Seroprevalence of Aspergillus IgG and disease prevalence of chronic pulmonary aspergillosis in a country with intermediate burden of tuberculosis: a prospective observational study.

OBJECTIVES: Chronic pulmonary aspergillosis (CPA) is an emerging global disease with tuberculosis (TB) being the most important risk factor. Epidemiologic data on the seroprevalence of Aspergillus IgG and prevalence of CPA in different areas, especially in country with intermediate burden of TB, are lacking. METHODS: We prospectively recruited healthy volunteers, TB close contacts, active TB patients and participants with old pulmonary TB in Taiwan during 2012-2019. We measured serum Aspergillus fumigatus and niger-specific IgG levels and assessed if the participants were having CPA. RESULTS: A total of 1242 participants (including 200 healthy volunteers, 326 TB close contacts, 524 active TB patients and 192 old TB cases) were recruited. Using 27 mgA/L (milligrams of antigen-specific antibodies per liter) as cut-off level, the seropositive rate of A. fumigatus-specific IgG was 33.0% (66/200), 37.7% (123/326), 26.5% (139/524) and 43.2% (83/192) among the four groups, respectively. In multivariate logistic regression, pulmonary cavitation (OR 1.73; 95% CI 1.07-2.80), female sex (OR 1.49; 95% CI 1.14-1.95), old TB (OR 1.59; 1.05-2.42) were independent risk factors for Aspergillus IgG positivity. One (0.2%) active TB patient and four (2.1%) old TB patients developed CPA. Correlation between A. fumigatus and A. niger-specific IgG was high (Spearman correlation coefficient: 0.942). DISCUSSION: Geographic variation in Aspergillus IgG seroprevalence and CPA prevalence exists. A universal cut-off value for Aspergillus IgG may not exist. In areas and populations in which background Aspergillus IgG level is unknown, Aspergillus IgG may be better used as a test of exclusion for CPA using prespecified cut-off level.

MiR-335 promotes cell proliferation by inhibiting MEF2D and sensitizes cells to 5-Fu treatment in gallbladder carcinoma.

OBJECTIVE: Gallbladder carcinoma is a malignant tumor in the bile duct with poor prognosis. Although aberrant expression of miR-335 has been reported in the tumor tissues of gallbladder carcinoma, the biological role of miR-335 was still largely unknown. This study was intended to explore the role of miR-335 in the progression of gallbladder carcinoma. PATIENTS AND METHODS: The gallbladder carcinoma cell lines GBC-SD and SGC-996 were used in our study. MiR-335 mimic, miR-335 inhibitor, and si-myocyte enhancer factor 2D (MEF2D) were transfected into gallbladder carcinoma cells, respectively. (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay analysis was used to determine cell viability. The colony formation was also analyzed. Cell cycle progression was determined using flow cytometer. To verify the target gene of miR-335, the luciferase assay was used. RESULTS: MiR-335 overexpression inhibited cell viability and colony formation of GBC-SD and SGC-996 cells. The percentage of cells in first gap phase (G1)/resting phase (G0) was significantly increased, and the expression of cell division cycle 2 (cdc2) and cell division cycle 25 (cdc25) was decreased after miR-335 was overexpressed, indicating its role in inducing the cell cycle arrest of GBC-SD and SGC-996 cells. MEF2D was up-regulated in gallbladder cancer and associated with tumor size and clinical stage. Down-regulation of MEF2D inhibited cell viability and colony formation, induced cell cycle arrest in G1/G0 phase, and decreased the expression of cdc2 and cdc25 in GBC-SD and SGC-996 cells. Bioinformatics analysis by TargetScan and luciferase assay verified that MEF2D could be targeted by miR-335. Importantly, the effects of miR-335 inhibitor on cell growth were rescued by small interfering RNA of MEF2D (siMEF2D) in GBC-SD and SGC-996 cells. Besides, miR-335 overexpression increased cell sensitivity to 5-Fluoracil (Fu) treatment and decreased the expression levels of ATP-binding cassette transporter B1 (ABCB1) and ATP-binding cassette G2 (ABCG2) in GBC-SD and SGC-996 cells. CONCLUSIONS: MiR-335 participates in the progression of gallbladder carcinoma by targeting MEF2D. MiR-335 may be a potential therapeutic target for gallbladder carcinoma.

