 treated group. Mechanistically, reduced 4-HNE, in situ lesional apoptosis and enhanced efferocytosis were involved in mice treated with NOX2 inhibitor. Further analysis in mouse macrophages confirmed the role of NOX2 inhibition in enhancing macrophage efferocytosis by regulating the MertK/PI3K/AKT pathway. In summary, our data defined previously few recognized roles of NOX2 in vulnerable plaque pathogenesis and an undescribed NOX2-ROS-MerTK axis acts involved in regulating macrophage efferocytosis in the formation of rupture-prone vulnerable plaques.

Circularly polarized luminescence and magneto-optic effects from chiral Dy(III) single molecule magnets.

A new pair of multifunctional Zn(II)-Dy(III) enantiomers based on the chiral Schiff-base ligands [R,R-ZnLDy(H2O)(NO3)3] (1R2R-ZnDy) and [S,S-ZnLDy(H2O)(NO3)3] (1S2S-ZnDy) (H2L = phenol, 2,2'-[[(1R,2R/1S,2S)-1,2-diphenyl-1,2-ethanediyl]bis[(E)-nitrilomethylidyne]]bis[6-methoxy]) was synthesized and characterized. Magnetic studies indicate that 1R2R-ZnDy behaves as a single-molecule magnet. Enantiomers 1R2R-ZnDy and 1S2S-ZnDy show chiroptical activity and circularly polarized luminescence in the N,N-dimethylformamide (DMF) solution. The chiral Zn(II)-Dy(III) complexes display magnetic circular dichroism signals at room temperature. Accordingly, these complexes will inspire intriguing research on single-molecule magnets with circular polarization of luminescence activity and magneto-optic effects, which will give new clues to design multifunctional molecular magnetic materials.

Mirabegron Ameliorated Atherosclerosis of ApoE-/- Mice in Chronic Intermittent Hypoxia but Not in Normoxia.

PURPOSE: It has been established that obstructive sleep apnea (OSA) is an independent risk factor for atherosclerosis. Chronic intermittent hypoxia (CIH) activates sympathoadrenal system and upregulates ß3 adrenergic receptor (ß3 AR). However, the effect of selective ß3 AR agonist mirabegron in CIH-induced atherosclerosis remains unknown. METHODS: We generated a CIH-induced atherosclerosis model through exposing ApoE-/- mice to CIH (8 h per day, cyclic inspiratory oxygen fraction 5-21%, 60-s cycle) for 6 weeks after 4-week high-fat dieting and investigated the effects of mirabegron, a selective ß3 AR agonist, on CIH-induced atherosclerosis. The coronary endarterectomy (CE) specimens from coronary artery disease patients with OSA and without OSA were collected. RESULTS: The expression of ß3 AR was significantly elevated in CIH-induced atherosclerosis model. Furthermore, treatment with mirabegron (10mg/kg per day by oral administration for 6 weeks) ameliorated atherosclerosis in ApoE-/- mice in CIH but not in normoxia. Mechanistically, mirabegron activated ß3 AR and ameliorated intraplaque oxidative stress by suppressing p22phox expression and reactive oxygen species (ROS) level. In addition, in human CE specimens, ß3 AR was also upregulated associated with increased p22phox expression and ROS level both in the lumen and in the plaque of coronary artery in OSA subjects. CONCLUSION: This study first demonstrated that mirabegron impeded the progression of CIH-induced atherosclerosis, at least in part, via ß3 AR-mediated oxidative stress, suggesting a promising therapeutic strategy for protecting against atherosclerosis induced by CIH.

Brown Adipose Tissue Activation Is Involved in Atherosclerosis of ApoE-/- Mice Induced by Chronic Intermittent Hypoxia.

