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Intratumoural heterogeneity (ITH) has been implicated in tumour growth and progression as well as therapy resistance. However, the extent of ITH of somatic copy number alterations (ITH-SCNAs) as a result of tumour evolution and its influence on clinical outcomes in diffuse glioma (DG) remain poorly understood.We used an integrated computational method to infer clonal and subclonal SCNAs in 760 untreated primary DGs from The Cancer Genome Atlas. ITH-SCNAs at the genome-wide, peak (region with recurrent SCNAs) and gene level were calculated. We used the Kaplan-Meier estimators and Cox proportional hazards models to examine the associations of ITH-SCNA with patient outcomes. An independent cohort of 243 patients with paired initial and recurrent tumours from the Glioma Longitudinal Analysis Consortium was used for validation.DGs showed widespread ITH-SCNA, with a median of 25.5% of SCNAs identified as subclonal. We found that clonal SCNA burden had stronger prognostic power than total SCNAs in IDH-mutant astrocytoma. Coamplifications of receptor tyrosine kinases (RTKs) tended to be subclonal, and subclonal RTK amplification was significantly associated with high tumour proliferative potential and unfavourable clinical outcomes in IDH-wild-type glioblastoma. In addition, we found that the prognostic values of the peak-level SCNAs were related to their mutated clonal architecture, from which three clonality-dependent prognostic patterns of SCNAs were proposed, including clonal-dominant, subclonal-dominant and clonality-independent schemas.The systematic analysis of ITH-SCNAs in large cohorts of DGs highlighted the importance of considering the clonality of SCNA in discovery of tumour prognostic markers.

The present study aimed to examine the antidepressant actions of the composition fractions of Schisandra chinensis using LPS-induced mice. Animals were treated with total extracts (SCE), lignans (SCL), polysaccharides (SCPS), and essential oil (SCVO), and then subjected to behavioral tests. The forced swimming test (FST) and tail suspension test (TST) were used as predictive animal models of antidepressant activity. Total extracts and lignans significantly decreased the duration of immobility in FST and TST. We found that treatment with SCE and SCL could significantly decrease the levels of pro-inflammatory cytokines both in the periphery and central nervous system (CNS). This was confirmed by the histopathological examination of the colon. The RT-PCR results demonstrated that SCE and SCL could greatly inhibit the TLR4/NF-κB/IKKα signaling pathway. In addition, the concentrations of Butyric acid and Propionic acid were upregulated by the administration, and the decreased diversity of intestinal microbiota and alterations of the relative proportions of Bacteroidetes and Firmicutes phylum members, Barnesiella and Lactobacillus genus members in LPS-induced mice were restored as well. All results suggested that lignans is the effective fraction of S.chinensis to ameliorating depressive disorders, which its anti-inflammation activity possibly involved in the bidirectional connection between gut microbiota and brain.

A goal of the International Prophylaxis Study Group (IPSG) is to provide an accurate instrument to measure MRI-based disease severity of haemophilic arthropathy at various time points, so that longitudinal changes in disease severity can be identified to support decisions on treatment management. We review and discuss in this paper the evaluative purpose of the IPSG MRI scale in relation to its development and validation processes so far. We also critically appraise the validity, reliability and responsiveness of using the IPSG MRI scale in different clinical and research settings, and whenever applicable, compare these clinimetric properties of the IPSG MRI scale with those of its precursors, the compatible additive and progressive MRI scales.

Insomnia is a common clinical disease that can seriously damage the normal lives of sufferers. Suan-Zao-Ren decoction has been used to treat insomnia for a long time. However, the underlying molecular mechanism of Suan-Zao-Ren decoction is still not clear. In this study, the nontargeted metabolomics based on high-resolution mass spectrometry and multiple statistical approaches were initially used to investigate the changes of potential serum and brain biomarkers and metabolic pathways in the insomnia model rat. Principal component analysis-discriminate analysis indicated that the Suan-Zao-Ren decoction treatment improved the metabolic phenotype insomnia. Moreover, the heatmap analysis identified the most important biomarkers involved in insomnia. According to the pathway analysis, phenylalanine metabolism, tryptophan metabolism, and so on were recognized as the most affected metabolic pathways associated with insomnia disease. These findings provided a comprehensive understanding of the regulative effects of Suan-Zao-Ren decoction on the host metabolic phenotype of the insomnia rats. Our work demonstrated that the metabolomics approach is a promising tool that could help us to conduct the exploration of the therapeutic effects and mechanism of traditional Chinese medicines.