A composite of exhaled LTB4 , LXA4 , FeNO, and FEV1 as an "asthma classification ratio" characterizes childhood asthma.

BACKGROUND: Aberrant generation of eicosanoids is associated with asthma, but the evidence remains incomplete and its potential utility as biomarkers is unclear. Major eicosanoids in exhaled breath condensates (EBCs) were assessed as candidate markers for childhood asthma. METHODS: Ten exhaled eicosanoid species was evaluated using ELISA in the discovery phase, followed by prediction model-building and validation phases. RESULTS: Exhaled LTB4 , LTE4 , PGE2, and LXA4 showed significant difference between asthmatics (N = 60) and controls (N = 20). For validation, an expanded study population consisting of 626 subjects with asthma and 161 healthy controls was partitioned into a training subset to establish a prediction model and a test sample subset for validation. Receiver operating characteristic (ROC) analyses of the training subset revealed the level of exhaled LTB4 to be the most discriminative among all parameters, including FeNO, and a composite of exhaled LTB4 , LXA4 , together with FeNO and FEV1 , distinguishing asthma with high sensitivity and specificity. Further, the Youden index (J) indicated the cut point value of 0.598 for this composite of markers as having the strongest discriminatory ability (sensitivity = 85.2% and specificity = 83.6%). The predictive algorithm as "asthma classification ratio" was further validated in an independent test sample with sensitivity and specificity being 84.4% and 84.8%, respectively. CONCLUSIONS: In a pediatric study population in Taiwan, the levels of exhaled LTB4 , LTE4 , LXA4, and PGE2 in asthmatic children were significantly different from those of healthy controls, and the combination of exhaled LTB4 and LXA4 , together with FeNO and FEV1 , best characterized childhood asthma.

Longitudinal investigation of nasopharyngeal methicillin-resistant Staphylococcus aureus colonization in early infancy: The PATCH birth cohort study.

OBJECTIVES: The study aimed to determine the long-term Staphylococcus aureus colonization patterns and strain relatedness, and the association between maternal and infant colonization in infancy. METHODS: A birth cohort study was conducted from January 2012 to November 2014. Nasopharyngeal swabs for S. aureus detection were collected from infants at the age of 1, 2, 4, 6 and 12 months and from mothers when their children were 1-month-old. RESULTS: In total, 254 samples were collected at each planned visit during the first 12-month study. The prevalence of S. aureus colonization decreased in the first year of life, ranging from 61.0% (155/254) at the age of 1 month to 12.2% (31/254) at 12 months. Persistent colonization, defined as a positive culture on four or five occasions, was detected in only 13.8% (35/254) of carriers. Most of the persistent carriers were colonized with methicillin-resistant S. aureus (MRSA) only, and among persistent MRSA carriers, 61.1% (11/18) had indistinguishable genotypes. Of the mothers with MRSA colonization, 77.1% (27/35) had infants who were concomitantly colonized at the age of 1 month; 70.4% (19/27) of the infant-mother paired isolates belonged to indistinguishable or related subtypes, which suggests that surrounding carriers, probably their mothers, may be the possible source for MRSA acquisition in early infancy. CONCLUSIONS: Staphylococcus aureus colonization including MRSA was commonly observed in our cohort. Strains of persistent MRSA among infant-mother pairs were usually of indistinguishable genotypes. Therefore, horizontal spread within households is possibly an important factor related to infant MRSA colonization.

Phthalates suppress type I interferon in human plasmacytoid dendritic cells via epigenetic regulation.