Background: Obstructive sleep apnea is an atherogenesis factor of which chronic intermittent hypoxia is a prominent feature. Chronic intermittent hypoxia (CIH) exposure can sufficiently activate the sympathetic system, which acts on the ß3 adrenergic receptors of brown adipose tissue (BAT). However, the activity of BAT and its function in CIH-induced atherosclerosis have not been fully elucidated. Methods: This study involved ApoE-/- mice which were fed with a high-fat diet for 12 weeks and grouped into control and CIH group. During the last 8 weeks, mice in the CIH group were housed in cages to deliver CIH (12 h per day, cyclic inspiratory oxygen fraction 5-20.9%, 180 s cycle). Atherosclerotic plaques were evaluated by Oil Red O, hematoxylin and eosin, Masson staining, and immunohistochemistry. Afterward, we conducted immunohistochemistry, western blotting, and qRT-PCR of uncoupling protein 1 (UCP1) to investigate the activation of BAT. The level of serum total cholesterol (TC), triglyceride, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and free fatty acid (FFA) were measured. Finally, RNA-Sequencing was deployed to explore the differentially expressed genes (DEGs) and their enriched pathways between control and CIH groups. Results: Chronic intermittent hypoxia exposure promoted atherosclerotic plaque area with increasing CD68, α-SMA, and collagen in plaques. BAT activation was presented during CIH exposure with UCP1 up-regulated. Serum TC, triglyceride, LDL-c, and FFA were increased accompanied by BAT activation. HDL-c was decreased. Mechanistically, 43 lipolysis and lipid metabolism-associated mRNA showed different expression profiling between the groups. Calcium, MAPK, and adrenergic signaling pathway included the most gene number among the significantly enriched pathways. Conclusion: This study first demonstrated that BAT activation is involved in the progression of CIH-induced atherosclerosis, possibly by stimulating lipolysis.

Slow magnetic relaxation in high-coordinate Co(II) and Fe(II) compounds bearing neutral tetradentate ligands.

The first-row transition metal compounds, [MII(L1)2](ClO4)2 (M = Ni (1); Co (2)), have been prepared by treatment of a neutral tetradentate ligand (L1 = N2,N9-dibutyl-1,10-phenanthroline-2,9-dicarboxamide) with metal perchlorate salts in MeOH. Both compounds have been structurally characterized by X-ray crystallography and it was found that the coordination numbers are 6 and 7, respectively. The reaction of 6,6'-bis(2-tbutyl-tetrazol-5-yl)-2,2'-bipyridine (L2) with hydrated FeII(ClO4)2 afforded a 8-coordinate Fe(II) compound, [FeII(L2)2](ClO4)2 (3); however its reaction with hydrated CoII(ClO4)2 resulted in 6-coordinate [CoII(L2)2](ClO4)2. It is interesting to observe field-induced slow magnetic relaxation in the 7-coordinate Co(II) compound 2 and 8-coordinate Fe(II) compound 3, which further supports the validity of designing high coordination number compounds as single-molecule magnets. Direct current magnetic studies demonstrate that 2 has a very large positive D value (56.2 cm-1) and a small E value (0.66 cm-1), indicating easy plane magnetic anisotropy. Consistent with the larger D value, an effective spin-reversal barrier of Ueff = 100 K (71.4 cm-1) is obtained, which is the highest value reported for 7-coordinate Co(II) complexes with a pentagonal bipyramidal geometry. In contrast, 8-coordinate Fe(II) compound 3 exhibits uniaxial magnetic anisotropy.

Slow magnetic relaxation in structurally similar mononuclear 8-coordinate Fe(II) and Fe(III) compounds.

A pair of structurally-similar and stable 8-coordinate high-spin Fe(ii) and Fe(iii) compounds have been obtained. Both compounds exhibit field-induced slow magnetic relaxation behaviour. The Fe(iii) compound represents the first example of 8-coordinate Fe(iii) single-molecule magnets (SMM).

Hepatitis B virus X protein promotes liver cell pyroptosis under oxidative stress through NLRP3 inflammasome activation.

OBJECTIVE: Hepatitis B virus X protein (HBx) is a pivotal factor for HBV-induced hepatitis. Herein, we sought to investigate HBx-mediated NLR pyrin domain containing 3 (NLRP3) inflammasome activation and pyroptosis under oxidative stress. METHODS: The effect of HBx on the NLRP3 inflammasome was analyzed by enzyme-linked immunosorbent assays, quantitative reverse transcription-polymerase chain reaction, western blotting, and immunofluorescence in hepatic HL7702 cells. Pyroptosis was evaluated by western blotting, lactate dehydrogenase release, propidium iodide staining, and transmission electron microscopy. NLRP3 expression in the inflammasome from liver tissues was assessed by immunohistochemistry. RESULTS: In hydrogen peroxide (H2O2)-stimulated HL7702 cells, HBx triggered the release of pro-inflammatory mediators apoptosis-associated speck-like protein containing a CARD (ASC), interleukin (IL)-1ß, IL-18, and high-mobility group box 1 (HMGB1); activated NLRP3; and initiated pro-inflammatory cell death (pyroptosis). HBx localized to the mitochondria, where it induced mitochondrial damage and production of mitochondrial reactive oxygen species (mitoROS). Treatment of HL7702 cells with a mitoROS scavenger attenuated HBx-induced NLRP3 activation and pyroptosis. Expression levels of NLRP3, ASC, and IL-1ß in liver tissues from patients were positively correlated with HBV DNA concentration. CONCLUSIONS: The NLRP3 inflammasome was activated by elevated mitoROS levels and mediated HBx-induced liver inflammation and hepatocellular pyroptosis under H2O2-stress conditions.

