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The immunologic features involved in the immune-tolerant phase of chronic hepatitis B (CHB) virus (HBV) infection are unclear. The hepatitis B virus X (HBx) protein disrupts IFN-β induction by downregulating MAVS and may destroy subsequent HBV-specific adaptive immunity. We aimed to analyse the impacts of genetic variability of HBx in CHB patients on the immune-tolerant phase during long-term follow-up.Children with CHB in the immune-tolerant phase were recruited and followed longitudinally. HBx gene sequencing of infecting HBV strains was performed, and the effects of HBx mutations on the immune-tolerant phase were assessed. Restoration of the host immune response to end the immune-tolerant phase was investigated by immunoblotting, immunostaining, ELISA and reporter assays of MAVS/IFN-β signalling in liver cell lines, patient liver tissues and the HBV plasmid replication system.A total of 173 children (median age, 6.92 years) were recruited. Patients carrying HBx R87G, I127V and R87G + I127V double mutations exhibited higher cumulative incidences of immune-tolerant phase breakthrough (p = .011, p = .006 and p = .017 respectively). Cells transfected with HBx R87G and I127V mutants and pHBV1.3-B6.3 replicons containing the HBx R87G and I127V mutations exhibited statistically increased levels of IFN-β, especially under poly(I:C) stimulation or Flag-MAVS cotransfection. HA-HBx wild-type interacted with Flag-MAVS and enhanced its ubiquitination, but this ability was diminished in the R87G and I127V mutants.HBx suppresses IFN-β induction. R87G and I127V mutation restored IFN-β production by preventing MAVS degradation, contributing to curtailing the HBV immune-tolerant phase in CHB patients.

Human glioblastoma (GBM) is one of the common cancer death in adults worldwide, and its metastasis will lead to difficult treatment. Finding compounds for future to develop treatment is urgent. Bisdemethoxycurcumin (BDMC), a natural product, was isolated from the rhizome of turmeric (Curcuma longa), which has been shown to against many human cancer cells. In the present study, we evaluated the antimetastasis activity of BDMC in human GBM cells. Cell proliferation, cell viability, cellular uptake, wound healing, migration and invasion, and western blotting were analyzed. Results indicated that BDMC at 1.5-3 μM significantly decreased the cell proliferation by MTT assay. BDMC showed the highest uptake by cells at 3 h. After treatment of BDMC at 12-48 h significantly inhibited cell motility in GBM 8401 cells by wound healing assay. BDMC suppressed cell migration and invasion at 24 and 48 h treatment by transwell chamber assay. BDMC significantly decreased the levels of proteins associated with PI3K/Akt, Ras/MEK/ERK pathways and resulted in the decrease in the expressions of NF-κB, MMP-2, MMP-9, and N-cadherin, leading to the inhibition of cell migration and invasion. These findings suggest that BDMC may be a potential candidate for the antimetastasis of human GBM cells in the future.

Mangiferin is a naturally occurring polyphenol, widely distributed in Thymeraceae families, and presents pharmacological activity, including anti-cancer activities in many human cancer cell lines. Mangiferin has also been reported to affect immune responses; however, no available information concerning the effects of mangiferin on immune reactions in leukemia mice in vivo. In the present study, we investigated the effects of mangiferin on leukemia WEHI-3 cell generated leukemia BLAB/c mice. Overall, the experiments were divided into two parts, one part was immune responses experiment and the other was the survival rate experiment. The immune responses and survival rate study, 40 mice for each part, were randomly separated into five groups (N = 8): Group I was normal animals and groups II-V WEHI-3 cell generated leukemia mice. Group II mice were fed normal diet as a positive control; group III, IV, and V mice received mangiferin at 40, 80, and 120 mg/kg, respectively, by intraperitoneal injection every 2 days for 20 days. Leukocytes cell population, macrophage phagocytosis, and NK cell activities were analyzed by flow cytometry. Isolated splenocytes stimulated with lipopolysaccharide (LPS) and concanavalin A (Con A) were used to determine the proliferation of B and T cells, respectively, and subsequently were analyzed by flow cytometry. Results indicated that mangiferin significantly increased body weight, decreased the liver and spleen weights of leukemia mice. Mangiferin also increased CD3 T-cell and CD19 B cell population but decreased Mac-3 macrophage and CD11b monocyte. Furthermore, mangiferin decreased phagocytosis of macrophages from PBMC and peritoneal cavity at 40, 80, and 120 mg/kg treatment. However, it also increased NK cell activity at 40 and 120 mg/kg treatment. There were no effects on T and B cell proliferation at three examined doses. In survival rate studies, mangiferin significantly elevated survival rate at 40 and 120 mg/kg treatment of leukemia mice in vivo.

