Functional association of NR4A3 downregulation with impaired differentiation in myeloid leukemogenesis.

The coincident downregulation of NR4A1 and NR4A3 has been implicated in myeloid leukemogenesis, but it remains unknown how these two genes function in myeloid cells and how their combined downregulation promotes myeloid leukemogenesis. Since NR4A1 abrogation is thought to confer a survival and proliferation advantage to myeloid cells, we hypothesized that downregulation of NR4A3 may have a complementary effect on myeloid cell differentiation. First, we tested the association between differentiation status of leukemic cells and NR4A3 expression using two large clinical datasets from patients with different acute myeloid leukemia (AML) subtypes. The analysis revealed a close association between differentiation status and different subtypes of AML Then, we probed the effects of differentiation-inducing treatments on NR4A3 expression and NR4A3 knockdown on cell differentiation using two myeloid leukemia cell lines. Differentiation-inducing treatments caused upregulation of NR4A3, while NR4A3 knockdown prevented differentiation in both cell lines. The cell culture findings were validated using samples from chronic myeloid leukemia (CML) patients at chronic, accelerated and blastic phases, and in acute promyelocytic leukemia (APL) patients before and after all trans-retinoic acid (ATRA)-based differentiation therapy. Progressive NR4A3 downregulation was coincident with impairments in differentiation in patients during progression to blastic phase of CML, and NR4A3 expression was increased in APL patients treated with ATRA-based differentiating therapy. Together, our findings demonstrate a tight association between impaired differentiation status and NR4A3 downregulation in myeloid leukemias, providing a plausible mechanistic explanation of how myeloid leukemogenesis might occur upon concurrent downregulation of NR4A1 and NR4A3.

[Content determination of five flavonoids in Tibetan medicine Rhododendron anthopogonoides by quantitative analysis of multi-components by single marker (QAMS)].

To establish a quantitative analysis of multi-components by single marker(QAMS) method for five flavonoids in Rhododendron anthopogonoides and verify its feasibility and applicability in the medicinal materials of R. anthopogonoides. With hyperoside as the internal reference, relative correction factors(RCF) of rutin, quercetin, quercitrin and kaempferol were established by high-performance liquid chromatography(HPLC) analysis. RCFs were used to calculate the content of each component, system durability and relative retention time. Simultaneously, QAMS and external standard method(ESM) were used to determine the content of five flavonoids in 12 batches of R. anthopogonoides from different origins. The results were statistically analyzed to verify the accuracy and feasibility. The fingerprints and cluster analysis data of R. anthopogonoides analyzed and discussed differences among the batches. According to the results, the RCFs of rutin, quercetin, quercetin and kaempferol in R. anthopogonoides were 1.242 6, 0.990 5, 0.535 0, and 0.781 3, respectively. The RCFs represented a good reproducibility under different experimental conditions. Besides, there was no significant difference between QAMS and ESM. Besides, the fingerprint and cluster analysis data showed the consistency between the classification and with the origin distribution of the herbs. In conclusion, the QAMS method shows a good stability and accuracy in the quality control of R. anthopogonoides.

Effects of probiotic supplementation on serum trimethylamine-N-oxide level and gut microbiota composition in young males: a double-blinded randomized controlled trial.

