Reduction of acetate synthesis, enhanced arginine export, and supply of precursors, cofactors, and energy for improved synthesis of L-arginine by Escherichia coli.

L-arginine (L-Arg) is a semi-essential amino acid with many important physiological functions. However, achieving efficient manufacture of L-Arg on an industrial scale using Escherichia coli (E. coli) remains a major challenge. In previous studies, we constructed a strain of E. coli A7, which had good L-Arg production capacity. In this study, E. coli A7 was further modified, and E. coli A21 with more efficient L-Arg production capacity was obtained. Firstly, we reduced the acetate accumulation of strain A7 by weakening the poxB gene and overexpressing acs gene. Secondly, we improved the L-Arg transport efficiency of strains by overexpressing the lysE gene from Corynebacterium glutamicum (C. glutamicum). Finally, we enhanced the supplies of precursors for the synthesis of L-Arg and optimized the supplies of cofactor NADPH and energy ATP in strain. After fermentation in a 5-L bioreactor, the L-Arg titer of strain A21 was found to be 89.7 g/L. The productivity was 1.495 g/(L·h) and the glucose yield was 0.377 g/g. Our study further narrowed the titer gap between E. coli and C. glutamicum in the synthesis of L-Arg. In all recent studies on the L-Arg production by E. coli, this was the highest titer recorded. In conclusion, our study further promotes the efficient mass synthesis of L-Arg by E. coli. KEY POINTS: • The acetate accumulation of starting strain A7 was decreased. • Overexpression of gene lysE of C. glutamicum enhanced L-Arg transport in strain A10. • Enhance the supplies of precursors for the synthesis of L-Arg and optimize the supplies of cofactor NADPH and energy ATP. Finally, Strain A21 was detected to have an L-Arg titer of 89.7 g/L in a 5-L bioreactor.

Cofactor Engineering for Efficient Production of α-Farnesene by Rational Modification of NADPH and ATP Regeneration Pathway in Pichia pastoris.

α-Farnesene, an acyclic volatile sesquiterpene, plays important roles in aircraft fuel, food flavoring, agriculture, pharmaceutical and chemical industries. Here, by re-creating the NADPH and ATP biosynthetic pathways in Pichia pastoris, we increased the production of α-farnesene. First, the native oxiPPP was recreated by overexpressing its essential enzymes or by inactivating glucose-6-phosphate isomerase (PGI). This revealed that the combined over-expression of ZWF1 and SOL3 increases α-farnesene production by improving NADPH supply, whereas inactivating PGI did not do so because it caused a reduction in cell growth. The next step was to introduce heterologous cPOS5 at various expression levels into P. pastoris. It was discovered that a low intensity expression of cPOS5 aided in the production of α-farnesene. Finally, ATP was increased by the overexpression of APRT and inactivation of GPD1. The resultant strain P. pastoris X33-38 produced 3.09 ± 0.37 g/L of α-farnesene in shake flask fermentation, which was 41.7% higher than that of the parent strain. These findings open a new avenue for the development of an industrial-strength α-farnesene producer by rationally modifying the NADPH and ATP regeneration pathways in P. pastoris.

Review of DNA repair enzymes in bacteria: With a major focus on AddAB and RecBCD.

DNA recombination repair systems are essential for organisms to maintain genomic stability. In recent years, we have improved our understanding of the mechanisms of RecBCD/AddAB family-mediated DNA double-strand break repair. In E. coli, it is RecBCD that plays a central role, and in Firmicute Bacillus subtilis it is the AddAB complex that functions. However, there are open questions about the mechanism of DNA repair in bacteria. For example, how bacteria containing crossover hotspot instigator (Chi) sites regulate the activity of proteins. In addition, we still do not know the exact process by which the RecB nuclease or AddA nuclease structural domains load RecA onto DNA. We also know little about the mechanism of DNA repair in the industrially important production bacterium Corynebacterium glutamicum (C. glutamicum). Therefore, exploring DNA repair mechanisms in bacteria may not only deepen our understanding of the DNA repair process in this species but also guide us in the targeted treatment of diseases associated with recombination defects, such as cancer. In this paper, we firstly review the classical proteins RecBCD and AddAB involved in DNA recombination repair, secondly focus on the novel helical nuclease AdnAB found in the genus Mycobacterium.