Flavonoids extracted from leaves of Diospyros kaki regulates RhoA activity to rescue synapse loss and reverse memory impairment in APP/PS1 mice.

Synapse dysfunction is an early hallmark of Alzheimer's disease (AD), and was considered to be closely related to memory loss. The molecular mechanisms that trigger synapse loss and dysfunction remain poorly understood. Increasing evidence shows a link between Rho GTPases and synapse plasticity. Rho GTPases play a role in controlling synapse function by regulating actin cytoskeleton and dendritic spines. Observations have suggested that phytochemicals, such as flavonoids, alleviate cognition impairment in AD. However, to date, the link between the protective effect of flavonoids on AD and the activity of Rho GTPases remains uninvestigated. In this study, APP/PS1 mice were used as an AD model, and we found that synapse loss occurred in AD mice brain. Flavonoids extracted from leaves of Diospyros kaki (FLDK) were used to investigate whether its protective effects on synapse were related to Rho GTPases activity in AD mice. The Rho GTPases Activation Kit showed that Ras homologous member A (RhoA)-GTP was significantly higher and Ras-related C3 botulinum toxin substrate 1 (Rac1)-GTP was significantly lower in APP/PS1 mice than in normal mice, and RhoA-GTP activity was significantly inhibited by FLDK. We also found that FLDK improved learning and memory function, and antagonized the downregulation expressions of synapse-related proteins such as synaptophysin and drebrin. These findings suggest that FLDK is a potential therapeutic agent for AD, and modulation of Rho GTPases activity might contribute toward its protective effect.

Heptanuclear CoII5CoIII2 Cluster as Efficient Water Oxidation Catalyst.

Inspired by the transition-metal-oxo cubical Mn4CaO5 in photosystem II, we herein report a disc-like heptanuclear mixed-valent cobalt cluster, [CoII5CoIII2(mdea)4(N3)2(CH3CN)6(OH)2(H2O)2·4ClO4] (1, H2mdea = N-methyldiethanolamine), for photocatalytic oxygen evolution. The topology of the Co7 core resembles a small piece of cobaltate protected by terminal H2O, N3-, CH3CN, and multidentate N-methyldiethanolamine at the periphery. Under the optimal photocatalytic conditions, 1 exhibits water oxidation activity with a turnover number (TON) of 210 and a turnover frequency (TOFinitial) of 0.23 s-1. Importantly, electrospray mass spectrometry (ESI-MS) was used to not only identify the possible main active species in the water oxidation reaction but also monitor the evolutions of oxidation states of cobalt during the photocatalytic reactions. These results shed light on the design concept of new water oxidation catalysts and mechanism-related issues such as the key active intermediate and oxidation state evolution in the oxygen evolution process. The magnetic properties of 1 were also discussed in detail.

Level of Pregnancy-associated Plasma Protein-A Correlates With Coronary Thin-cap Fibroatheroma Burden in Patients With Coronary Artery Disease: Novel Findings From 3-Vessel Virtual Histology Intravascular Ultrasound Assessment.