The COVID-19 pandemic has had a globally devastating impact. This highly contagious virus has significantly overburdened and undermined medical systems. While most infected patients experience only mild symptoms, those who are severely affect require urgent medical interventions and some develop acute respiratory failure and require mechanical ventilation. The broad and potentially deadly impact of infection underscores the critical need for early recognition, especially for those at risk for respiratory failure. Those who are severely impacted and at high risk for respiratory failure have been found to present high levels of serum cytokines, such as interleukin-6 (IL-6). Timely diagnosis and management of those at risk for respiratory failure is crucial. Measurement of IL-6 may provide a means for distinguishing such patients. Currently, most serum IL-6 detection relies on the use of laboratory-based conventional enzyme-linked immunosorbent assays. Although some rapid assays have been developed recently, they need to be conducted by specific technicians in central laboratory settings with advanced and expensive equipment. In this study, we propose an IL-6 test strip combined with a spectrum-based optical reader for early recognition of COVID-19-infected patients at imminent risk of acute respiratory failure requiring mechanical ventilator support. For our analyses, clinical demographic data and sera samples were obtained from three medical centers, and test strip specificity and detection performance were analyzed. This would help healthcare personnel stratify the risk of respiratory failure and provide prompt, and suitable management.

This study examined the molecular characterization of a prenatal case with true fetal mosaicism of small supernumerary marker chromosome 16 (sSMC(16)). A 41-year-old female underwent amniocentesis at 19 weeks of gestation due to advanced maternal age. Chromosomal analysis for cultured amniocytes revealed a karyotype of 47,XY,+mar[4]/46,XY[16]. Spectral karyotyping and metaphase fluorescence in situ hybridization (FISH) demonstrated that the sSMC was derived from chromosome 16 (47,XY,+mar.ish der(16)(D16Z1+)[13/20]). Confined placental mosaicism was initially suspected because the prenatal ultrasound revealed a normal structure and the pregnancy was uneventful. However, interphase FISH of cord blood performed at 28 weeks of gestation showed 20% mosaicism of trisomy chromosome 16 (nuc ish(D16Z2×3)[40/200]). Chromosome microarray analysis further demonstrated 55% mosaicism of an 8.02 Mb segmental duplication at the subcentromeric region of 16p12.1p11.1 (arr[GRCh37] 16p12.1p11.1(27021975_35045499)×3[0.55]). The results demonstrated a true fetal mosaicism of sSMC(16) involving chromosome16p12.1p11.1 that is associated with chromosome 16p11.2 duplication syndrome (OMIM #614671). After non-directive genetic counseling, the couple opted for late termination of pregnancy. This case illustrated the use of multiple molecular cytogenetic tools to elucidate the origin and structure of sSMC, which is crucial for prenatal counseling, decision making, and clinical management.