Environmentally relevant concentrations of mercury facilitate the horizontal transfer of plasmid-mediated antibiotic resistance genes.

Abundant antibiotic resistance genes (ARGs) are typically found in mercury (Hg)-contaminated aquatic environments. This phenomenon is partly attributed to the co-resistance, cross-resistance, and shared regulatory responses to Hg and antibiotics. However, it remains unclear whether and how Hg influences the conjugative transfer of ARGs mediated by mobilizable plasmids. In the present study, we found that Hg2+ at the environmentally relevant concentrations (0.001-0.5 mg L-1) facilitated the conjugative transfer of ARGs through the mobilizable plasmid RP4 from the donor Escherichia coli HB101 to the recipient E. coli K12. Exposure to Hg2+ significantly increases the formation of reactive oxygen species, malondialdehyde production, antioxidant enzyme activities, and cell membrane permeability, while decreasing the concentration of glutathione. Scanning electron microscopy and transmission electron microscopy showed that the cell membrane suffered from oxidative damage, which is beneficial for conjugative transfer. The expression of global regulatory genes (korA, korB, and trbA) negatively regulating conjugative transfer was restrained by Hg2+, while promoting the expression of positive regulatory genes involved in the mating pair formation system (trbBp and traF) and the DNA transfer and replication systems (trfAp and traJ). Although a high Hg2+ concentration (1.0 mg L-1) suppressed ARGs conjugative transfer, our results suggest that Hg2+ facilitates the dissemination of ARGs in aquatic environments at environmentally relevant concentrations. This study improves our understanding of ARGs dissemination in Hg-contaminated aquatic environments.

Effects of the Sn100 kVp Tube Voltage Mode on the Radiation Dose and Image Quality of Dual-Source Computed Tomography Pulmonary Angiography.

OBJECTIVE: This study aimed to investigate the effects of the Sn100 kVp tube voltage mode on the image quality and radiation dose of computed tomography pulmonary angiography (CTPA). METHODS: A total of 145 patients who underwent CTPA were randomly divided into five groups: control group (120 kVp, 150 mAs), test group A (Sn100 kVp, 270 mAs), test group B (120 kVp, 30 mAs), test group C (70 kVp, 150 mAs), and test group D (80 kVp, 70 mAs). After image post-processing, the image quality and radiation dose of each group were analyzed. RESULTS: The computed tomography values of images in the four test groups were more than 250 HU, which met the criteria for diagnosis. The signal-to-noise ratio and contrast-to-noise ratio of the images in the four test groups were lower than those in the control group. The radiation dose in each test group was lower than in the control group. The radiation dose was lowest in test group A. CONCLUSION: The Sn100 kVp energy spectrum purification protocol can meet the requirements for clinical diagnosis, ensure image quality, and reduce the dose of radiation that patients receive.

Polymerization-Induced Self-Assembly to Produce Prodrug Nanoparticles with Reduction-Responsive Camptothecin Release and pH-Responsive Charge-Reversible Property.

Polymerization-induced self-assembly has been demonstrated to be a powerful strategy for fabricating polymeric nanoparticles in the last two decades. However, the stringent requirements for the monomers greatly limit the chemical versatility of PISA-based functional nanoparticles and expanding the monomer family of PISA is still highly desirable. Herein, a camptothecin analogue (CPTM) is first used as the monomer in PISA. Prodrug nanoparticles with reduction-responsive camptothecin release behavior are fabricated at 10% solid concentration (100 mg g-1 ). Poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA) and poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) are used as the macro RAFT agents to comediate the RAFT dispersion polymerization of CPTM in ethanol to produce the PHPMA/PDEAEMA-stabilized nanoparticles. The PDEAEMA chains become hydrophobic and are in the collapsed state at physiological pH values. In contrast, in the vicinity of an acidic tumor, the tertiary amine groups of PDEAEMA chains are rapidly protonated, leading to fast hydrophobic-hydrophilic transitions and charge reversal. Such fast charge-reversal results in enhanced cancer cell internalization of the prodrug nanoparticles, thus achieving superior anticancer efficacy.

