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Head and neck squamous cell carcinoma (HNSCC) represents the most frequent malignancy in the head and neck region, and the survival rate has not been improved significantly over the past three decades. It has been reported the infiltrated macrophages contribute to the malignant progression of HNSCC. However, the crosstalk between macrophages and cancer cells remains poorly understood. In the present study, we explored interactions between monocytes/macrophages and HNSCC cells by establishing the direct co-culture system, and found that the crosstalk promoted the migration and invasion of cancer cells by enhancing the invadopodia formation through a CCL2/EGF positive feedback loop. Our results demonstrated HNSCC cells educated monocytes into M2-like macrophages by releasing C-C motif chemokine ligand 2 (CCL2, or MCP-1). And the M2-like macrophages secreted epithelial growth factor (EGF), which increased the motility of HNSCC cells by enhancing the invadopodia formation. These subcellular pseudopodia degraded extracellular matrix (ECM), facilitating tumor local invasion and distant metastasis. Moreover, EGF up-regulated CCL2 expression in HNSCC cells, which recruited monocytes and turned them into M2-like macrophages, thus forming a positive feedback paracrine loop. Finally, we reported that curcumin, a powerful natural drug, suppressed the production of EGF and CCL2 in macrophages and cancer cells, respectively, blocking the feedback loop and suppressing the migration and invasion of HNSCC cells. These results shed light on the possibilities and approaches based on targeting the crosstalk between cancer cells and monocytes/macrophages in HNSCC for potential cancer therapy.

Purpose: Microvascular endothelial integrity is important for maintaining the blood-brain barrier (BBB). However, subarachnoid hemorrhage (SAH) disrupts this integrity, making the BBB dysfunctional-an important pathophysiological change after SAH. Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) regulate microvascular permeability by balancing each other's expression., Methods: This study investigated the dynamics of Ang-1 and Ang-2 expression after SAH and the protective effect of Ang-1 on BBB functioning using an endovascular puncture model of rat SAH. The Ang-1 and Ang-2 expression in brain tissue was determined by immunohistochemistry. In addition, Western blotting was used to estimate Ang-1 and Ang-2 concentration and to compare them at 6-72 hours post-SAH cortex and hippocampus. Evans blue viability assay was used to evaluate BBB permeability, and neurological testing was implemented to evaluate neurological impairment during SAH., Results: It was found that following SAH, Ang-1 expression decreases and Ang-2 expression increases in the cortex, hippocampus, and microvessels. The Ang-1/Ang-2 ratio decreased as quickly as 6 hours after SAH and reached its lowest 1 day after SAH. Finally, it was found that exogenous Ang-1 reduces SAH-associated BBB leakage and improves neurological function in post-SAH rats., Conclusions: Our findings suggest that the equilibrium between Ang-1 and Ang-2 is broken in a period shortly after SAH, and the treatment of exogenous Ang-1 injection alleviates neurological dysfunctions through decreasing BBB destruction., Competing Interests: No potential conflict of interest relevant to this article was reported.

This study compared the radiographic and clinical outcomes of pediatric diaphyseal femur fractures treated by submuscular plating, flexible retrograde intramedullary nailing, or rigid antegrade intramedullary nailing with a trochanteric entry point in skeletally immature patients who were 8 years and older. A retrospective review was conducted of skeletally immature patients 8 years and older who were treated for femur fracture with submuscular plating, flexible intramedullary nailing, or rigid intramedullary nailing from 2001 to 2014 with a minimum 12-week follow-up. Treatment outcomes were compared for statistical significance, including time to union, malunion, nonunion, heterotopic ossification, avascular necrosis, time to full weight bearing, limb length discrepancy, residual limp, painful hardware, and infection. The study identified 198 femur fractures in 196 patients (mean age, 11.9 years). Each femur fracture was treated with submuscular plating (35), flexible intramedullary nailing (61), or rigid intramedullary nailing (102). Mean follow-up across the cohort was 48 weeks, ranging from 12 to 225 weeks. Flexible nailing was associated with an increased incidence of malunion (P<.0001) and hardware irritation (P=.0204) and longer time to full weight bearing (P=.0018). Rigid nailing was associated with an increased incidence of limp at 12-week followup (P=.0412). Additionally, 23.5% of patients who were treated with rigid nailing had heterotopic ossification. Of all surgical methods, submuscular plating allowed for the most rapid return to full weight bearing (mean, 7 weeks) and offered the fastest healing rate (mean, 6 weeks). Submuscular plating resulted in faster times to union and full weight bearing, with minimal complication rates. Rigid intramedullary nailing with trochanteric entry resulted in a lower incidence of malunion and hardware-related complications; however, these patients had an increased incidence of heterotopic ossification and residual limp postoperatively. Flexible retrograde intramedullary nailing resulted in the highest rates of malunion and hardware irritation and the longest time to full weight bearing. [Orthopedics. 2016; 39(6):353-358.]., (Copyright 2016, SLACK Incorporated.)

Objective: To determine the age-related coronary risk factors in Chinese patients with acute myocardial infarction (AMI). Methods: Among 31 provinces, municipalities or autonomous districts in China, from January 1st 2013 to September 30th 2014, 24 394 consecutive AMI patients who were admitted to 107 hospitals were divided into five groups according to age. Cardiovascular risk factors of groupⅠ (<45 years, n =2 307), group Ⅱ (45-54 years, n =4 448), group Ⅲ (55-64 years, n =7 029), group Ⅳ (65-74 years, n =6 147) and group Ⅴ (≥75 years, n =4 463) patients were compared. Results: Among 24 394 AMI patients [with a mean age of (62.2±13.8) years, 18 162 males], 24.7% patients had three and more conventional modifiable cardiovascular risk factors. ST-elevation myocardial infarction (STEMI) was diagnosed in 18 209 (74.6%) patients. The ratios of female, hypertension and diabetes tended to increase with the increase of age. Young AMI patients were predisposed to smoking, overweight/obesity and hyperglycemia. Nearly 90% patients in group Ⅰ and group Ⅱ were male. The ratio of male patients (92.3% to 58.0%), overweight/obesity (63.9% to 37.4%), current smoking (68.7% to 19.8%), dyslipidemia (9.1% to 4.5%), family history of premature coronary artery disease (CAD) (6.2% to 1.2%) and eating greasy food (86.1% to 66.2%) decreased markedly from group Ⅰ to Ⅴ patients. Proportion of hypertension gradually increased from 34.3% in group Ⅰ patients to 57.9% in group Ⅴ patients. Diabetes was most common to group Ⅳ (65-74 years) patients. Conclusion: There were different risk factors for AMI patients in different age groups, and young AMI patients were predisposed to live an unhealthy lifestyle.

Many future therapeutic applications of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 and related RNA-guided nucleases are likely to require their use to promote gene targeting, thus necessitating development of methods that provide for delivery of three components-Cas9, guide RNAs and recombination templates-to primary cells rendered proficient for homology-directed repair. Here, we demonstrate an electroporation/transduction codelivery method that utilizes mRNA to express both Cas9 and mutant adenoviral E4orf6 and E1b55k helper proteins in association with adeno-associated virus (AAV) vectors expressing guide RNAs and recombination templates. By transiently enhancing target cell permissiveness to AAV transduction and gene editing efficiency, this novel approach promotes efficient gene disruption and/or gene targeting at multiple loci in primary human T-cells, illustrating its broad potential for application in translational gene editing.

Background: Pain, the most common reasons for physician consultation, is a major symptom in many medical conditions that can significantly interfere with a person's life quality and general functioning. Almost all painkillers have its untoward effects. Therefore, seeking for a safe medication for pain relieve is notable nowadays. Paeonia lactiflora is a well-known traditional Chinese medicine. Paeoniflorin is an active component found in Paeonia lactiflora, which has been reported to inhibit formalin-induced nociceptive behavior in mice. Aims of this present study were to investigate effects of paeoniflorin on excitatory amino acid agonist- or high-dose morphine-induced nociceptive behaviors in mice., Results: Paeoniflorin (100, 200, 500 nmol, i.c.v.) alone and combined with glutamatergic antagonists (MK-801 14.8 pmol, or NBQX 5 nmol, i.t.) inhibited nociception. Those agents also inhibited the clonic seizure-like excitation induced by high-dose morphine (250 nmol, i.t) in mice. Antisense oligodeoxynucleotides of NMDA receptor subunits NR1, NR2A, NR2B significantly enhanced the inhibition of paeoniflorin on excitatory amino acid-and high-dose morphine-induced nociception. Docking energy data revealed that paeoniflorin had stronger binding activity in NR2A and NR2B than NR2C of NMDA receptors., Conclusions: Results of this study indicate that paeoniflorin-induced inhibition of excitatory amino acid agonist- and high-dose morphine-induced nociceptive behaviors might be due to modulation of NMDA receptors, specifically the NR2B subunit.