Background/aim Demethoxycurcumin (DMC), one of the components of curcuminoids, has antitumor activities in many human cancer cells and is known to induce apoptosis in human leukemia cells. However, there are no reports showing the effects of DMC on the immune response in leukemia mice in vivo. Herein, we evaluated the impact of DMC on immune responses in WEHI-3-generated leukemia mice in vivo. Materials and methods Fifty male BALB/c mice were separated randomly into five groups. Group I is normal mice, and groups II-V mice of generated leukemia by WEHI-3 cells. Group II-V mice were intraperitoneally injected with dimethyl sulfoxide (DMSO, as the positive control), 15, 30, and 60 mg/kg of DMC, respectively, every two days for 14 days. The body weight, blood, peritoneal fluid, liver, and spleen were individually analyzed. Results DMC did not significantly affect animal appearance and body weight. It decreased liver and spleen weight at a high dose. DMC did not affect the cluster of differentiation 3 (CD3) and CD19 cell populations but induced decrease of CD11b at 30 mg/kg treatment. However, DMC at low dose significantly increased the cluster of macrophage (Mac-3) cell populations, but at high dose it decreased them. DMC increased macrophage phagocytosis from peripheral blood mononuclear cells at 15 mg/kg treatment and peritoneal cavity at 15, 30 and 60 mg/kg of DMC treatments. DMC did not significantly affect the cytotoxic activity of natural killer (NK) cells. Furthermore, DMC decreased B and T cell proliferation at high doses. Conclusion DMC elevated macrophage phagocytosis in leukemia mice in vivo.

Background/aim Bufalin, bufadienolide present in Chan Su, has been shown to induce cancer cell apoptosis in many human cancer cells, including human leukemia cells, but its effects on immune responses are unknown. Materials and methods This study investigated whether bufalin affected immune responses of mice with WEHI-3 cell-generated leukemia in vivo. BALB/c mice were intraperitoneally injected with WEHI-3 cells to develop leukemia and then were treated with oral treatment with bufalin at different doses (0, 0.1, 0.2 and 0.4 mg/kg) for 2 weeks. At the end of treatment, all mice were weighted and blood was collected; liver and spleen tissues were collected for cell marker, phagocytosis, natural killer (NK) cell activity and T- and B-cell proliferation measurements by using flow cytometric assays. Results When compared with the leukemia control group, bufalin increased the body weight, but reduced liver and spleen weights, and reduced CD3, CD16 and Mac-3 cell markers at 0.4 mg/kg treatment and increased CD11b marker at 0.1 and 0.2 mg/kg treatment. Furthermore, bufalin at 0.4 mg/kg increased phagocytosis by macrophages isolated from peripheral blood mononuclear cells and at 0.1 mg/kg by those from the peritoneal cavity. Bufalin (0.2 and 0.4 mg/kg) increased NK cell cytotoxic activity at effector:target ratio of 50:1. Bufalin increased B-cell proliferation at 0.1 and 0.2 mg/kg treatment but only increased T-cell proliferation at 0.1 mg/kg. Bufalin increased glutamate oxaloacetate transaminase level at all dose treatments, increased glutamic pyruvic transaminase level only at 0.1 mg/kg treatment, but reduced the level of lactate dehydrogenase at all dose levels in mice with WEHI-3 cell-induced leukemia in vivo. Conclusion Bufalin increased immune responses by enhancing phagocytosis in mice with leukemia mice.

Ouabain, a cardiotonic steroid and specific Na+ /K+ -ATPase inhibitor, has a potential to induce cancer cell apoptosis but the mechanisms of apoptosis induced by ouabain are not fully understand. The aim of this study was to investigate the cytotoxic effects of ouabain on human prostate cancer DU 145 cells in vitro. Cell morphological changes were examined by phase contrast microscopy. Cell viability, cell cycle distribution, cell apoptosis, DNA damage, the production of ROS and Ca2+ , and mitochondrial membrane potential (ΔΨm ) were measured by flow cytometry assay. Results indicated that ouabain induced cell morphological changes, decreased total cell viability, induced G0/G1 phase arrest, DNA damage, and cell apoptosis, increased ROS and Ca2+ production, but decreased the levels of ΔΨm in DU 145 cells. Ouabain also increased the activities of caspase-3, -8, and -9. Western blotting was used for measuring the alterations of apoptosis-associated protein expressions in DU 145 cells and results indicated that ouabain increased the expression of DNA damage associated proteins (pATMSer1981 , p-H2A.XSer139 , and p-p53Ser15 ) and ER-stress-associated proteins (Grp78, ATF6β, p-PERKThr981 , PERK, eIF2A, GADD153, CaMKIIβ, and caspase-4) in time-dependently. Furthermore, ouabain increased apoptosis-associated proteins (DR4, DR5, Fas, Fas Ligand, and FADD), TRAIL pathway, which related to extrinsic pathway, promoted the pro-apoptotic protein Bax, increased apoptotic-associated proteins, such as cytochrome c, AIF, Endo G, caspase-3, -8, and -9, but reduced anti-apoptotic protein Bcl-2 and Bcl-x in DU 145 cells. In conclusion, we may suggest that ouabain decreased cell viability and induced apoptotic cell death may via caspase-dependent and mitochondria-dependent pathways in human prostate cancer DU 145 cells.