BACKGROUND: Exposure to environmental endocrine-disrupting chemicals (EDCs) is associated with allergy, chronic inflammation, and immunodeficiency. Phthalates, the common EDCs used in plastic industry, may act as adjuvants to disrupt immune system and enhance allergy. Plasmacytoid DCs (pDCs) are predominant cells secreting type I interferon (IFN) against infection and are professional antigen-presenting cells in regulating adaptive immunity. However, the effects of phthalates on the function of pDCs are unknown. METHODS: Circulating pDCs were isolated from healthy subjects, were pretreated with diethylhexyl phthalate (DEHP) and butyl benzyl phthalate (BBP), and were stimulated with Toll-like receptor (TLR)-9 agonist CpG. IFN-α/IFN-ß levels, surface markers, and T-cell stimulatory function were investigated using ELISA, flow cytometry, and pDC/T-cell coculture assay. Mechanisms were investigated using receptor antagonists, pathway inhibitors, Western blotting, and chromatin immunoprecipitation. RESULTS: Diethylhexyl phthalate and butyl benzyl phthalate suppressed CpG-induced IFN-α/IFN-ß expression in pDCs, and the effect was reversed by aryl hydrocarbon receptor (AHR) antagonist. Diethylhexyl phthalate suppressed CpG-activated mitogen-activated protein kinase (MAPK)-MEK1/2-ERK-ELK1 and NFκB signaling pathways. Diethylhexyl phthalate suppressed CpG-induced interferon regulatory factor (IRF)-7 expression by suppressing histone H3K4 trimethylation at IRF7 gene promoter region through inhibiting translocation of H3K4-specific trimethyltransferase WDR5 from cytoplasm into nucleus. Butyl benzyl phthalate or diethylhexyl phthalate-treated pDCs suppressed IFN-γ but enhanced IL-13 production by CD4+ T cells. CONCLUSION: Phthalates may interfere with immunity against infection and promote the deviation of Th2 response to increase allergy by acting on human pDCs via suppressing IFN-α/IFN-ß expression and modulating the ability to stimulate T-cell responses.

Long-term efficacy and safety of exemestane in the treatment of breast cancer.

Exemestane, a steroidal aromatase inhibitor, is licensed for postmenopausal patients with estrogen receptor (ER)-positive breast cancer as second-line therapy in metastatic disease following antiestrogen failure and as part of sequential adjuvant therapy following initial tamoxifen. This study is a systematic literature review, evaluating exemestane in different clinical settings. The Ovid Medline (1948-2012), Embase (1980-2012), and Web of Science (1899-2012) databases were searched. Forty-two relevant articles covering randomized controlled trials were reviewed for efficacy and safety, and three for adherence. With regard to efficacy in metastatic disease, exemestane is superior to megestrol acetate after progression on tamoxifen. There is evidence for noninferiority to fulvestrant (following a prior aromatase inhibitor) and to nonsteroidal aromatase inhibitors in the first-line setting. Combined use with everolimus is shown to be more efficacious than exemestane alone following previous aromatase inhibitor use. In the adjuvant setting, a switch to exemestane after 2-3 years of tamoxifen is superior to 5 years of tamoxifen. Exemestane is noninferior to 5 years of tamoxifen as upfront therapy, and may have a role as an extended adjuvant therapy. Used as neoadjuvant therapy, increased breast conservation is achievable. As chemoprevention, exemestane significantly reduces the incidence of breast cancer in "at-risk" postmenopausal women. Exemestane is associated with myalgias and arthralgias, as well as reduced bone mineral density and increased risk of fracture, which do not appear to persist at follow-up, with subsequent return to pretreatment values. Compared with tamoxifen, there is a reduced incidence of endometrial changes, thromboembolic events, and hot flashes. Limited evidence shows nonadherence in 23%-32% of patients. Evidence is growing in support of exemestane in all clinical settings. It is generally more efficacious and has a better safety profile than tamoxifen. How it compares with the nonsteroidal aromatase inhibitors remains to be established. Further studies are required on adherence to ensure that maximum benefit is obtained.

Reference values of exhaled nitric oxide in healthy Asian children aged 5 to 18 years.