Objective: To investigate the medical care resources of acute myocardial infarction (AMI) in Chinese hospitals of different regions and levels., Methods: We selected 115 hospitals in China, including 61 northern hospitals, 54 southern hospitals, 52 eastern hospitals, 26 central hospitals, 37 western hospitals, 79 tertiary hospitals, 36 secondary hospitals, 34 pro vincial-level hospitals, 46 prefectural-level hospitals and 35 county hospitals. From November 2012 to August 2013, we sent questionnaire to the cardiologists in each hospital, to collect related information., Results: (1) The number of AMI admitted each year of northern hospital was more than the number of southern hospital (220 (120, 400) cases vs. 220 (80, 350) cases, P=0.033), while number of coronary care unit (CCU), thrombolytic therapy, percutaneous coronary intervention (PCI), primary PCI and coronary artery bypass grafting (CABG) were similar (all P> 0.05). (2) The number of AMI admitted each year of eastern, central and western hospital was 295(150, 501) cases, 175(75, 300) cases and 170(50, 250) cases respectively(P=0.007), with no significant difference among them for setting CCU, carrying out thrombolytic therapy, PCI, primary PCI and CABG (all P>0.05). (3) The total number of the in-patient beds and AMI admitted each year of tertiary hospitals were significantly higher than that in the secondary hospitals(104(70, 152)vs. 47(30, 52), P<0.001) and (300(200, 460)cases vs.80(47, 135)cases, P<0.001) respectively. There was a significant difference between tertiary and secondary hospitals for the number of CCU (97.5% (77/79)and 75.0%(27/36)), PCI (98.7%(78/79)and 27.8%(10/36)), primary PCI (96.2%(76/79)and 22.2%(8/36)), CABG (81.0%(64/79)and 11.1%(4/36)), intra-aortic balloon pump (IABP) (91.1%(72/79) and 13.9%(5/36)) respectively (all P<0.001). (4) There were obvious differences among provincial-level, prefectural-level and country-level hospitals for the admitted AMI patient numbers annually which was 400(250, 600), 232(100, 380)and 80(50, 162)cases, CCU proportion which was 100 %(34/34), 95.7%(44/46) and 74.3%(26/35), thrombolytic therapy proportion which was 88.2%(30/34), 100%(46/46)and 91.4%(32/35), PCI proportion which was 100%(34/34), 89.1%(41/46)and 37.1%(13/35), primary PCI proportion which was 100%(34/34), 84.8%(39/46)and 31.4%(11/35), CABG proportion which was 97.1%(33/34), 67.4%(31/46) and 11.4%(4/35)respectively (P<0.01 or 0.05) ., Conclusions: Different regional hospitals have no significant difference in number of CCU and reperfusion therapies, while there is a big difference on medical care resources of AMI between different-level hospitals, which may affect the diagnosis and treatment effect of patients with AMI. Clinical Trail Registry: National Institutes of Health, NCT01874691.

Background: Consolidated bioprocessing (CBP), integrating cellulase production, cellulose saccharification, and fermentation into one step has been widely considered as the ultimate low-cost configuration for producing second-generation fuel ethanol. However, the requirement of a microbial strain able to hydrolyze cellulosic biomass and convert the resulting sugars into high-titer ethanol limits CBP application., Results: In this work, cellulolytic yeasts were developed by engineering Saccharomyces cerevisiae with a heterologous cellodextrin utilization pathway and bifunctional minicellulosomes. The cell-displayed minicellulosome was two-scaffoldin derived, and contained an endoglucanase and an exoglucanase, while the intracellular cellodextrin pathway consisted of a cellodextrin transporter and a β-glucosidase, which mimicked the unique cellulose-utilization system in Clostridium thermocellum and allowed S. cerevisiae to degrade and use cellulose without glucose inhibition/repression on cellulases and mixed-sugar uptake. Consequently, only a small inoculation of the non-induced yeast cells was required to efficiently co-convert both cellulose and galactose to ethanol in a single-step co-fermentation process, achieving a high specific productivity of ~62.61 mg cellulosic ethanol/g cell·h from carboxymethyl cellulose and ~56.37 mg cellulosic ethanol/g cell·h from phosphoric acid-swollen cellulose., Conclusions: Our work provides a versatile engineering strategy for co-conversion of cellulose-mixed sugars to ethanol by S. cerevisiae, and the achievements in this work may further promote cellulosic biofuel production.

Background: Lymphatic malformations (LMs), slow-flow vascular anomalies resulting from abnormal development of lymphatic channels, often progress rapidly after trauma or infection., Objectives: To explore the possible mechanism by which local infection promotes the progression of LMs., Methods: Immunohistochemistry in serial sections and immunofluorescence were performed to label polarized macrophages. Tertiary lymphoid organs (TLOs) in LMs were identified using antibodies against CD3 (a T-cell marker), CD20 (a B-cell marker) and PNAd (a high endothelial venule marker). Pearson's correlation and cluster analysis were carried out to delineate the relationship between macrophage infiltration and TLO formation. Rat models of LM were established to examine the role of lipopolysaccharide in LM development., Results: Compared with normal skin tissues, both M1- and M2-polarized macrophages were prevalent in LMs. Moreover, M2-polarized macrophages were significantly increased in infected LMs with an elevated density of TLOs. M2-polarized macrophages were observed in the centre of TLOs accompanied by intensive staining of macrophage colony-stimulating factor, a strong chemotactic factor for monocytes/macrophages, suggesting that macrophages might be recruited through TLOs. Cluster analysis and Pearson's correlation suggested a close relationship between macrophage infiltration and TLO formation. Furthermore, the expression of CD68 was also correlated with that of vascular endothelial growth factor (VEGF)-C and Ki67. Importantly, in an established LM rat model, lipopolysaccharide promoted the progression of the malformations with increased macrophage infiltration and TLO formation., Conclusions: M2-polarized macrophages that may be recruited through TLOs in infected LMs may contribute to the progression of the disease by secreting VEGF-C, and therefore accelerating the proliferation of lymphatic endothelial cells., (© 2016 British Association of Dermatologists.)

Atlastin is a member of the dynamin protein superfamily and it can mediate homotypic fusion of endoplasmic reticulum (ER) membranes, which is required for many biological processes. In this study, a new Atlastin homologous protein, BmAtlastin-n, was characterized in silkworms and was found to contain an N-terminal conserved GTPase domain and a coiled-coil middle domain. BmAtlastin-n is localized in the cytoplasm and enriched in silkworm midgut. Results also showed that overexpression of BmAtlastin-n in BmN-SWU1 cells could enhance resistance to BmNPV. To better confirm its antiviral effect, microRNA was used to knock down the expression of BmAtlastin-n in BmE-SWU1 cells with inducing the reproduction of BmNPV. A transgenic expression vector of BmAtlastin-n was constructed and introduced to silkworm embryos by microinjection. The transgenic silkworm also showed considerable antiviral capacity. In conclusion, these findings demonstrate that BmAtlastin-n plays an important role in BmNPV defense. More importantly, the current study may provide a new clue for Atlastin research.

Background: The aim of this study was to elucidate recurrent pregnancy loss (RPL)-associated psychosocial effects and sexual functions of Chinese men whose partners experience a history of RPL., Methods: Questionnaire data from a total of 236 men whose partners experience RPL(RPL group) and another 236 non-RPL male volunteers(control group) were analyzed. The self-administered questionnaires included anxiety and depression measures (SAS & SDS), the Index of Sexual Satisfaction (ISS) and the International Index of Erectile Function (IIEF-5) for evaluating psychological burden, sexual satisfaction and erectile function, respectively., Results: The mean age of the RPL group and control group was 29.8 ± 8.6 and 28.2 ± 7.3, respectively. The incidence of erectile dysfunction was significantly higher in the RPL group than in the control group (19.07 % vs. 7.63 %, P < 0.001). Anxiety and depression were also more prevalent in RPL group than in the control group (anxiety: 36.90 % vs. 19.08 %, P < 0.001; depression: 26.30 % vs. 7.63 %, P < 0.001). Furthermore, after adjusting for age in the RPL group, negative relationships were observed between the IIEF-5 score and anxiety and depression (P < 0.001), and a positive correlation was found between the ISS and anxiety and depression (P < 0.001). In addition, history of RPL, anxiety and depressive symptoms were significantly associated with a higher risk of ED., Conclusions: Psychological functioning, sexual satisfaction and erectile function are impaired in infertile men with RPL partners. These men should be targeted for psychological consultation.