A Quantitative Study of the Dimensional Change of Inferior Vena Cava on Computed Tomography During Acute Hemorrhage Shock in Swine.

Background: The purpose of this study was to examine the dimensional change of IVC during acute hemorrhage through a volume-controlled acute hemorrhagic shock model in swine. Methods: Volume-controlled hemorrhage was performed in 10 adult Bama mini pigs. Enhanced CT scan and hemodynamic monitoring were performed when the cumulative blood loss volume reached 0%, 10%, 20%, 30%, and 40%. The transverse diameter (T) and anteroposterior diameter (AP) of IVC were measured in axial images. Hemodynamic parameters were obtained with Pulse Contour Cardiac Output (PiCCO) hemodynamic monitor device. Arterial blood samples were also collected for artery blood gas analysis at each time point. Results: As the blood loss volume increased, the collapsibility (T/AP) and cross section area (CSA) of IVC significantly changed first in hepatic level and pre-renal level. The significant decrease of the CSA of IVC (shrink) occurred early when the blood loss volume reached only 10%, but the collapse of IVC occurred until the blood loss volume reached 30%. Conclusions: IVC shrank early but collapsed late during the acute hemorrhage in swine. The finding of collapsed IVC on CT scans suggested severe hypovolemic shock. Evaluation of the IVC at the CT scans can be an adjunctive test of the hemodynamic status in trauma patients.

Accurate deduction of infrared imaging features of subpixel targets based on the conversion of radiation fields of measured area targets.

The accurate generation of infrared (IR) imaging features of subpixel targets plays a very important role in the demonstration, verification, and optimization of system design schemes as well as in research into detection algorithms for small targets in the development of remote IR early warning systems. Based on the generation mechanism of target full-link IR imaging features, this study theoretically considers target radiation characteristics, the working environment, and the spatial response and energy-conversion characteristics of IR sensors, and an accurate deduction model of IR imaging features of subpixel targets is proposed and established. First, the surface-radiation field distribution of the target and background are inverted based on the measured data and the model of radiation calibration; then, the accurate simulation of IR imaging features of subpixel targets is realized by considering the geometric transformation of the spatial imaging, the aperiodic transfer function, scale registration of spatial sampling, and radiation coupling. Finally, the accuracy of the proposed model is verified by using the outfield experiment data. The experimental results show that the IR imaging-diffusion features of subpixel targets with different duty cycles are in good agreement with the prediction results of the model. The results obtained provide data support for the demonstration, verification, and optimization of the system design scheme, as well as for research into detection algorithms of small targets in the development of remote IR early warning systems.

Antisense RNA: the new favorite in genetic research.

Antisense RNA molecule represents a unique type of DNA transcript that comprises 19-23 nucleotides and is complementary to mRNA. Antisense RNAs play the crucial role in regulating gene expression at multiple levels, such as at replication, transcription, and translation. In addition, artificial antisense RNAs can effectively regulate the expression of related genes in host cells. With the development of antisense RNA, investigating the functions of antisense RNAs has emerged as a hot research field. This review summarizes our current understanding of antisense RNAs, particularly of the formation of antisense RNAs and their mechanism of regulating the expression of their target genes. In addition, we detail the effects and applications of antisense RNAs in antivirus and anticancer treatments and in regulating the expression of related genes in plants and microorganisms. This review is intended to highlight the key role of antisense RNA in genetic research and guide new investigators to the study of antisense RNAs.