PURPOSE: To explore whether probiotic supplementation could attenuate serum trimethylamine-N-oxide (TMAO) level and impact the intestinal microbiome composition. DESIGN: Forty healthy males (20-25 years old) were randomized into the probiotic group (1.32 × 1011 CFU live bacteria including strains of Lactobacillus acidophilus, Lactobacillus rhamnosus GG, Bifidobacterium animalis, and Bifidobacterium longum daily) or the control group for 4 weeks. All participants underwent a phosphatidylcholine challenge test (PCCT) before and after the intervention. Serum TMAO and its precursors (TMA, choline and betaine) were measured by UPLC-MS/MS. The faecal microbiome was analyzed by 16S rRNA sequencing. RESULTS: Serum TMAO and its precursors were markedly increased after the PCCT. No statistical differences were observed in the probiotic and the control group in area under the curve (AUC) (14.79 ± 0.97 µmol/L 8 h vs. 19.17 ± 2.55 µmol/L 8 h, P = 0.106) and the pre- to post-intervention AUC alterations (∆AUC) (- 6.33 ± 2.00 µmol/L 8 h vs. - 0.73 ± 3.04 µmol/L 8 h, P = 0.131) of TMAO; however, higher proportion of participants in probiotic group showed their TMAO decrease after the intervention (78.9% vs. 45.0%, P = 0.029). The abundance of Faecalibacterium prausnitzii (P = 0.043) and Prevotella (P = 0.001) in the probiotic group was significantly increased after the intervention but without obvious differences in α- and ß-diversity. CONCLUSIONS: The current probiotic supplementation resulted in detectable change of intestinal microbiome composition but failed to attenuate the serum TMAO elevation after PCCT. CLINICALTRIALS. GOV IDENTIFIER: NCT03292978. CLINICALTRIALS.GOV WEBSITE: https://clinicaltrials.gov/ct2/show/NCT03292978 .

Investigating the health disparities in the association between lifestyle behaviors and the risk of head and neck cancer.

Many studies have reported a positive association between lower socioeconomic status (SES) and higher head and neck cancer (HNC) risk. Fewer studies have examined the impact of SES on the association between alcohol or cigarette use and HNC risk. The current case-control study (1104 HNC cases and 1363 controls) investigated the influence of education, a SES indicator, on the association between HNC and the use of alcohol, cigarettes, or betel quids in Taiwan, a country with universal health care. Our results showed a larger increase in HNC risk associated with alcohol among those with lower educational level (odds ratio [OR] = 2.07; 95% confidence interval [CI], 1.53-2.80) than those with higher educational level (OR = 1.38; 95% CI, 1.04-1.85) (heterogeneity-P = .03). Educational level had an influence on the association between alcohol use and HNC risk among those with genetic susceptibility (ALDH2-deficient) to the carcinogenic effect of alcohol. The association between cigarette or betel quid use and HNC risk was similar between the high and low educational groups. National policies and social interventions have led to the decline in the prevalence of cigarette and betel quid users in Taiwan. In contrast, due to the lack of adequate alcohol control policies, alcohol consumption in Taiwan has continued to rise. A higher impact of alcohol on HNC risk among lower SES individuals even with universal health care could be the result of insufficient alcohol control policies in Taiwan.

The photodynamic activity and toxicity evaluation of 5,10,15-tris(ethoxylcarbonyl)corrole phosphorus(V) in vivo and in vitro.

The development of novel, efficient and nontoxic photosensitizers (PSs) is a challenging task for photodynamic therapy (PDT). In our previous study, corrole had been demonstrated to be a promising PS in PDT for cancer cells. In this paper, a novel electron-deficient flat phosphorus tris(ethoxycarbonyl) corrole (1-P) was synthesized and characterized. In vitro photodynamic activities and toxicity of 1-P in HepG2 xenograft tumours was evaluated by standard assay. The results shown 1-P displayed a potential efficient and low-toxic PS, which suggesting this kind of corrole is a powerful and promising antitumor PS for PDT. In addition, the potential anti-tumour mechanism study of 1-P was also investigated by the apoptosis antibody array, immunohistochemical and western blotting assay (WB) experiments, we found that the PDT activity of 1-P can degrade SIRT1 (an important deacetylase), and activate the Fas signal pathway to inhibit the growth of liver cancer cells.

[Tending of wild Heterosmilax yunnanensis].

