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B-cell acute lymphoblastic lymphoma (B-ALL) is a disease found mainly in children and in young adults. B-ALL is characterized by the rapid proliferation of poorly differentiated lymphoid progenitor cells inside the bone marrow. In the United States, ~4,000 of these patients are diagnosed each year, accounting for ~30% of childhood cancer types. The tumorigenesis of the disease involves a number of abnormal gene expressions (including TEL-AML1, BCR-ABL-1, RAS and PI3K) leading to dysregulated cell cycle. Risk factors of B-ALL are the history of parvovirus B 19 infection, high birth weight and exposure to environmental toxins. These risk factors can induce abnormal DNA methylation and DNA damages. Treatment procedures are divided into three phases: Induction, consolidation and maintenance. The goal of treatment is complete remission without relapses. Apart from traditional treatments, newly developed approaches include gene targeting therapy, with the aim of wiping out leukemic cells through the inhibition of mitogen-activated protein kinases and via c-Myb inhibition enhancing sensitivity to chemotherapy. To evaluate the efficacy of ongoing treatments, several indicators are currently used. The indicators include the expression levels of microRNAs (miRs) miR-146a, miR-155, miR-181a and miR-195, and soluble interleukin 2 receptor. Multiple drug resistance and levels of glutathione reductase can affect treatment efficacy through the increased efflux of anti-cancer drugs and weakening the effect of chemotherapy through the reduction of intracellular reactive oxygen species. The present review appraised recent studies on B-ALL regarding its pathogenesis, risk factors, treatments, treatment evaluation and causes of disease relapse. Understanding the mechanisms of B-ALL initiation and causes of treatment failure can help physicians improve disease management and reduce relapses.

Epidemiological studies have reported that elderly patients with metabolic syndrome (MetS) are significantly more likely to develop neuronal degenerative diseases than those without MetS. Our previous study showed that patients with MetS had significantly higher levels of negatively charged very low density lipoproteins (VLDLs) in the plasma than healthy controls. Highly electronegative VLDL is a key risk factor for endothelial dysfunction and atrial fibrillation. However, the impact of negatively charged VLDL in brain immunity remains unclear. In this study, VLDLs were isolated from normal healthy (nVLDL) individuals or patients with MetS (metVLDL). Primary astroglia and microglia mixed cell cultures as well as microglial-enriched cultures were used to test the effects of VLDLs. Microglia/astroglia activation as evidenced by their morphological changes and production of pro-inflammatory factors, such as tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2), were assessed by immunofluorescence staining and ELISA, respectively. Our results showed that metVLDLs mainly act on the microglia, and not the astroglia, with low concentration (0.05–0.5 μg/mL) inducing cell morphological changes and decreased cellular processes in the microglia. However, nVLDL treatment at these concentrations had no effects on microglia and astroglia. Most importantly, TNF-α and PGE2 levels significantly increased in the microglia treated with metVLDL via a dose-dependent manner. Together, our data indicate that metVLDLs can contribute to MetS-associated brain disorders through microglia activation and neuroinflammation.

The incidence of colon cancer continues to increase annually, and it is the leading cause of cancer-associated mortality worldwide. Altering cell metabolism and inducing autophagic cell death have recently emerged as novel strategies in preventing tumor growth. Autophagy plays an essential role in energy production by degrading damaged cellular components and is also associated with tumor proliferation suppression. Itraconazole is an FDA-approved drug used as an antifungal medication and has been reported to induce autophagic cell death in breast cancer. However, the effects of itraconazole on cell metabolism and induction of apoptosis in colon cancer remain unclear. The present study analyzed extensive data from patients diagnosed with colon cancer using itraconazole between January 2011 and December 2015, from the Taiwanese National Health Insurance Research Database. The underlying molecular mechanisms of itraconazole in autophagy-induced cell death were also investigated. The results demonstrated that the 5-year survival rate was significantly higher in patients with colon cancer who received itraconazole treatment. In addition, itraconazole decreased the viability and cell colony formation, and induced cleaved caspase-3 expression and G1 cell cycle arrest of COLO 205 and HCT 116 cells. Notably, itraconazole induced autophagy by enhancing LC3B and p62 expression. Following LC3 knockdown, the viability of itraconazole-treated COLO 205 and HCT 116 cells notably improved. Taken together, the results of the present study suggest that itraconazole may have a beneficial effect on patients with colon cancer, and its underlying molecular mechanisms may be associated with the induction of autophagic cell death.

