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Extraction of the leaves of Zanthoxylum ailanthoides Sieb. & Zucc. affords extracts and four isolated compounds which exhibit activities against leukemia cells. The chloroform-soluble fraction (ZAC) of the crude extract of this plant showed cytotoxic activity against human promyelocytic leukemia (HL-60) and myelomonocytic leukemia (WEHI-3) cells with IC(50) values of 73.06 and 42.22 μg/mL, respectively. The active ZAC was further separated to yield pheophorbide-a methyl ester (1), pheophorbide-b methyl ester (2), 13(2)-hydroxyl (13(2)-S) pheophorbide-a methyl ester (3) and 13(2)-hydroxyl (13(2)-R) pheophorbide-b methyl ester (4) whose structures were confirmed by spectroscopic methods. Compounds 2-4 showed cytotoxic activities against both leukemia cells with IC(50) value in the range of 46.76-79.43 nM, whereas compound 1 exhibited only weak cytotoxic activity. The extracts and compounds 1-4 also induced apoptosis and DNA damage in leukemia cells after treatment. The results suggested that the Z. ailanthoides is biologically active against leukemia cells. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the effectiveness of an adjusting lifestyle intervention with a smartphone application (app) in managing obstructive sleep apnea (OSA) among overweight and obese high-tech employees. A 6-months three-armed randomized controlled trial was employed. A total of 144 eligible participants were randomly allocated into the smartphone app 'MyFitnessPal' plus education (MFPE; n = 48), 'MyFitnessPal'-only (MFP-only; n = 50) and the control group (n = 46) at a 1:1:1 ratio. The data were collected using related questionnaires and portable sleep monitor. Generalized estimating equation was used to analyze data. Results revealed that there was a significant interaction between time and group in BMI (Wald χ2 = 4.47, p = 0.04) in the MFPE after the 12th week of the intervention. Nevertheless, there was no significant interaction between group and time observed in apnea-hypopnea index (AHI) score after 24 weeks of intervention. The adjustment lifestyle integrated with an app may offer a simple and cost-effective approach. The findings of this study may provide precious information for occupational healthcare providers, facilitating health promotion in the workplace for overweight employees with OSA., (© 2024 John Wiley & Sons Australia, Ltd.)

The gut microbiota prevents harmful microbes from entering the body, a function known as colonization resistance. The enteric pathogen Salmonella enterica serovar (S.) Typhimurium uses its virulence factors to break colonization resistance through unknown mechanisms. Using metabolite profiling and genetic analysis, we show that the initial rise in luminal pathogen abundance was powered by a combination of aerobic respiration and mixed acid fermentation of simple sugars, such as glucose, which resulted in their depletion from the metabolome. The initial rise in the abundance of the pathogen in the feces coincided with a reduction in the cecal concentrations of acetate and butyrate and an increase in epithelial oxygenation. Notably, these changes in the host environment preceded changes in the microbiota composition. We conclude that changes in the host environment can weaken colonization resistance even in the absence of overt compositional changes in the gut microbiota., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Thyroid radiofrequency ablation and microwave ablation are widely adopted minimally invasive treatments for diverse thyroid conditions worldwide. Fundamental skills such as the trans-isthmic approach and the moving shot technique are crucial for performing thyroid ablation, and advanced techniques, including hydrodissection and vascular ablation, improve safety and efficacy and reduce complications. Given the learning curve associated with ultrasound-guided therapeutic procedures, operators need training and experience. While training models exist, limited attention has been given to ultrasound maneuvers in ablation needle manipulation. This article introduces two essential maneuvers, the zigzag moving technique and the alienate maneuver, while also reviewing the latest ultrasound techniques in thyroid ablation, contributing valuable insights into this evolving field.

Background: Immune checkpoint inhibitors (ICI) are promising treatment options for various cancers. However, their use is associated with immune-related adverse events (irAEs), including ICI-induced diabetes mellitus (ICI-DM). This study aimed to investigate the clinical features of ICI-DM, with a particular focus on alterations to pancreatic volume., Methods: We conducted a retrospective review of 2829 patients who received ICI treatment at the Chang Gung Memorial Hospital, Linkou, between January 2014 and December 2021. New-onset diabetes or diabetic ketoacidosis (DKA) was identified in ten patients receiving ICI therapy. Pancreatic volumes were assessed by manual segmentation of computed tomography (CT) images before and after ICI-DM diagnosis., Results: Among these ten patients, nivolumab was the most commonly used ICI (50.0%), followed by pembrolizumab (30.0%) and atezolizumab (20.0%). One patient received combination therapy with nivolumab and ipilimumab. The median age was 63.01 years (range: 40.1 - 87.8). ICI-DM developed after a median of 13.5 cycles (range: 2 - 42) of ICI treatment or 9.85 months (range:1.5 - 21.3) since ICI initiation. The initial presentation was DKA in 60.0% of patients. All patients had low or undetectable C-peptide levels (range: <0.033 - 0.133 nmol/L) and were negative for most type 1 diabetes mellitus (T1DM)-related autoantibodies; only one patient tested positive for glutamic acid decarboxylase antibodies. CT imaging revealed significant pancreatic atrophy, with a median pancreatic volume decrease of 19.92% (P = 0.038) from baseline and sustained significant decline at last follow-up (median - 37.14%, P = 0.012)., Conclusions: ICI-DM is often accompanied by pancreatic atrophy and approximately two-thirds of patients initially present with DKA. Although the majority of ICI-DM patients lack T1DM-related autoantibodies, identifying diminished pancreatic volumes through CT imaging provides valuable clues into the subclinical aspects of ICI-DM development, aiding in the prevention of diabetic emergencies., Trial Registration: Not applicable., (© 2024. The Author(s).)