To minimize the predatory harvest of Heterosmilax yunnanensis and maintain the sustainable utilization of its resources, a study on the tending technology of wild H. yunnanensis was carried out. The results showed that the tuber tending model had a higher seed emergence rate, shorter growth period and easier control of male and female ratios than other tending models; by removing shrubs, topping, bending pruning, controlling insects and pests and other effective technical measures, the growth period of H. yunnanensis was shortened; the average annual net income of the tending area was 1 086 yuan/mu (1 mu≈666.67 m²), which was 86.9% higher than before. This study was conducive to increasing the yield and quality of H. yunnanensis in Karst landform area, and instructive for the tending of other wild traditional Chinese medicinal herbs in this area.

[Complementary Therapy for Patients With Limb Trauma Pain in the Emergency Department].

Acute pain is the main cause for patient visits to the emergency department. An important issue faced in emergency medical care is to resolve patient pain. Moreover, limb traumatic pain is noted in 58-66% of emergency trauma patients. This paper explored the effectiveness of using non-pharmacological complementary interventions, including body operation therapies that used trauma limb care and therapeutic touch and mind-body interventions, in order to strengthen the support system and create a healing environment. The experience described herein is hoped to facilitate the provision of multifaceted emergency care for patients with limb trauma pain in the emergency department in order to improve the comfort and return rate of patients.

A Population-Based Cohort Study on the Ability of Acupuncture to Reduce Post-Stroke Depression.

Objective: Post-stroke depression (PSD) is common and has a negative impact on recovery. Although many stroke patients in Taiwan have used acupuncture as a supplementary treatment for reducing stroke comorbidities, little research has been done on the use of acupuncture to prevent PSD. Accordingly, our goal is to investigate whether using acupuncture after a stroke can reduce the risk of PSD. Method: This population-based cohort study examined medical claims data from a random sample of 1 million insured people registered in Taiwan. Newly diagnosed stroke patients in the period 2000-2005 were recruited in our study. All patients were followed through to the end of 2007 to determine whether they had developed symptoms of depression. A Cox proportional hazard model was used to estimate the relative risk of depression in patients after being diagnosed as having had a stroke, with a focus on the differences in those with and without acupuncture treatment. Results: A total of 8487 newly-diagnosed stroke patients were included in our study; of these, 1036 patients received acupuncture more than five times following their stroke, 1053 patients received acupuncture 1-5 times following their stroke and 6398 did not receive acupuncture. After we controlled for potential confounders (e.g., age, sex, insurance premium, residential area, type of stroke, length of hospital stay, stroke severity index, rehabilitation and major illness-related depression), we found that acupuncture after stroke significantly reduced the risk of depression, with a hazard ratio (HR) of 0.475 (95% CI, 0.389-0.580) in frequent acupuncture users and 0.718 (95% CI, 0.612-0.842) in infrequent acupuncture users, indicating that acupuncture may lower the risk of PSD by an estimated 52.5% in frequent users and 28.2% in infrequent users. Conclusions: After we controlled for potential confounders, it appears that using acupuncture after a stroke lowers the risk of depression. Additional strictly-designed randomized controlled trials are needed to better understand the specific mechanisms relating acupuncture to health outcomes.

Antihyperlipidaemic and hepatoprotective activities of acidic and enzymatic hydrolysis exopolysaccharides from Pleurotus eryngii SI-04.

BACKGROUND: Hyperlipidaemia is the major risk factor contributing to the development and progression of atherosclerosis, fatty liver and cerebrovascular disease. Pleurotus eryngii (P. eryngii) is rich in biologically active components, especially polysaccharides that exhibit various biological activities, including reducing blood lipids. In the present study, three novel polysaccharide types, including exopolysaccharides (EPS), enzymatic EPS (EEPS) and acidic EPS (AEPS) were isolated, and the hypolipidaemic and hepatoprotective effects were investigated to better understand possible hypolipidaemic mechanisms and their hepatoprotective effects. METHODS: The EPS was hydrolysed by snailase (dissolved in 1% acetic acid, pH = 6) and H2SO4 (1 M) to obtain EEPS and AEPS, respectively. The in vitro antioxidant activities were measured by investigating the reducing power and the scavenging effects on radicals of hydroxyl, 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide anion. The hyperlipidaemic mice were induced by perfusing a high-fat emulsion. In addition to the hepatic histopathology, the following biochemical analyses were performed to investigate the antioxidative effects, including the activities of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT). Triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), malondialdehyde (MDA) and lipid peroxidation (LPO) levels were also measured in serum and liver homogenate. RESULTS: Supplementation of EPS, EEPS and AEPS could significantly improve blood lipid levels (TC, TG, HDL-C, and LDL-C), hepatic lipid levels (TC and TG), hepatic enzyme activities (ALP, ALT, and AST) and antioxidant status (GSH-Px, SOD, T-AOC, MDA, and LPO). In addition, histopathological observations indicated that these polysaccharides had potential effects in attenuating hepatocyte damage. CONCLUSION: These results demonstrated that both EPS and its hydrolysates EEPS and AEPS might effectively reduce serum lipid levels and protect against high-fat diet-induced hyperlipidaemia, indicating that they could be used as functional foods and natural hepatoprotectants.