Long noncoding RNAs (lncRNAs) are an emerging class of RNA species that could participate in some critical pathways and disease pathogenesis. However, the underlying molecular mechanism of lncRNAs in atrial fibrillation (AF) is still not fully understood. In the present study, we analyzed RNA-seq data of paired left and right atrial appendages from five patients with AF and other five patients without AF. Based on the gene expression profiles of 20 samples, we found that a majority of genes were aberrantly expressed in both left and right atrial appendages of patients with AF. Similarly, the dysregulated pathways in the left and right atrial appendages of patients with AF also bore a close resemblance. Moreover, we predicted regulatory lncRNAs that regulated the expression of adjacent protein-coding genes (PCGs) or interacted with proteins. We identified that NPPA and its antisense RNA NPPA-AS1 may participate in the pathogenesis of AF by regulating the muscle contraction. We also identified that RP11 - 99E15.2 and RP3 - 523K23.2 could interact with proteins ITGB3 and HSF2, respectively. RP11 - 99E15.2 and RP3 - 523K23.2 may participate in the pathogenesis of AF via regulating the extracellular matrix binding and the transcription of HSF2 target genes, respectively. The close association of the lncRNA-interacting proteins with AF further demonstrated that these two lncRNAs were also associated with AF. In conclusion, we have identified key regulatory lncRNAs implicated in AF, which not only improves our understanding of the lncRNA-related molecular mechanism underlying AF but also provides computationally predicted regulatory lncRNAs for AF researchers.

Introduction For persons with hemophilia, optimization of joint outcomes is an important unmet need. The aim of this initiative was to determine use of ultrasound in evaluating arthropathy in persons with hemophilia, and to move toward consensus among hemophilia care providers regarding the preferred ultrasound protocols for global adaptation. Methods A global survey of hemophilia treatment centers was conducted that focused on understanding how and why ultrasound was being used and endeavored to move toward consensus definitions of both point‐of‐care musculoskeletal ultrasound (POC‐MSKUS) and full diagnostic ultrasound, terminology to describe structures being assessed by ultrasound, and how these assessments should be interpreted. Next, an in‐person meeting of an international group of hemophilia health care professionals and patient representatives was held, with the objective of achieving consensus regarding the acquisition and interpretation of POC‐MSKUS and full diagnostic ultrasound for use in the assessment of musculoskeletal (MSK) pathologies in persons with hemophilia. Results The recommendations were that clear definitions of the types of ultrasound examinations should be adopted and that a standardized ultrasound scoring/measurement system should be developed, tested, and implemented. The scoring/measurement system should be tiered to allow for a range of complexity yet maintain the ability for comparison across levels. Conclusion Ultrasound is an evolving technology increasingly used for the assessment of MSK outcomes in persons with hemophilia. As adoption increases globally for clinical care and research, it will become increasingly important to establish clear guidelines for image acquisition, interpretation, and reporting to ensure accuracy, consistency, and comparability across groups.