This study was undertaken to establish reference values of exhaled nitric oxide fraction (F(eNO)) and its determinants in healthy Asian children. 693 healthy Asian children aged 5-18 yrs were assessed using a single-breath online F(eNO) measurement (exhaled flow 50 mL·s(-1)), questionnaires, anthropometric measurements, spirometry and total and specific immunoglobulin (Ig) E. Geometric mean F(eNO) and the upper 95% CI were 13.7 ppb and 49.7 ppb, respectively, for healthy children, and 11.2 ppb and 30.2 ppb, respectively, for those without allergic sensitisation. F(eNO) was positively associated with age, allergic sensitisation, total IgE, ambient nitric oxide, measurement in the afternoon, and drinking water within 1 h before testing, and was negatively associated with weight. In healthy children without allergic sensitisation, age was the single best explanatory variable. The F(eNO) predicted values were 1-2 ppb higher in Asian than in Caucasian children in earlier studies, while the upper 95% CI were 9-10 ppb higher. In conclusion, the upper limits of normal F(eNO) in Asian children depend on age, from 21 ppb in young children to 39 ppb in adolescents. Ethnicity, age, allergic sensitisation, total IgE, ambient nitric oxide, time of testing, drinking water and weight are important determinants.

Randomised clinical trial: rabeprazole plus aspirin is not inferior to rabeprazole plus clopidogrel for the healing of aspirin-related peptic ulcer.

BACKGROUND: Clopidogrel does not inhibit prostaglandin synthesis. As a result, clopidogrel's incidence of peptic ulcer disease (PUD) and ulcer bleeding is lower than aspirin's. AIM: To compare the healing rate in aspirin-related dyspeptic ulcer patients who were given proton pump inhibitor (PPI) plus aspirin or PPI plus clopidogrel. METHODS: Patients with aspirin-related nonbleeding symptomatic ulcers were randomised to receive rabeprazole (20 mg/day) plus aspirin (100 mg/day) or rabeprazole (20 mg/day) plus clopidogrel (75 mg/day) for 12 weeks. The primary endpoint was the successful treatment of PUD as characterised by intention-to-treat at the end of therapy. RESULTS: Two hundred and eighteen patients (109 in the aspirin group and 109 in the clopidogrel group) were enrolled. There were no statistical demographic differences between the group that received aspirin and the group that received clopidogrel. The PUD treatment success rate was also statistically equal between the clopidogrel and aspirin groups (86.2% vs. 90.0%, P = 0.531). Neither group experienced ulcer-related bleeding. Multivariate logistic regression analysis showed that large ulcer size (>10 mm) (OR: 6.29, 95% CI: 2.58-15.37) and past history of PUD (OR: 3.69, 95% CI: 1.24-10.97) were important predictors of unsuccessful therapy for aspirin-related PUD. CONCLUSIONS: Rabeprazole plus aspirin is not inferior to rabeprazole plus clopidogrel in treating aspirin-related symptomatic PUD. Large ulcer size (>10 mm) and past history of PUD are important predictors of unsuccessful therapy (NCT 01037491).

Exhaled nitric oxide discriminates children with and without allergic sensitization in a population-based study.