The Effect of Auricular Acupoint Stimulation in Overweight and Obese Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To investigate the effect of auricular acupoint stimulation on overweight and obese adults. METHODS: We searched databases including PubMed, EMBASE, Allied and Complementary Medicine Database, National Knowledge Infrastructure, and the PerioPath Index to Taiwan Periodical Literature. The modified Jadad scale was used to assess study quality. We investigated the effect of auricular acupoint stimulation on anthropometric measurements. RESULTS: Eighteen randomized controlled trials (RCTs) were included in our systematic review. Thirteen RCTs were pooled in a meta-analysis that revealed a significant reduction in body weight (BW) with a mean difference (MD) of -1.21 kg and a 95% confidence interval (CI) from -1.94 to -0.47 with a heterogeneity of I2 = 88%. Significant decreases in body mass index (BMI; MD: -0.57 kg/m2; 95% CI -0.82 to -0.33; I2 = 78%), body fat (BF; MD: -0.83%; 95% CI -1.43 to -0.24; I2 = 0%), and waist circumference (WC; MD: -1.75 cm; 95% CI -2.95 to -0.55; I2 = 87%) were also revealed. CONCLUSIONS: This meta-analysis shows that auricular acupoint stimulation improves physical anthropometric parameters including BW, BMI, BF, and WC in overweight and obese adults. These methods are less effective on hip circumference and waist-to-hip ratio.

Tea consumption and risk of head and neck cancer.

BACKGROUND: The current study evaluated the association between tea consumption and head and neck cancer (HNC) in Taiwan, where tea is a major agricultural product and a popular beverage. METHODS: Interviews regarding tea consumption (frequency, duration, and types) were conducted with 396 HNC cases and 413 controls. Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) of HNC risk associated with tea drinking, adjusted for sex, age, education, cigarette smoking, betel quid chewing, and alcohol drinking. RESULTS: A reduced HNC risk associated with tea drinking (OR for every cup per day = 0.96, 95% CI: 0.93-0.99; OR for ≧5 cups per day = 0.60, 95% CI: 0.39-0.94) was observed. The association was especially significant for pharyngeal cancer (OR for every cup per day = 0.93, 95% CI: 0.88-0.98; OR for ≧5 cups per day = 0.32, 95% CI: 0.16-0.66). A significant inverse association between HNC and tea consumption was observed particularly for green tea. CONCLUSIONS: This study suggests that tea drinking may reduce the risk of HNC. The anticancer property of tea, if proven, may offer a natural chemopreventive measure to reduce the occurrence of HNC.

Effects of auricular acupressure on body weight parameters in patients with chronic schizophrenia.

Auricular acupressure is widely used in complementary and alternative medicine to reduce body weight, but little is known about the effects of auricular acupressure on body weight parameters in patients with chronic schizophrenia. The purpose of this study was to evaluate the effects of auricular acupressure on body weight parameters in patients with chronic schizophrenia. Eighty-six inpatients with schizophrenia were recruited from chronic wards in a psychiatric center. The participants were randomly divided into experimental (acupressure at 4 acupuncture sites: hunger, stomach, shenmen and endocrine) and control groups, and body weight parameters were determined weekly for 8 weeks. There was no significant difference between the experimental and control groups in mean body weight, waist circumference, or body fat percentage at the pretest or during the entire 8-week study period. Therefore, auricular acupressure did not cause body weight reduction in patients with chronic schizophrenia.