The efficacy of microwave irradiation in the quaternization of amino-functionalized MIL-53 metal-organic framework (MOF) as well as the catalytic activity of the resultant MOF in the cycloaddition of carbon dioxide with epoxides under solvent-free conditions has been studied. A series of NH2-MIL-53 were synthesized and quaternized by reacting alkyl halide of various alkyl chains and anions under microwave irradiation. The post-functionalized F-MIL-53-AXs were characterized through solid-state XRD, FT-IR, XPS, and TGA. F-MIL-53-Mel prepared by microwave method showed higher AGC yield than that by the conventional heating method. F-MIL-53-AXs with iodide anion exhibited the best catalytic activity irrespective of the alkyl chain length, in agreement with the generally accepting order of nucleophilicity, Cl

Objective: To analyze the age-related differences in the clinical symptoms and triggering factors among Chinese patients with acute myocardial infarction., Methods: Acute myocardial infarction Patients (n=14 854) registered in the China Acute Myocardial Infarction Registry from January 2013 to March 2014 were included in this study. Patients were divided into 4 groups: <55 years old group (3 950 patients), 55-64 years old group (4 361 patients), 65-74 years old group ( 3 759 patients), and ≥75 years old group (2 784 patients). Demographic features, medical history, clinical presentation and triggering factors were obtained via electronic data capture system., Results: (1)Persistent chest pain and sweat were the major typical symptoms 66.4%(9 863/14 854) and 63.8%(9 471/14 854)) in the whole cohort. Prevalence of persistent chest pain among four groups were 73.8%(2 915/3 950), 69.2%(3 016/4 361), 63.6%(2 394/3 759) and 55.2%(1 538/2 784), and radiating pain among four groups were 36.2%(1 428/3 950), 34.1%(1 487/4 361), 30.9%(1 160/3 759)and 25.9%(722/2 784), and sweat among four groups were 70.0%(2 765/3 950), 66.5%(2 898/4 361), 61.8%%(2 323/3 759)and 53.3%(1 485/2 784), and there were statistical significance for all above symptoms among groups (all P<0.001). (2)triggering factors before acute myocardial infarction could be found in 19.4%(2 879/14 854) of the patients. Prevalence of existed triggering factors among four groups were 23.8%(941/3 950), 21.0%(914/4 361), 16.6%(625/3 759) and 14.3%(399/2 784, P<0.001). Recent excessive unhealthy lifestyles among four groups were 20.8%(196/3 950), 11.9%(109/4 361), 10.1%(63/3 759) and 9.0%(36/2 784) among the 4 groups (P<0.001)., Conclusions: Persistent chest pain and sweat are absent in nearly half of Chinese patients in ≥75 years old group. Triggering factors prior to acute myocardial infarction could be evidenced in about twenty percent patients, and which are more often in young patients. Clinical Trail Registry: National Institutes of Health，NCT018746.

Background: Transradial percutaneous coronary intervention (PCI) has been increasingly adopted in clinical practice, given its potential advantages over transfemoral intervention; however, the impact of different access strategies on costs and clinical outcomes remains poorly defined, especially in the developing world., Methods and Results: Using data from a consecutive cohort of 5306 patients undergoing PCI in China in 2010, we compared total hospital costs and in-hospital outcomes for transradial intervention (TRI) and transfemoral intervention. Patients receiving TRI (n=4696, 88.5%) were slightly younger (mean age 57.4 versus 59.5 years), less often women (21.6% versus 33.1%), more likely to undergo PCI for single-vessel disease, and less likely to undergo PCI for triple-vessel or left main diseases. The unadjusted total hospital costs were 57 900 Chinese yuan (¥57 900; equivalent to 9190 US dollars [$9190]) for TRI and ¥67 418 ($10,701) for transfemoral intervention. After adjusting for all observed patient and procedural characteristics using the propensity score inverse probability weighting method, TRI was associated with a lower total cost (adjusted difference ¥8081 [$1283]). More than 80% of the cost difference was related to lower PCI-related costs (adjusted difference -¥5162 [-$819]), which were likely driven by exclusive use of vascular closure devices in transfemoral intervention, and lower hospitalization costs (-¥1399 [-$222]). Patients receiving TRI had shorter length of stay and were less likely to experience major adverse cardiac events or post-PCI bleeding. These differences were consistent among clinically relevant subgroups with acute myocardial infarction, acute coronary syndrome, and stable angina., Conclusions: Among patients undergoing PCI, TRI was associated with lower cost and favorable clinical outcomes compared with transfemoral intervention., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Oral lichen planus (OLP) is a common T cell-mediated chronic inflammatory disease of unknown etiology. Recent increasing evidence indicates that microRNA-146a (miR-146a) plays a vital role in inflammatory diseases and T cell regulation. This study aimed to investigate the expression of miRNA-146a in peripheral blood CD4(+) T cells and local OLP lesions and to evaluate its relationship with clinical forms of OLP. Sixteen patients with OLP were divided into two groups: erosive OLP and nonerosive OLP. The expression of miR-146a was examined by quantitative real-time polymerase chain reaction. The expression of miR-146a in peripheral blood CD4(+) T cells showed no significant difference between OLP group and control group (P > 0.05), and among erosive OLP, nonerosive OLP, and control groups (P > 0.05 for all). The expression in local lesions of the OLP group was significantly higher than that of the control group (P = 0.003), and it was significantly higher in the erosive OLP group than in the non-erosive OLP (P = 0.010) and control groups (P = 0.007). However, miR-146a expression in the nonerosive OLP group did not significantly differ from that in the control group (P > 0.05). These data indicate that miR-146a might be more involved in the local immune disorder of OLP. MiR-146a might be utilized as a candidate biomarker to estimate the severity of OLP.

Aims and Objectives: The aim of this study was to improve the postoperative handover process and immediate postoperative patient outcomes. The objective was to implement a postoperative handover protocol in the neurosurgical intensive care unit of a tertiary teaching hospital., Background: Postoperative handover is a multidisciplinary collaborative medical activity that involves information transfer, sequenced tasks and high-quality teamwork. Evidence suggests that a lack of a standardised postoperative handover protocol adversely influences care quality and potentially compromises patient safety. As there is a lack of such protocols in China, there is an identified need for improvement., Design: This was a pretest/post-test study with follow-up after three months., Methods: A postoperative handover protocol that included a postoperative handover checklist, a standardised handover pathway and core team member involvement was developed based on research evidence and expert opinions and was then implemented and evaluated., Results: Following the implementation of this protocol, improved teamwork was achieved, surgeons were more frequently present at bedside handovers, the rate of transferring key messages increased, the rate of ventilator weaning within the first six hours of neurosurgical intensive care unit admission increased, and the ventilation duration per patient decreased without any clinical incident occurring in the first 24 hours after neurosurgical intensive care unit admission., Conclusions: Following the implementation of a tailored standardised handover protocol, communication, teamwork and short-term patient outcomes were improved., Relevance to Clinical Practice: This clinically based research highlights the need for policy makers and administrators to create unit-specific protocols for improving postoperative handovers., (© 2016 John Wiley & Sons Ltd.)

Objective: To explore the diagnostic values of ratios of early diastolic peak transmitral velocity(E) to late velocity(A) (E/A) and E to early diastolic peak mitral annulus velocity (E/E') for heart failure patients with preserved ejection fraction (HF-PEF)., Methods: Two hundred and sixteen healthy people were divided into <50 years, 50-59 years, 60-69 years, and ≥70 years groups to clarify the impact of aging on E/A and E/E'. Two hundred and two newly diagnosed consecutive in-patients with HF-PEF and 221 age- and sex-matched non-heart-failure subjects with risk factors of HF-PEF (negative controls) were enrolled.The diagnostic values and cutoff points of E/A and E/E' for HF-PEF were derived from receiver operating characteristic curve (ROC) analysis., Results: E/A and E/E' were significantly different among age groups in healthy controls (all P<0.01). Compared with <50 years group, average E/A was lower and average E/E' was higher in ≥70 years group(both P<0.01). E/A ratio was less than 1 in 68%(71/105), E/E' was >8 cm/s in 48% (50/105)healthy people with age≥60 years. Neither E/A nor E/E' of HF-PEF patients was statistically different regarding to NYHA classification (grade Ⅱ, Ⅲ, Ⅳ), but NT-proBNP value increased in proportion to higher NYHA classification(P<0.01). The area of E/E' under ROC for diagnosing HF-PEF was 0.839(P<0.01), and the corresponding cutoff point was 9.5 with a sensitivity of 86% and a specificity of 69%. The areas of E/A (larger value or smaller value indicating positive) under ROC for diagnosing HF-PEF were 0.469 and 0.531, respectively(all P>0.05)., Conclusions: Aging exerts significant impacts on both E/A and E/E'. E/E' has moderate diagnostic accuracy while E/A is of limited value for diagnosing HF-PEF.