BACKGROUND: Fraction of exhaled nitric oxide (FeNO) as a biomarker of airway inflammation in children warrants better clarification. OBJECTIVE: To identify the determinants of FeNO in children and assess the validity of FeNO as a discriminative tool for asthma, rhinitis or allergic sensitization in a population setting. METHODS: Children aged 5-18 years (N=1717) were evaluated using online FeNO measurements, questionnaires, anthropometric measurements, pulmonary function tests and total and specific serum IgE. RESULTS: FeNO levels were age-dependent, with an average increase of 7.4% per year of age. It decreased with increasing body mass index (BMI), estimated at 1.5% decrease per kg/m(2) . Children with allergic sensitization had elevated FeNO independent of allergic symptoms. In the combined analyses of asthma, rhinitis and allergic sensitization, elevated FeNO levels were confined mainly to children having allergic sensitization. After adjusting for allergic sensitization, a significant association between rhinitis and FeNO remained, but no such association was seen with asthma. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) of FeNO at the optimum cut-off of 28 p.p.b. for diagnosing asthma were 64.3%, 69.9%, 8.8%, and 97.7%, respectively (area under the ROC curve [AUC] 0.67), and were slightly better for diagnosing allergic asthma: 70.0%, 70.4%, 9.0%, 98.3%, respectively (AUC 0.71). FeNO had modest accuracy in discriminating rhinitis with an AUC value of 0.70, and performed better in discriminating allergic rhinitis (AUC 0.78). FeNO was a robust discriminator of allergic sensitization independent of symptoms at a cut-off of 15.4 p.p.b. (AUC 0.80; sensitivity 72.2%; specificity 71.2%; PPV 76.9%; NPV 65.8%). CONCLUSION AND CLINICAL RELEVANCE: FeNO measurement discriminates children with and without allergic sensitization independent of allergic symptoms. On the other hand, low FeNO levels in children may help exclude allergic asthma but high levels may be caused by allergic sensitization, older age, rhinitis, and lower BMI, in addition to asthma.

Malignant pleural effusion cells show aberrant glucose metabolism gene expression.

Malignant pleural effusion (MPE) accompanying lung adenocarcinoma indicates poor prognosis and early metastasis. This study aimed to identify genes related to MPE formation. Three tissue sample cohorts, seven from healthy lungs, 18 from stage I-III lung adenocarcinoma with adjacent healthy lung tissue and 13 from lung adenocarcinomas with MPE, were analysed by oligonucleotide microarray. The identified genes were verified by quantitative real-time PCR (qRT-PCR), immunohistochemical staining, and immunofluorescence confocal microscopy. 20 up- or down-regulated genes with a two-fold change in MPE cancer cells compared to healthy tissues were differentially expressed from early- to late-stage lung cancer. Of 13 genes related to cellular metabolism, aldolase A (ALDOA), sorbitol dehydrogenase (SORD), transketolase (TKT), and tuberous sclerosis 1 (TSC1) were related to glucose metabolism. qRT-PCR validated their mRNA expressions in pleural metastatic samples. Immunohistochemical staining confirmed aberrant TKT, ALDOA, and TSC1 expressions in tumour cells. Immunofluorescence confirmed TKT co-localisation and co-distribution of ALDOA with thyroid transcription factor 1-positive cancer cells. TKT regulated the proliferation, vascular endothelial growth factor secretion in vitro and in vivo vascular permeability of cancer cell. Glucose metabolic reprogramming by ALDOA, SORD, TKT and TSC1 is important in MPE pathogenesis.

The antiapoptotic protein, FLIP, is regulated by heterogeneous nuclear ribonucleoprotein K and correlates with poor overall survival of nasopharyngeal carcinoma patients.

Heterogeneous nuclear ribonucleoprotein K (hnRNP K) mediates antiapoptotic activity in part by inducing downstream antiapoptotic genes. To systematically identify hnRNP K targets in nasopharyngeal carcinoma (NPC), affymetrix chips were used to identify genes that were both overexpressed in primary NPC and downregulated by hnRNP K knockdown in NPC-TW02 cells. The resulting gene set included the antiapoptotic gene, FLIP, which was selected for further study. In cells treated with hnRNP K siRNA, TRAIL-induced apoptosis was enhanced and the FLIP protein level was reduced. Promoter, DNA pull-down and chromatin-immunoprecipitation assays revealed that hnRNP K directly interacts with the poly(C) element on the FLIP promoter, resulting in transcriptional activation. Through iTRAQ-mass spectrometric identification of proteins differentially associated with the poly(C) element or its mutant, nucleolin was determined to be a cofactor of hnRNP K for FLIP activation. Furthermore, FLIP was highly expressed in tumor cells, and this high-level expression was significantly correlated with high-level hnRNP K expression (P=0.002) and poor overall survival (P=0.015) as examined in 67 NPC tissues. A multivariate analysis confirmed that FLIP was an independent prognostic factor for NPC. Taken together, these findings indicate that FLIP expression is transcriptionally regulated by hnRNP K and nucleolin, and may be a potential prognostic and therapeutic marker for NPC.