Cardamonin, the chalcone class, is one of the natural components from the spicy herbaceous plant (Alpinia conchigera Griff) and has anticancer activities in many human cancer cell lines. There is, however, no information to show that cardamonin induces cell apoptosis and alters apoptosis associated gene expressions in mouse leukemia cells. Thus, we investigated the effects of cardamonin on the apoptotic cell death and associated gene expression in mouse leukemia WEHI-3 cells in vitro. Results indicated that cardamonin decreased total viable cell number via induced cell morphological changes and apoptotic cell death in WEHI-3 cells that were assay by contrast-phase microscopy and flow cytometry examinations, respectively. The flow cytometry assay indicated that cardamonin increased reactive oxygen species (ROS) and Ca[Formula: see text] production, decreased the levels of mitochondrial membrane potential ([Formula: see text] and increased caspase-3, -8 and -9 activities in WEHI-3 cells. Western blotting was performed to analyze expression of relevant pro- and anti-apoptotic proteins and results showed that cardamonin decreased anti-apoptotic protein of Bcl-2 but increased pro-apoptotic protein of Bax in WEHI-3 cells. Furthermore, cardamonin increased cytochrome c, AIF and Endo G release, increased GRP78, caspase-12 that were associated with ER stress and increased Fas, Fas-Ligand and FADD expression. Furthermore, cardamonin increased the gene expressions of DAP (death-associated protein), TMBIM4 transmembrane (BAX inhibitor motif containing 4), ATG5 (autophagy related 5) but decreased the gene expression of DDIT3 (DNA-damage inducible transcript 3), DDIT4 (DNA-damage-inducible transcript 4), BAG6 (BCL2-associated athanogene 6), BCL2L13 [BCL2-like 13 (apoptosis facilitator)] and BRAT1 (BRCA1-associated ATM activator 1) that are associated with apoptosis pathways. Based on those findings, we may suggest cardamonin induced apoptotic cell death through Fas and Fas-Ligand-, caspase- and mitochondria-dependently pathways and also affects the apoptotic gene expression in WEHI-3 cells in vitro.

Circulating fetal cells (CFCs) in maternal blood are rare but have a strong potential to be the target for noninvasive prenatal diagnosis (NIPD). &ldquo, Cell RevealTM system&rdquo, is a silicon-based microfluidic platform capable to capture rare cell populations in human circulation. The platform is recently optimized to enhance the capture efficiency and system automation. In this study, spiking tests of SK-BR-3 breast cancer cells were used for the evaluation of capture efficiency. Then, peripheral bloods from 14 pregnant women whose fetuses have evidenced non-maternal genomic markers (e.g., de novo pathogenic copy number changes) were tested for the capture of circulating fetal nucleated red blood cells (fnRBCs). Captured cells were subjected to fluorescent in situ hybridization (FISH) on chip or recovered by an automated cell picker for molecular genetic analyses. The capture rate for the spiking tests is estimated as 88.1%. For the prenatal study, 2&ndash, 71 fnRBCs were successfully captured from 2 mL of maternal blood in all pregnant women. The captured fnRBCs were verified to be from fetal origin. Our results demonstrated that the Cell RevealTM system has a high capture efficiency and can be used for fnRBC capture that is feasible for the genetic diagnosis of fetuses without invasive procedures.