Post-acute sequelae of COVID-19 (PASC, "Long COVID") pose a significant global health challenge. The pathophysiology is unknown, and no effective treatments have been found to date. Several hypotheses have been formulated to explain the etiology of PASC, including viral persistence, chronic inflammation, hypercoagulability, and autonomic dysfunction. Here, we propose a mechanism that links all four hypotheses in a single pathway and provides actionable insights for therapeutic interventions. We find that PASC are associated with serotonin reduction. Viral infection and type I interferon-driven inflammation reduce serotonin through three mechanisms: diminished intestinal absorption of the serotonin precursor tryptophan; platelet hyperactivation and thrombocytopenia, which impacts serotonin storage; and enhanced MAO-mediated serotonin turnover. Peripheral serotonin reduction, in turn, impedes the activity of the vagus nerve and thereby impairs hippocampal responses and memory. These findings provide a possible explanation for neurocognitive symptoms associated with viral persistence in Long COVID, which may extend to other post-viral syndromes., Competing Interests: Declaration of interests E.J.W. is an advisor for Danger Bio, Janssen, New Limit, Marengo, Pluto Immunotherapeutics Related Sciences, Rubius Therapeutics, Santa Ana Bio, Synthekine, and Surface Oncology. E.J.W. is a founder of and holds stock in Surface Oncology, Danger Bio, and Arsenal Biosciences. N.J.M. reports consulting fees from Endpoint Health Inc and AstraZeneca and receives funding from Quantum Leap Healthcare Collaborative outside of the published work., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Many patients with papillary thyroid cancer (PTC) demonstrate satisfactory outcomes. However, 8%-28% of patients with PTC show tumor recurrence, which may affect prognosis. Therefore, identifying factors associated with tumor recurrence in patients with PTC may be helpful to refine therapeutic strategies., Methods: To identify factors associated with PTC recurrence, we retrospectively reviewed demographic features (sex and age), operation method, image character, serum thyroglobulin (Tg), accumulated radioactive iodine (I-131) therapeutic dose, I-131 uptake, and metastases at diagnosis in 829 patients with PTC. Patients were grouped into early (stage I and II; n = 698) and advanced (stage III and IV; n = 131) tumor-node-metastasis (TNM) stages. Recurrence rate, mortality rate, risk factors of recurrence, recurrent free survival and overall survival curve were compared between two groups., Results: Patients in the early stage demonstrated a lower recurrence rate (7.2%) than did those in the advanced stage (28.2%, p < 0.05). The mortality rate of patients with recurrence in the advanced stage was higher than that of those in the early stage (51.4% vs. 12.0%). The major impact factors on tumor recurrence in early TNM stage were distant metastasis and lymph node metastasis, while in advanced TNM stage were distant metastasis, male gender, total thyroidectomy with limited lymph node dissection, and a high serum Tg level., Conclusions: Strategies to monitor tumor recurrence might be refined according to the TNM stages of PTC patients., Competing Interests: Conflicts of interest The authors have no financial or ethical conflicts of interest to report., (Copyright © 2021 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Changes in the microbiota composition are associated with many human diseases, but factors that govern strain abundance remain poorly defined. We show that a commensal Escherichia coli strain and a pathogenic Salmonella enterica serovar Typhimurium isolate both utilize nitrate for intestinal growth, but each accesses this resource in a distinct biogeographical niche. Commensal E. coli utilizes epithelial-derived nitrate, whereas nitrate in the niche occupied by S. Typhimurium is derived from phagocytic infiltrates. Surprisingly, avirulent S. Typhimurium was shown to be unable to utilize epithelial-derived nitrate because its chemotaxis receptors McpB and McpC exclude the pathogen from the niche occupied by E. coli. In contrast, E. coli invades the niche constructed by S. Typhimurium virulence factors and confers colonization resistance by competing for nitrate. Thus, nutrient niches are not defined solely by critical resources, but they can be further subdivided biogeographically within the host into distinct microhabitats, thereby generating new niche opportunities for distinct bacterial species., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Radiofrequency ablation (RFA) for benign thyroid nodules is one kind of scarless treatment for symptomatic or cosmetic benign thyroid nodules. However, how to train RFA-naive physicians to become qualified operators for thyroid RFA is an important issue. Our study aimed to introduce a successful training model of thyroid RFA., Materials and Methods: We used a food-assisted and -simulated training model of thyroid RFA. Chicken hearts were simulated into thyroid nodules, three-layer pork meats were simulated into peri-thyroid structure, and gel bottles were simulated into trachea, respectively. Successful training ablations were defined as chicken hearts that were fully cooked. After repeating training ablations of chicken hearts at least 100 times with the nearly 100% success rates for three young trainees, they served as the first assistant for the real procedures of thyroid RFA and then were qualified to perform thyroid RFA on real patients under the supervision of one experienced interventional radiologist., Results: 23 real patients who received RFA and follow-up at least 6 months after treatment were included in Linkou Chang Gung Memorial Hospital from January 1, 2020 to October 1, 2021. Three young endocrinologists performed thyroid RFA independently. The outcomes were volume reduction rate (VRR), major complications and minor complications. The median VRR at 12 months was 82.00%, two major complications were transient hoarseness, and three minor complications were wound pain. All complications were completely recovered within three days., Conclusions: For young and RFA-native physicians without any basic skills of echo-guided intervention, this food-assisted and -simulated training model of thyroid RFA was useful for medical training and education., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Chou, Chan, Cheng, Sun, Liu, Chen and Liou.)

Background: this study was designed to compare the long-term survival outcomes of patients prepared for radioiodine (RAI) therapy using either thyroid hormone withdrawal (THW) or recombinant human thyrotropin (rhTSH) stimulation, by specifically focusing on cases with distant metastases from papillary thyroid cancer (PTC)., Methods: A retrospective analysis was performed on 88 patients with distant metastases from PTC. Fifty-one and thirty-seven patients were prepared for RAI treatment by either THW or rhTSH stimulation, respectively. The primary endpoints were progression-free survival (PFS) and disease-specific survival (DSS)., Results: The 10-year DSS rates of patients prepared for RAI therapy using either THW or rhTSH stimulation were 62.2% and 73.3%, respectively. Using multivariate analysis, RAI-avid metastases ( p = 0.025) and preparation with rhTSH ( p = 0.041) were identified as independent prognostic factors for PFS. Notably, PFS in the group of patients with RAI-avid metastases and preparation with rhTSH was significantly better than that in the other groups ( p = 0.025)., Conclusions: Preparation for RAI therapy using rhTSH stimulation is not inferior to THW preparation in terms of long-term survival outcomes experienced by patients with PTC and distant metastasis. Patients with RAI-avid metastases and preparation with rhTSH had the most favorable PFS.

Differentiated thyroid cancer (DTC) from follicular epithelial cells is the most common form of thyroid cancer. Beyond the common papillary thyroid carcinoma (PTC), there are a number of rare but difficult-to-diagnose pathological classifications, such as follicular thyroid carcinoma (FTC). We employed deep convolutional neural networks (CNNs) to facilitate the clinical diagnosis of differentiated thyroid cancers. An image dataset with thyroid ultrasound images of 421 DTCs and 391 benign patients was collected. Three CNNs (InceptionV3, ResNet101, and VGG19) were retrained and tested after undergoing transfer learning to classify malignant and benign thyroid tumors. The enrolled cases were classified as PTC, FTC, follicular variant of PTC (FVPTC), Hürthle cell carcinoma (HCC), or benign. The accuracy of the CNNs was as follows: InceptionV3 (76.5%), ResNet101 (77.6%), and VGG19 (76.1%). The sensitivity was as follows: InceptionV3 (83.7%), ResNet101 (72.5%), and VGG19 (66.2%). The specificity was as follows: InceptionV3 (83.7%), ResNet101 (81.4%), and VGG19 (76.9%). The area under the curve was as follows: Incep-tionV3 (0.82), ResNet101 (0.83), and VGG19 (0.83). A comparison between performance of physicians and CNNs was assessed and showed significantly better outcomes in the latter. Our results demonstrate that retrained deep CNNs can enhance diagnostic accuracy in most DTCs, including follicular cancers.

A central goal of microbiome research is to understand the factors that balance gut-associated microbial communities, thereby creating longitudinal and cross-sectional heterogeneity in their composition and density. Whereas the diet dictates taxa dominance, microbial communities are linked intimately to host physiology through digestive and absorptive functions that generate longitudinal heterogeneity in nutrient availability. Additionally, the host differentially controls the access to electron acceptors along the longitudinal axis of the intestine to drive the development of microbial communities that are dominated by facultatively anaerobic bacteria in the small intestine or obligately anaerobic bacteria in the large intestine. By secreting mucus and antimicrobials, the host further constructs microhabitats that generate cross-sectional heterogeneity in the colonic microbiota composition. Here we will review how understanding the host factors involved in generating longitudinal and cross-sectional microbiota heterogeneity helps define physiological states that are characteristic of or appropriate to a homeostatic microbiome., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A highly specific and sensitive proton nuclear magnetic resonance ( 1 H-NMR) method has been developed for the quantification of ephedrine alkaloid derivatives in Ephedra herbal commercial prescriptions. At the region of δ 4.0 to 5.0 ppm in the 1 H NMR spectrum, the characteristic signals are separated well from each other, and six analogues in total, methylephedrine (ME), ephedrine (EP), norephedrine (NE), norpseudoephedrine (NP), pseudoephedrine (PE), and methylpseudoephedrine (MP) could be identified. The quantities of these compounds are calculated by the relative ratio of the integral values of the target peak for each compound to the known concentrations of the internal standard anthracene. The present method allows for a rapid and simple quantification of ephedrine alkaloid derivatives in Ephedra -related commercial prescriptions without any preliminary purification steps and standard compounds, and accordingly it can be a powerful tool to verify different Ephedra species. In comparison to conventional chromatographic methods, the advantages of this method include the fact that no standard compounds are required, the quantification can be directly performed on the crude extracts, a better selectivity for various ephedrine alkaloid derivatives, and the fact that a very significant time-gain may be achieved.