Midterm Follow-up of Coronary Artery Bypass Grafting with 64-Slice Multi-detector Computed Tomography: Identification of Risk Factors Affecting Graft Patency.

To identify the risk factors that are associated with the midterm coronary artery bypass grafting (CABG) functionality by assessing patency of left internal mammary artery (LIMA) graft and saphenous vein (SV) graft with 64-slice multi-detector computed tomography (64-MDCT).Methods Patients who underwent CABG operation and postoperative 64-MDCT follow-up examinations from August 2012 to December 2015 were included. The graft patent status was classified into patent and poor patent according to MDCT findings predominantly on 3D reconstructed images by two radiologists. The clinical data and imaging findings of the patients were collected and compared between the patent group and poor patent group. Univariate analysis and the multivariate logistic regression analysis were performed to identify the risk factors that affect graft patency.Results Among 341 patients in the study, there were 330 LIMA grafts [326 anastomosed to the left anterior descending artery (LAD), 4 to right coronary artery (RCA)] and 564 SV grafts (SVG) [100 anastomosed to the diagonal branch (D), 226 to the obtuse marginal branch (OM), and 238 to the RCA territory]. The approximal vessel stenosis exceeding 90% occurred in 268 of 292 patent LIMA grafts, and in 1 of 34 poor patent grafts (χ 2=167, P<0.001). The patency rate was higher when SVG was anastomosed to OM (85.4%) or RCA territory (81.9%) than to D (69.0%) (χ 2=15.471, P=0.004). The proximal target vessel stenosis < 90% (OR= 0.015, 95% CI: 0.01-0.14, P=0.000) was independently associated with the closure risk of LIMA grafts, the dyslipidemia (OR= 1.52, 95% CI: 1.0-2.5, P=0.048), history of diabetes (OR = 1.28, 95% CI : 0.90-2.26, P=0.045) and typical angina symptoms (OR=1.81, 95% CI :1.33-4.15, P=0.003) were independently associated with the closure risk of SVG. Conclusions The proximal LAD stenosis less than 90% was adversely associated with graft patency in LIMA recipients; dyslipidemia, diabetes and angina symptoms were associated with the midterm failure in SVG recipients. The choice of the target anastomosis sites may affect the patency of SVG.

Co-production of microbial oil and exopolysaccharide by the oleaginous yeast Sporidiobolus pararoseus grown in fed-batch culture.

The production cost of microbial oil was reduced by improving the exopolysaccharide (EPS) production to share the production cost using Sporidiobolus pararoseus JD-2. Batch fermentation demonstrated that S. pararoseus JD-2 has the potential to co-produce oil and EPS with 120 g L-1 glucose, 20 g L-1 corn steep liquor and 10 g L-1 yeast extract as carbon and nitrogen sources. Using fed-batch fermentation for 72 h resulted in oil and EPS production of 41.6 ± 2.5 g L-1 and 13.1 ± 0.6 g L-1 with the productivity of 0.58 g L-1 h-1 and 0.182 g L-1 h-1, respectively. The fat soluble nutrients in the oil were studied, indicating that it was constituted of 79.19% unsaturated fatty acids and contained 505 mg per kg-oil of carotenoids. Moreover, the EPS contained only one type of polysaccharide; the main monosaccharide compositions were galactose, glucose and mannose in a proportion of 16 : 8 : 1. These results implied that EPS produced by S. pararoseus JD-2 was a new type of EPS.

Puerarin Induces Hepatocellular Carcinoma Cell Apoptosis Modulated by MAPK Signaling Pathways in a Dose-dependent Manner.