Ouabain, a cardiotonic steroid, was used for the treatment of heart failure and atrial fibrillation and induces cancer cell apoptosis in many human cancer cells including human leukemia cells. However, there are no reports to show the effects on immune responses in a leukemia mouse model. In this study, WEHI-3 cell generated leukemia mice were developed and treated by oral ouabain at 0, 0.75, 1.5, and 3 mg/kg for 15 days. Results indicated that ouabain did not affect body appearance, but decreased liver and spleen weights, B- and T-cell proliferation at all three doses treatment and increased CD19 cells at 3.0 mg/kg treatment, decreased CD3, CD11b, and Mac-3 cells levels compared with positive control. Furthermore, ouabain increased the macrophage phagocytosis from peripheral blood mononuclear cell and peritoneal cavity at all three doses treatment and increased NK cell activities. Ouabain restored GOT, GPT and LDH levels in WEHI-3 leukemia mice in vivo.

Background/Aim: Ursolic acid (UA), a triterpene compound present in natural plants, has been shown to induce cytotoxic effects on many human cancer cells through induction of cell-cycle arrest and apoptosis. This study investigated the effects of UA on human lung cancer NCI-H292 cells in vitro. Materials and Methods: Flow cytometric assay was used to measure the percentage of cell viability, apoptotic cell death by double staining of annexin V and propidium iodide (PI), production of reactive oxygen species (ROS) and Ca(2+), and mitochondriaI membrane potential (Ψ(m)). UA-induced chromatin condensation and DNA fragmentation were examined by 4’,6-diamidino-2-phenylindole staining and DNA gel electrophoresis, respectively. Western blotting was used to examine the changes of apoptosis-associated protein expression in NCI-H292 cells. Results: UA reduced cell viability and induced apoptotic cell death. UA increased Ca(2+) production, reduced Ψ(m), but did not affect ROS production in NCI-H292 cells. UA increased apoptosis-inducing factor (AIF) and endonuclease G in NCI-H292 cells. Conclusion: Based on these observations, we suggest UA induces apoptotic cell death via AIF and Endo G release through a mitochondria-dependent pathway in NCI-H292 cells.

Background/aim Laminarin, mainly found in the fronds of Laminaria, has antimicrobial characteristics and induces immune responses. However, there are no available information to show the laminarin effect on glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels in mice with leukemia in vivo. Materials and methods Fifty normal BALB/c mice were separated randomly into five groups. Group I mice received normal diet as control. Leukemia was generated in groups II-V using WEHI-3 cells: Group II mice received normal diet as positive control; group III, IV and V mice received laminarin at 1, 2.5 and 5 mg/ml with ddH2O, respectively, by oral gavage every 2 days for 14 days (total of seven times). All mice were weighed during the treatment. After treatment, mice were sacrificed, blood was collected for determination of cell markers, liver and spleen samples were weighed, and spleens were used for phagocytosis and natural killer (NK) cell activity and cell proliferation using flow cytometric assay. Results Laminarin did not affect animal appearances, but increased the body weight at all doses. It reduced the weight of liver at 2.5 and 5 mg/ml and of spleen at 5 mg/ml. Laminarin increased CD3 (2.5 mg/ml) and CD19 (1 and 5 mg/ml) cell populations but reduced CD11b (5 mg/ml) cell populations, however, these did not affect Mac-3 marker level. Laminarin at 1 mg/ml increased phagocytosis by macrophages from peripheral blood mononuclear cell, but did not affect those from the peritoneal cavity. Laminarin increased NK cell cytotoxic activity at all doses and at a target ratio of 25:1 and 50:1. Laminarin did not affect B-cell proliferation, but at 5 mg/ml significantly reduced T-cell proliferation. Laminarin restored glutamate oxaloacetate transaminase (2.5 and 5 mg/ml) and glutamate pyruvate transaminase (2.5 mg/ml) levels. Based on these results, we suggest that laminarin can promote immune responses and protect against liver injury.