Purpose: The goal of this study is to investigate whether combined application of ultrasound and 99mTc-sestamibi SPECT/CT had the incremental value in accurately detecting parathyroid tissue in patients with SHPT over either method alone., Patients and Methods: Sixty patients with SHPT on hemodialysis were evaluated preoperatively with parathyroid 99mTc-sestamibi SPECT/CT scintigraphy and ultrasound prior to parathyroidectomy. The sensitivity, specificity and accuracy of 99mTc-sestamibi SPECT/CT scintigraphy, ultrasound and combined application were determined respectively., Results: The sensitivity, specificity and accuracy of ultrasound were 81% (155/192), 47% (17/36) and 82% (172/228), respectively. The sensitivity, specificity and accuracy of 99mTc-sestamibi SPECT/CT were 85% (163/192), 58% (21/36) and 89% (184/228) respectively. The accuracy of 99mTc-sestamibi SPECT/CT in the diagnosis of parathyroid tissue in patients with SHPT is significantly higher than that of ultrasound. The sensitivity, specificity and accuracy of combined application of ultrasound and 99mTc-sestamibi SPECT/CT were 93% (178/192), 61% (22/36) and 97% (200/228). The sensitivity, specificity and accuracy of combined application of ultrasound and 99mTc-sestamibi SPECT/CT were higher than those of either ultrasound or 99mTc-sestamibi SPECT/CT., Conclusions: The combined application of ultrasound and 99mTc-sestamibi SPECT/CT had incremental value in accurately detecting parathyroid tissue in patients with SHPT over either method alone., (Copyright © 2015 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Various novel hypercrosslinked porous polymers with phosphonium salt incorporated into their networks were developed. These porous materials have high BET surface areas (up to 1168 m(2) g(-1)) and can be used to selectively capture CO2 and efficiently convert CO2 into cyclic carbonates.

Despite the ubiquitous role of ATP-binding cassette (ABC) importers in nutrient uptake, only the Escherichia coli maltose and vitamin B12 ABC transporters have been structurally characterized in multiple conformations relevant to the alternating access transport mechanism. To complement our previous structure determination of the E. coli MetNI methionine importer in the inward facing conformation (Kadaba et al. (2008) Science 321, 250-253), we have explored conditions stabilizing the outward facing conformation. Using two variants, the Walker B E166Q mutation with ATP+EDTA to stabilize MetNI in the ATP-bound conformation and the N229A variant of the binding protein MetQ, shown in this work to disrupt methionine binding, a high affinity MetNIQ complex was formed with a dissociation constant measured to be 27 nm. Using wild type MetQ containing a co-purified methionine (for which the crystal structure is reported at 1.6 Å resolution), the dissociation constant for complex formation with MetNI is measured to be ∼40-fold weaker, indicating that complex formation lowers the affinity of MetQ for methionine by this amount. Preparation of a stable MetNIQ complex is an essential step towards the crystallographic analysis of the outward facing conformation, a key intermediate in the uptake of methionine by this transport system.

Background: The N400 component of event-related potentials (ERP) has recently drawn widespread attention at home and abroad. This study was to explore the relationship between N400 changes and risperidone treatment and rehabilitation infirst-episode schizophrenia (FES)., Methods: ERP component N400 was recorded by Guangzhou Runjie WJ-1 ERP instruments, in 58 FES before and 6 months, 15 months after risperidone treatment, and in 62 normal controls. The patients' syndromes were assessed by Positive and Negative Syndrome Scale (PANSS). And the stimuli are Chinese sentences with matching (congruent) or mismatching (incongruent) ending words., Results: N400 latencies were prolonged, and amplitudes were decreased in Cz, Pz, Fz, C3, C4, in FES compared with in NC, before treatment. The prolonged N400 latencies and decreased amplitudes were negatively correlated with the patients' positive scale and total scale of PANSS. There are significant differences of N400 amplitudes and latencies in 6 months and 15 months follow-up after treatment. Before treatment, 6 months and 15 months after treatment, N400 latencies are 446 ± 35 ms, 440 ± 37 ms, 414 ± 31 ms (F = 9.72, P < 0.01) in incongruent situation; N400 amplitudes are 5.2 ± 4.6 μV, 5.7 ± 4.8 μV, 7.3 ± 5.0 μV (F = 2.06, P > 0.05) in congruent situation, and 8.5 ± 5.9 μV, 10.1 ± 5.0 μV, 11.9 ± 7.0 μV (F = 3.697, P < 0.05) in incongruent situation., Conclusions: N400 could be used to predict the effects of treatment of schizophrenia to some degree. The linguistic and cognitive impairment in schizophrenia can be improved by antipsychotic drugs.

Cyclic di-AMP (c-di-AMP) is a relatively new member of the family of bacterial cyclic dinucleotide second messengers. It has attracted significant attention in recent years because of the abundant roles it plays in a variety of Gram-positive bacteria. The structural features that allow diverse bacterial proteins to bind c-di-AMP are not fully understood. Here we report the biophysical and structural studies of c-di-AMP in complex with a bacterial cation-proton antiporter (CpaA) RCK (regulator of the conductance of K(+)) protein from Staphylococcus aureus (Sa). The crystal structure of the SaCpaA&#95;RCK C-terminal domain (CTD) in complex with c-di-AMP was determined to a resolution of 1.81 Å. This structure revealed two well-liganded water molecules, each interacting with one of the adenine bases by a unique H2Olp-π interaction to stabilize the complex. Sequence blasting using the SaCpaA&#95;RCK primary sequence against the bacterial genome database returned many CpaA analogues, and alignment of these sequences revealed that the active site residues are all well-conserved, indicating a universal c-di-AMP binding mode for CpaA&#95;RCK. A proteoliposome activity assay using the full-length SaCpaA membrane protein indicated that c-di-AMP binding alters its antiporter activity by approximately 40%. A comparison of this structure to all other reported c-di-AMP-receptor complex structures revealed that c-di-AMP binds to receptors in either a "U-shape" or "V-shape" mode. The two adenine rings are stabilized in the inner interaction zone by a variety of CH-π, cation-π, backbone-π, or H2Olp-π interaction, but more commonly in the outer interaction zone by hydrophobic CH-π or π-π interaction. The structures determined to date provide an understanding of the mechanisms by which a single c-di-AMP can interact with a variety of receptor proteins, and how c-di-AMP binds receptor proteins in a special way different from that of c-di-GMP.

Using acupuncture to treat cerebral hypoperfusion is a hot topic. However, there is a lack of effective tools to clarify the therapeutic effect of acupuncture on cerebral hypoperfusion. Here, we show in a mouse model of cerebral hypoperfusion that photoacoustic tomography (PAT) can noninvasively image cerebral vasculature and track total hemoglobin (HbT) concentration changes in cerebral hypoperfusion with acupuncture stimulation on the YangLingQuan (GB34) point. We measured the changes of HbT concentration and found that the HbT concentration in hypoperfusion regions was clearly lower than that in the control regions when the acupuncture was absent; however, it was significantly increased when the acupuncture was implemented on the GB34 point. We also observed the increase of vessel size and the generation of new vessels in cerebral hypoperfusion during acupuncture. Laser speckle imaging (LSI) was employed to validate some of the PAT findings.

Unintended pregnancies can have negative consequences for both mother and child. The focus of this study was to utilize perceived behavioral control measures (PBC; part of the theory of planned behavior) to identify relevant behavioral determinants of birth control use. This study also tested associations between direct and indirect PBC measures and intention of birth control use and between intention and birth control use. The methods included a randomly selected sample of patients at a health care system in the Upper Midwest who were sent a self-administered survey, with 190 non-pregnant women returning completed surveys. Participants indicated a high level of control over using birth control, and a significant positive correlation was observed between direct and indirect PBC measures. Participants also reported high intentions to use birth control, and a significant positive correlation was observed between intention and PBC. Additionally, both PBC measures and intention were independently and significantly associated with behavior, and PBC remained significantly associated with behavior when intention was added into the model. In conclusion, compared to the previous literature, this study is unique in that it examines indirect PBC measures and also the important role that PBC plays with actual birth control behavior.

The MetNI methionine importer of Escherichia coli, an ATP binding cassette (ABC) transporter, uses the energy of ATP binding and hydrolysis to catalyze the high affinity uptake of D- and L-methionine. Early in vivo studies showed that the uptake of external methionine is repressed by the level of the internal methionine pool, a phenomenon termed transinhibition. Our understanding of the MetNI mechanism has thus far been limited to a series of crystal structures in an inward-facing conformation. To understand the molecular mechanism of transinhibition, we studied the kinetics of ATP hydrolysis using detergent-solubilized MetNI. We find that transinhibition is due to noncompetitive inhibition by L-methionine, much like a negative feedback loop. Thermodynamic analyses revealed two allosteric methionine binding sites per transporter. This quantitative analysis of transinhibition, the first to our knowledge for a structurally defined transporter, builds upon the previously proposed structurally based model for regulation. This mechanism of regulation at the transporter activity level could be applicable to not only ABC transporters but other types of membrane transporters as well., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

Purpose: The aim of this study was to investigate the expression of uncoupling protein 2 (UCP2) and zonula occludens-1 (ZO-1) in the trabecular meshwork (TM) of neovascular glaucoma (NVG) patients treated with trabeculectomy., Materials and Methods: Six eyes with NVG underwent trabeculectomy for therapeutic purposes. The data consisted of patient demographics, presurgical and postsurgical visual acuity, intraocular pressure, gonioscopy, and neovascularization of iris and/or the anterior chamber angle. TM samples were obtained from the NVG eyes that had undergone surgery. Immunofluorescence and confocal laser scanning microscopy were carried out to determine the expression of UCP2 and ZO-1 in the TM cells., Results: The baseline median visual acuity was light perception, and the mean intraocular pressure (standard error) was 52.5 (8.3) mm Hg. All eyes displayed neovascularization of the iris and the anterior chamber angle. The expression of UCP2 was significantly decreased in TM cells of NVG compared with the control (P=0.000), whereas increase in ZO-1 expression was detected in staining cells with NVG in comparison with the control (P=0.000). The necrotic cells in the TM were increased (P=0.000), whereas the viable cells were reduced (P=0.000) in comparison with the control., Conclusions: The decreased UCP2 expression and increased ZO-1 expression suggest that the oxidative stress-induced mitochondrial dysfunction and tight junction formation may play pivotal roles in the progress of NVG.

