Non-linear Association of CAR with all-Cause and Cardiovascular Mortality in Coronary Heart Disease: A Retrospective Cohort Study from NHANES.

OBJECTIVE: To investigate the relationship between C-reactive protein and albumin ratios (CAR) and all-cause and cardiovascular disease(CVD)-specific mortality in individuals with coronary heart disease(CHD). METHODS: The data from 1895 patients were extracted from the National Health and Nutrition Examination Survey (NHANES) database from 1999-2010. We used weighted COX regression analyses to explore the association between CAR, all-cause, and CVD-specific mortality. Restricted cubic spline(RCS) regression models and threshold effects analysis were used to analyze nonlinear relationships. Subgroup analyses were also performed to explore these relationships further. RESULTS: During a mean follow-up of 115.78 months, 61.48% of deaths occurred, and 21.85% were due to CVD. After adjusting for potential confounders, each 1-unit increase in CAR was associated with a 65% increase in all-cause mortality and a 67% increase in CVD-specific mortality. The RCS model revealed a non-linear association between CAR and the risk of all-cause mortality and CVD-specific mortality in CHD patients (all non-linear P < 0.001). Threshold effects analysis identified inflection points in regression models of all-cause mortality (0.04, P < 0.001) and CVD-specific mortality (0.05, P = 0.0024). The interaction tests found sex, smoking and diabetes influenced the association between CAR and all-cause mortality and sex, smoking and HF influenced its association with CVD-specific mortality (all P < 0.05). CONCLUSION: There was a nonlinear association between CAR and all-cause mortality and CVD mortality in patients with CHD, with a higher hazard ratio before the inflection point. Sex, smoking, diabetes, and HF might have an effect on the associations between CAR and death risks.

Effects of Vanadium Microalloying and Intercritical Annealing on Yield Strength-Ductility Trade-Offs of Medium-Manganese Steels.

In this paper, we investigate the effects of vanadium on the strength and ductility of medium-manganese steels by analyzing the microstructural evolution and strain hardening rates and performing quantitative calculations. Two significantly different contents of vanadium, 0.05 and 0.5 wt.%, were independently added to model steel (0.12C-10Mn) and annealed at different intercritical temperatures. The results show that higher vanadium addition increases the yield strength but decreases the ductility. The maximum yield strength can increase from 849 MPa to 1063 MPa at low temperatures. The model calculations reveal that this is due to a precipitation strengthening increment of up to 148 MPa and a dislocation strengthening increment of 50 MPa caused by a higher quantity of V4C3 precipitates. However, the high density of vanadium carbides leads them to easily segregate at grain boundaries or phase interfaces, which prevents strain from uniformly distributing throughout the phases. This results in stress concentrations which cause a high strain hardening rate in the early stages of loading and a delayed transformation-induced plasticity (TRIP) effect. Additionally, the precipitates decrease the austenite proportion and its carbon concentrations, rendering the TRIP effect unsustainable. Accordingly, the ductility of high vanadium steels is relatively low.

Glass-Forming Ability and Thermal Properties of Al70Fe12.5V12.5X5(X = Zr, Nb, Ni) Amorphous Alloys via Minor Alloying Additions.

The Al70Fe12.5V12.5Ni5, Al70Fe12.5V12.5Zr5 and Al70Fe12.5V12.5Nb5 alloys were prepared via mechanical alloying. The influence of Zr, Nb or Ni addition on the glass-forming ability of Al-Fe-V amorphous alloys have been investigated. The structure of Al70Fe12.5V12.5Ni5 was amorphous and Al70Fe12.5V12.5Zr5 was not completely amorphous by transmission electron microscopy, selected area electron diffraction and differential scanning calorimetry. Different criteria were used to evaluate the influence of the addition of alloy elements on the Glass-forming ability. The Al70Fe12.5V12.5Ni5 amorphous alloys exhibits higher glass-forming ability and activation energies of crystallization. Comparison of the effective atomic size ratio and mixture enthalpy on the glass-forming ability of these amorphous alloys demonstrates that the effective atomic size ratio value becomes more significant than the values of mixture enthalpy.

Compressive and Energy Absorption Properties of Pyramidal Lattice Structures by Various Preparation Methods.