Pregnancy-associated plasma protein-A (PAPP-A) level is an independent predictor of acute cardiovascular event occurrence. To test the hypothesis that increased PAPP-A levels would be associated with a higher burden of coronary thin-cap fibroatheroma (TCFA) thereby underlying the heightened risk for cardiovascular events in patients with coronary artery disease; 154 patients (462 vessels and 975 plaques) with stable angina or non-ST-segment elevation acute coronary syndrome (NSTE-ACS) referred for percutaneous coronary intervention were assessed using 3-vessel virtual histology (VH)-intravascular ultrasound (IVUS). Thin-cap fibroatheroma virtual histology was defined as focal, necrotic core (NC)-rich (≥10% of cross-sectional area) plaques in contact with the lumen, and plaque burden ≥40%. Pregnancy-associated plasma protein-A levels were determined by sandwich enzyme-linked immunosorbent assay, and patients were divided into 3 groups based on PAPP-A level tertiles. Although the highest PAPP-A level tertile was not associated with 3-vessel plaque number, it was associated with 3-vessel VH-TCFA number and necrotic core volume. Patients with ≥3 VH-TCFAs had a higher PAPP-A level than patients with 1 to 3 VH-TCFAs or without any VH-TCFA (13.3 ±â€Š11.8 versus 7.8 ±â€Š4.7 versus 7.4 ±â€Š4.7 mIU/L, P < 0.001, respectively). Moreover, PAPP-A level was an independent predictor of higher total number of VH-TCFAs (OR 1.18; 95% CI 1.07-1.29, P = 0.001). This VH-IVUS study demonstrated, for the first time to our knowledge, that higher PAPP-A levels are associated with higher 3-vessel TCFA burden in patients with coronary artery disease. Pregnancy-associated plasma protein-A, therefore, might be a useful serum biomarker to predict increased coronary TCFA burden and plaque instability.

Attenuated plaque is associated with plaque prolapse accompanied by cardiac enzyme elevation after drug-eluting stent implantation.

OBJECTIVES: This study aimed to evaluate the relationship between grayscale intravascular ultrasound-attenuated plaque (AP) and poststenting plaque prolapse (PP) as well as their influence on creatine kinase-myocardial band (CK-MB) elevation after drug-eluting stent (DES) implantation. BACKGROUND: The relationship between baseline AP and poststenting PP and their impacts on percutaneous coronary intervention (PCI) are not well known. PATIENTS AND METHODS: A total of 141 single, native, de-novo coronary lesions in 141 patients with normal pre-PCI CK-MB levels who underwent intravascular ultrasound before and after DES implantation were studied. RESULTS: AP was found in 72 (51.1%) lesions and PP occurred in 43 (30.5%) lesions. Baseline AP was associated with greater plaque area, lesion eccentricity, and positive remodeling, and was associated with higher frequency of poststenting PP (47.2 vs. 13.0%, P<0.001) as well as greater poststenting PP volume (2.2±1.3 vs. 1.9±1.1 mm, P=0.045). Elevated CK-MB levels were observed in 34 (24.1%) lesions and significantly more frequently in patients with baseline AP and poststenting PP than without both of these findings. Multivariate analysis indicated that AP with PP was the predictor of post-PCI CK-MB elevation. CONCLUSION: Baseline AP was associated with high-risk characteristics, higher frequency, and greater volume of poststenting PP accompanied by CK-MB elevation in patients with DES implantation.

Pregnancy-associated plasma protein-A as a marker of culprit lesion instability in unstable angina patients: an intravascular ultrasound study.

BACKGROUND: We evaluated the relationship between pregnancy-associated plasma protein-A (PAPP-A) and coronary plaque instability as assessed by intravascular ultrasound (IVUS). METHODS: We performed greyscale IVUS analysis in culprit lesions of 93 patients with unstable angina (UA) and 72 with stable angina (SA). A sandwich enzyme-linked immunosorbent assay technique was used to assay circulating PAPP-A. RESULTS: Patients with UA had higher PAPP-A levels than those with SA 10.8 mIU/l [interquartile range (IQR) 8.3-14.4] vs. 5.4 (IQR 2.9-9.8) mIU/l, p < 0.001]. Lesions in patients with higher PAPP-A levels were associated with larger plaque burden than lesions in patients with lower PAPP-A levels. IVUS attenuated plaque, positive remodeling and plaque rupture. Thrombus and angiographic Ambrose type-II eccentric lesions or multiple irregularities were more common in patients with higher PAPP-A levels than in those with lower PAPP-A levels. They were also more common in patients with UA and higher PAPP-A levels than in patients with (1) SA and higher PAPP-A levels, (2) UA and lower PAPP-A levels or (3) SA and lower PAPP-A levels. CONCLUSIONS: Higher PAPP-A levels were associated with coronary plaque instability in vivo and unstable symptoms in patients with coronary artery disease.

[Evaluation on the relationship between pregnancy associated plasma protein-a and intravascular ultrasound detected culprit coronary plaque morphology in patients with unstable angina].