Background: The impact of body mass index (BMI) on the clinical outcomes after percutaneous coronary intervention (PCI) in patients ≥ 75 years old remained unclear., Methods: A total of 1098 elderly patients undergoing PCI with stent implantation were recruited. Patients were divided into four groups by the value of BMI: Underweight (≤ 20.0 kg/m 2 ), normal weight (20.0-24.9 kg/m 2 ), overweight (25.0-29.9 kg/m 2 ) and obese (≥ 30.0 kg/m 2 ). Major clinical outcomes after PCI were compared between the groups. The primary endpoint was defined as in-hospital major adverse cardiovascular events (MACEs), which included death, myocardial infarction (MI) and target vessel revascularization. The secondary endpoint was defined as 1 year death. Logistic regression analysis was performed to adjust for the potential confounders., Results: Totally, 1077 elderly patients with available BMIs were included in the analysis. Patients of underweight, normal weight, overweight and obese accounted for 5.6%, 45.4%, 41.5% and 7.5% of the population, respectively. Underweight patients were more likely to attract ST-segment elevation MI, and get accompanied with anemia or renal dysfunction. Meanwhile, they were less likely to achieve thrombolysis in MI 3 grade flow after PCI, and receive beta-blocker, angiotensin converting enzyme inhibitor or angiotensin receptor blocker after discharge. In underweight, normal weight, overweight and obese patients, in-hospital MACE were 1.7%, 2.7%, 3.8%, and 3.7% respectively (P = 0.68), and 1 year mortality rates were 5.0%, 3.9%, 5.1% and 3.7% (P = 0.80), without significant difference between the groups. Multivariate regression analysis showed that the value of BMI was not associated with in-hospital MACE in patients at 75 years old., Conclusions: The BMI "obese paradox" was not found in patients ≥ 75 years old. It was suggested that BMI may not be a sensitive predictor of adverse cardiovascular events in elderly patients.

Background: A comprehensive assessment of various vascular anomalies and variants associated with venous pulsatile tinnitus (PT) by radiography is essential for therapeutic planning and improving the clinical outcome. This study evaluated the incidence of various vascular anomalies and variants on the PT side and determined whether these lesions occurred as multiple or single entities., Methods: The dual-phase contrast-enhanced computed tomography images of 242 patients with unilateral venous PT were retrospectively reviewed. The vascular anomalies and variants on the symptomatic and asymptomatic sides were analyzed, and the incidences of anomalies or variants on each side were compared. The number of anomalies and variants on the symptomatic side in each patient was calculated., Results: (1) A total 170 patients (170/242) had more than one anomaly or variant on the symptomatic side, and 58 patients (58/242) had a single lesion on tomography. (2) There was a statistically significant difference in the incidence of dehiscent sigmoid plate (P = 0.000), lateral sinus stenosis (P = 0.014), high jugular bulb (P = 0.000), sigmoid sinus diverticulum (P = 0.000), jugular bulb diverticulum (P = 0.000), dehiscent jugular bulb (P = 0.000), and a large emissary vein (P = 0.006) between the symptomatic and asymptomatic sides. (3) Dehiscent sigmoid plate (86.4%) was the most frequent lesion on the symptomatic side, followed by lateral sinus stenosis (55.8%), high jugular bulb (47.1%), sigmoid sinus diverticulum (34.3%), jugular bulb diverticulum (13.6%), dehiscent jugular bulb (13.6%), large emissary vein (4.1%), sinus thrombosis (1.2%), and petrosquamosal sinus (0.8%)., Conclusions: Various vascular anomalies and variants occur more frequently on the venous PT side. Preliminary findings suggest that venous PT patients may have multiple vascular anomalies or variants on the symptomatic side.

Tropisetron is an adjuvant for butorphanol used in intravenous patient-controlled analgesia (PCA) and has been reported to provide superior pain control. It is efficacious in reducing the incidence of postoperative nausea and vomiting. However, this admixture is not available commercially and stability data applicable to hospital practice are limited. This study aimed to describe the drug compounding and evaluates the long-term (up to 14 days) stability of butorphanol and tropisetron in 0.9% sodium chloride injection for PCA use.In this study, commercial solutions of butorphanol tartrate and tropisetron hydrochloride were combined and further diluted with 0.9% sodium chloride injection to final concentrations of butorphanol tartrate 0.08 mg/mL and tropisetron hydrochloride 0.05 mg/mL. The polyolefin bags and glass bottles were stored at 4°C and 25°C for up to 14 days. The drug stabilities were determined by visual inspection, pH measurement, and high-pressure liquid chromatography assay of drug concentrations.The data obtained for admixtures prepared and stored at temperatures of 25°C and 4°C show the drugs have maintained at least 98% of the initial concentration. All solutions remained clear and colorless over the 14-day period, and the pH value did not change significantly.The results indicate that admixtures of butorphanol tartrate 0.08 mg/mL and tropisetron hydrochloride 0.05 mg/mL in 0.9% sodium chloride injection solution were stable for 14 days when stored in polyolefin bags or glass bottles at 4°C and 25°C and protected from light. The infusion is feasible for manufacturing in pharmacy aseptic units and can be stored for up to 14 days for routine use in PCA infusions.

Peanut (Arachis hypogaea) is one of the most important oil crops and food legumes worldwide. China sows approximately 3.5 million hectares each year and produces 40% of the world's peanuts. Fungal diseases are among the main biotic stresses affecting peanut production. Root rot is a serious disease caused by several fungi. Pythium spp., Fusarium spp., and Rhizopus spp. are some of the root rot fungi that have been reported in China. In 2012 and 2013, root rot symptoms were observed in several fields in Laixi District, Qingdao City, Shandong Province, China. The first symptoms appeared in July. Initial symptoms of the disease were brown spots on the stem base and root. Affected plants were stunted, with leaf chlorosis, reduced growth, or sudden wilting. As disease progressed, the infected tissues showed brown discoloration and rot, and abundant dark brown and black powdery spores were visible on the surfaces of affected parts. Eventually, affected plants collapsed and died. To isolate the causal organism, roots and stems were cut into sections, which were surface-disinfected with 70% ethanol solution (v/v) for 20 s, soaked in 0.1% mercuric chloride solution for 50 s, rinsed with sterilized water three times, dried, placed on Czapek's Dox agar supplemented with chloramphenicol (100 μg/ml), and incubated at 28°C for 7 days. Fungal colonies were white initially and then covered with a dense layer of dark brown or black conidial heads. The conidial head was radiate; vesicles were nearly spherical and covered with irregular metulae and phialides. Conidia were globose or subglobose (3.0 to 5.5 μm in diameter), dark brown to black, with rough cell walls. Total genomic DNA was extracted from mycelia using the EasyPure Genomic DNA Kit (TransGEN, Beijing, China). The rDNA-ITS region was amplified using PCR with the universal fungal primers ITS1 and ITS4 (2). The purified products were separately sequenced in both directions using the same primer pair. The sequences (GenBank Accession No. KJ848716) obtained were 99% similar to the ITS sequence of isolates of Aspergillus niger. This, together with the morphological characters (1) described above, suggested that the microorganism we had isolated was A. niger. Koch's postulates were completed in the laboratory by inoculating peanut. Thirty Huayu20 peanut seeds were placed in a 500-ml sterile pot with 300 g of autoclaved soil. Twenty days after seedling emergence, 15 peanut plants were wounded with a needle and inoculated with 5 ml of conidia suspension (10 6 ml -1 ). The same number of peanuts were similarly wounded and inoculated with 5 ml of sterile distilled water to serve as controls in the same pot. All peanuts were kept in a randomized complete block design at 30°C under a 12-h photoperiod. After 7 days, disease symptoms similar to those observed in the field appeared in all inoculated but not in non-inoculated peanuts. The tests were repeated three times in the greenhouse. Koch's postulates were satisfied after re-isolating the A. niger from inoculated peanuts using the method described above. To our knowledge, this is the first report of A. niger causing root rot in peanut in China. References: (1) M. A. Klich. Page 12 in: Identification of Common Aspergillus Species. Centraalbureau voor Schimmelcultures, Utrecht, The Netherlands, 2002. (2) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, CA, 1990.