The present study was undertaken to explore the interactions between sleep deprivation (SD) and Schisandrae Chinensis Fructus (SCF) treatment in the antidepressant-like effects. We observed that SD aggravated the anxiety-like behavior induced by chronic unpredictable mild stress (CUMS) in the elevated plus maze test. However, the forced swimming test and sucrose preference test showed that SD (12 hr) alleviated the depressive symptoms and SD (72 hr) has the opposite effects. Administration of SCF showed a promising therapeutic effect on depression and anxiety induced by CUMS and SD. Moreover, SCF could potential strengthen the antidepressant-like effects of SD (12 hr) according to the behavioral tests. In addition, the BDNF level in hippocampus was elevated by SD (12 hr) and SCF treatment and together with the upregulation of TrkB/CREB/ERK and PI3K/AKT/GSK3β/mTOR signaling pathways. Besides, the protein levels of p70S6K and PSD95, which are downstream targets of mTOR, also increased by the treatment. These results indicated that the antidepressant-like effect of SCF in the CUMS depends on the activation of BDNF and the modulation of TrkB/CREB/ERK and PI3K/AKT/GSK3β/mTOR signaling cascades, and SD (12 hr) shared a common etiology consisting of complex bidirectional interactions with SCF.

The correlation of genetic alterations with response to neoadjuvant chemotherapy (NAC) has not been fully revealed. In this study, we enrolled 247 breast cancer patients receiving anthracycline‐taxane‐based NAC treatment. A next generation sequencing (NGS) panel containing 36 hotspot breast cancer‐related genes was used in this study. Two different standards for the extent of pathologic complete response (pCR), ypT0/isypN0 and ypT0/is, were used as indicators for NAC treatment. TP53 mutation (n = 149, 60.3%), PIK3CA mutation (n = 109, 44.1%) and MYC amplification (n = 95, 38.5%) were frequently detected in enrolled cases. TP53 mutation (P = 0.019 for ypT0/isypN0 and P = 0.003 for ypT0/is) and ERBB2 amplification (P

OBJECTIVE To clarify the mechanism of heat shock protein 27 (HSP27) as a diagnostic biomarker in coronary heart disease (CHD) and atherosclerosis (AS). METHOD Expressions of HSP27 in patients with CHD and healthy controls were determined by enzyme-linked immunosorbent assay and the expressions of HSP27 in aortas of patients with CHD and healthy controls were measured by immunohistochemistry. Receiver operating characteristic curve was applied to assess the diagnostic performance of HSP27 in CHD. ApoE-/- mice were included and accordingly grouped. The expressions of HSP27 in AS plaque were measured by quantitative real-time polymerase chain reaction, immunohistochemistry, and Western blot analysis. AS plaque was observed using hematoxylin and eosin staining. DHE was used to detect reactive oxygen species (ROS) levels in aortas. The expressions of mitochondrial apoptosis-related proteins were measured by Western blot analysis. Cell apoptosis was determined by TUNEL staining. RESULTS HSP27 was highly expressed in patients with CHD than in healthy controls ( P

Proximal to distal Y stenting technique is a modified bifurcation technique based on the original Y stenting technique described over 20 years ago. We use a bench top model to illustrate the steps of the technique, which can provide both provisional and full coverage options, using radial artery access. This technique may be applied in clinical settings on a wide range of bifurcation anatomies with a number of unique advantages.

AIM We aimed to investigate the potential role of endothelin-1 (ET-1) in the regulation of the expression of α-smooth muscle actin (α-SMA) in human myometrial fibroblasts. METHODS Primary myometrial fibroblasts were obtained from myometrium and were identified by immunocytochemical staining. Then, 1 × 107 cells were treated with ET-1 at a concentration of 0.1, 1.0, 10.0, or 100.0 nM for 24 h. To investigate the time course effects of ET-1 on the growth of fibroblasts, 1 × 107 cells were treated with 10.0 nM ET-1 for 6, 12, 24, and 48 h. Real-time quantitative PCR (qPCR) and Western blot analysis were used to determine the expression of α-SMA mRNA and protein, respectively. RESULTS Human myometrial fibroblasts were identified by immunohistochemistry. Compared with the control group, the expression levels of α-SMA mRNA and protein were identified in cells treated with ET-1 at a concentration of 0.1, 1.0, 10.0, or 100.0 nM for 24 h (P