Metallic three-dimensional lattice structures exhibit many favorable mechanical properties including high specific strength, high mechanical efficiency and superior energy absorption capability, being prospective in a variety of engineering fields such as light aerospace and transportation structures as well as impact protection apparatus. In order to further compare the mechanical properties and better understand the energy absorption characteristics of metal lattice structures, enhanced pyramidal lattice structures of three strut materials was prepared by 3D printing combined with investment casting and direct metal additive manufacturing. The compressive behavior and energy absorption property are theoretically analyzed by finite element simulation and verified by experiments. It is shown that the manufacturing method of 3D printing combined with investment casting eliminates stress fluctuations in plateau stages. The relatively ideal structure is given by examination of stress-strain behavior of lattice structures with varied parameters. Moreover, the theoretical equation of compressive strength is established that can predicts equivalent modulus and absorbed energy of lattice structures.

An Enhanced Three-Dimensional Auxetic Lattice Structure with Improved Property.

In order to enhance the mechanical property of auxetic lattice structures, a new enhanced auxetic lattice structure was designed by embedding narrow struts into a three-dimensional (3D) re-entrant lattice structure. A series of enhanced lattice structures with varied parameters were fabricated by 3D printing combined with the molten metal infiltration technique. Based on the method, parameter studies were performed. The enhanced auxetic lattice structure was found to exhibit superior mechanical behaviors compared to the 3D re-entrant lattice structure. An interesting phenomenon showed that increasing the diameter of connecting struts led to less auxetic and non-auxetic structures. Moreover, the compressive property of the enhanced structure also exhibited obvious dependence on the base material and compression directions. The present study can provide useful information for the design, fabrication and application of new auxetic structures with enhanced properties.

Crystallization Behavior of Al70Fe12.5V12.5Nb5 Amorphous Alloy Formed by Mechanical Alloying.

In this study, the formation and crystallization of the Al70Fe12.5V12.5Nb5 amorphous alloys has been investigated. The addition of Nb enhances the supercooled liquid region and glass forming ability of the Al-Fe-V amorphous alloys. The Al70Fe12.5V12.5Nb5 amorphous alloy exhibits two distinct crystallization steps and a large supercooled liquid region at more than 100 K. Kissinger and Ozawa analyses showed that the two activation energies for crystallization (Ex) were estimated to be 366.3 ± 23.9 and 380.5 ± 23.9 kJ/mol. Large supercooled liquid regions are expected to gain an application field of Al-based amorphous alloys.

Midrange ejection fraction as a risk factor for deterioration of cardiofunction after permanent pacemaker implantation.

PURPOSE: To determine whether the midrange ejection fraction (mrEF) is associated with increased risk of deterioration of cardiac function (DCF) after dual chamber permanent pacemaker (PPM) implantation. METHODS: We performed a prospective cohort study of relevance in patients with EF ≥ 40% and indications for PPMs. Patient characteristics were recorded at baseline and 1 day, 1 month, 3 months, and 6 months after PPM implantation with leads placed in the right ventricular apex. These included clinical symptoms, signs, biochemical parameters, BNP, echocardiography and ECG parameters, and pacing-related parameter changes. The patients were followed-up for 6 months. Univariate and multivariable Cox regression analyses were performed. RESULTS: A total of 879 patients were included, aged 35 to 88 years (mean age 67.2 ± 9.6); a total of 81 patients (9.2%) developed DCF after PPM implantation, including LVEF < 40% (57 cases) and increased NYHA class (24 cases). Cox models demonstrated that age ≥ 75 years (HR 2.273 [95% CI, 1.541-3.626]), OMI (HR 2.078 [95% CI, 1.275-3.604]), mrEF (HR 2.762 [95% CI, 1.558-4.769]), moderate mitral regurgitation (HR 2.819 [95% CI, 1.604-4.153]), and right ventricular pacing ≥ 50% (HR 2.311 [95% CI, 1.478-3.937]) were strong predictors for DCF, and NT-proBNP > 1000 ng/L and paced QRS duration ≥ 180 ms were also the independent predictors of DCF. CONCLUSIONS: MrEF was associated with increased risk of deterioration of cardiac function after PPM implantation. Moderate mitral regurgitation and increased NT-proBNP levels are also potential independent predictors for deterioration of cardiac function after PPM implantation.

Uric acid: a potent molecular contributor to pluripotent stem cell cardiac differentiation via mesoderm specification.