Background: Acute lymphoblastic leukemia (ALL) is a malignant disease characterized by an excessive number of immature lymphocytes, including immature precursors of both B- and T cells. ALL affects children more often than adults. Immature lymphocytes lead to arrested differentiation and proliferation of cells. Its conventional treatments involve medication with dexamethasone, vincristine, and other anticancer drugs. Although the current first-line drugs can achieve effective treatment, they still cannot prevent the recurrence of some patients with ALL. Treatments have high risk of recurrence especially after the first remission. Currently, novel therapies to treat ALL are in need. Autophagy and apoptosis play important roles in regulating cancer development. Autophagy involves degradation of proteins and organelles, and apoptosis leads to cell death. These phenomena are crucial in cancer progression. Past studies reported that many potential anticancer agents regulate intracellular signaling pathways. Methods: The authors discuss the recent research findings on the role of autophagy and apoptosis in ALL. Results: The autophagy and apoptosis are widely used in the treatment of ALL. Most studies showed that many agents regulate autophagy and apoptosis in ALL cell models, clinical trials, and ALL animal models. Conclusions: In summary, activating autophagy and apoptosis pathways are the main strategies for ALL treatments. For ALL, combining new drugs with traditional chemotherapy and glucocorticoids treatments can achieve the greatest therapeutic effect by activating autophagy and apoptosis.

Objectives: The clinical effect of traditional Chinese medicine (TCM) on survival in patients with advanced lung adenocarcinoma treated with first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is a major concern and requires more evidence from large-scale clinical studies. Materials and Methods: This population-based cohort study used the Taiwan National Health Insurance Research Database to enroll patients between 2006 and 2012 who had newly diagnosed locally advanced and metastatic lung adenocarcinoma treated with first-line gefitinib or erlotinib. Survival was tracked until 2013. The patients were separated into TCM users and nonusers, and Cox regression models were applied to determine the association between the use of TCM and the survival of patients. Results: A total of 1988 patients receiving first-line gefitinib or erlotinib for the treatment of EGFR-mutated advanced lung adenocarcinoma, with the exclusion of TCM users after tumor progression, were included in this cohort study. Compared with TCM nonuse, TCM use for ≥180 days was associated with a significantly decreased risk of mortality by 68% (adjusted hazard ratio [HR], 0.32 [95% CI, 0.21-0.50], P < .0001). Compared with TCM nonuse, TCM use for ≥180 days was associated with a significantly decreased risk of disease progression by 59% (adjusted HR, 0.41 [95% CI, 0.29-0.58], P < .0001). Conclusion: This cohort study suggests that adjunctive TCM therapy could improve overall survival and progression-free survival in patients with advanced lung adenocarcinoma treated with first-line TKIs. Future randomized, controlled trials are required to validate these findings.

The standard treatment regimen for patients diagnosed with non-small cell lung cancer (NSCLC) with locally advanced stage III disease is concurrent chemoradiotherapy (CCRT). This study investigated the molecular effects of vinca alkaloid vinorelbine (VNR)-based CCRT. We reviewed the records of 68 patients with stage III NSCLC: 42 patients received VNR-based CCRT, and 26 were treated with radiation alone. Human lung adenocarcinoma cells were used in this study to investigate the molecular effects of glucosylceramide synthase inhibition on VNR-based CCRT. There was response rate of 66.7% with CCRT, which was better than the response rate observed with radiation alone (30.8%; P