Background and Hypothesis: The Overhead Shoulder and Elbow Score (Kerlan-Jobe Orthopaedic Clinic [KJOC] score) among healthy or uninjured professional baseball pitchers is lacking. We hypothesized that shoulder function and performance status measured by the KJOC score among active Minor League professional baseball pitchers were high at pre-participation and that the pitchers who had not been previously treated for a shoulder injury and were playing without arm trouble had significantly higher KJOC scores than their counterparts., Methods: In this cross-sectional survey, data on pre-participation KJOC scores, along with other study measures, were collected from a cohort of Minor League professional baseball pitchers. Generalized estimating equations with a Poisson distribution were used for analysis., Results: A total of 366 Minor League professional pitchers were included, with a mean KJOC score of 92.8 points (SD, 12.1 points), suggesting that participating pitchers' shoulder function and performance were high. Participating pitchers who had not received treatment for a shoulder injury had significantly higher KJOC scores than those who had received treatment, either surgical or nonsurgical (β = 0.0238, P = .0495). In addition, pitchers who were not currently injured, were playing without arm trouble, or had not missed games in the past 12 months because of a shoulder injury also had statistically significantly higher KJOC scores than their counterparts., Conclusion: This study provides an empirical profile of the KJOC score for a large sample of active Minor League professional baseball pitchers and identifies risk factors associated with decreased KJOC scores., (Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Megakaryocytes (MKs) are one of the few cell types that become polyploid; however, the mechanisms by which these cells are designated to become polyploid are not fully understood. In this investigation, we successfully established two relatively synchronous polyploid cell models by inducing Dami and CMK cells with SP600125. We found that SP600125 induced the polyploidization of Dami and CMK cells, concomitant with the phosphorylation of ribosomal protein S6 kinase 1 (S6K1) at Thr421/Ser424 and dephosphorylation at Thr389. The polyploidization was partially blocked by H-89, a cAMP-dependent protein kinase (PKA) inhibitor, through direct binding to S6K1, leading to dephosphorylation at Thr421/Ser424 and phosphorylation at Thr389, independent of PKA. Overexpression of a rapamycin-resistant mutant of S6K1 further enhanced the inhibitory effect of LY294002 on the SP600125-induced polyploidization of Dami and CMK cells. SP600125 also induced the polyploidization of Meg-01 cells, which are derived from a patient with chronic myelogenous leukemia, without causing a significant change in S6K1 phosphorylation. Additionally, SP600125 induced the polyploidization of HEL cells, which are derived from a patient with erythroleukemia, and phosphorylation at Thr389 of S6K1 was detected. However, the polyploidization of both Meg-01 cells and HEL cells as a result of SP600125 treatment was lower than that of SP600125-induced Dami and CMK cells, and it was not blocked by H-89 despite the increased phosphorylation of S6K1 at Thr389 in both cell lines in response to H-89. Given that the Dami and CMK cell lines were derived from patients with acute megakaryocytic leukemia (AMKL) and expressed high levels of platelet-specific antigens, our data suggested that SP600125-induced polyploidization is cell-type specific, that these cell lines were more differentiated, and that phosphorylation at Thr421/Ser424 and dephosphorylation at Thr389 of S6K1 may play an important role in the SP600125-induced polyploidization of these cell lines synergistically with other signaling pathways.

Supercontinuum (SC) source is a new kind of artificial light source, having the characteristics of both laser and traditional incoherent light source, i.e., high brightness, good direction, and super broadband spectrum. The rapid development of SC source stimulates our concern on its ocular damage potency. However, the damage effects of SC source have never been explored. The retinal damage threshold of chinchilla grey rabbit induced by a Vis-infrared SC source was determined for the first time. Additionally, a theoretical method was also developed for analyzing the hazard risks of SC source.

The aim of this study was to evaluate the outcomes of multiple advanced surgical treatments (i.e. microsurgery, laparoscopic surgery and endoscopic surgery) for acquired obstructive azoospermia. We analyzed the surgical outcomes of 51 patients with suspected acquired obstructive azoospermia consecutively who enrolled at our center between January 2009 and May 2013. Modified vasoepididymostomy, laparoscopically assisted vasovasostomy and transurethral incision of the ejaculatory duct with holmium laser were chosen and performed based on the different obstruction sites. The mean postoperative follow-up time was 22 months (range: 9 months to 52 months). Semen analyses were initiated at four postoperative weeks, followed by trimonthly (months 3, 6, 9 and 12) semen analyses, until no sperm was found at 12 months or until pregnancy was achieved. Patency was defined as >10,000 sperm ml⁻¹ of semen. The obstruction sites, postoperative patency and natural pregnancy rate were recorded. Of 51 patients, 47 underwent bilateral or unilateral surgical reconstruction; the other four patients were unable to be treated with surgical reconstruction because of pelvic vas or intratesticular tubules obstruction. The reconstruction rate was 92.2% (47/51), and the patency rate and natural pregnancy rate were 89.4% (42/47) and 38.1% (16/42), respectively. No severe complications were observed. Using multiple advanced surgical techniques, more extensive range of seminal duct obstruction was accessible and correctable; thus, a favorable patency and pregnancy rate can be achieved.

We investigated mutations and polymorphisms of the coronary artery disease (CAD)-related myocyte enhancer factor 2A (MEF2A) gene in a Chinese population. Polymerase chain reaction-single-strand conformation polymorphism and DNA sequencing were used to detect exon 11 of the MEF2A gene in 210 Hubei patients with CAD and 190 healthy controls. The following mutations were identified: a) a synonymous heterozygous mutation (147191G→T) combined with a 6-base deletion (147123-147128); b) a synonymous heterozygous or homozygous mutation (147191G→T) combined with a 9-base deletion (147123-147131); c) a synonymous mutation (147143G→A); d) a synonymous mutation (147191G→T) combined with an 18-base deletion (147111-147128); and e) a 21-base deletion (147108-147128). Mutations (a) and (b) and a 3-base deletion (147126-147128) with or without the synonymous heterozygous mutation (147191G→T) occurred in more than 1% of controls. However, mutations (c), (d), and (e) were not observed in the control group. The polymorphism in exon 11 of the MEF2A gene was observed in the Chinese population. Six or seven amino acid deletions and synonymous mutations (147143G→A) may be correlated with susceptibility to CAD.

Background: Lower extremity atherosclerosis (LEA) is among the most serious diabetic complications and leads to non-traumatic amputations. The recently developed dual-source CT (DSCT) and 320- multidetector computed tomography (MDCT) may help to detect plaques more precisely. The aim of our study was to evaluate the differences in LEA between diabetic and non-diabetic patients using MDCT angiography., Methods: DSCT and 320-MDCT angiographies of the lower extremities were performed in 161 patients (60 diabetic and 101 non-diabetic). The plaque type, distribution, shape and obstructive natures were compared., Results: Compared with non-diabetic patients, diabetic patients had higher peripheral neuropathy, history of cerebrovascular infarction and hypertension rates. A total of 2898 vascular segments were included in the analysis. Plaque and stenosis were detected in 681 segments in 60 diabetic patients (63.1%) and 854 segments in 101 non-diabetic patients (46.9%; p <0.05). Regarding these plaques, diabetic patients had a higher incidence of mixed plaques (34.2% vs. 27.1% for non-diabetic patients). An increased moderate stenosis rate and decreased occlusion rate were observed in diabetic patients relative to non-diabetic patients (35.8% vs. 28.3%; and 6.6% vs. 11.4%; respectively). In diabetic patients, 362 (53.2%) plaques were detected in the distal lower leg segments, whereas in non-diabetic patients, 551 (64.5%) plaques were found in the proximal upper leg segments. The type IV plaque shape, in which the full lumen was involved, was detected more frequently in diabetic patients than in non-diabetic patients (13.1% vs. 8.2%)., Conclusion: Diabetes is associated with a higher incidence of plaque, increased incidence of mixed plaques, moderate stenosis and localisation primarily in the distal lower leg segments. The advanced and non-invasive MDCT could be used for routine preoperative evaluations of LEA.

Objectives: A healthcare decision-making support model and rule management system is proposed based on a personalized rule-based intelligent concept, to effectively manage chronic diseases., Methods: A Web service was built using a standard message transfer protocol for interoperability of personal health records among healthcare institutions. An intelligent decision service is provided that analyzes data using a service-oriented healthcare rule inference function and machine-learning platform; the rules are extensively compiled by physicians through a developmental user interface that enables knowledge base construction, modification, and integration. Further, screening results are visualized for the self-intuitive understanding of personal health status by patients., Results: A recommendation message is output through the Web service by receiving patient information from the hospital information recording system and object attribute values as input factors. The proposed system can verify patient behavior by acting as an intellectualized backbone of chronic diseases management; further, it supports self-management and scheduling of screening., Conclusions: Chronic patients can continuously receive active recommendations related to their healthcare through the rule management system, and they can model the system by acting as decision makers in diseases management; secondary diseases can be prevented and health management can be performed by reference to patient-specific lifestyle guidelines.