Negative regulation of UCP2 by TGFß signaling characterizes low and intermediate-grade primary breast cancer.

The histological manifestation of growth-regulating and differentiation-inducing signals in cancer cells is considered as a key component for clinical outcome prediction and commonly defined as tumor differentiation grade. However, the molecular and functional framework underlying this clinical parameter remains poorly understood. Our correlative data display a significant association (P>0.001) between mitochondrial uncoupling protein 2 (UCP2) and tumor grade in primary breast cancer (n=234). Through mechanistic analyses, we show a synergistic link between UCP2 and established cellular pathways in conferring grade-associated functional phenotypes. Here, the application of well to moderately differentiated primary tumor cell lines has enabled direct observation of SMAD recruitment to the UCP2 promoter underlying repression of gene transcription. In contrast, poorly differentiated tumor cells, known to be TGFß resistant, displayed aberrant UCP2 regulation, and consequently, gene overexpression, which reduced mitochondrial calcium and facilitated the maintenance of mitochondrial membrane potential, thereby significantly decreasing oxidative stress and inhibiting cell death. Conversely, UCP2 silencing in such cells rapidly led to the induction of apoptosis and cell differentiation, concurrent with reduced cell survival and proliferation, confirming gene-specific effects. Demonstration of a biologically driven role for UCP2 dysregulation in promoting multiple characteristics of tumor aggressiveness strongly endorses assessment of gene expression at clinical presentation to augment therapeutic decision-making and improve patient outcome through personalized targeting approaches.

Molecular and immunocytochemical identification of coxsackievirus A-24 variant from the acute haemorrhagic conjunctivitis outbreak in Taiwan in 2007.

AIMS: Acute haemorrhagic conjunctivitis (AHC) is a highly contagious conjunctivitis associated with enteroviruses. Coxsackie A-24 variant (CA-24v) and enterovirus-70 (EV-70) are the two major causative agents. During October 2007, an epidemic of AHC occurred in Taiwan, affecting more than 11 000 people. The aim of this study was to determine the aetiological agent associated with the outbreak in patients diagnosed with AHC and treated at the Cathay General Hospital, Taipei (CGHT) and Cathay General Hospital Sijhih (CGHS), Taiwan during October 2007. METHODS: Virus isolates were obtained from six patients (four from CGHS and two from CGH), and a total of seven specimens (one throat and one rectal, and five eye swabs) were collected. The specimens were inoculated onto the MRC-5 cell lines. The viral isolation was confirmed by performing real-time reverse transcription-polymerase chain reaction (RT-PCR) and indirect immunofluorescence assay (IFA). RESULTS: The conjunctival, throat, and rectal swabs collected in this study were all tested positive for a variant of CA-24. All seven viral isolates were characterized as a variant of CA-24 and confirmed by IFA and real-time RT-PCR. CONCLUSIONS: The findings suggest that the outbreak of AHC that occurred during October 2007 in the northern area of Taiwan was caused by a variant of coxsackie A-24. Further phylogenic analysis is underway to further classify this CA-24v strain.

Drug-use pattern of Chinese herbal medicines in insomnia: a 4-year survey in Taiwan.