Efficacy of Chinese herbal medicine compared with a macrolide in the treatment of chronic rhinosinusitis without nasal polyps.

BACKGROUND: This study was designed to examine the efficacy of Chinese herbal medicine (CHM) in the treatment of chronic rhinosinusitis (CRS) without nasal polyps. METHODS: Patients with CRS without nasal polyps were enrolled in the study. Before treatment, they were evaluated by the Taiwanese version of the 20-item Sino-Nasal Outcome Test (TWSNOT-20), nasal endoscopy, saccharin test, and bacterial culture. Then, they were randomized to take CHM (Tsang-Erh-San extract granules and Houttuynia extract powder) or erythromycin for 8 weeks. After treatment, they were evaluated again by the TWSNOT-20, nasal endoscopy, saccharin test, and bacterial culture. RESULTS: Fifty-three patients completed the study with 26 in the CHM group and 27 in the erythromycin group. In both the CHM and the erythromycin groups, TWSNOT-20 scores significantly decreased after treatment, but the decrease was not significantly different between the two groups. However, the saccharin transit times were shortened in more patients in the CHM group than in patients in the erythromycin group. CONCLUSION: Our results showed CHM had an efficacy similar to that of macrolides in the treatment of CRS without nasal polyps. However, a placebo effect remained possible in both treatment groups.

Effusion immunocytochemistry as an alternative approach for the selection of first-line targeted therapy in advanced lung adenocarcinoma.

INTRODUCTION: Tumor tissue is often not obtainable or suitable for molecular-based epidermal growth factor receptor (EGFR) mutational analysis in advanced non-small-cell lung cancer (NSCLC). This retrospective and single-institution study was conducted to evaluate the role of effusion immunocytochemistry using two EGFR mutant-specific antibodies for the detection of relevant EGFR mutations in NSCLC, along with the selection of candidates for first-line therapy with EGFR tyrosine kinase inhibitors (TKIs). METHODS: Immunocytochemistry using two antibodies binding specifically to the major forms of mutant EGFR, L858R, and E746-A750 deletion (delE746-A750), was performed on cell blocks of malignant pleural effusion (MPE) from 78 patients with lung adenocarcinoma, who received first-line EGFR TKIs. The yield of EGFR-mutation detection and prediction of response rate and progression-free survival to TKI treatment by immunocytochemistry were compared with those by clinical characteristics and EGFR sequencing using cell-derived RNA from MPEs. RESULTS: Of the 78 MPE samples, direct sequencing using cell-derived RNA identified L858R mutation in 42 cases, deletions in exon 19 in 12 cases (delE746-A750 in eight cases), other types of mutations in three cases, and wild-type EGFR in 21 cases. Effusion immunocytochemistry with these two mutant-specific antibodies exhibited a sensitivity of 71% and 88% and a specificity of 86% and 96% for identifying predefined L858R and delE746-A750 mutations, respectively. Effusion immunocytochemistry provided a superior prediction of tumor response and progression-free survival to first-line EGFR TKIs than did clinical characteristics like sex and smoking status. Patients whose effusion immunocytochemistry showed a reaction to either of the two antibodies had a comparable TKI response rate (67% versus 72%) to those with EGFR mutations assessed by direct sequencing from cell-derived RNA. CONCLUSIONS: Effusion immunocytochemistry could be introduced into clinical practice to identify more NSCLC patients likely to have benefit from first-line TKI treatment, especially for those without adequate tissue for molecular-based EGFR analysis.

Atorvastatin attenuates inflammatory infiltration and vascular remodeling in lung of hypercholesterolemia rabbits.