Congenital heart disease (CHD) is the most common cause of congenital anomaly and a leading cause of morbidity and mortality worldwide. Generation of cardiomyoctyes derived from pluripotent stem cells (PSCs) has opened new avenues for investigation of human cardiac development. Here we report that uric acid (UA), a physiologically abundant compound during embryonic development, can consistently and robustly enhance cardiac differentiation of human PSCs including hESCs and hiPSCs, in replacement of ascorbic acid (AA). We optimized treatment conditions and demonstrate that differentiation day 0-2, a period for specification of mesoderm cells, was a critical time for UA effects. This was further confirmed by UA-induced upregulation of mesodermal markers. Furthermore, we show that the developing mesoderm may be by directly promoted by SNAI pathway-mediated epithelial-mesenchymal transition (EMT) at 0-24 h and a lengthened G0/G1 phase by increasing the ubiquitination degradation in 24-48 h. These findings demonstrate that UA plays a critical role in mesoderm differentiation, and its level might be a useful indicator for CHD in early fetal ultrasound screening.

Risk factors for noninvasive ventilation failure in patients with acute cardiogenic pulmonary edema: A prospective, observational cohort study.

PURPOSE: We identified risk factors for noninvasive ventilation (NIV) failure in patients with acute cardiogenic pulmonary edema (ACPE). MATERIALS AND METHODS: We conducted an observational cohort study over a 3-year period in a 28-bed emergency intensive care unit (EICU) and prospectively included all consecutive patients in whom NIV was attempted as initial ventilatory support for ACPE. The primary outcome variables were NIV failure rate and risk factors for NIV failure. RESULTS: Among the 118 patients in the study, NIV failed for 44 (37.3%) patients. Risk factors for NIV failure were Killip class IV (odds ratio [OR], 28.56; 95% confidence interval [CI], 2.17-375.73; p=0.011), left ventricular ejection fraction (LVEF) <30% (OR, 9.54; 95% CI, 1.01-90.55; p=0.050) and B-type natriuretic peptide (BNP) ≥3350pg/mL (OR, 39.63; 95% CI, 3.92-400.79; p=0.002) at baseline, and fluid balance ≥400mL within 24h after ACPE (OR, 13.19; 95% CI, 1.18-147.70; p=0.036). CONCLUSIONS: NIV failure occurred in 37.3% of ACPE patients in a real-world EICU. When patients had Killip class IV, a lower LVEF, a higher BNP, and a more positive fluid balance within 24h after ACPE, the risk of failure was higher. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER: NCT02653365.

Perioperative management of antithrombotic therapy in patients receiving cardiovascular implantable electronic devices: a network meta-analysis.

PURPOSE: Network meta-analysis (NMA) has advantages including being able to simultaneously compare and rank multiple treatments over traditional meta-analysis. We evaluated by a NMA the optimal antithrombotic strategy during the perioperative period of implantation of cardiovascular implantable electronic devices (CIEDs). METHODS: We performed a network meta-analysis of observational studies (cohort and case-control studies). The eligible studies tested the following antithrombotic therapy during the CIED placement: aspirin, clopidogrel, warfarin, novel oral anticoagulants (NOACs), and heparin bridging. RESULTS: Thirty-one observational studies with 119 study arms were included (41,174 patients receiving long-term antithrombotic therapy; median age, 72.6 years; 70.1% males; median follow-up, 3.6 years). Aspirin (4.26 [2.88-7.22]), warfarin (3.37 [2.17-5.23]), and clopidogrel (3.30 [1.49-5.88]) reduced the risk of bleeding as compared with heparin bridging, and there was no significance difference between continued NOACs and heparin bridging (0.67 [0.21-2.18]). The comparison of commonly used protocols in the management of anticoagulant therapy revealed that continued warfarin (0.38 [0.20-0.74]), continued NOACs (0.19 [0.04-0.89]), and heparin bridging therapy (0.01 [0.05-0.21]) increased the risk of bleeding as compared that of control, and continued warfarin (3.74 [1.96-7.16]), interrupted warfarin (4.89 [2.20-10.88]), and interrupted NOACs (12.5 [1.25-100]) reduced the risk of bleeding compared with that of heparin bridging. CONCLUSIONS: Among various antithrombotic drugs, aspirin had the lowest bleeding risk, followed by warfarin, clopidogrel and NOACs, and heparin, with the greatest bleeding risk. NOACs therapy appears safe and effective, and interrupted NOACs may be the optimal anticoagulation protocol for use during the perioperative period of CIED implantation.