The colonic microbiota exhibits cross-sectional heterogeneity, but the mechanisms that govern its spatial organization remain incompletely understood. Here we used Citrobacter rodentium, a pathogen that colonizes the colonic surface, to identify microbial traits that license growth and survival in this spatial niche. Previous work showed that during colonic crypt hyperplasia, type III secretion system (T3SS)-mediated intimate epithelial attachment provides C. rodentium with oxygen for aerobic respiration. However, we find that prior to the development of colonic crypt hyperplasia, T3SS-mediated intimate attachment is not required for aerobic respiration but for hydrogen peroxide (H 2 O 2 ) respiration using cytochrome c peroxidase (Ccp). The epithelial NADPH oxidase NOX1 is the primary source of luminal H 2 O 2 early after C. rodentium infection and is required for Ccp-dependent growth. Our results suggest that NOX1-derived H 2 O 2 is a resource that governs bacterial growth and survival in close proximity to the mucosal surface during gut homeostasis., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Daphne genkwa , a Chinese medicinal herb, is used frequently in Southeast Asian countries to treat diseases; the flavonoid hydroxygenkwanin (HGK) is extracted from its flower buds. The bioactivity of HGK, particularly as an anti-liver cancer agent, has not been explored. In this study, human hepatocellular carcinoma (HCC) cell lines and an animal xenograft model were employed to investigate both the activity of HGK against liver cancer and its cellular signaling mechanisms. HCC cells treated with HGK were subjected to cell function assays. Whole transcriptome sequencing was used to identify genes whose expression was influenced by HGK, and the flavonoid's cancer suppression mechanisms were further investigated through gain- and loss-of-function assays. Finally, in vitro findings were tested in a mouse xenograft model. The data showed that HGK induced the expression of the microRNA miR-320a, which in turn inhibited the expression of the transcription factor 'forkhead box protein M1' (FOXM1) and downstream FOXM1-regulated proteins related to epithelial-mesenchymal transition, thereby leading to the suppression of liver cancer cell growth and invasion. Significant inhibition of tumor growth was also observed in HGK-treated mice. Hence, the present study demonstrated the activity of HGK against liver cancer and validated its potential use as a therapeutic agent.

Background: In Asian countries, many patients with type 2 diabetes fail to achieve controlled glycated hemoglobin (HbA1c) levels while taking several classes of oral hypoglycemic agents (OHAs). Traditional Chinese medicine could be an alternative therapeutic option for poorly controlled type 2 diabetes. YH1 is a concentrated Chinese herbal extract formula that combines Rhizoma Coptidis and Shen-Ling-Bai-Zhu-San. This randomized, double-blind, placebo-controlled pilot study evaluated YH1 as an add-on medication for poorly controlled type 2 diabetes., Methods: Forty-six patients with poorly controlled type 2 diabetes were randomly assigned 1:1 to the YH1 or placebo group. Before the trial, all subjects had received three or more classes of OHAs with HbA1c > 7.0% (53 mmol/mol) and a body mass index ≥ 23 kg/m2. During the 12-week trial, participants continued to take OHAs without any dose or medication changes. The primary endpoint was the percentage change in HbA1c level. Per-protocol analysis was applied to the final evaluation., Results: At week 12, there was an 11.1% reduction in HbA1c from baseline and a 68.9% increase in homeostatic model assessment (HOMA) of β cell function in the YH1 group, which also exhibited significant reductions in two-hour postprandial glucose (-26.2%), triglycerides (-29.5%), total cholesterol (-21.6%), low-density lipoprotein cholesterol (-17.4%), body weight (-0.5%), and waist circumference (-1.1%). The changes in fasting plasma glucose, HOMA insulin resistance and symptom scores were not significantly different between the YH1 and placebo groups. No serious adverse events occurred during this clinical trial., Conclusions: This pilot study indicates that YH1 together with OHAs can improve hypoglycemic action and β-cell function in overweight/obese patients with poorly controlled type 2 diabetes. YH1 is a safe add-on medication for OHAs and has beneficial effects on weight control and lipid metabolism. A larger study population with longer treatment and follow-up periods is required for further verification., Competing Interests: The authors have declared that no competing interests exist.

The Machilus genus (Lauraceae) had been extensively utilized in folk medicine due to its broad range of bioactivities. In the present study, a series of chromatographic separations of the methanol extract of stems of M. philippinensis led to the identification of thirty eight compounds totally. Among these, biscinnamophilin (1), machilupins A-C (2-4), machilutone A (5), and machilusoxide A (6) were new compounds reported for the first time. In addition, 5 was characterized with a unprecedented carbon skeleton. Other known compounds, including the major compounds cinnamophilin (7) and meso -dihydroguaiaretic acid (8), are identified by comparison of their physical and spectroscopic data with reported values. One of the reported compounds, cinnamophilin A (10), should be revised as dehydroguaiaretic acid (9) after careful comparison of all the 1 H and 13 C NMR data. Moreover, the neuroprotective activity of cinnamophilin (7) was examined in a primary cortical neuron culture and the results indicated that 7 was effective against glutamate induced excitotoxicity., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Lack of reproducibility is a prominent problem in biomedical research. An important source of variation in animal experiments is the microbiome, but little is known about specific changes in the microbiota composition that cause phenotypic differences. Here, we show that genetically similar laboratory mice obtained from four different commercial vendors exhibited marked phenotypic variation in their susceptibility to Salmonella infection. Faecal microbiota transplant into germ-free mice replicated donor susceptibility, revealing that variability was due to changes in the gut microbiota composition. Co-housing of mice only partially transferred protection against Salmonella infection, suggesting that minority species within the gut microbiota might confer this trait. Consistent with this idea, we identified endogenous Enterobacteriaceae, a low-abundance taxon, as a keystone species responsible for variation in the susceptibility to Salmonella infection. Protection conferred by endogenous Enterobacteriaceae could be modelled by inoculating mice with probiotic Escherichia coli, which conferred resistance by using its aerobic metabolism to compete with Salmonella for resources. We conclude that a mechanistic understanding of phenotypic variation can accelerate development of strategies for enhancing the reproducibility of animal experiments.

Background: Thyroid cancer is the most common endocrine tumor and generally has relatively good clinical outcomes. However, 15-20% of patients ultimately develop recurrence or disease-related death. The appropriate prognostic factors for thyroid cancer are still elusive. This study evaluated whether the number of circulating tumor cells/circulating epithelial cells (CECs) expressing either epithelial cell adhesion molecule (EpCAM), podoplanin (PDPN), or thyrotropin receptor (TSHR) is related to remission and disease-specific mortality (DSM) of patients with thyroid cancer., Methods: Blood samples were collected from patients (n = 128) after thyroidectomy or radioactive iodide therapy. CECs were enriched by lysis of red blood cells and depletion of leukocytes. Subtyping and quantification of the enriched cells were performed with immunofluorescence staining using antibodies against EpCAM, TSHR, and PDPN, respectively. Whether the number of a specific subtype of CECs is related to remission and DSM of patients was determined by univariate and multivariate analyses., Results: The EpCAM + -CECs, TSHR + -CECs, and PDPN + -CECs counts for patients in the non-remission group (n = 43) were significantly higher when compared to the remission group (n = 85; p < 0.001). Receiver operating characteristic analysis showed that the number of EpCAM + -CECs, TSHR + -CECs, and PDPN + -CECs was able to distinguish the status of remission from non-remission. The cutoff point for EpCAM + -CECs, TSHR + -CECs, and PDPN + -CECs was 40, 47, and 14 (cells/mL), with the accuracy of the assay equivalent to 80.4%, 76.6%, and 77.3%, respectively. On the other hand, the number of EpCAM + -CECs (p < 0.001), PDPN + -CECs (p = 0.013), and TSHR + -CECs (p < 0.001) for patients in the DSM group (n = 17) was significantly higher when compared to the patients who survived (n = 111). Receiver operating characteristic analysis showed that EpCAM + -CECs, TSHR + -CECs, and PDPN + -CECs counts were able to distinguish mortality from survival status. The cutoff point for EpCAM + -CECs, TSHR + -CECs, and PDPN + -CECs was 27, 25, and 9 (cells/mL), with the accuracy of the assay equivalent to 69.5%, 67.2%, and 68.5%, respectively., Conclusions: CEC testing is a useful tool for analysis of overall survival and remission status of patients with thyroid cancer. Implementation of CEC testing into routine clinical test may be worthy to consider for patient clinical care.