Hypercholesterolemia contributes to cardiovascular diseases, but its direct effect on lung is little known. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to exert numerous effects that are dependent and independent of their cholesterol-lowering property. The authors hypothesized that atorvastatin would attenuate hypercholesterolemia-induced lesion in lung. Fifteen rabbits were randomly divided into control group, high-cholesterol forage group, and atrovastatin treatment group. Body weight and blood lipid were measured. All lung tissue and pulmonary arteries were collected for histopathology and immunohistochemistry. Alveolar macrophages (AMs) were cultured and activation of nuclear factor (NF)-κB was detected. Concentrations of interleukin (IL)-6 were measured in serum, bronchoalveolar lavage fluid (BALF), and culture supernatants of AMs. Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) of high-cholesterol forage group were higher than control group (P < .05). There were infiltrating of AMs and lymphocytes in lung tissue of high-cholesterol forage group. NF-κB activity in AMs and concentrations of IL-6 in serum, BALF, and culture supernatants of AMs were higher than those of control group (P < .01), and so were all vascular remodeling indexes. TC and LDL-C and other indexes of atrovastatin treatment group were decreased (P < .05). Hypercholesterolemia induced pulmonary inflammatory Infiltration and vascular remodeling. Atorvastatin attenuated inflammatory infiltration and vascular remodeling in lung of hypercholesterolemia rabbits.

Role of pollen allergy in Taiwanese patients with allergic rhinitis.

BACKGROUND/PURPOSE: Pollen allergy is believed to be less common in East Asia, Latin America, and tropical areas. The purpose of this study was to understand the role of pollen allergy in Taiwan. METHODS: Patients with clinically diagnosed allergic rhinitis were enrolled. All subjects received a 30-item skin test panel that included perennial allergens (house dust mix, Dermatophagoides pteronyssinus, Dermatophagoides farinae, dog epithelium, cat hairs, cockroach mix, and Candida albicans) and pollen allergens (acacia, pine mix, eucalyptus, beefwood, juniper mix, willow, mulberry mix, pepper tree, cedar, Johnson grass, Bermuda grass, ragweed mix, Timothy grass, spiny pigweed, cocklebur, sage mix, sheep sorrel, dog fennel, pigweed mix, English plantain, castor bean, alfalfa, and dandelion). RESULTS: A total of 419 patients were recruited. A total of 313 (74.7%) had a positive skin test. A total of 288 patients (68.7%) were sensitive to perennial allergens, and 11 8 patients (28.2%) were sensitive to pollen allergens. However, 93 pollen-sensitive patients were also sensitive to perennial allergens, and only 25 were sensitive to pollen allergens alone. The most common allergens were D. pteronyssinus, D. farinae, house dust mix, and cockroach, but the most common pollen allergens were spiny pigweed, Johnson grass, and sheep sorrel. All nasal symptoms tended to be more severe in patients who were sensitive to perennial allergens than in those who were sensitive to pollen allergens alone. CONCLUSION: Most patients with allergic rhinitis in Taiwan are sensitive to perennial allergens, and pollens are a less common allergen.

Water transformation in the media of biofilters controlled by Rhodococcus fascians in treating an ethyl acetate-contaminated airstream.

Biofilters do not provide much water for bacteria to grow. To use them efficiently and properly, it is essential to understand the kinetics of water transformation and to control moisture levels. This study aims to clarify whether the metabolism of microorganisms will improve the water-holding capacity of media or will intensify drying. This experiment was conducted in duplicate, that is, both with and without bacterial inoculation. Both the constant water content mode and the declining water content mode show that microbial growth in a log phase will enhance drying. In contrast, the bacteria growing in a logarithmic decline phase will improve water-holding capacity. Basically, water evaporation can result from the latent heat obtained from microbial respiration or from the physical temperature difference between the unsaturated air and the wet media. Two ways that biofilters can gain water are from water incorporated into bacteria cells and from water obtained from the oxidation of volatile organic compounds (VOCs).