BACKGROUND/AIM: Puerarin possesses a battery of therapeutic values in diverse disorders, including pro-apoptotic actions in multiple cancers. Herein, we investigated the effects of puerarin on hepatocellular carcinoma (HCC) in vitro. MATERIALS AND METHODS: MTT and flow cytometry were carried out to evaluate the viability and apoptosis of SMMC-7721 HCC cells in the presence of different concentrations of puerarin. Moreover, expression levels, as well as phosphorylation status of several canonical components in mitogen-activated protein kinase (MAPK) pathways, including extracellular signal-regulated kinase 1/2 (ERK1/2), c- Jun N-terminal kinase (JNK), p38, were measured by reverse transcription and quantitative real-time polymerase chain reaction (RT-PCR) and western blot analysis at indicated time intervals. RESULTS: Puerarin inhibited proliferation of SMMC-7721 cells and promoted their apoptosis in a dose- and time-dependent fashion (p<0.05). Both the expression and phosphorylation levels of MAPK proteins were dramatically increased on puerarin treatment. CONCLUSION: Puerarin could be employed as a potential anti-carcinogen that exhibits pro-apoptotic effects on HCC cells, in a dose- and time-dependent manner, with emphasis on MAPK pathways whose initiation may contribute to this process.

Clinical analysis of hyperkalemia after esophagectomy: A case report.

RATIONALE: The occurrence of hyperkalemia after esophagectomy is clinically rare. Patients who underwent esophagectomy often have a serum potassium level due to perioperative reduced intake, fluids loss, consumption and other reasons. These patients often require the artificial administration of potassium. Rapid fluid loss and physiological consumption lead to the deficiency of potassium, even hypokalemia. Patients often require the addition of a large amount of potassium after operation. The occurrence of hyperkalemia after esophagectomy is never been reported. PATIENT CONCERNS: The patient presented with continuous tachycardia, palpitations, chest tightness, progressive nausea, irritability, progressive myasthenia gravis. DIAGNOSES: Hyperkalemia, sepsis, acidosis, diabetes, postoperative esophageal cancer. INTERVENTIONS: Prompt anti-infection treatment and the management of blood sugar, hemodialysis was performed to correct sthe acidosis and electrolyte disorder OUTCOMES:: All symptoms were alleviated. LESSONS: Therefore, there is a need to regularly test electrolytes, especially in patients with diabetes, as well as better blood glucose control. Attention should be paid to the potential of infection, and to avoiding ketoacidosis and risk of sepsis.

Aesculetin (6,7-dihydroxycoumarin) exhibits potent and selective antitumor activity in human acute myeloid leukemia cells (THP-1) via induction of mitochondrial mediated apoptosis and cancer cell migration inhibition.

PURPOSE: The main target of the present research was to examine the antitumor properties of aesculetin in human acute myeloid leukemia cancer cells (THP-1) and peripheral blood mono-nucleated cells (PBMCs) (used as normal cell line model) along with the determination of its effects on induction of apoptosis, inhibition of cancer cell migration and changes in Bcl-2/Bax protein expressions. METHODS: MTT colorimetric bioassay was performed to study the impact of this natural compound on cytotoxicity of both cell types. Moreover, transmission electron microscopy (TEM), inverted phase contrast and fluorescence microscopic techniques were used to study the effects on cell morphology and cellular ultrastructural details connected with apoptosis. The effects of aesculetin on Bcl-2/Bax protein expressions were assessed by Western blot method. RESULTS: Selective and dose-dependent antiproliferative activity of aesculetin in human acute myeloid leukemia cancer cells was observed. However, the compound did not induce significant cell growth inhibition of PBMCs, which were used as normal cell controls. Fluorescence and inverted phase contrast microscopic techniques revealed that aesculetin led to morphological changes suggestive of apoptosis (cell shrinkage, chromatin abridgment and membrane blebbing). TEM analysis showed that aesculetin led to fragmented plasma membrane along with appearance of spherical projections (apoptotic bodies). The wound scratch widened after aesculetin treatment, indicating that aesculetin exhibits anticancer effects by suppressing the cancer cell migration. Aesculetin led to significant and dose-dependent reduction in the Bcl-2 expression while the expression of Bax was significantly enhanced resulting in overall reduction of Bcl-2/Bax ratio. CONCLUSION: The results of the present work revealed that aesculetin exhibits selective anticancer effects in THP-1 human leukemia cells without causing much cytotoxicity in PBMCs. It also led to significant apoptosis induction, inhibition of cancer cell migration and decrease in Blc-2/Bax ratio.