BACKGROUND AND OBJECTIVE: Insomnia is a common complaint in the general population. Interest in the use of alternative treatments for insomnia is increasing exponentially and is fairly common in Taiwan. We undertook a survey to define the drug utilization patterns of Chinese herbal medicines (CM) for insomnia in Taiwan. METHODS: The survey was conducted over a period of 4 years, from January 2003 to December 2006. Outpatients with primary insomnia and being treated with CM were studied. Core drug-use indicators were the number of CM items per prescription, the dosing frequency and duration of CM prescriptions, the most common prescribed CM herbs and CM formulae used. RESULTS: Six thousand eight hundred and sixty patients, using 37,046 CM herb items, were screened during the study period. The average CM items per prescription was 5.40. Most of prescriptions (95.23%) were prescribed for administration three times a day. The most often prescribed Chinese herbal products were Hong-Hwa (Carthamus tinctorius) and Jia-Wey-Shiau-Yau-San, which includes Angelica sinensis, Atractylodes macrocephala, Paeonia lactiflora, Bupleurum chinense, and Poria coco. CONCLUSION: This is the first extensive survey examining the drug utilization patterns of Chinese herbal medicines in the treatment of insomnia. Although the data were generated in Taiwan, the herbs and practices identified are likely to be widely generalizable wherever Chinese herbal remedies are used for insomnia. Multiple herbs and complex formulae were commonly used. The baseline data generated should be of use in informing subsequent studies, including those aimed at a thorough evaluation of the herbs' effectiveness.

Thymidine phosphorylase mRNA stability and protein levels are increased through ERK-mediated cytoplasmic accumulation of hnRNP K in nasopharyngeal carcinoma cells.

The cytoplasmic level of heterogeneous nuclear ribonucleoprotein K (hnRNP K) is significantly correlated with the elevated expression of thymidine phosphorylase (TP), and high levels of both proteins are predictive of a poor prognosis in nasopharyngeal carcinoma (NPC). We herein show that TP is highly induced by serum deprivation in NPC cells, and that this is due to an increase in the half-life of the TP mRNA, as shown by nuclear run-on and actinomycin D assays. We further show that the CU-rich element of the TP mRNA directly interacts with hnRNP K, as demonstrated by immunoprecipitation RT-PCR assays, and the nucleus-to-cytoplasm translocation of hnRNP K. Blockade of hnRNP K expression reduces TP expression, suggesting that hnRNP K acts in the upregulation of TP. Mechanistically, both MEK inhibitor and the hnRNP K ERK-phosphoacceptor-site mutant decrease cytoplasmic accumulation of hnRNP K, suggesting that ERK-dependent phosphorylation is critical for TP induction. Furthermore, we found that hnRNP K-mediated TP induction allows NPC cells to resist hypoxia-induced apoptosis. Our results collectively establish the regulation and role of ERK-mediated cytoplasmic accumulation of hnRNP K as an upstream modulator of TP, suggesting that hnRNP K may be an attractive candidate as a future therapeutic target for cancer.

Effects of piroxicam-beta-cyclodextrin sachets on abnormal postural sway in patients with chronic low back pain.

BACKGROUND: The clinical effects of piroxicam-beta-cyclodextrin (PBC) in sachet form have been surveyed in patients with osteoarthritic or acute pain in western countries, but scarcely studied in those with chronic low back pain (LBP), and never investigated in the field of postural sway. The aim of this study was to evaluate the clinical effects of PBC in sachet form prescribed in patients with chronic backache in local Asian when compared with those of plain piroxicam. METHODS: After randomized allocation and experimental exclusion, a total of 42 eligible patients were randomized into two groups, the sachet group (n = 23) and the piroxicam tablet group (n = 19). Both groups were administered the same dosage, orally per day (daily dose = 20 mg). The duration of trial was 28 days. Efficacy was assessed with pain score, disability index and postural sway. RESULTS: The patients in sachet group showed greater improvement in pain score and disability index than those who took piroxicam tablets. There were significantly lower sway velocity and intensity at almost all different conditions than baseline profiles in both groups (P < 0.05). However, there was no significant difference of sway velocity and intensity in the piroxicam tablets group with regard to eyes open or eyes closed in 20 degrees dorsiflexion. CONCLUSIONS: Piroxicam-beta-cyclodextrin (PBC) sachet may have greater improvement in the treatment of chronic LBP and possess the extended effects on postural abnormality relevant to chronic LBP.

Hot Photoluminescence in γ-In2Se3Nanorods.