Burkholderia pseudomallei and B. mallei are the causative agents of melioidosis and glanders, respectively, and are often fatal to humans and animals. Owing to the high fatality rate, potential for spread by aerosolization, and the lack of efficacious therapeutics, B. pseudomallei and B. mallei are considered biothreat agents of concern. In this study, we investigate the proteome of Burkholderia thailandensis , a closely related surrogate for the two more virulent Burkholderia species, during infection of host cells, and compare to that of B. thailandensis in culture. Studying the proteome of Burkholderia spp. during infection is expected to reveal molecular mechanisms of intracellular survival and host immune evasion; but proteomic profiling of Burkholderia during host infection is challenging. Proteomic analyses of host-associated bacteria are typically hindered by the overwhelming host protein content recovered from infected cultures. To address this problem, we have applied bio-orthogonal noncanonical amino acid tagging (BONCAT) to B. thailandensis , enabling the enrichment of newly expressed bacterial proteins from virtually any growth condition, including host cell infection. In this study, we show that B. thailandensis proteins were selectively labeled and efficiently enriched from infected host cells using BONCAT. We also demonstrate that this method can be used to label bacteria in situ by fluorescent tagging. Finally, we present a global proteomic profile of B. thailandensis as it infects host cells and a list of proteins that are differentially regulated in infection conditions as compared to bacterial monoculture. Among the identified proteins are quorum sensing regulated genes as well as homologs to previously identified virulence factors. This method provides a powerful tool to study the molecular processes during Burkholderia infection, a much-needed addition to the Burkholderia molecular toolbox.

Background: Serum thyroglobulin (Tg) is not a reliable tumor marker for monitoring disease status after treatment in patients with papillary thyroid carcinoma (PTC) with positive anti-thyroglobulin antibody (TgAb). The aim of this study was to evaluate the clinical role of circulating epithelial cells (CECs) in PTC patients with positive serum TgAb and undetectable serum Tg., Methods: A pilot study was performed to evaluate CECs in 25 PTC patients with positive serum TgAb and undetectable serum Tg. CECs were isolated and enriched from peripheral blood with a negative selection system PowerMag. Immunofluorescence staining with anti-epithelial cell adhesion molecule (anti-EpCAM) and anti-thyroid stimulating hormone receptor (anti-TSHR) antibodies were used to define EpCAM + -CECs and TSHR + -CECs. After CECs testing, 25 patients were classified into two groups: recurrence group (n=7) and remission group (n=18) based on biopsy or imaging studies. The diagnostic accuracy and cutoff points of EpCAM + -CECs and TSHR + -CECs were evaluated using receiver operating characteristic (ROC) curves. The optimal cut-off values of CECs were determined by the Youden index (sensitivity+specificity-1)., Results: The median numbers of EpCAM + -CECs (72.5 vs. 10.75) and TSHR + -CECs (54 vs. 5.25) were significantly increased in recurrence group compared to remission group. The area under the curve (AUC) showed good performance of EpCAM + -CECs (0.937) and TSHR + -CECs (0.825) to discriminate between recurrence and remission. The cut-off value for EpCAM + -CECs and TSHR + -CECs were set at 48cells/ml and 10cells/ml, respectively and showed a sensitivity (EpCAM + -CECs: 85.7%; TSHR + -CECs: 85.7%) and a specificity (EpCAM + -CECs: 100%; TSHR + -CECs: 77.8%) in predicting the recurrence., Conclusions: Our study suggests CECs testing could be a potential biomarker to identify recurrence in PTC patients with positive serum TgAb and undetectable serum Tg., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The cardiovascular safety and efficacy of linagliptin, a dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes mellitus (T2DM) after acute coronary syndrome (ACS) or acute ischemic stroke (AIS) are unclear. The aim of our real-world cohort study was to evaluate the cardiovascular outcomes of linagliptin in patients with T2DM after ACS or AIS., Methods: An open observational noncrossover retrospective cohort study was conducted between June 1, 2012 and December 31, 2013 utilizing Taiwan National Health Insurance Research Database. A total of 1203 patients with T2DM after ACS or AIS were selected as the study cohort. Cardiovascular safety and efficacy of linagliptin were evaluated by comparing outcomes of 401 subjects receiving linagliptin after ACS or AIS to 802 matched control subjects not receiving any incretin-based therapy after ACS or AIS. The primary composite outcome included cardiovascular death, non-fatal myocardial infarction and non-fatal ischemic stroke., Results: The primary composite outcome after 15-month follow-up was 7% (28 patients) in the linagliptin group compared with 6.1% (49 patients) in the control group [hazard ratio (HR) 1.06; 95% confidence interval (CI) .66-1.68]. The linagliptin group also had similar risks of all-cause mortality, hospitalization for heart failure, percutaneous coronary intervention and coronary artery bypass grafting compared to the control group in terms of the secondary outcomes., Conclusions: In T2DM patients after ACS or AIS, treatment with linagliptin was not associated with increased risks of cardiovascular death, non-fatal myocardial infarction, or non-fatal ischemic stroke.

Background: Evidences support the benefits of moderate- to high-intensity statins for patients with acute myocardial infarction (AMI) except for those with type 2 diabetes mellitus (T2DM) on dialysis after AMI. This study was aimed to investigate the safety and efficacy of secondary prevention of cardiovascular diseases using moderate- to high-intensity statins in T2DM patients on dialysis after AMI., Methods: A simulated prospective cohort study was conducted between January 1st, 2001 and December 31st, 2013 utilizing data from the Taiwan National Health Insurance Research Database. A total of 882 patients with T2DM on dialysis after AMI were selected as the study cohort. Cardiovascular efficacy and safety of moderate- to high-intensity statins were evaluated by comparing outcomes of 441 subjects receiving statins after AMI to 441 matched subjects not receiving statins after AMI. The primary composite outcome included cardiovascular death, non-fatal myocardial infarction and non-fatal ischemic stroke., Results: The Kaplan-Meier event rate for the primary composite outcomes at 8 years was 30.2% (133 patients) in the statin group compared with 25.2% (111 patients) in the non-statin group (hazard ratio [HR], .98; 95% confidence interval [CI] .76-1.27). Significantly lower risks of non-fatal ischemic stroke (HR, .58; 95% CI .35-.98) and all-cause mortality (HR, .70; 95% CI .59-.84) were found in the statin group., Conclusions: In T2DM patients on dialysis after AMI, the use of moderate- to high-intensity statins has neutral effects on composite cardiovascular events but may reduce risks of non-fatal ischemic stroke and all-cause mortality.