Partial nephrectomy has gained wider acceptance as a surgical technique in treating small renal tumors. Laparoscopic partial nephrectomy (LPN) still remains a technically demanding surgery to this day. We present our technique of laparoscopic partial nephrectomy, one that is performed without intracorporeal suturing. We performed LPN on 31 patients with localized renal parenchymal tumor (stage T1). The procedures were done from September 2009 to March 2015 at the Kaohsiung Medical University Hospital and the Kaohsiung Municipal Ta-Tung Hospital. Our technique involves the covering of renal defect layer by layer with FloSeal, Tisseel and a fat pad after monopolar coagulation. Thirty-one patients were included in this study. Mean patient age was 53 years old (range 39–70). Mean tumor size was 2.9 cm (range 1.8–6.3). Mean RENAL nephrometry score was 5.3 (range 4–7). The average operation time was 188 min (range 120–290), and the average warm ischemic time was 19.0 min (range 9–26). Mean estimated blood loss was 171 ml (range 10–650), with no postoperative bleeding among the total 31 patients. No recurrent tumors were identified at a mean follow-up of 29 months postoperatively. The mean change in eGFR was 6.5 (ml/min/m2). Laparoscopic partial nephrectomy is a feasible surgical method for most patients with stage 1 tumor. Our technique has shown to reduce warm ischemic time significantly and provide patients with excellent functional outcomes without affecting oncological results. With this technique, surgeons can perform LPN with more efficiency and with fewer complications.

Background/aim Oral cancer has been reported to be one of the major cancer-related diseases in human populations and the treatment of oral cancer is still unsatisfied. Fisetin, is a flavonoid from plants and has several biological activities such as antioxidant, anti-inflammatory and anticancer function, but its cytotoxicity in human oral cancer cells is unknown. In the present study, we investigated fisetin-induced cytotoxic effects on HSC3 human oral cancer cells in vitro. Materials and Methods/Results: We used flow cytometric assay to show fisetin induced apoptotic cell death through increased reactive oxygen species and Ca2+, but reduced the mitochondrial membrane potential and increased caspase-8, -9 and -3 activities in HSC3 cells. Furthermore, we also used 4' 6-diamidino-2-phenylindole staining to show that fisetin induced chromatin condensation (apoptotic cell death), and Comet assay to show that fisetin induced DNA damage in HSC3 cells. Western blotting was used to examine the levels of apoptotic-associated protein and results indicated that fisetin increased expression of pro-apoptotic proteins such as B-cell lymphoma 2 (BCL2) antagonist/killer (BAK) and BCL2-associated X (BAX) but reduced that of anti-apoptotic protein such as BCL2 and BCL-x, and increased the cleaved forms of caspase-3, -8 and -9, and cytochrome c, apoptosis-inducing factor (AIF) and endonuclease G (ENDO G) in HSC3 cells. Confocal microscopy showed that fisetin increased the release of cytochrome c, AIF and ENDO G from mitochondria into the cytoplasm. Conclusion Based on these observations, we suggest that fisetin induces apoptotic cell death through endoplasmic reticulum stress- and mitochondria-dependent pathways.

Background The emergence of imipenem-nonsusceptible (INS) Acinetobacter baumannii complex has had a great impact on healthcare systems worldwide. Understanding the risk factors related to INS infection is useful for infection control. The risk factors for INS A. baumannii have been well documented; however, the risk factors related to INS Acinetobacter nosocomialis infection lack documentation. The purpose of this study was to identify the risk factors associated with INS A. nosocomialis bacteremia. Methods This retrospective 9-year study included 329 adults with A. nosocomialis bacteremia in a tertiary medical center in Taiwan. Acinetobacter nosocomialis was identified using a multiplex polymerase chain reaction method and sequence analysis of a 16S–23S intergenic spacer. Results Among 329 patients with A. nosocomialis bacteremia, 67 had INS isolates (20.4%). Patients with INS isolates tended to have a more severe form of the diseases [with ICU admission and a higher APACHE (Acute Physiology and Chronic Health Evaluation) II score], specific underlying diseases (associated with chronic lung diseases and end-stage renal diseases, but less commonly alcoholism and chemotherapy), multiple invasive procedures, pneumonia as a primary focus of infection, and prior antimicrobial use (sulbactam, antipseudomonal penicillins, aminoglycosides, and carbapenems). Multivariable analysis showed that ICU admission, chronic lung diseases, arterial line catheterization, total parenteral nutrition, and prior use of carbapenems were independent risk factors; prior use of carbapenems was found to be the most influential (odds ratio 6.36, 95% confidence interval 2.00–20.21; p = 0.002). Conclusion To our knowledge, this is the first study describing the risk factors associated with INS A. nosocomialis bacteremia. Regulated antibiotic control policy, especially for carbapenem, and infection control measures targeting patients hospitalized in ICU, with chronic lung diseases and multiple invasive procedures, may be helpful in reducing INS A. nosocomialis infection.