The present study verified the antidepressant-like effects of the total flavonoids of Alpinia oxyphylla Miq. (AOF) using the chronic unpredictable mild stresses paradigm and explored the mechanism that underlies antidepressant-like effects of AOF in mice. Previous research has shown that tropomyosin-related kinase B (TrkB) receptor-mediated extracellular regulated protein kinases (ERK) signaling pathways participate in depression pathophysiology. Therefore, we aimed to explore whether AOF improved depression-like behaviors by increasing activity of ERK pathways mediated by TrkB. Results showed that AOF significantly reduced the immobility time in the forced swimming test and increased the sucrose preference in sucrose preference test. In addition, decreased phosphorylated cyclic adenosine monophosphate response element-binding protein (pCREB)/CREB, pERK/ERK, and pTrkB/TrkB levels in the hippocampus induced by chronic unpredictable mild stresses were reversed by intragastric administration of AOF. Results suggested that AOF increased pCREB/CREB, pERK/ERK, and pTrkB/TrkB levels by acting on the TrkB receptor. To verify this hypothesis, mice were pretreated with the TrkB inhibitor K252a (or 0.1% dimethyl sulfoxide, intraperitoneally, 2 weeks), before the intragastric administration of AOF. This resulted in an absence of antidepressant-like effects, as well as no activation of pERK/pCREB/BDNF signaling pathways. Results demonstrated that AOF might exert antidepressant-like effects by targeting TrkB receptor-mediated pERK/pCREB/BDNF signal systems, which could help to identify the AOF receptor. Copyright © 2016 John Wiley & Sons, Ltd.

A novel plasma jet driven by an alternating current voltage is developed to generate atmospheric pressure non-equilibrium plasma plumes in the downstream region and in the upstream one of the argon flow. The angle between the rod electrode and the gas flow can be changed easily, and the plume lengths in the downstream and upstream regions are investigated as a function of the angle and the peak voltage. With increasing the peak voltage, the discharge pulse number tends to increase for every half voltage cycle. Using an intensified charge-coupled device camera, the dynamics of the plasma plumes is also investigated in the downstream and upstream regions. The dynamics of the plumes is qualitatively explained by the streamer propagations influenced by residual charges.

Yolk-shell nanoreactors with metal nanoparticle core and ultrathin porous polymer shells are effective catalysts for heterogeneous reactions. Polymer shells provide size-selectivity and improved reusability of catalyst. Nanocapsules with single-nanometer porous shells are prepared by vesicle-templated directed assembly. Metal nanoparticles are formed either by selective initiation in pre-fabricated nanocapsules or simultaneously with the creation of a crosslinked polymer shell. In this study, we investigated the oxidation of benzyl alcohol and benzaldehyde catalyzed by gold nanoparticles and hydrogenation of cyclohexene catalyzed by platinum nanoparticles. Comparison of newly created nanoreactors with commercially available nanoparticles revealed superior reusability and size selectivity in nanoreactors while showing no negative effect on reaction kinetics.

Schisandrin C (SCH-C) is a main and typical antioxidative lignan isolated from the fruits of Schisandra chinensis (Trucz.) Baill (a widely used traditional Chinese medicine). The present study aimed to characterize the effect of SCH-C on memory impairment and further research on pathological changes in Aβ1-42 -induced Alzheimer's disease mice. Mice were administration with SCH-C daily for 5 days in the lateral cerebral ventricles using sterotaxically implanted cannula. Cognitive functions were assessed by Y-maze test, active avoidance test and Morris water maze test in all groups, and the level of Aβ1-42 and neuronal injury induced by Aβ1-42 were reversed remarkably following SCH-C treatment compared with sham group; meanwhile the impairment of short-term or working memory was dramatically improved. In addition, SCH-C significantly inhibited total cholinesterase (ChEtotal), and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activity glutathione (GSH) levels in the hippocampus and cerebral cortex. It can be speculated that SCH-C offers protection against Aβ1-42 -induced dysfunction in learning and memory by inhibiting ChEtotal and its antioxidant action. Copyright © 2015 John Wiley & Sons, Ltd.