There were insufficient data regarding radiation exposure to the household environment from patients with thyroid cancer who received radioactive iodine (RAI) therapy in Asia; we therefore performed the present study at the Chang Gung Memorial Hospital in Keelung, Taiwan.Patients with papillary or follicular thyroid cancer who received 3.7 GBq (100 mCi) RAI were enrolled in this prospective hospital-based study. The enrolled patients were asked to place a thermoluminescent dosimeter in the living room, bedroom, and bathroom of their houses for 4 weeks to measure radiation exposure to the household environment.A total of 43 patients (18 men and 25 women; mean age 51 ± 13 years) who received 3.7 GBq (100 mCi) RAI completed the study. The mean value of total radiation exposure over 4 weeks from the patients to the bedroom, bathroom, and living room (eliminating the background radiation factor) was 0.446 ± 0.304 (0.088-1.382) mSv. We divided the patients into 2 groups: those with more than and less than the mean value of total radiation exposure to the bedroom, bathroom, and living room. Factors associated with the higher amount of radiation exposure from the patients to the household environment were patient body weight (P = .025, univariate analysis; P = .037, multivariate analysis, odds ratio [95% confidence interval] 1.067 [1.004-1.134]) and distant metastases based on I post-therapy scanning (P = .041, univariate analysis; P = .058, multivariate analysis, odds ratio [95% confidence interval] 6.453 [0.938-44.369]); age, sex, body mass index, renal function, serum stimulated thyroglobulin level, and recombinant human thyroid-stimulating hormone use were not associated with the amount of radiation exposure from the patients to the household environment.Higher body weight and distant metastases may be the best predictors for higher radiation exposure to the household environment from patients with thyroid cancer after RAI therapy.

Loco-regional recurrence or distant metastasis usually leads to the death of patients with papillary thyroid carcinoma (PTC). Whether or not circulating epithelial cells (CECs) count is a valuable marker in monitoring the therapeutic outcome of PTC was investigated. Patients with PTC (n=129) were treated in our medical center and were categorized into 4 groups with excellent (n=45), biochemical incomplete (n=15), indeterminate (n=37), and structural incomplete (n=32) responses. CECs were enriched from the peripheral blood by the PowerMag negative selection system. Three subtypes of CECs expressing epithelial cell adhesion molecule (EpCAM), thyroid-stimulating hormone receptor (TSHR, a marker for thyroid cells), and podoplanin (PDPN, a marker related to poor prognosis in patients with PTC) were defined by immunofluorescence staining, respectively. The median number of CECs (cells/mL of blood) expressing EpCAM, TSHR, and PDPN was 23 (interquartile range 10-61), 19 (interquartile range 8-50), and 8 (interquartile range 3-22), respectively, for patients enrolled in this study. The number of EpCAM + -CECs, TSHR + -CECs, and PDPN + -CECs was statistically different among patients in different treatment response groups without interference from anti-thyroglobulin antibody (P<0.0001). Patients with structural incomplete response had higher counts for all three CECs subtypes when compared to other patients. EpCAM + -CECs was better in distinguishing patients with excellent response from structural incomplete response among the three subtypes of CECs. The sensitivity and specificity of the assay was 84.4% and 95.6%, respectively, when the cut off value was 39 EpCAM + -CECs/mL. CECs testing can supplement the current standard methods for monitoring the therapeutic outcome of PTC., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.

Despite the well-known toxicity of uranium (U) to bacteria, little is known about how cells sense and respond to U. The recent finding of a U-specific stress response in Caulobacter crescentus has provided a foundation for studying the mechanisms of U- perception in bacteria. To gain insight into this process, we used a forward genetic screen to identify the regulatory components governing expression of the urcA promoter (P urcA ) that is strongly induced by U. This approach unearthed a previously uncharacterized two-component system, named UzcRS, which is responsible for U-dependent activation of P urcA . UzcRS is also highly responsive to zinc and copper, revealing a broader specificity than previously thought. Using ChIP-seq, we found that UzcR binds extensively throughout the genome in a metal-dependent manner and recognizes a noncanonical DNA-binding site. Coupling the genome-wide occupancy data with RNA-seq analysis revealed that UzcR is a global regulator of transcription, predominately activating genes encoding proteins that are localized to the cell envelope; these include metallopeptidases, multidrug-resistant efflux (MDR) pumps, TonB-dependent receptors and many proteins of unknown function. Collectively, our data suggest that UzcRS couples the perception of U, Zn and Cu with a novel extracytoplasmic stress response., (© 2016 John Wiley & Sons Ltd.)

Papillary thyroid carcinoma (PTC) accounts for about 80% of the cases in thyroid cancer. Routine surveillance by serum thyroglobulin (Tg) and medical imaging is the current practice to monitor disease progression of the patients. Whether enumeration of circulating epithelial cells (CECs) helps to define disease status of PTC patients was investigated. CECs were enriched from the peripheral blood of the healthy control subjects (G1, n = 17) and the patients at disease-free status (G2, n = 26) or with distant metastasis (G3, n = 22). The number of CECs expressing epithelial cell adhesion molecule (EpCAM) or thyroid-stimulating hormone receptor (TSHR) was determined by immunofluorescence microscopy analyses. The medium number of EpCAM+-CECs was 6 (interquartile range 1-11), 12 (interquartile range 7-16) and 91 (interquartile range 31-206) cells/ml of blood for G1, G2 and G3, respectively. EpCAM+-CEC counts were significantly higher in G3 than in G1 (p < 0.05) and G2 (p < 0.05). The medium number of TSHR+-CECs was 9 (interquartile range 3-13), 16 (interquartile range 10-24) and 100 (interquartile range 31-226) cells/ml of blood for G1, G2 and G3, respectively. The TSHR+-CEC counts also distinguished G3 from G1 (p < 0.05) and G2 (p < 0.05). With an appropriate cut off value of CEC count, the disease status for 97.9% (47/48) of the cases was clearly defined. Notably, the metastatic disease for all patients in G3 (22/22) was revealed by combined analysis of serum Tg and CEC. This study implicates that CEC testing can supplement the current standard methods for monitoring disease status of PTC.

Background. The aims of this study were to analyze the clinical characteristics of SPM in patients with well-differentiated thyroid cancer and to determine the long-term prognosis in patients with double malignancies. Materials and Methods. We retrospectively analyzed 2,864 patients with well-differentiated thyroid cancer and a mean age of 44.0 ± 14.4 years. Of these, 200 (7.0%) were diagnosed with SPM, 115 of which were diagnosed with metachronous SPM. Results. Of 2,864 patients, 163 (5.7%) patients died of thyroid cancer and 301 (10.5%) died of any cause by the end of the follow-up period. Multivariate analysis identified age, SPM, external radiotherapy, TNM stage, and postoperative serum Tg level to be factors independently associated with decreased survival. Of 200 patients with SPM, 74 (37.0%) died. In comparison to the anachronous and synchronous groups, the metachronous SPM group had a higher mean age; more advanced tumor, node, and metastasis stage; lower remission rate; higher postoperative radioactive iodide ((131)I) accumulated dose; a higher proportion of patients who underwent external radiotherapy; and higher thyroid cancer and total mortality rates. Conclusions. Patients with well-differentiated thyroid carcinoma and metachronous SPM had worse prognoses compared to patients without SPM.