OBJECTIVE: To assess the relationship between pregnancy associated plasma protein-A (PAPP-A) and culprit coronary plaque morphology in patients with unstable angina (UA). METHODS: Sixty-eight UA patients undergoing diagnostic coronary angiography and intravascular ultrasound were included in this study. A sandwich enzyme-linked immunosorbent assay technique was used to assay the circulating PAPP-A. Plaque characteristics of culprit lesion were analyzed for UA patients with various PAPP-A levels. RESULTS: PAPP-A level was significantly higher in high-risk UA than in non-high-risk UA [(19.9 ± 20.1) mIU/L vs. (6.9 ± 5.7) mIU/L, P = 0.002]. Optimal threshold of PAPP-A to predict high-risk UA was determined as 11.0 mIU/L with a sensitivity of 78.6% and a specificity of 77.5%. Patients with higher PAPP-A level (≥ 11.0 mIU/L) was associated with larger external elastic membrane cross-sectional area, plaque area and more plaque burden compared with patients with lower PAPP-A level (all P < 0.01). Positive remodeling, attenuated plaque and plaque rupture were significantly more often in patients with higher PAPP-A than in patients with lower PAPP-A level (all P < 0.01). PAPP-A ≥ 11.0 mIU/L (OR = 5.921, P = 0.014) and attenuated plaque (OR = 7.541, P = 0.038) were independent risk predictors for high-risk UA. CONCLUSIONS: PAPP-A was associated with instability of culprit plaque in UA patients. PAPP-A ≥ 11.0 mIU/L and attenuated plaque were independent predictors for high-risk UA.

[Quantitative coronary angiography and intravascular ultrasound assessments on target lesion and reference vessel in patients with diabetes mellitus].

OBJECTIVE: To evaluate the accuracy of quantitative coronary angiography (QCA) assessment on target lesion and reference vessel in patients with diabetes mellitus with intravascular ultrasound (IVUS) measurements as golden standard. METHODS: QCA and IVUS were performed in 52 diabetes mellitus patients [35 males, mean age (62.3 +/- 7.1) years]. Regression equation was ascertained with the IVUS derived plaque burden as dependent and QCA derived vessel stenosis as independent variable. The measurement results derived from the two modalities on proximal and distal reference vessels were compared. RESULT: The regression equation (constant = 0.8286, P = 0.001) of plaque burden and vessel stenosis derived from two modalities were significantly correlated (r = 0.691, P < 0.001) but QCA overestimated the stenosis severity (57.9% +/- 15.5% vs. 53.5% +/- 12.9%, P < 0.01). Target vessels negative remodeling index in these patient was 0.87 +/- 0.23. QCA significantly underestimated the proximal and distal reference segments vessel diameters [(0.81 +/- 0.24) mm, (0.64 +/- 0.17) mm, all P < 0.05] as compared to IVUS results. CONCLUSION: Due to the significant negative vessel remodeling, QCA overestimated the stenosis severity and underestimated the reference segments vessel diameters in patients with diabetes mellitus.

[Value of intravascular ultrasound, 64 multi-detector computed tomography and quantitative coronary angiography on lesion of coronary artery in unstable angina pectoris patient].

OBJECTIVE: To compare the value of intravascular ultrasound (IVUS) and assess the value of quantitative coronary angiography (QCA) and 64 multi-detector computed tomography (MDCT) on unstable anginas (UAP) risk stratification. METHOD: A total of 61 UAP patients (low risk: 17, middle risk: 33 and high risk: 11) were recruited, 71 vessels were examined by MDCT, QCA and IVUS. Plaque characteristics (soft, fibrous, calcified and mixed plaques) and plaque burden at minimum area (< or = 50%, 51% - 74% and > or = 75%) were detected, calculated and analyzed. Results derived from various detection methods were compared. RESULTS: Plaque burden detection by QCA was comparable to IVUS results for low and middle risk UAP (r = 0.768 and r = 0.721, respectively; all P < 0.01) but not for high risk UAP (67% + or - 14% vs.75% + or - 16%, P < 0.01) due to significant positive vessel remodeling (remodeling index = 1.21 + or - 0.31). The high negative predict value of MDCT for stenosed coronary vessels (87.8% - 96.3%)was valuable for exclusion of coronary heart disease but MDCT was not able to identify fibrous cap (kappa = 0.235) and lipid core (kappa = 0.245). Extent of remodeling index, external elastic membrane area, minimum lumen area, plaque burden, plaque rupture and thrombosis increased in proportion to increasing risks of UAP patients. CONCLUSIONS: QCA is a suitable tool for assessing UAP patients with low and middle vessel stenosis but underestimated the stenosis degree in UAP patients with high vessel stenosis. MDCT is valuable for exclusion vessel disease but not useful for identifying soft and fibrous plaque. Soft plaque with positive remodeling index and minimum lumen area < 4 mm(2) derived from IVUS could correctly identify UAP patients with high degree of vessel stenosis.