Smac mimetic­induced caspase­independent necroptosis requires RIP1 in breast cancer.

There is an urgent requirement for the development of novel targeted therapies to treat breast cancer, which is the most comment type of malignancy among women. The evasion of apoptosis is a hallmark of cancer, and is often due to the upregulation of inhibitor of apoptosis proteins (IAPs) in tumor cells. Second mitochondrial­derived activator of caspase/direct IAP­binding protein with low PI is a natural IAP antagonist, which is found in the mitochondrion; this protein has a motif, which binds to a surface groove on the baculovirus IAP repeat domains of the IAPs. In the present study, the effects of the LCL161 Smac mimetic, a small molecule IAP antagonist, on breast cell lines was examined. The results from MTT and colony formation assays demonstrated that LCL161 markedly inhibited the proliferation and induced the apoptosis of MDA­MB­231 and MCF­7 cell lines. As determined by western blotting, cIAP1 was degraded in the breast cancer cells, which occurred in an LCL161­dependent manner. Upon caspase activation, LCL161 treatment induced necroptosis, another form of programmed cell death. The downregulation of receptor­interacting protein kinase­1 via small interfering RNA protected the cells from LCL161­induced necroptosis. Taken together, the results of the present study showed that LCL161 can induce multiple forms of programmed cell death in breast cancer cells, and may thus offer promise as an anticancer agent in diverse genotypic backgrounds.

Ischemic postconditioning improves the expression of cellular membrane connexin 43 and attenuates the reperfusion injury in rat acute myocardial infarction.

To investigate the effects of cellular membrane connexin 43 (Cx43) and the potential details in ischemic postconditioning (IPOC)-induced cardioprotection, ischemia/reperfusion (IR) models were generated in 8-week-old male Sprague-Dawley rats by ligating the left coronary artery anterior descending branch. The serum levels of myocardial creatases, nitric oxide (NO) and malondialdehyde (MDA) levels, infarct size, arrhythmia events, expression and distribution of Cx43, ultrastructure and apoptosis in the myocardium in different treatments with IR, IR + IPOC, IR + diazoxide or IR + IPOC + 5-hydroxydecanoate acid (5-HD) were investigated. Consequently, IPOC decreased infarct size (10.9 vs. 43.3%, P<0.01) and the levels of myocardial creatases, NO and MDA, and improved the expression (16.8 vs. 25.2% and 6.4 vs. 32.8%, after 1- and 3-h reperfusion, respectively; P<0.01) and distribution of Cx43, ultrastructure and apoptosis (19.2 vs. 42.9%, P<0.01) significantly. Diazoxide partly simulated the effects, and 5-HD attenuated but not completely abolished the effects of IPOC. In addition, the phosphorylated Cx43 (p-Cx43) level in the IR + IPOC group was lower than that in the IR + diazoxide group after 1-h reperfusion (26.1 vs. 29.4%, P>0.05); however, it was reversed after 3-h reperfusion and the p-Cx43 level in the IR + IPOC group was significantly higher than that in the IR + diazoxide group (32.8 vs. 18.7%, P<0.01). In conclusion, cell membrane Cx43 is also involved in the process of IPOC-induced cardioprotection and the improvement of membrane Cx43 is more dependent on mitochondrial KATP in the earlier phase of IPOC compared to the late phase of IPOC.

Activation of protein kinase C ε enhanced movement ability and paracrine function of rat bone marrow mesenchymal stem cells partly at least independent of SDF-1/CXCR4 axis and PI3K/AKT pathway.

OBJECTS: to probe into the effects of PKCε on migration and paracrine functions of stem cells and potential molecular mechanisms. METHODS: Bone Marrow mesenchymal stem cells (BMMSCs) were obtained from rat femur and passaged. mRNA and protein levels of capital proteins in PKCε signaling, SDF-1/CXCR4 axis and PI3K/AKT pathway in the MSCs in different conditions treating with PKC agonist, specific PKCε inhibitor, CXCR4 antagonist or PI3K inhibitor for 24 hours were analyzed by real-time PCR and western blot, and migration abilities were observed by migration assay in vitro and the changes of paracrine factors in different treatments were analyzed by protein clips assay. RESULTS: the levels of p-JNK, p-P38MAPK, SDF-1, CXCR4, PI3K and p-AKT increased significantly after treating with PKC agonist (P < 0.05) and decreased obviously after treating with specific PKCε inhibitor. Migration ability and paracrine function of MSCs were enhanced in PMA group and attenuated in PKCε inhibitor group, and inhibiting activity of CXCR4 or PI3K attenuated the effects of PKCε, but not abolished completely. CONCLUSION: There was cross-talking between PKCε signaling and SDF-1/CXCR4 axis and PI3K/AKT pathway in signal transduction of MSCs. Activating PKCε could improve migration ability and paracrine function of MSCs partly at least independent of SDF-1/CXCR4 axis and PI3K/AKT pathway.