Patients with bipolar II disorder (BDII) have a higher prevalence rate of metabolic disturbance. Whether BDII itself, in addition to its current standard treatment, is a risk factor for metabolic syndrome warrants additional study. The dopamine receptor D3 (DRD3) gene, one of the candidate genes for BDII, is also involved in the dopaminergic system. We investigated whether it is related to changes in the metabolic indices of patients with BDII given 12 weeks of standard treatment. Patients with a first diagnosis of BDII (n = 117) were recruited. Metabolic profiles (cholesterol, triglycerides, fasting serum glucose, body mass index) were measured at baseline and at 2, 8, and 12 weeks. The genotype of the DRD3 Ser9Gly polymorphism (rs6280) was determined. Multiple linear regressions with generalized estimating equation methods were used. Seventy-six (65.0%) patients completed the 12-week intervention. Significant differences in triglyceride change were associated with the DRD3 Ser9Gly genotype (P = 0.03). Patients with the Ser/Ser genotype had significantly smaller triglyceride increases and a lower risk of developing metabolic syndrome than did those with the Ser/Gly+Gly/Gly genotype. However, the associations between the DRD3 Ser9Gly polymorphism with changes in triglyceride level become nonsignificant after correcting for multiple comparisons. We conclude that the DRD3 Ser9Gly polymorphism is nominally associated with changes in triglycerides and metabolic syndrome after 12 weeks of standard BDII treatment.

Patients with subthreshold hypomania (SBP; subthreshold bipolar disorder) were indistinguishable from those with bipolar disorder (BP)-II on clinical bipolar validators, but their analyses lacked biological and pharmacological treatment data. Because inflammation and neuroprogression underlies BP, we hypothesized that cytokines and brain-derived neurotrophic factor (BDNF) are biomarkers for BP. We enrolled 41 drug-naïve patients with SBP and 48 with BP-II undergoing 12 weeks of pharmacological treatment (valproic acid, fluoxetine, risperidone, lorazepam). The Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were used to evaluate clinical responses at baseline and at weeks 0, 1, 2, 4, 8, and 12. Inflammatory cytokines (tumour necrosis factor [TNF]-α, transforming growth factor [TGF]-β1, interleukin [IL]-6, IL-8 and IL-1β) and BDNF levels were also measured. Mixed models repeated measurement was used to examine the therapeutic effect and changes in BDNF and cytokine levels between the groups. HDRS and YMRS scores significantly (P

Aim of the study Baicalin is an active compound originating from the root of Scutellaria baicalensis Georgi, which has been used for anti-inflammation, anti-bacteria, anti-hypertension, anti-allergy and sedation since ancient China, though the neuronal mechanisms involved in the sedative effect is still unclear. Baicalin possesses the ability to decrease the expression of pro-inflammatory cytokines and nuclear factor (NF)-κB activity. Furthermore, baicalin has demonstrated an anxiolytic-like effect via activation of γ-aminobutyric acid-A (GABA A ) receptors. Pro-inflammatory cytokines (e.g. interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α) and the GABAergic system promote sleep. This study was designed to determine whether the GABA A receptor activation and/or the suppression of pro-inflammatory cytokines mediate(s) baicalin-induced sleep alterations. Materials and methods Baicalin was intracerebroventricularly (ICV) administered 20 min either prior to the beginning of the light period or before the onset of the dark period. Electroencephalogram (EEG) and gross body movement were acquired for sleep analysis. Pharmacological blockade of IL-1 and GABA A receptors were employed to elucidate the involvements of IL-1 and GABA A receptors in baicalin-induced sleep alterations. IL-1β concentrations obtained after baicalin administration in several distinct brain regions were determined by ELISA. Results ICV administration of baicalin decreased slow wave sleep (SWS) during the first 2 h of the light period. Rapid eye movement sleep (REMS) was not altered. The blockade of IL-1β-induced SWS enhancement by baicalin suggests that the antagonism of IL-1 receptors is involved in baicalin-induced SWS decrement during the light period. However, IL-1β concentrations during the light period were not altered after baicalin administration. In contrast, baicalin increased both SWS and REMS during hours 8–10 of the dark (active) period when baicalin was administered at the beginning of the dark period, and its effects were blocked by the GABA A receptor antagonist bicuculline. Conclusion Baicalin exhibits biphasic effects on sleep–wake regulation; the decrease of SWS during the light period and increases of SWS and REMS during the dark period. Inhibition of IL-1 action and enhancement of GABA A receptor activity may mediate baicalin's effects during the light and dark period, respectively.

1Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan 2Institute of Behavioral Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan 3Institute of Allied Health Sciences, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan 4Addiction Research Center, National Cheng Kung University, Tainan, Taiwan 5Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan 6Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan *Correspondence author: Ru-Band Lu, Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, E-mail: rblu@mail.ncku.edu.tw

Diatoms are a renewable (biologically reproducible) source of three-dimensional (3-D) nanostructured silica that could be attractive for a variety of photonic devices, owing to the wide range of quasi-periodic patterns of nano-to-microscale pores available on the silica microshells (frustules) of various diatom species. We have investigated the optical behavior of the silica frustule of a centric marine diatom, Coscinodiscus wailesii, using a coherent broadband (400-1700 nm) supercontinuum laser focused to a fine (20 µm diameter) spot. The C. wailesii frustule valve, which possessed a quasi-periodic hexagonal pore array, exhibited position-dependent optical diffraction. Changes in such diffraction behavior across the frustule were consistent with observed variations in the quasi-periodic pore pattern.

This paper defines and discusses a glass dispersion formula that is adaptive. The formula exhibits superior convergence with a minimum number of coefficients. Using this formula we rationalize the correction of chromatic aberration per spectrum order. We compare the formula with the Sellmeier and Buchdahl formulas for glasses in the Schott catalogue. The six coefficient adaptive formula is found to be the most accurate with an average maximum index of refraction error of 2.91 × 10(-6) within the visible band.

Design and experimental verification of a microscope-based circular-polarization interferometer developed for measuring the vibration of miniature specimens is detailed. This interferometer, which comes in either a two-detector or a four-detector configuration, demonstrates that the optimum operating point of a circular-polarization interferometer de- pends strongly on the signal detection and processing algorithms adopted. The influence of the specimen surface optical properties on the desired operating conditions is also examined. The optimum operating point of the two-detector configuration demands that the two returning light beams emitting from the specimen possess equal intensity, which matches the understanding of traditional interferometers, where two equal interference arms achieves the best interference efficiency. Sur- prisingly, it appears that the optimum intensity ratio for the four-detector configuration occurs if the two interference arms possess equal intensity before it hits the specimen. That is, under the constraint of a constant light source, it appears that the optimum operating point of a four- photodetector circular-polarization interferometer is independent of the surface optical properties. Both theoretical and experimental results that verify the interaction between the optoelectronic configuration and the signal-processing algorithms implemented are presented. © 2005 Society of

Ineffective therapeutic treatments and inadequate repair ability in the central nervous system are disturbing problems for several neurological diseases. Fortunately, the development of clinically applicable populations of stem cells has provided an avenue to overcome the failure of endogenous repair systems and substitute new cells into the damaged brain. However, there are still several existing obstacles to translating into clinical application. Here we review the stem-cell based therapies for Parkinson's disease and discuss the potential advantages and drawbacks. We hope this review may provide suggestions for viable strategies to overcome the current technical and biological issues associated with the application of stem cells in Parkinson's disease.

Cancer patients frequently rely on implanted infusion catheter (Port-A) for injection of anti-cancer drugs, but Port-A-related bloodstream infections affect patient outcomes and increase mortality. Thus, to maintain a good quality of care and patient safety, we utilize interdepartmental teamwork cooperation and medical breakthrough series techniques (BTS) to formulate improvement strategies including: (1) introduce 2% Chlorhexidine gluconate for skin disinfection; (2) conduct training program and produce Port-A health education video files combined with action task vehicles; (3) introduce and execute maximal protection policy grade; (4) implement hand hygiene compliance and accuracy audit; (5) develop specialist quality control indicators: clinical outcome indicators according to Taiwan Clinical Practice Improvement (TCPI) indicators to define oncology ward “ Port-A-related bloodstream infections." ; (6) establish port-A teaching model aids. Through the implementation of the above strategies, the results were: (a) Port-Arelated bloodstream infections decreased from 2.01 & to 1.50 & ( decreased 0.51 &); oncology ward healthcare-associated bloodstream infections decreased from 1.65 & to 1.24 & ( decrease 0.41 &). (b) Accuracy rate of Port-A infusion procedure increased from 58.8% to 100% ( an increase of 41.2 %); (c) Oncology world average hospital stay decreased from 8.2 to 7.1 days ( shortened 1.1 days ) . By collaborating interdepartmental teamwork cooperation, establishment of standard Port-A infusion procedures, implementation of hand hygiene audit and skin disinfection technique can indeed reduce Port-A-related bloodstream infection.