[Development and validation of risk score model for acute myocardial infarction in China: prognostic value thereof for in hospital major adverse cardiac events and evaluation of revascularization].

OBJECTIVE: To develop a simple risk score model of in-hospital major adverse cardiac events (MACE) including all-cause mortality, new or recurrent myocardial infarction (MI), and evaluate the efficacy about revascularization on patients with different risk. METHODS: The basic characteristics, diagnosis, therapy, and in-hospital outcomes of 1512 ACS patients from Global Registry of Acute Coronary Events (GRACE) study of China were collected to develop a risk score model by multivariable stepwise logistic regression. The goodness-of-fit test and discriminative power of the final model were assessed respectively. The best cut-off value for the risk score was used to assess the impact of revascularization for ST-elevation MI (STEMI) and non-ST elevation acute coronary artery syndrome (NSTEACS) on in-hospital outcomes. RESULTS: (1) The following 6 independent risk factors accounted for about 92.5% of the prognostic information: age > or =80 years (4 points), SBP < or =90 mm Hg (6 points), DBP > or =90 mm Hg (2 points), Killip II (3 points), Killip III or IV (9 points), cardiac arrest during presentation (4 points), ST-segment elevation (3 points) or depression (5 points) or combination of elevation and depression (4 points) on electrocardiogram at presentation. (2) CHIEF risk model was excellent with Hosmer-Lemeshow goodness-of-fit test of 0.673 and c statistics of 0.776. (3)1301 ACS patients previously enrolled in GRACE study were divided into 2 groups with the best cut-off value of 5.5 points. The impact of revascularization on the in-hospital MACE of the higher risk subsets was stronger than that of the lower risk subsets both in STEMI [OR (95% CI) = 0.32 (0.11, 0.94), chi2 = 5.39, P = 0.02] and NSTEACS [OR (95% CI) = 0.32 (0.06, 0.94), chi2 =4.17, P = 0.04] population. However, both STEMI (61.7% vs. 78.3%, P = 0.000) and NSTEACS (42.0% vs 62.3%, P = 0.000) patients with the risk scores more than 5.5 points had lower revascularization rates. CONCLUSION: The risk score provides excellent ability to predict in-hospital death or (re) MI quantitatively and accurately. The patients undergoing revascularization with risk score greater than 5.5 have lower incidence rates of endpoint.

Synergistic effect of amlodipine and atorvastatin on blood pressure, left ventricular remodeling, and C-reactive protein in hypertensive patients with primary hypercholesterolemia.

Our aim in this study was to investigate the changes of serum high-sensitive C-reactive protein (hs-CRP) and uric acid (UA), and evaluate the synergistic effect of amlodipine and atorvastatin on blood pressure and left ventricular remodeling in hypertensive patients with primary hypercholesterolemia. One hundred and twenty-six hypertensive patients with hypercholesterolemia were randomized into amlodipine group (10 mg/day, group A, n = 65) and amlodipine (10 mg/day) plus atorvastatin group (20 mg/day, group B, n = 61), treated for 4 months continuously. Serum concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, hs-CRP, and UA were determined, and blood pressure of both groups was examined before and after treatment. Left ventricular posterior wall thickness and interventricular spectum thickness were measured by echocardiography, and left ventricular mass index (LVMI) was calculated. After 4-months of treatment with atorvastatin, serum concentrations of total cholesterol, low-density lipoprotein cholesterol, triglycerides, hs-CRP, and UA were significantly decreased in group B (P < 0.05, P < 0.01), while serum concentrations of high-density lipoprotein cholesterol was elevated (P < 0.05). Meanwhile, systolic blood pressure and diastolic blood pressure were reduced in both groups (P < 0.05), and blood pressure in group B was markedly lower than that in group A after treatment (P < 0.05). Compared with that before treatment, LVMI in both groups decreased (P < 0.05), to a significantly lower degree in group B than in group A (P < 0.05). Atorvastatin can decrease serum concentrations of hs-CRP and UA. The amlodipine-atorvastatin combination markedly reduces blood pressure and reverses left ventricular hypertrophy more than amlodipine monotherapy. The positive effect suggests that in hypertensive and hypercholesterolemic patients, the combination of amlodipine and atorvastatin could be the treatment of choice.