Enantiomerically pure (R, R)-2,3-butanediol has unique applications due to its special chiral group and spatial configuration. Currently, its chemical production route has many limitations. In addition, no native microorganisms can accumulate (R, R)-2,3-butanediol with an enantio-purity over 99%. Herein, we constructed a synthetic metabolic pathway for enantiomerically pure (R, R)-2,3-butanediol biosynthesis in Escherichia coli. The fermentation results suggested that introduction of the synthetic metabolic pathway redistributed the carbon fluxes to the neutral (R, R)-2,3-butanediol, and thus protected the strain against the acetic acid inhibition. Additionally, it showed that the traditionally used isopropyl beta-D-thiogalactoside (IPTG) induction displayed negative effect on (R, R)-2,3-butanediol biosynthesis in the recombinant E. coli, which was probably due to the protein burden. With no IPTG addition, the (R, R)-2,3-butanediol concentration reached 115 g/L by fed-batch culturing of the recombinant E. coli, with an enantio-purity over 99%, which is suitable for the pilot-scale production.

A selective liquid chromatographic-mass spectrometric method has been developed and validated for simultaneous determination of senkyunolide I (SEI) and senkyunolide H (SEH) from Chuanxiong Rhizoma in rat plasma. Plasma samples were extracted by liquid-liquid extraction with ethyl acetate and separated on a Kromasil C18 column (250 × 4.6 mm, 5 µm), with methanol-water (55:45, v/v) as mobile phase. The linear range was 0.05-25 µg/mL for SEI and 0.01-5.0 µg/mL for SEH, with lower limits of quantitation of 0.05 and 0.01 µg/mL, respectively. Intra- and inter-day precision were within 10.0 and 9.8%, and the accuracies (relative errors) were

Objectives Focused ultrasound waves penetrate superficial tissues and are aimed toward the target tissues at specific depths to exert their biological effects. Focused ultrasound has been applied for a number of clinical indications, including vulval dystrophies and low-grade vulval disease. This study aimed to assess the efficacy and safety of focused ultrasound treatment of high-grade vulval intraepithelial neoplasia (VIN). Methods Eighteen women with high-grade VIN were recruited and treated with focused ultrasound. During each posttreatment follow-up, the safety of, side effects of, and clinical responses to focused ultrasound were evaluated by a standardized protocol, including symptoms, clinical appearance, and histologic findings. Results All patients completed the designed follow-ups. In most cases, superficial mild to moderate swelling and blisters were seen in the focused ultrasound-treated skin but not in adjacent normal skin. Of the 18 patients, 16 showed complete histologic regression and resolution of symptoms 6 months after treatment. Of the other 2 patients, 1 showed complete regression after a second focused ultrasound treatment. The other patient did not respond to the focused ultrasound treatment and underwent a partial vulvectomy 6 months after treatment. None of the patients developed invasive carcinoma of the vulva during the follow-up period. One patient had local pruritus that was not alleviated by anti-inflammatory medication and local care. Conclusions The complete responses observed in women with high-grade VIN treated by focused ultrasound, together with the preservation of adjacent normal tissue, suggest that focused ultrasound may be considered for treatment of high-grade VIN.

Objectives To systematically review the effects of tolerogenic dendritic cells (Tol-DCs) induced by different methods on liver transplantation and their possible mechanisms of action. Methods PubMed and EMbase were searched for relevant articles through 31 December 2013. The effects of Tol-DCs on liver allograft survival were semiquantitatively evaluated, and the possible mechanisms by which Tol-DCs prolong graft survival were analyzed. Results Seven articles were included, and classified according to methods of induction, sources, and methods of infusing Tol-DCs. Tol-DCs induced from immature DCs (imDCs), with cytokines, and by gene modification induced liver transplant tolerance for 33.1 ± 32.5 days (2.7-fold vs. control), 26.17 ± 16.20 days (1.8-fold vs. control), and 11.7 ± 1.6 days (2.3-fold vs. control), respectively. DCs derived from recipient bone marrow, donor bone marrow, and donor spleen induced liver transplant tolerance for 51.0 ± 0.0 days (5.9-fold vs. control), 21.4 ± 26.8 days (2.4-fold vs. control), and 15.0 ± 0.0 days (2.3-fold vs. control), respectively. The primary mechanisms by which Tol-DCs induce liver transplant tolerance were the induction of T-cell hyporeactivity and Th2 differentiation. Conclusions Tol-DCs induced by three different methods could extend liver allograft survival, with imDCs showing optimal results. The optimal infusion method was intravenous injection of 1–2 × 106 Tol-DC, similar to findings in renal transplantation. Tol-DCs prolonged liver transplant tolerance more than renal transplant tolerance.