In this retrospective study, we sought to investigate the prevalence and the clinical significance of thyroid uptake discovered by FDG PET/CT within the thyroid gland during imaging investigation of non-thyroid disorders. This study included 5,877 subjects with no previous history of thyroid malignancy referred to our PET/CT center (1,596 for cancer screening and 4,281 for primary staging or restaging purposes) from June 2006 to April 2009. All of the patients had at least 12 months of follow-up or were censored on the date of the last follow-up. The disease status was analyzed for correlation with the maximum standardized uptake value (SUVmax). Receiver operating characteristics (ROC) curves were constructed to determine the optimal cutoff values for SUVmax. In the screening group (n=1,596), 55 patients (4%) had thyroid FDG uptake. Twenty-two subjects were referred for cytological or histological assessment and 4 (18%) were diagnosed with thyroid carcinoma. In the primary staging/restaging group (n=4,281), 165 patients (4%) had thyroid FDG-avid sites. Thirty-three patients were referred for cytological or histological assessment and 4 (12%) were found to have thyroid carcinoma. Of the 8 malignant lesions, 7 were papillary thyroid carcinoma, and 1 medullary thyroid carcinoma. Surgical resection was performed in seven out of eight patients. Three patients had lymph node metastasis (one case detected by preoperative PET/CT) and three bilateral malignant diseases (all false negative in PET/CT scans). Of the 47 benign lesions, 35 were nodular goiter or nodular hyperplasia, 6 multinodular goiter, and 6 autoimmune thyroid disease. The average value of SUVmax of malignant thyroid lesions was significantly higher than that of benign thyroid lesions (8.2±4.5 vs. 5.6±3.2, P=0.048). However, we were unable to identify an optimal SUVmax cutoff because the total area under the curve was small. The prevalence of thyroid uptake on FDG PET/CT in this study is 3.7%, which is consistent with previous observations. Of patients who received verification by cytology or histology, 14% (8/55) were found to have thyroid malignancies. However, we were unable to establish an optimal SUVmax cutoff value to differentiate benign from malignant lesions. FDG PET/CT scans were false negative in a significant proportion of patients with thyroid carcinoma and regional lymph node metastases or separate tumor nodule(s) in a contralateral lobe. Further diagnostic tests (thyroid ultrasound/fine needle aspiration) are recommended in presence of focal thyroid uptake detected by FDG PET/CT scans.

Objective: To assess the efficacy, safety, and tolerability of a combination of 10 mg ezetimibe and 20 mg simvastatin in Taiwanese patients with hypercholesterolemia., Research Design and Methods: A prospective, open-label, multi-center, hospital-based cohort study was conducted to evaluate the efficacy, safety, and tolerability of a single tablet combination of ezetimibe/simvastatin for the treatment of hypercholesterolemia. Taiwanese adults without low-density lipoprotein cholesterol (LDL-C) goal achievement, based on the National Cholesterol Education Program Adult Treatment Panel III guidelines, were treated with ezetimibe/simvastatin once daily for 6 weeks. The primary endpoint was the percentage of patients achieving LDL-C treatment goals after 6 weeks of treatment. Secondary endpoints included percentage change from baseline of LDL-C, total cholesterol, high-density lipoprotein cholesterol, and triglyceride. Safety and tolerability were assessed via clinical and laboratory examinations. The clinicaltrial.gov identifier of this study was NCT00654628., Results: In total, 173 patients with a mean age of 57.9 ± 10.4 years were included. Of these, 57.8% were female and the average body mass index was 25.5 ± 3.4 kg/m(2). After 6 weeks of treatment, the great majority of the patients had reached their treatment goals (90.4% for LDL-C; 87% for TC; and 59% for TG). LDL-C levels were significantly reduced from 156.8 ± 30.8 mg/dL at baseline to 75.9 ± 25.4 mg/dL (51.4%, P < 0.0001) after only 6 weeks of therapy. Forty-nine adverse events (AEs), including one non-drug related serious AE, were reported. For non-serious AEs, the most common reported AEs during the entire study period were myalgia and upper respiratory infection (both n = 7). Nine patients dropped out of the study, reportedly due to AEs., Conclusions: A single tablet combination of 10 mg ezetimibe and 20 mg simvastatin in Taiwanese patients with hypercholesterolemia provided high LDL-C goal attainment rates and resulted in significant reductions in LDL-C.

Aims: Angiogenesis from thyroid cancer cell plays the important roles in post-surgical persistent, recurrent, and metastatic papillary thyroid cancer (PTC). This study is to investigate the expression of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), Tek/Tie-2 receptor, and vascular endothelial growth factors (VEGF) in normal, benign thyroid tissues and different stage of PTC. We expect angiogenetic factors are important in the presentation of local-regional neck or distant metastases in PTC., Materials and Results: A total of 101 tissues from the subjects underwent thyroidectomy were enrolled in the study. There were 22 control and 79 thyroid cancer patients in different TNM stagings were collected. Ang-1 illustrated highest mean immunostaining score in metastatic group. Comparing with normal and benign thyroid tissues, thyroid cancer tissues illustrated significantly high expression of three angiogenetic factors and Tie-2 receptor. Of the PTC, significantly high expression of three angiogenetic factors and Tie-2 receptor were illustrated in recurrent cases. VEGF showed statistical difference in disease-free cancer mortality, and recurrent groups., Conclusions: Immunochemical staining illustrated VEGF, Ang-1, Ang-2 expression in PTC tissues related to clinical staging; however, we need more information concerning these factors with long-term follow-up results., (Copyright © 2010 Wiley-Liss, Inc.)

We performed a retrospective analysis of follicular neoplasm data obtained from frozen section examinations of thyroid nodules. A total of 5,660 patients underwent preoperative neck ultrasonography and fine-needle aspiration cytology (FNAC), surgical treatment, and follow-up at a medical institute. Patients with papillary thyroid microcarcinoma were excluded from this study. In 971 cases, frozen section examination was performed during the surgical treatment of follicular neoplasm that was diagnosed via FNAC. Thyroid malignancies were histologically confirmed in 25.1% of cases (244/971). Among the patients with papillary thyroid carcinoma, 45 were diagnosed with the follicular variant of papillary thyroid carcinomas (27.4%). The diagnostic sensitivity of frozen section for the nonfollicular variant of papillary thyroid carcinoma was better than that for the follicular variant of papillary thyroid carcinoma (89.1% versus 78.9%; P = 0.1023). For 12 cases the diagnosis was atypical follicular adenomas. The diagnostic accuracy of frozen section in cases of follicular neoplasm was 76.9% with a sensitivity of 84.8% and a specificity of 98.9%. In conclusion, our analysis revealed high rates of accuracy when using frozen tissue sections for early diagnosis and treatment of follicular neoplasm; thus, an early decision to extent of surgery prevents a risky follow-up surgery., (© 2009 Wiley-Liss, Inc.)

Using dendrimers in cancer therapy as nonviral vectors for gene delivery seems promising. The biological performance of a dendrimer-based gene delivery system depends heavily on its molecular architecture. The transfection activity of dendrimers is significantly improved by processes activated in the heat degradation treatment of solvolysis. However, very little is known about the molecular mechanisms that dendrimers produce in cancer cells. We studied the changes in global gene-expression profiles in human cervical cancer HeLa cells exposed to nonactivated and activated poly(amidoamine) (PAMAM) dendrimers, alone or in complexes with plasmid DNA (dendriplexes). Real-time quantitative reverse transcriptase-polymerase chain reaction was used to confirm four regulated genes (PHF5A, ARNTL2, CHD4, and P2RX7) affected by activated dendrimers and dendriplexes. Activated and nonactivated dendrimers and dendriplexes alike induced multiple gene expression changes, some of which overlapped with their dendriplexes. Dendrimer activation improved transfection efficiency and induced additional gene expression changes in HeLa cells. Dendrimers and dendriplexes principally affect genes with the molecular functions of nucleic acid binding and transcription activity, metal-ion binding, enzyme activity, receptor activity, and protein binding. Our findings provide a deeper insight into the changes in gene expression patterns caused by the molecular structure of PAMAM dendrimers for gene-based cancer therapy.