Prostate cancer (PCa) is the most common type of cancer in males in the USA and the incidence is increasing. For castration-resistant PCa (CRPC), previous studies have identified docetaxel-based chemotherapy as the first-line therapy. In the present study, the efficacy of docetaxel-based chemotherapy was investigated in a population of patients with CRPC. This study included 26 individuals (mean age, 73 years) with CRPC who were patients between July 2007 and October 2012 at the Kaohsiung Medical University Hospital (Kaohsiung, Taiwan). The regimen consisted of intravenous docetaxel (70 mg/m2) once every four weeks plus oral prednisolone (5 mg) twice daily for five days. Prostate-specific antigen (PSA) response (defined as a PSA decrease of >50% over four weeks), time to PSA progression, PCa-specific survival and overall survival (OS) were evaluated. For these 26 patients, the mean PSA level prior to chemotherapy treatment was 335.58 ng/ml. During follow-up, the average number of cycles of chemotherapy was approximately seven and 15 patients (58%) achieved a PSA response. PSA response was found to significantly correlate with OS and PCa-specific survival (P=0.014 and P=0.028, respectively). The mean value of the PSA nadir level was 89.97 ng/ml and time to PSA nadir was five months. The most common adverse event was leucopenia, which affected 88% of the patients. The results indicated that the length of time to PSA nadir and the occurrence of leucopenia may impact the PSA response. The docetaxel-based chemotherapy was a feasible and effective treatment regimen in patients with CRPC. However, the occurrence of adverse events, particularly the high incidence of leucopenia, may be cause for concern.

Pyrrole–5-(2,6-dichlorobenzyl)sulfonylindolin-2-ones of scaffold 4 with various C-3′ side chains were designed as potent Met kinase inhibitors. Structural optimization led to compounds 10, 20, and 22–24 which demonstrated subnanomolar IC50 values in the biochemical assay. The potent compound 20 inhibited Met with IC50 value of 0.37 nM and the proliferation of MKN45 cells with IC50 of 0.22 μM. It suppressed Met autophosphorylation with the downstream signaling through Gab-1, PLC-γ, FAK, Akt, STAT3, and ERK in cell. Complete inhibition of STAT3 and ERK phosphorylation was observed in MKN45 cells treated with 20 at the concentration of 100 nM. A computation simulation study was performed to reveal the interaction of 20 with Met.

Radical surgery (RS) with adjuvant chemotherapy (AC) or radiotherapy has been conventionally used for patients with advanced urothelial carcinoma (AUC). Recent research has indicated that systemic neoadjuvant chemotherapy (NC) with RS yields better outcomes than RS alone for patients with locally advanced bladder cancer. However, there are no reports indicating whether NC or AC would be beneficial for patients with AUC. The present study compared the survival rate for AUC patients receiving NC or AC. A retrospective analysis was conducted using data for 64 patients with AUC who underwent RS and systemic chemotherapy at our institution between March 2002 and March 2011. Of the 64 patients, 30 received NC before RS and 34 received RS followed by systemic AC. Pathologic stages (p=0.002), grades (p=0.018) and lymphovascular invasion (p=0.047) were significantly lower in the patients who received NC first than in those who received RC first. Furthermore, analysis of the surgical specimens revealed that 26.7% of patients who received NC before RS had complete remission. There were no significant differences in demographic data, surgical complications, and chemotoxicity between the two patient groups. The progression-free survival (PFS) and overall survival (OS) of patients who received initial NC were significantly better than those of patients who received initial RC (p=0.002 and 0.018, respectively). Our results indicate that NC administration before RS significantly improved the PFS and OS of AUC patients, without increasing surgical complications and chemotoxicity. Further prospectively controlled trials need to be conducted to confirm the effectiveness of NC for AUC patients.