Objective The aim of this study was to systematically review the effects of transfusing Tol-DCs induced by different methods on renal transplantation and survival time. Method PubMed and EMbase were searched for relevant articles from inception to July 20th, 2013. Renal allograft survival time was regarded as the endpoint outcome. The effects of Tol-DCs on renal transplantation were evaluated semi-quantitatively. Results Sixteen articles were included. There were three sources of Tol-DCs, including bone marrow, spleen, and thoracic duct lymph node. Rats were administrated cells intravenously and 83% of mice through the portal vein. Four subtypes of bone marrow Tol-DCs enhanced renal allograft time: immature DCs enhanced allograft survival 4.9-fold in rats and 2.0-fold in mice, gene modified DCs enhanced allograft survival 4.4-fold in rats and 2.2-fold in mice, and drug and cytokine induced enhanced allograft survival 2.9-fold and 2.7-fold, respectively, in rats. Tol-DCs from the spleen and thoracic duct lymph nodes prolonged allograft survival 2.7-fold and 1.8-fold, respectively, in rats. 1-2×106 doses of Tol-DCs extended the survival time of rats following renal transplantation. The key mechanisms by which Tol-DCs enhance allograft and overall survival included: (i) inducing T-cell hyporeactivity; (ii) reducing the effects of cytotoxic lymphocytes; and (iii) inducing Th2 differentiation. Conclusion Bone marrow Tol-DCs can extend allograft survival and induce immune tolerance in fully MHC-mismatched renal transplantation in rats and mice. The effects of imDCs and gene modified Tol-DCs in mice are less marked. In conclusion, a single-injection of 1-2×106 doses of bone marrow Tol-DCs (i.v.), in combination with an immune-suppressor, a co-stimulator, and accessory cells can significantly extend renal allograft survival.

Background To correlate right ventricular volumes measured by real-time three-dimensional echocardiography (RT3DE) with left ventricular volume indices in patients with or without left-sided heart diseases. Methods For this retrospective, we reviewed 806 consecutive RT3DE examinations with quantitative evaluation of both the left and the right (RV) ventricle. We excluded cases of disease or surgery that would directly affect the size of the RV (eg, intracardiac shunt, significant tricuspid, or pulmonic regurgitation) as well as poor sonographic image quality, leaving a total of 701 studies for analysis. RV volumetric quantification was performed using dedicated software. Results Linear regression analysis showed that left ventricular stroke volume index significantly correlated with RV end-diastolic volume index (RVEDVI) (r = 0.78, p

Aims To examine the relationship between perioperative anxiety and postoperative pain in children and adolescents undergoing elective surgical procedures and the differences in children's perioperative anxiety and postoperative pain among subgroups of demographics. Background While anxiety and pain are regarded as two common problems experienced by children and adolescents perioperatively and the relationship between them has been reported in previous studies, there has been no review paper examining this phenomenon. Design A quantitative systematic review. Data sources Nine electronic databases were searched for studies published in English from the inception date of the databases to December 2010, using various combinations of search terms of 'adolescents', 'anxiety', 'child', 'pain', 'surgery' and 'correlation/relationship'. Review methods Using the Joanna Briggs Institute's comprehensive systematic review strategies, relevant studies were independently appraised and extracted by two reviewers using the standardized critical appraisal instruments and data extraction tool from Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument. Results Ten studies were included in this review from 943 studies initially retrieved. Children and adolescents who had higher level of perioperative anxiety experienced a higher level of postoperative pain. Inconclusive evidence was found regarding differences of perioperative anxiety and postoperative pain between demographic subgroups of gender, age and past surgical experience. ConclusionResults of this review inform healthcare providers of the role perioperative anxiety plays on children's and adolescents' postoperative pain and indicate the need to use interventions to reduce perioperative anxiety and, therefore, optimize their postoperative pain management during the perioperative period.