Wild tomato mosaic virus (WTMV), a potyvirus, has been reported in Laichau, Vietnam, infecting Solanum torvum (wild tomato) in 2008 (3), and Kanchanaburi, Thailand, infecting Capsicum spp. in 2013 (KF250353). In mid-May 2013, Nicotiana tabacum showing yellowing, mosaic, and/or ringspot symptoms were found in natural tobacco fields of Nanxiong, Guangdong Province, China. Total RNA was extracted from symptomatic leaves and reverse transcribed with M4T (5'-GTTTTCCCAGTCACGAC (T) 15 -3') as the 3' anchoring primer (1). The cDNA was used as template in a PCR assay using primers M4: 5'-GTTTTCCCAGTCACGAC-3' and Sprimer: 5'-GGXAAYAAYAGYGGXCAZCC-3', which amplifies a region comprising part of the NIb protein gene, the entire coat protein (CP) gene and the 3' nontranslated region (UTR) of a potyvirus (1). A ~1,700-bp product was amplified from the cDNA derived from three of the five diseased plants. The product (KF639967) showed 87% and 84% nucleotide sequence identities with those of WTMV isolates KAN and Laichau, respectively. The CP deduced from the sequence of the product shared 87% and 86% nucleotide and 94% and 93% amino acid sequence identities with those of WTMV isolates KAN and Laichau, respectively. The 3'-UTR of the putative virus shared 93% and 92% nucleotide sequence identities to those of WTMV isolates KAN and Laichau, respectively. Thus, according to the molecular criteria for potyvirus species demarcation (2), the virus we identified should be an isolate of WTMV (isolate GD1). One of the diseased samples was homogenized in 0.1 mol/liter phosphate buffer (pH 7.0) and used to inoculate the potyvirus to healthy, two to four leaf-stage Capsicum annuum L., N. tabacum, and N. benthamiana. The inoculated, as well as mock-treated plants, which were inoculated only with phosphate buffer, were grown in soil under 12 h day/12 h night at 25°C. All inoculated N. tabacum and N. benthamiana plants developed yellowing and mosaic symptoms by 14 days post inoculation (dpi). For N. benthamiana, the symptom became very severe by 21 dpi and some diseased plants died prematurely. About 10% of inoculated C. annuum L. developed very mild veinal chlorosis 18 dpi. Cloning and sequencing experiments showed that all the symptomatic plants tested were WTMV positive, but Cucumber mosaic virus, Tobacco mosaic virus, and Tobacco etch virus negative. To our knowledge, this is the first report of WTMV in China. Also, it is the first report that WTMV infects Nicotiana spp. Although further experiments are needed to definitively attribute the disease observed in the field to WTMV, our results indicate that WTMV, which forms a monophyletic clade with a number of other potyviruses infecting Solanaceae species in phylogenetic analysis, is widely distributed, or is spreading in Southeast Asia. It may pose a threat to Solanaceae species cultivation in this region. References: (1) Chen et al. Arch. Virol. 146:757, 2001. (2) Adams et al. Arch. Virol. 150:459, 2005. (3) Ha et al. Arch. Virol. 153:25, 2008.

Although substantial progress has been achieved in the structural analysis of exporters from the superfamily of adenosine triphosphate (ATP)-binding cassette (ABC) transporters, much less is known about how they selectively recognize substrates and how substrate binding is coupled to ATP hydrolysis. We have addressed these questions through crystallographic analysis of the Atm1/ABCB7/HMT1/ABCB6 ortholog from Novosphingobium aromaticivorans DSM 12444, NaAtm1, at 2.4 angstrom resolution. Consistent with a physiological role in cellular detoxification processes, functional studies showed that glutathione derivatives can serve as substrates for NaAtm1 and that its overexpression in Escherichia coli confers protection against silver and mercury toxicity. The glutathione binding site highlights the articulated design of ABC exporters, with ligands and nucleotides spanning structurally conserved elements to create adaptable interfaces accommodating conformational rearrangements during the transport cycle.

FleQ is a master regulator that controls bacterial flagellar gene expression. It is a unique enhancer-binding protein or repressor protein comprising an N-terminal FleQ domain, an AAA(+)/ATPase σ54-interaction domain and a helix-turn-helix DNA-binding domain. FleN is a putative ATPase with a deviant Walker A motif that works together with FleQ by binding to the FleQ N-terminal domain to fully express pel, psl and cdr operons in the presence of c-di-GMP to enhance biofilm formation. Stenotrophomonas maltophilia is an emerging human pathogen that causes fatal infections in humans. In order to understand the interaction between the FleN and FleQ domains and its effect on S. maltophilia biofilm formation, determination of the FleQ-c-di-GMP and FleN-FleQ-c-di-GMP complex structures was embarked upon. Towards this goal, the FleQ N-terminal domain from S. maltophilia was first cloned and expressed in Escherichia coli. Native and SeMet-labelled FleQ domains were successfully crystallized and diffracted to resolutions of 2.08 and 2.58 Å, respectively.

Purpose: To evaluate the variation in macular retinal thickness and volume in young Chinese myopic patients using time-domain optical coherence tomography (Stratus TD-OCT) and spectral-domain optical coherence tomography (Cirrus HD-OCT)., Methods: Ninety-two eyes of 92 myopic subjects were recruited in this study. Based upon spherical equivalence (SE), subjects were divided into two groups: the low to moderate myopia group (-0.5 D ≤ SE < -6.0 D), and the high myopia group (SE ≥ -6.0 D). Stratus TD-OCT and Cirrus HD-OCT were used to compare macular retinal thickness and volume between the two groups. Bland-Altman analysis and Pearson correlation were used to measure agreement between the two OCT systems., Results: Average macular retinal thickness and total macular volume measured by Cirrus HD-OCT and Stratus TD-OCT of the low to moderate myopia group were 283.52 ± 12.14 μm and 245.38 ± 8.55 μm, respectively, and 10.08 ± 0.37 mm3 and 6.85 ± 0.26 mm3, respectively, and the high myopia groups were 269.58 ± 10.72 μm and 235.65 ± 7.54 μm, respectively, and 9.71 ± 0.36 mm3 and 6.52 ± 0.25 mm3, respectively. The measurements of the two OCTs showed that macular retinal thickness of the parafovea was significantly lower in the high myopia group compared with the low to moderate myopia group, except at the fovea (all P-values less than 0.001, except at the fovea). Using the Bland-Altman method and Pearson correlation, measurements of macular thickness in nine macular retinal subfields and total macular volumes showed good agreement between the two OCTs in myopic eyes (all P-values less than 0.001), with better agreement in the low to moderate myopia group than in the high myopia group., Conclusions: The average macular retinal thickness of the fovea did not vary with myopia, while the total volume and retinal thickness of the parafovea were thinner with increasing myopia. There was good agreement between the two OCTs in myopic eyes in all macular subfields, and the Cirrus HD-OCT system provided thicker macular retinal thickness measurements than the Stratus TD-OCT system., Virtual Slides: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1683223414107652.

Objective: To establish a multilocus model for studying the effect of steroid-related genes on advanced stage endometriosis., Materials and Methods: A total of 121 patients with advanced stage endometriosis and 171 control women were included. Eighteen single-nucleotide polymorphisms (SNPs) from nine genes (HSD17B1, HSD17B2, HSD17B5, HSD17B6, CYP17, CYP19, ERα, ERβ, and PGR) were genotyped using the TaqMan assays. Logistic regression models were used to evaluate the genetic effects, with adjustment for other covariates., Results: Only the presence of the mutant CYP19 (aromatase gene) was associated with a significantly increased risk of endometriosis after adjusting for age, BMI, and parity (p = 0.002, OR = 2.69; 95% CI = 1.44-5.02). No association was ascertained between the other investigated SNPs and endometriosis., Conclusion: Polymorphisms of the aromatase gene confer susceptibility to advanced stage endometriosis in the Taiwanese Han population., (Copyright © 2013. Published by Elsevier B.V.)

Polycomb group (PcG) proteins are transcription regulatory proteins that control the expression of a variety of genes and the antero-posterior neural patterning from early embryogenesis. Although expression of PcG genes in the nervous system has been noticed, but the expression pattern of PcG proteins in early embryonic nervous system is still unclear. In this study, we analyzed the expression pattern of PRC1 complex members (BMI-1 and RING1B) and PRC2 complex members (EED, SUZ12 and EZH2) in early embryonic nervous system in mouse and human by Western blot and Immunohistochemistry. The results of Western blot showed that EED protein was significantly up-regulated with the increase of the day of pregnancy during the early embryogenesis in mouse. BMI-1 protein level was significantly increased from the day 10 of pregnancy, when compared with the day 9 of pregnancy. But the SUZ12, EZH2 and RING1B protein level did not change significantly. From the results of Immunohistochemistry, we found that the four PcG proteins were all expressed in the fetal brain and fetal spinal cord in mouse. In human, the expression of EED, SUZ12, and EZH2 was not significantly different in cerebral cortex and sacral spinal cord, but BMI-1 and RING1B expression was enhanced with the development of embryos in early pregnancy. Collectively, our findings showed that PRC1 and PRC2 were spatiotemporally expressed in brain and spinal cord of early embryos., (Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.)