The aim of this study was to evaluate the efficacy, safety, and tolerability of weekly alendronate administration on male osteoporosis in Taiwan. This 6-month, randomized, open-label controlled trial enrolled 46 men with osteoporosis who were randomized to either 70 mg alendronate once weekly (n = 23) or control (n = 23). Bone mineral density (BMD) of lumbar spine and hip and biochemical bone turnover markers were measured; adverse events and tolerability were assessed. Subjects treated with alendronate showed a significant increase in BMD of 5.5% (vs. 2% in control group) at the lumbar spine and 2.7% (vs. 0.7%) at the femoral neck (P < 0.05) at 6 months, respectively. There were also significant decreases in serum level of bone formation marker (bone-specific alkaline phosphatase) and urinary excretion of bone resorption marker (deoxypyridinoline) at 3 and 6 months. Thus, alendronate showed anti-osteoporotic effects by increasing BMD and decreasing the concentrations of bone markers. The adverse events were mild and showed no significant difference between the two groups on safety assessments.

Purpose: To correlate sonographic (US) characteristics and results of fine-needle aspiration biopsy (FNAB) of thyroid nodules in autoimmune thyroiditis (AT) with surgical pathological findings., Method: Forty AT patients with 40 nodular lesions were analyzed retrospectively. Five sonographic characteristics were recorded for each nodule: diameter, echogenicity, microcalcification, halo sign, and margin. Preoperative sonograms and FNAB results were compared with postoperative histopathological findings., Result: Twenty-four of the 40 nodules were malignant, including 20 papillary carcinomas, 3 follicular carcinomas, and 1 medullary carcinoma. Of the 16 benign nodules, 8 were nodular hyperplasia, 6 lymphocytic thyroiditis, and 1 each follicular adenoma and Hürthle cell adenoma. The only US parameter that was significant in malignant vs. benign nodules was the presence of poorly defined margins. Based on preoperative cytology, 22 of the 23 malignant nodules were correctly diagnosed, and 10 of the 14 benign nodules were correctly identified. The positive predictive value was 78.6%, and the negative predictive value was 93.7%., Conclusion: No single US parameter can predict thyroid malignancy in patients with AT. A combination of US and FNAB provides the most sensitive and specific approach available preoperatively., ((c) 2009 Wiley Periodicals, Inc. J Clin Ultrasound, 2009.)

Introduction: Most of the glyphosate-surfactant herbicides (GlySH) are formulated commercial products containing isopropylamine (IPA) salt of glyphosate (IPAG), variable amount of a surfactant, and water. Although glyphosate is only slightly toxic to rats, ingestion of GlySH may lead to severe effects, including death, in humans. We conducted a study to evaluate the cardiovascular effects of the components of GlySH., Methods: We used five groups of male piglets, each receiving infusion of normal saline (control), glyphosate in NaOH base, IPA, IPAG, and polyoxyethyleneamine (POEA), respectively. We chose concentrations that are similar to those in the commonly used GlySH (41% of IPAG and 15% surfactant)., Results: We found that IPAG reduced the mean arterial blood pressure (MABP) and left-ventricular stroke work index (LVSWI) during the infusion, but both recovered gradually. It also decreased the cardiac index but increased the pulmonary capillary wedge pressure, central venous pressure (CVP), and mean pulmonary arterial pressure (MPAP). POEA infusion reduced the cardiac index and LVSWI, but not the MABP. It also increased the pulmonary capillary wedge pressure, CVP, MPAP, and pulmonary vascular resistance index. IPA increased the MABP, which was higher than those in the control, IPAG, and POEA groups. Glyphosate in NaOH base infusion did not affect the hemodynamics but slightly reduced the blood pH and base excess (BE) values. POEA and IPAG also resulted in metabolic acidosis, with lactate formation and decreased BE values., Conclusion: We conclude that both POEA and IPAG infusion affected hemodynamics and resulted in death in piglets, whereas glyphosate (NaOH base) had no similar effects.

A phytochemical investigation of the leaves of Erythrophleum fordii Oliv. has led to the isolation of three new cassaine-type diterpenoids, erythrofordin A (1), erythrofordin B (2) and erythrofordin C (3), as well as a norcassaine diterpenoid with a novel skeleton, norerythrofordin A (4), and 27 known compounds (5-31). The structures of 1-4 were elucidated on the basis of spectroscopic analysis. Selected compounds from this plant were examined for anti-inflammatory activity. Taraxerol (16) displayed potent NO-reducing activity in microglial cells, and gallic acid (27) exhibited excellent DPPH radical-scavenging effects.

Five new furanoditerpenoids, epi-8-hydroxycolumbin (1), fibaruretin B (2), C (3), E (5), and F (6), were isolated from the stems of Fibraurea tinctoria, as well as fibaruretin D (4) from the natural source for the first time, and 39 known compounds. The structures (1-6) were elucidated on the basis of spectroscopic analysis. All the isolated furanoditerpenoids (1-16) were examined for their in vitro activity and some were in vivo anti-inflammatory activity. Compounds 8 and 9 showed significant anti-inflammatory action administered at a dose of 100mg/kg of reducing carrageenan mice paw edema, whereas compound 7, 9, 10, 14, and 16 were more potent to inhibit NO production. The inhibitory effects of these compounds are dose-dependent (1-4 microg/ml).

Goethite (alpha-FeOOH), one of soil contents, can be dissolved in acidic water to produce ferrous ions initiating Fenton reaction with hydrogen peroxide to degrade explosive. In this study, a series of catalytic degradation of nitro aromatic explosives, namely picric acid (PA) and ammonium picrate (AP) have been investigated using the FeOOH/H2O2 process. The controlling factors, such as adsorption of goethite dosage, hydrogen peroxide concentration and UV-light exposure on the oxidation of nitro aromatic explosives were investigated. The results showed that target compounds were adsorbed on the surface of goethite while the oxidation was proceeding. Furthermore, inhibition effect of nitro aromatic intermediates on the reaction was also discussed. A half-life kinetic model has been proposed to predict the half-lives of explosive oxidation in the goethite/H2O2 system.

This study determined cancer survival rates and follow-up status at different pTNM stages to stratify risk groups in follicular thyroid carcinoma. Two hundred and fourteen follicular thyroid cancer patients (167 females, 47 males) who underwent surgery and followed-up treatment at a single medical center were enrolled in this retrospective study. Tumors were staged by UICC-TNM criteria (6th edition). Low risk for follicular thyroid cancer was defined as pT1N0M0. (Moderate-risk group) was defined as all other patients in pTNM stage I, and high risk as patients in stages II-IV. After mean follow-up of 9.6+/-0.3 years, 1.6% (2/120), 21.9% (7/32), 5.6% (1/18) and 52.3% (23/44) of patients in pTNM stages I-IV, respectively, died of thyroid cancer. Of 214 follicular thyroid cancer patients, 35 (16.4%), 85 (39.7%) and 94 (43.9%) were defined as low-, moderate- and high-risk groups at the time of surgery. None of the low-risk patients died, and all achieved disease-free status. In the moderate- and high-risk groups, 2.4% (2/85) and 27.7% (26/94) died of thyroid cancer. The moderate- and high-risk groups underwent near-total thyroidectomy and (131)I therapies, and 15 of 107 (14.9%) died of thyroid cancer while 18 (16.8%) had persistent disease at the end of the study period. Multiple regression analysis demonstrated that tumor size, radioactive iodide therapy and post-operative thyroglobulin level significantly differ between the mortality and survival groups. In conclusion, the low-risk follicular thyroid cancer group as defined by pTNM staging had excellent prognosis. Total thyroidectomy and post-operative radioactive iodide therapy are mandatory in moderate- and high-risk groups. Over one-fourth of the follicular thyroid cancer patients in the high-risk group died of thyroid cancer despite aggressive treatment.