Neurotransmitters and their metabolites in central nervous system were known to play a significant role in sedation and hypnosis. A rapid and sensitive UFLC-MS/MS method for simultaneous determination of serotonin, 5-hydroxyindole acetic acid (5-HIAA), tryptophan (Try), dopamine (DA), norepinephrine (NE), γ-aminobutyric acid (GABA), glutamic acid (Glu) and acetylcholine (Ach) in rat brain without derivatization, ion-pairing reagent or pre-concentration was developed. Analytes and IS were separated on a Inertsil ODS-EP column (150 mm × 4.6 mm, 5 µm particles) and analyzed in a single chromatographic run in less than 9.0 min, using gradient elution with the mobile phase consisting of methanol and 0.01% acetic acid in water at a flow rate of 1.2 ml min−1. The detection of the analytes was performed on 4000Q UFLC-MS/MS system with turbo ion spray source in positive ion and multiple reaction monitoring mode. The developed method provided excellent linear calibration curves for the assay of analytes (R2 ≥ 0.9915). Limits of quantification were in the range of 1.0 ng ml−1 to 1.0 µg ml−1 for the analytes in rat brain. Intra- and inter-day precision and accuracy of analytes were well within acceptance criteria (15%). Mean extraction recoveries of analytes and IS from rat brain were all more than 80.0%. Furthermore, the validated method was successfully applied to comparing profiles of analytes in normal and insomnic rat brains. Results indicated that there were statistically significant differences for serotonin, 5-HIAA, DA, NE, Glu and Ach, but no significant difference for Try and GABA between two groups. Copyright © 2013 John Wiley & Sons, Ltd.

Purpose.The purpose of this study was to examine the influencing factors of postoperative pain among children undergoing elective surgery.Design and Methods. A survey was conducted in 2011 with a convenience sample of 66 children, 6 to 14 years old, in a tertiary hospital in Singapore.Results. Children experienced moderate preoperative anxiety and postoperative pain. Gender, preoperative anxiety, and negative emotional behaviors were significant influencing factors for postoperative pain. Boys reported less postoperative pain than girls.Practice Implications. Effective strategies for assessing and managing children's preoperative anxiety are needed to achieve an optimal postoperative pain management outcome.

Objectives To assess the occurrence, correlation, and clinical outcome of intraprocedural stent thrombosis (IPST) in patients undergoing primary percutaneous coronary intervention (PCI) in the setting of acute coronary syndromes (ACSs). Background Stent thrombosis (ST), a rare complication of PCI, is more common in the setting of ACS. It is not known whether IPST carries the same prognosis as postprocedural ST. Methods This retrospective study comprised a review of 1,901 consecutive ACS patients who received primary PCI in our center from January 2006 to January 2011. IPST was defined as new, reappearing or increased thrombus within the deployed stent before the index PCI procedure was completed. All angiograms were independently reviewed frame by frame for the incidence of IPST. Patients with and without IPST were compared with respect to clinical characteristics, angiographic parameters, and major adverse cardiac events (MACEs) at 30 days and 1-year follow-up. Results Overall, there were 23 cases of IPST detected, thus, the prevalence of IPST was 1.2%. There were no significant differences in baseline clinical characteristics between the 2 groups. Patients with compared to those without IPST had significantly more bifurcation lesions involved, and more thrombus burden at baseline. IPST group compared to no IPST group had more MACEs on 30 days (26.1% vs. 8.7%, P = 0.01) and 1-year follow-up (30.4% vs. 14.4%, P = 0.02). Conclusions IPST was a rare complication of PCI in the setting of ACS. It correlated with lesion morphology, presence of thrombus at baseline and was more likely to cause MACEs in 30 days and 1-year follow-up. (J Interven Cardiol 2013;26:215–220)