Design and Synthesis of Pyridone-Containing 3,4-Dihydroisoquinoline-1(2H)-ones as a Novel Class of Enhancer of Zeste Homolog 2 (EZH2) Inhibitors.

A new enhancer of zeste homolog 2 (EZH2) inhibitor series comprising a substituted phenyl ring joined to a dimethylpyridone moiety via an amide linkage has been designed. A preferential amide torsion that improved the binding properties of the compounds was identified for this series via computational analysis. Cyclization of the amide linker resulted in a six-membered lactam analogue, compound 18. This transformation significantly improved the ligand efficiency/potency of the cyclized compound relative to its acyclic analogue. Additional optimization of the lactam-containing EZH2 inhibitors focused on lipophilic efficiency (LipE) improvement, which provided compound 31. Compound 31 displayed improved LipE and on-target potency in both biochemical and cellular readouts relative to compound 18. Inhibitor 31 also displayed robust in vivo antitumor growth activity and dose-dependent de-repression of EZH2 target genes.

Application of iron oxide nanoparticles in glioma imaging and therapy: from bench to bedside.

Gliomas are the most common primary brain tumors and have a very dismal prognosis. However, recent advancements in nanomedicine and nanotechnology provide opportunities for personalized treatment regimens to improve the poor prognosis of patients suffering from glioma. This comprehensive review starts with an outline of the current status facing glioma. It then provides an overview of the state-of-the-art applications of iron oxide nanoparticles (IONPs) to glioma diagnostics and therapeutics, including MR contrast enhancement, drug delivery, cell labeling and tracking, magnetic hyperthermia treatment and magnetic particle imaging. It also addresses current challenges associated with the biological barriers and IONP design with an emphasis on recent advances and innovative approaches for glioma targeting strategies. Opportunities for future development are highlighted.

Effects of Incorporating Carboxymethyl Chitosan into PMMA Bone Cement Containing Methotrexate.

Treatment of bone metastases usually includes surgical resection with local filling of methotrexate (MTX) in polymethyl methacrylate (PMMA) cement. We investigated whether incorporating carboxymethyl chitosan (CMCS) in MTX-PMMA cement might overcome disadvantages associated with MTX. To determine the optimal CMCS+MTX concentration to suppress the viability of cancer cells, an integrated microfluidic chip culturing highly metastatic lung cancer cells (H460) was employed. The mechanical properties, microstructure, and MTX release of (CMCS+MTX)-PMMA cement were evaluated respectively by universal mechanical testing machine, scanning electron microscopy (SEM), and incubation in simulated body fluid with subsequent HPLC-MS. Implants of MTX-PMMA and (CMCS+MTX)-PMMA cement were evaluated in vivo in guinea pig femurs over time using spiral computed tomography with three-dimensional image reconstruction, and SEM at 6 months. Viability of H460 cells was significantly lowest after treatment with 57 µg/mL CMCS + 21 µg/mL MTX, which was thus used in subsequent experiments. Incorporation of 1.6% (w/w) CMCS to MTX-PMMA significantly increased the bending modulus, bending strength, and compressive strength by 5, 2.8, and 5.2%, respectively, confirmed by improved microstructural homogeneity. Incorporation of CMCS delayed the time-to-plateau of MTX release by 2 days, but increased the fraction released at the plateau from 3.24% (MTX-PMMA) to 5.34%. Relative to the controls, the (CMCS+MTX)-PMMA implants integrated better with the host bone. SEM revealed pores in the cement of the (CMCS+MTX)-PMMA implants that were not obvious in the controls. In conclusion, incorporation of CMCS in MTX-PMMA appears a feasible and effective modification for improving the anti-tumor properties of MTX-PMMA cement.