[The analysis of multi-drug resistance of doxorubicin with flow cytometry].

BACKGROUND: To evaluate the significance of flow cytometry (FCM) in the analysis of multi-drug resistance of doxorubicin. METHODS: The level of doxorubicin or Rh-123 in S-180R and BGC-823/DOX, which were two cell lines with different drug resistance, was measured by FCM comparatively and continuously. RESULTS: The total fluorescence profile peaks of S-180R, a high resistant cell line, were predominantly different from those of S-180, the parent cell line, by the FCM analysis. The subtle fluorescence profile differences between BGC-823/DOX (a low resistant cell line) and the parent cell line were quantitatively measured on the FCM map. The changes of each resistant cell fluorescence from the S 180R cells could be displayed by continuous tests, the more near the fluorescence level of each cell was, the more the fluorescence pike of whole cells centralized. CONCLUSIONS: FCM is a sensitive, accurate and quantitative test in the analysis of doxorubicin drug resistance.

[Detection of quorum-sensing pathway and construction of luxS gene allelic exchange plasmid of Streptococcus mutans].

OBJECTIVE: To detect the AI-2 quorum-sensing pathway and construct the luxS g-ene allelic exchange plasmid of Streptococcus mutans. METHODS: To detect AI-2 pathway in Streptococcus mutans, the Vibrio harveyi BB170 was used as reporter strain. The PCR fragments of the upstream and downstream regions of luxS and the Erythromycin resistance gene were amplified with the primers respectively, and these fragments were ligated into pUC19 vector with double endonuclease reaction sequentially, the ligated DNAs were transformed into Escherichia coli DH5alpha, then the reconstructed plasmids were isolated and identified by restricted endonuclease digestions. RESULTS: Streptococcus mutans Ingbritt C could induce luminescence of BB170, suggesting the presence of AI-2 quorum sensing pathway in Streptococcus mutans, and such stimulatory activity was maximal at the mid-log growth phase. The recombinant plasmid pUCluxKO was digested by PstI-BamHI, and the digest product were 1000 bp and 5000 bp. When the pUCluxKO was digested by BamHI-KpnI, the digest product were 1500 bp and 4500 bp. While it was digested by KpnI-EcoRI, the digest product were 1000 bp and 5000 bp. All PCR product was in a single belt respectively. CONCLUSIONS: The recombinant plasmid was cloned effectively and can be used in the construction of S.mutans luxS mutant.

[Modified radical operation for early breast cancer for preserving nipple-areolar complex and breast reconstruction using transverse rectus abdominis myocutaneous (TRAM) flap].

BACKGROUND & OBJECTIVE: Modified radical mastectomy (MRM) operation has become an important surgical therapy for early stage breast cancer, but how to reconstruct breast and preserve nipple-areolar complex (NAC) is controversial. In this study, we applied a modified radical mastectomy for early stage breast cancer for preserving NAC and breast reconstruction using transverse rectus abdominis myocutaneous (TRAM) flap. METHODS: During operation we performed the subcutaneous glandular excision and axillary dissection, and reconstructed the breast using TRAM flap in 10 patients with early stage breast cancer; meanwhile, maximam extent of breast skin and NAC were preserved. RESULTS: The appearance of the reconstructed breast was better preserved after operation. No local recurrence and distant metastasis occurred in the patients during the follow up time (range 24-48 months). No skin flap necrosis, atrophy, and scleroses surround the NAC were observed; and no abdominal wall hernia occurred at the donor site. The nipple sensation was recovered half a year after surgery. CONCLUSION: Modified radical operation for preserving NAC and breast reconstruction using TRAM flap may be a better way for breast cancer patients in early stage who request well preserving of breast. More samples are needed for proving the effects of this operation.