A high-performance liquid chromatography coupled with Q-time of flight mass spectrometry (HPLC/Q-TOF MS) method was developed and validated for the determination of 1, 3-diaminopropane, putrescine, cadaverine, spermidine and spermine in human plasma. The plasma samples were first pretreated by 10% HClO(4) and then derived by benzoyl chloride with 1, 6-diaminohexane as internal standard. The derived polyamines were separated on a C(18) column using a gradient program. The detection was performed on a Q-TOF MS by positive ionization mode. Calibration curve for each polyamine was obtained in the concentration range of 0.4 ~ 200.0 ng • ml(-1), with limit of detection of 0.02 ~ 0.1 ng • ml(-1). The intra- and inter-day RSD for all polyamines were 2.5-14.0% and 2.9 ~ 13.4%, respectively. The method was applied to determine the polyamines in human plasma from cancer patients and healthy volunteers. Results showed that the mean levels of polyamines in the plasma of cancer patients were higher than that of healthy volunteers, which suggested that the plasma polyamines could be employed as cancer diagnostic indicators in clinical testing.

Activation of CD40, a member of the tumor necrosis factor receptor (TNF-R) family, results in growth inhibition or apoptosis in some tumor cells, making CD40 a potential antitumor therapeutic target. Although it is known that CD40 is able to induce tumor necrosis factor-alpha (TNF-α) secretion and potentiate cisplatin's anticancer activity, whether TNF-α induction is involved in sensitizing cisplatin by CD40 has not been addressed. In this report, we provide evidence substantiating an important role of autocrine TNF-α in potentiation of cisplatin-induced apoptosis by recombinant soluble CD40 ligand (rsCD40L) in different human cancer cell lines. Activation of CD40 by rsCD40L induces two phases of autocrine TNF-α: the rapid early phase involving p38 MAP kinase and the robust and persistent late phase through enhanced tnf-α gene transcription. Blocking TNF-α with either a specific TNFR1 siRNA or a neutralizing anti-TNF-α antibody dramatically attenuated the potentiation effect of rsCD40L on cisplatin-induced cancer cell death. These results reveal an important role of TNF-α induction in CD40's chemosensitization activity and suggest that modulating TNF-α autocrine from cancer cells is an effective option for increasing the anticancer value of chemotherapeutics such as cisplatin.

This study was designed to investigate mechanisms of the protective effects of Salvia miltiorrhiza polysaccharide (SMPS) against lipopolysaccharide (LPS)-induced immunological liver injury (ILI) in Bacille Calmette-Guerin (BCG)-primed mice. Two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis showed that three proteins are down-regulated and six proteins are up-regulated by SMPS. SMPS reduces the degree of liver injury by up-regulating the enzymes of the citric acid cycle, namely malate dehydrogenase (MDH) and 2-oxoglutarate dehydrogenase complex. LPS significantly increases nuclear factor kappa B (NF-κB) activation, inducible nitric oxide synthase (iNOS) expression and MDA level in BCG primed mice liver, whereas SMPS treatment protects against the immunological liver injury through inhibition of the NF-κB activation by up-regulation of PRDX6 and the subsequent attenuation of lipid peroxidation, iNOS expression and inflammation.

A simple and sensitive HPLC method was developed and validated for the determination of linarin in rat plasma. Plasma samples were carried out by protein precipitation with acetonitrile and separated on a Shim-pack VP-ODS analytical column (250 × 4.6 mm, 5 µm). The calibration curve was linear in the measured range of 20.8–4160 ng/mL and the lower limit of quantification was 20.8 ng/mL for linarin. The validated method was successfully applied to the pharmacokinetic study of linarin in rat plasma after intramuscular administration of monomeric compound and traditional Chinese medicinal preparation – Yejuhua injection. Copyright © 2014 John Wiley & Sons, Ltd.