Clopidogrel resistance response in patients with coronary artery disease and metabolic syndrome: the role of hyperglycemia and obesity.

BACKGROUND: Despite the proven benefits of clopidogrel combined aspirin therapy for coronary artery disease (CAD), CAD patients with metabolic syndrome (MS) still tend to have coronary thrombotic events. We aimed to investigate the influence of metabolic risk factors on the efficacy of clopidogrel treatment in patients with CAD undergoing percutaneous coronary intervention (PCI). METHODS: Cohorts of 168 MS and 168 non-MS subjects with CAD identified by coronary angiography (CAG) were enrolled in our study. MS was defined by modified Adult Treatment Panel III criteria. All subjects had taken 100 mg aspirin and 75 mg clopidogrel daily for more than 1 month, and administered loading doses of 600 mg clopidogrel and 300 mg aspirin before PCI. Blood samples were taken 24 h after the loading doses of clopidogrel and aspirin. Platelet aggregation was measured using light transmittance aggregometry (LTA) and thrombelastography (TEG). Clopidogrel resistance was defined as more than 50% adenosine diphosphate (ADP) induced platelet aggregation as measured by TEG. RESULTS: Platelet aggregation inhibition rate by ADP was significantly lower in patients with MS as measured both by TEG (55% ± 31% vs. 68% ± 32%; P < 0.001) and LTA (29% ± 23% vs. 42% ± 29%; P < 0.001). In the multivariate analysis, elderly [OR (95% CI): 1.483 (1.047-6.248); P = 0.002], obesity [OR (95% CI): 3.608 (1.241-10.488); P = 0.018], high fasting plasma glucose level [OR (95% CI): 2.717 (1.176-6.277); P = 0.019] and hyperuricemia [OR (95% CI): 2.583 (1.095-6.094); P = 0.030] were all statistically risk factors for clopidogrel resistance. CAD patients with diabetes and obesity were more likely to have clopidogrel resistance than the CAD patients without diabetes and obesity [75% (61/81) vs. 43% (67/156); P < 0.001]. CONCLUSIONS: CAD patients with MS appeared to have poorer antiplatelet response to clopidogrel compared to those without MS. Obesity, diabetes and hyperuricemia were all significantly associated with clopidogrel resistance.

Risk factors for deep vein thrombosis after orthopedic surgery and the diagnostic value of D-dimer.

BACKGROUND: This study was prospectively designed to determine the risk factors of deep vein thrombosis (DVT) in patients who underwent different surgeries, and to evaluate the efficacy and accuracy of plasma D-dimer level as a screening test. METHODS: From June 2013 to June 2014, 360 consecutive patients undergoing orthopedic surgery were evaluated. All patients underwent ultrasonography preoperatively and on postoperative day 7. Plasma D-dimer levels were estimated by latex immunoturbidimetry on the day of surgery and on postoperative days 1, 3, and 7. RESULTS: Of the 360 patients in this study, 339 patients completed the analysis. Among them, DVT was confirmed in 28 (8.26%) patients based on ultrasonographic findings. Multivariate logistic analysis revealed that body mass index was an independent risk factor for developing DVT (P = 0.018) and D-dimer levels on postoperative days 1 and 7 were independently correlated with the development of DVT (P = 0.019 and P < 0.001, respectively). The receiver operating characteristic curve analysis determined that the area under the curve was largest (0.752) when using D-dimer level on postoperative day 7 as diagnostic index, and the sensitivity and specificity were 71.4% and 81.7% at the cut-off value of 6.17 µg/mL, respectively. The elevated D-dimer levels followed the same tendency toward a double-peaked distribution with peaks at days 1 and 7 postoperatively. CONCLUSION: D-dimer level was a useful screening test to exclude DVT, and the cut-off values of D-dimer determined in this study will provide a reference for the absence of DVT to a certain extent.