Cyclic guanosine 3',5'-monophosphate (cyclic GMP) is a second messenger whose role in bacterial signalling is poorly understood. A genetic screen in the plant pathogen Xanthomonas campestris (Xcc) identified that XC&#95;0250, which encodes a protein with a class III nucleotidyl cyclase domain, is required for cyclic GMP synthesis. Purified XC&#95;0250 was active in cyclic GMP synthesis in vitro. The linked gene XC&#95;0249 encodes a protein with a cyclic mononucleotide-binding (cNMP) domain and a GGDEF diguanylate cyclase domain. The activity of XC&#95;0249 in cyclic di-GMP synthesis was enhanced by addition of cyclic GMP. The isolated cNMP domain of XC&#95;0249 bound cyclic GMP and a structure-function analysis, directed by determination of the crystal structure of the holo-complex, demonstrated the site of cyclic GMP binding that modulates cyclic di-GMP synthesis. Mutation of either XC&#95;0250 or XC&#95;0249 led to a reduced virulence to plants and reduced biofilm formation in vitro. These findings describe a regulatory pathway in which cyclic GMP regulates virulence and biofilm formation through interaction with a novel effector that directly links cyclic GMP and cyclic di-GMP signalling.

Objective: To evaluate the correlation of neutral alpha-glucosidase in seminal plasma with the location of epididymal obstruction in azoospermia men., Methods: We detected neutral alpha-glucosidase activity in the seminal plasma of 59 men with obstructive azoospermia followed by determining the location of epididymal obstruction by scrotal exploratory surgery. Then we analyzed the correlation between neutral alpha-glucosidase and the location of epididymal obstructive azoospermia., Results: Among the total number of patients, there were 25 cases of bilateral cauda epididymal obstruction, 15 bilateral corpus, 12 bilateral caput, 4 unilateral caput-opposite cauda, and 3 unilateral corpus-opposite cauda. The neutral alpha-glucosidase levels in the seminal plasma of bilateral cauda, corpus and capus epididymal obstructions were (4.1 +/- 1.9), (13.8 +/- 4.4) and (46.8 +/- 19.3) mU per ejaculate, respectively, with statistically significant differences among the three groups (P < 0.05)., Conclusion: Neutral alpha-glucosidase activity is significantly correlated with the location of epididymal obstruction in azoospermia men, which helps to locate epididymal obstruction, evaluate surgical prognosis and reduce the time of scrotal exploratory surgery.

Objective: To observe the pro-angiogenic effect of four Chinese medicines and three herbal prescriptions, screen the effective components from them., Methods: Chicken chorioallantoic membrane (CAM) model was employed to observe the pro-angiogenic activities of Angelicae Sinensis Radix, Salviae Miltiorrhizae Radix, Notoginseng Radix, Astragali Radix, Xuefuzhuyu decoction, Dangguibuxue decoction and Taohongsiwu decoction, all of them were claimed to promote angiogenesis. The effective components were screened from the extracts., Results: Compared with negative control group, the blood vessel densities in Angelicae Sinensis Radix and Notoginseng Radix groups were not increased significantly (P > 0.05). However, blood vessel densities in Astragali Radix group, Salviae Miltiorrhizae Radix group, Xuefuzhuyu decoction group, Dangguibuxue decoction group and Taohongsiwu decoction group were notably enhanced (P < 0.05). Dangguibuxue decoction showed a more than 90% of increase in blood vessel densities as compared with the negative control group (P < 0.01), and components contained ferulic acid and astragaloside from Dangguibuxue decoction displayed significantly pro-angiogenic effect (P < 0.05)., Conclusion: Dangguibuxue decoction and its extract, components contained ferulic acid and astragaloside, can improve angiogenesis in CAM model significantly.

Biological nitrogen fixation is a complex process requiring multiple genes working in concert. To date, the Klebsiella pneumoniae nif gene cluster, divided into seven operons, is one of the most studied systems. Its nitrogen fixation capacity is subject to complex cascade regulation and physiological limitations. In this report, the entire K. pneumoniae nif gene cluster was reassembled as operon-based BioBrick parts in Escherichia coli. It provided ~100% activity of native K. pneumoniae system. Based on the expression levels of these BioBrick parts, a T7 RNA polymerase-LacI expression system was used to replace the σ(54)-dependent promoters located upstream of nif operons. Expression patterns of nif operons were critical for the maximum activity of the recombinant system. By mimicking these expression levels with variable-strength T7-dependent promoters, ~42% of the nitrogenase activity of the σ(54)-dependent nif system was achieved in E. coli. When the newly constructed T7-dependent nif system was challenged with different genetic and physiological conditions, it bypassed the original complex regulatory circuits, with minor physiological limitations. Therefore, we have successfully replaced the nif regulatory elements with a simple expression system that may provide the first step for further research of introducing nif genes into eukaryotic organelles, which has considerable potentials in agro-biotechnology.

Objectives: To evaluate the clinical characteristics, in-hospital and three-year outcome in ST-elevation myocardial Infraction (STEMI) patients receiving conservative treatment (CT), thrombolytic treatment (TT) and primary percutaneous coronary intervention (PCI) in Beijing., Methods: This 12-month prospective, multicenter registry study was conducted in 19 hospitals with 808 patients with STEMI in Beijing between Jan. 2006 and Dec. 2006, 518 (64%) received PCI, 106 (16.1%) received TT and 184 (22.8%) received CT therapy. Patients were followed up for 3 years., Results: At baseline, the age of patients in CT group [(64.5 ± 13.5) years] was significantly higher than those in TT group p(57.9 ± 11.0) years] and in PCI group [ (60.4 ± 12.3) years, all P<0.01]; and the median time from symptom onset to hospital in CT group (207 min) was significantly longer than those in TT group (130 min) and PCI group (130 min, all P<0.01). Emergency Medical Service (EMS) use was significantly higher in PCI group (184/518, 35.5%) than in CT group (46/184, 27.3%) and TT group (29/107, 25.0%, all P<0.05). Health insurance holder was the highest in PCI group (P<0.01). PCI was performed less frequently than thrombolytic therapy [66.6% (345/518) vs. 80.2% (85/106)m P=0.02] during off-hours and more frequently performed in tertiary hospitals than in secondary hospitals[66.8%(437/651) vs. 52.6% (81/154, P<0.01)]. The in-hospital mortality and the cardiovascular mortality at 3 year after hospital discharge was significantly higher in CT group [9.2% (17/185) and 9.4% (15/159)] than in PCI group [3.5% (18/518), 4.5% (20/446)] and TT group [6.6% (7/106), 2.3% (2/86), all P<0.01]. Patients in PCI group had the highest adherence level of aspirin, β-blocker, angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers or statins at 3-years follow-up (all P<0.05). Multivariable Cox proportional hazards regression analysis showed that only PCI was associated with lower risk of cardiovascular death (HR-0.40, 95% CI:0.21-0.73, P<0.01)., Conclusions: Social and clinical setting may affect the physician's decision to provide reperfusion therapy in Beijing for STEMI patients. Better adherence of secondary preventive drugs and lower cardiovascular death are observed in STEMI patients receiving PCI during the 3-year follow-up

Objective: Many studies have assessed the association between serum adiponectin and the risk of cardiovascular disease (CVD), yet whether adiponectin is an independent risk factor for CVD remains controversial. We performed a meta-analysis of 17 prospective epidemiologic studies to evaluate this relationship in the general population., Methods: PubMed and Embase databases were searched through June 2012 to identify studies meeting a priori inclusion criteria, in addition to conducting a secondary reference review. Two principle investigators respectively extracted the information with either fixed-effect model or random-effect model to calculate the relationship between adiponectin and the risk of CVD., Results: We summarized 17 prospective studies with a total of 23,717 participants. Overall, higher serum adiponectin was related to an increased risk of ischemic stroke: pooled risk ratio (RR) of 1.34 [95% confidence intervals (CI): 1.06-1.69] with no heterogeneity (Q = 1.23; P = 0.541). Serum adiponectin was not related to coronary heart disease (CHD) or CVD: pooled RR of 0.96 (95% CI: 0.85-1.08) and 1.00 (95% CI: 0.89-1.13), respectively., Conclusions: Increased serum adiponectin was related to an elevated risk of ischemic stroke, but there was no clear evidence indicating a positive relationship between adiponectin and the risk of CHD or CVD., (Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.)