Background: To determine the incidence of cystic change of thyroid cancer detected by ultrasonography and to compare the diagnostic accuracy of fine-needle aspiration cytology (FNAC) postultrasonography in solid and cystic thyroid nodules., Methods: This retrospective study collected data for 6219 patients with thyroid nodules. Mean patient age was 49.7 +/- 13.6 years. Of these 6219 patients, 1983 had cystic changes of thyroid nodules and 4236 had solid masses as detected by ultrasonography. Following FNAC, 506 of the patients with solid masses (11.9%) underwent surgical treatment, compared with 143 of those with cystic change of thyroid masses (7.2%)., Results: Of the 649 nodules treated surgically in the solid and cystic change groups, 29.8% (151/506) and 9.1% (13/143) were malignant, respectively. Overall, after surgical treatment, 0.65% of cystic changes to thyroid lesions were diagnosed as thyroid cancer. Diagnostic accuracy of FNAC in cystic changes of the thyroid masses after ultrasonographic examination resembled that in solid thyroid nodules., Conclusions: Cystic changes of thyroid masses are common. Positive predictive value in diagnosing papillary carcinoma of thyroid masses with cystic changes is high. Notably, preoperative accurate diagnosis is difficult.

Background: Few data exist that have compared sulfonylurea formulations in differing ethnic populations. Most studies of sulfonylureas have been performed in white patients with type 2 diabetes mellitus., Objective: The aim of this study was to compare the efficacy and tolerability of a sustained-release glipizide (GSR) formulation with those of immediate-release glipizide (GIR) in Chinese patients with type 2 diabetes mellitus., Methods: This randomized, double-blind, double-dummy, placebo-controlled, parallel-group, clinical study enrolled adult patients with type 2 diabetes mellitus who were already being treated with diet and a sulfonylurea. Patients were randomized to receive either GSR 10 mg PO QD or GIR 5 mg PO BID for 12 weeks. Because these 2 formulations differed in appearance, each patient also received placebo resembling the alternate formulation, to be received at the alternate frequency. Drugs dispensed but not used were returned to the investigators and counted to monitor compliance with the protocol. For efficacy assessment, fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA(1c)) were measured before and after treatment. Tolerability was measured by adverse events (AEs), which were evaluated by the attending physician during each clinical visit., Results: Of the 57 patients (37 men, 20 women) enrolled in the study, 41 completed it. All were Han Chinese of Taiwanese origin, and had the following characteristics: age range, 33 to 69 years; mean (SE) height, 161.99 (9.42) cm; and mean (SE) body mass index, 25.21 (3.43) kg/m2. An intent-to-treat analysis found that the mean (SE) changes from baseline in FPG (-30.00 [10.67] vs -25.96 [11.15] mg/dL) and in HbA(1c) (-0.08% [0.24%] vs +0.14% [0.22%]) during the 12-week period of the study were not significantly different between the 2 formulations. For patients in the per-protocol analysis, mean (SE) changes from baseline in FPG (-30.00 [10.67] vs -16.52 [7.79] mg/dL) and HbA(1c) (-0.08% [0.24%] vs +0.11% [0.25%]) were also not significantly different. The most frequently reported AEs were urinary abnormality (22.2%) and tachycardia (6.7%) for the GSR group and GIR group, respectively. No serious drug-related AEs were observed in either group., Conclusion: In this small study, treatment with oral GSR (10 mg QD) was not significantly different from that of treatment with GIR (5 mg BID) with respect to short-term (12 weeks) FPG and HbA(1c) reductions in these ethnic Chinese adults with type 2 diabetes mellitus receiving treatment with a sulfonylurea.

Platelet-derived growth factor receptor (PDGFR) can bind to its ligand and consequently possess a kinase activity, and which is associated with the carcinogenesis of different cell types, including astrocytomas, oligodendrogliomas, and glioblastoma. In a cDNA microarray analysis, we observe the over-expressed mRNA of both PDGF-A and PDGF-alpha receptor in thyroid carcinoma cells. And the elevated protein expressions of PDGF-A and PDGF-alpha receptor in thyroid carcinoma cells were also confirmed by a Western blot analysis. The phosphorylation of PDGF-alpha receptor evaluated by an antibody against Tyr 720-phosphate was found in thyroid carcinoma cells. The tyrosine kinase activity of PDGF-alpha receptor was inhibited by tyrphostin AG1295 and showed a dose-dependent inhibition for the proliferation of thyroid carcinoma cells. These findings imply that autocrine activation of PDGF-alpha receptor plays a crucial role in the carcinogenesis of thyroid cells.

Papillary or follicular microcarcinoma of the thyroid comprises 10-20% of all thyroid malignancies. Most of these diseases exhibit slow progression and have a favorable prognosis. Distant metastasis caused by thyroid microcarcinoma is uncommon, and is usually found in the lung or bone. Thyroid microcarcinoma with metastasis to the kidney has not previously been reported. Clinically detectable well-differentiated metastatic thyroid carcinoma to the kidney is rare, and only 16 cases have been reported. Herein we describe a case of metastatic papillary thyroid microcarcinoma to the kidney in a patient with a pelvic fracture and pulmonary metastasis. The patient underwent a total thyroidectomy, radiotherapy, ablation treatment with 131I and thyroxine suppressive therapy. In conclusion, microcarcinoma cannot be ignored. Although uncommon, metastases may arise.

A series of photo-Fenton reactions have been performed for the degradation of 2,4,6-trinitrotoluene (TNT) in a 4.2-l reactor. The degradation reaction rate of TNT followed a pseudo-first-order behavior; and the rate constants for 2.4mW cm(-2)UV only, 2.4mW cm(-2)UV/H(2)O(2), Fenton, photo-Fenton (2.4mW cm(-2)) and photo-Fenton (4.7mW cm(-2)) were 0.002min(-1), 0.007min(-1), 0.014min(-1), 0.025min(-1) and 0.037min(-1), respectively. Increasing the intensity of UV light, and the concentrations of ferrous ions and hydrogen peroxide promoted the oxidation rate under the experimental conditions in this study. The weighting factor (f), the Fe(II)-promoted efficiency (r) and the promoted-UV light efficiency (p) were calculated to clarify their effects on the TNT oxidation. Moreover, the inhibition effect of hydroxyl radical was also observed in both Fenton and photo-Fenton oxidation when the concentration of Fe(II) were higher than 2.88mM. Solid phase micro-extraction was first applied to the separation of the organic byproducts from TNT oxidation. GC/MS was employed to identify the byproducts during the Fenton and photo-Fenton oxidation of TNT. These compounds were clarified as 1,3,5-trinitrobenzene, 1-methyl-2,4-dinitrobenzene 2,5-dinitrobenzoic acid and 1,3-dinitrobenzene. By these byproducts, the mechanisms of the methyl group oxidation, decarboxylation, aromatic ring breakage, and hydrolysis can be recognized and demonstrated. The pathway of TNT oxidation by photo-Fenton process was also proposed in this study.

In this study, the Fenton process was used to explore the possibility of treating explosives, namely 2,4,6-trinitrophenol (PA), ammonium picronitrate (AP), 2,4-dinitrotoluene (DNT), methyl-2,4,6-trinitrophenylnitramine (Tetryl) and 2,4,6-Trinitrotoluene (TNT), hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX). The photo-Fenton process was also conducted to compare its oxidation efficiency with the Fenton process. The inhibition of hydroxyl radical and theory of crystal field stabilization energy were introduced in this study. Results show that oxidation efficiencies in Fenton system are in the following sequence: DNT > PA > AP > TNT > Tetryl > RDX > HMX. The degradation of the explosives obeys a pseudo-first-order behavior, and possible decomposing mechanisms are also discussed. For all explosives, the oxidation rates significantly increased with increasing the concentration of Fe(II), as well as illumination with UV light.