The energy relaxation of electrons in γ-In2Se3nanorods was investigated by the excitation-dependent photoluminescence (PL). From the high-energy tail of PL, we determine the electron temperature (Te) of the hot electrons. TheTevariation can be explained by a model in which the longitudinal optical (LO)-phonon emission is the dominant energy relaxation process. The high-quality γ-In2Se3nanorods may be a promising material for the photovoltaic devices.

Electroluminescence enhancement of SiGe/Si multiple quantum wells through nanowall structures.

The enhancement of light extraction from Si(0.5)Ge(0.5)/Si multiple quantum wells (MQWs) with nanowall structures fabricated by electron cyclotron resonance (ECR) plasma etching is presented. It is shown that the ECR plasma treatment does not damage the crystalline quality. At a driving current of 5.5 × 10(6) A m(-2), the light output intensity of the MQWs with nanowall structures shows an enhancement of about 50% compared with that of the original MQWs. In addition to the enhanced light extraction, the improved optoelectronic properties are also attributed to the strain relaxation in nanowall structures.

Mechanism of bright red emission in Si nanoclusters.

A bright photoluminescence around 1.7 eV is observed for post-annealed samples of 1 MeV Si(2+) implanted in an SiO(2) matrix. A super-linear power dependence of photoluminescence intensity accompanied by pulse shortening under continuous wave laser excitation is recorded without any spectral narrowing. An emission process comprised of an initial non-radiative recombination (time constant ∼280-315 ps) of excited carriers in the defect states in SiO(2) matrices to the conduction band minima of nc-Si, followed by a slower process of radiative recombination in the direct band transition for nc-Si along with a non-radiative Auger recombination (time constant ∼2.67 ns) is proposed.

Topical pimecrolimus for eczema.

BACKGROUND: Pimecrolimus was developed as an alternative to topical corticosteroids for treating eczema (atopic dermatitis) but its efficacy and safety compared with existing treatments remains unclear. OBJECTIVES: To assess the effects of topical pimecrolimus for treating eczema. SEARCH STRATEGY: We searched the Cochrane Skin Group Specialised Register (to October 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2006), MEDLINE (from 2003 to October 2006), and EMBASE (from 2005 to October 2006). We also contacted researchers and manufacturers in the field. SELECTION CRITERIA: Randomised controlled trials of 1.0% topical pimecrolimus used twice daily compared against other topical comparators for treating eczema. DATA COLLECTION AND ANALYSIS: Two authors independently examined each retrieved study for eligibility and extracted data for efficacy, tolerability and safety. A random-effects model was used to estimate the pooled risk ratios (RRs) and 95% confidence intervals (95% CIs). MAIN RESULTS: We included 31 trials (8019 participants) in the analysis. In short-term (/=6 months), pimecrolimus was significantly better than vehicle in preventing flares (9 trials, 3091 participants, RR 1.47, 95% CI 1.32 to 1.64 at six months) and in improving quality of life. Pimecrolimus was significantly less effective than two topical corticosteroids, i.e. 0.1% triamcinolone acetonide for investigators' global assessment (1 trial, 658 participants, RR 0.75, 95% CI 0.67 to 0.83) and 0.1% betamethasone valerate for participants' global assessment (1 trial, 87 participants, RR 0.61, 95% CI 0.45 to 0.81) at three weeks. Pimecrolimus was also associated with significantly more overall withdrawals and skin burning. None of the trials reported on key adverse effects such as thinning of skin. Pimecrolimus was significantly less effective than 0.1% tacrolimus for investigators' global assessment at six weeks (RR 0.58, 95% CI 0.46 to 0.74) and led to more withdrawals due to lack of efficacy (RR 2.37, 95% CI 1.10 to 5.08) based on two trials involving 639 participants, but there was no significant difference in proportions of participants experiencing any adverse events. AUTHORS' CONCLUSIONS: Topical pimecrolimus is less effective than moderate and potent corticosteroids and 0.1% tacrolimus. The therapeutic role of topical pimecrolimus is uncertain due to the absence of key comparisons with mild corticosteroids.