Due to the rising awareness of national health insurance services and the wide-spread use of information systems, the implementation of National Healthcare Services Systems (NHSS) becomes an important objective to the countries in the world. However, it is not an easy task to implement such a large-scale system because we often counter a great number of managerial problems. This study identifies influential factors and constructs a model from the dimensions of user characteristics, organizational context, and system characteristics for explaining National Healthcare Services Systems (NHSS) success in Taiwan based on the survey of 1215 public healthcare workers. Several key findings have been proposed. First, eight salient factors were influential to NHSS success. Second, the NHSS is not a typical type of IS, since it is designed to provide accurate health information to support the routine NHS activities. The results demonstrate that information quality is the most critical factor in influencing system use and user satisfaction. Third, this study found that service quality has a strong and positive effect on system use and user satisfaction. Fourth, to increase system use and user satisfaction, this study suggests that the NHSS provider should communicate closely with its users to gather information about their needs and preferences, and pay more attention to each individual for providing quality service. It is hoped that the findings of current study can assist governments in other countries in developing more effective NHSS and better e-Government practices.

The incidence of upper tract urothelial cancer (UTUC) has gradually increased over the past 30 years. Although most reports have shown that UTUC occurs more frequently in men than in women, women have been found to have a worse prognosis than men. In Taiwan, a high incidence of UTUC has been reported, with an unusual minor predominance of female cases. The purpose of this study was to determine the influence of gender on the outcome of patients with UTUC after nephroureterectomy and bladder cuff excision. From January 1990 to December 2007, 301 patients diagnosed with UTUC were admitted at our institution. A retrospective analysis of the effect of gender on the clinical outcome was performed. We compared the 5-year bladder recurrence-free, progression-free, and disease-specific survival rates. While we did not observe any differences between men and women in bladder recurrence-free, progression-free, or disease-specific survival rates, we found that female patients had a significantly higher percentage of contralateral recurrence than the males (5.9% vs. 0.8%, p = 0.019).

Bone cancer is one of the cancer-related diseases, and there are increased numbers of patients with bone cancer worldwide. Therefore the efficacy of treatment of bone cancer is considered extremely vital. Bufalin has been showed to have biological activities including anticancer activities in vitro and in vivo. However, the exact associated mechanisms for bufalin induced apoptosis in human bone cancer cells are still unclear. In the present study, we investigated the effect of bufalin on the cytotoxic effects in U-2 OS human osteosarcoma cells. For examining apoptotic cell deaths, we used flow cytometry assay, Annexin V/PI double staining, and TUNNEL assay. Reactive oxygen species (ROS), Ca2+, mitochondrial membrane potential (ΔΨm), and caspase-8, -9 and -3 activities were measured by flow cytometry assay. Furthermore, western blotting and a confocal laser microscopy examination were used for measuring the alterations of apoptotic associated protein expression and translocation, respectively. The results indicated that bufalin induced cell morphological changes, decreased the viable cell number, induced apoptotic cell death, and increased the apoptotic cell number, and affected apoptotic associated protein expression in U-2 OS cells. Bufalin increased apoptotic proteins such as Bak, and decreased anti-apoptotic proteins such as Bcl-2 and Bcl-x in U-2 OS cells. Furthermore, bufalin increased the protein levels of cytochrome c (Cyto c), AIF (Apoptosis inducing factor) and Endo G (Endonuclease G) in cytoplasm that were also confirmed by confocal microscopy examination. Based on those findings, bufalin induced apoptotic cell death in U-2 OS cells may be via endoplasmic reticulum (ER) stress, caspase-, and mitochondria-dependent pathways; thus, we may suggest that bufalin could be used as an anti-cancer agent for the treatment of osteosarcoma in the future, and further in vivo studies are needed.

Ouabain, the specific Na+/K+-ATPase blocker, has biological activity including anti-proliferative and anti-metastasis effects in cancer cell. There is no study to show ouabain inhibiting cell migration and invasion in human osteosarcoma U-2 OS cells. Thus, we investigated the effect of ouabain on the cell migration and invasion of human osteosarcoma U-2 OS cells. Results indicated that ouabain significantly decreased the percentage of viable cells at 2.5-5.0 μM, thus, we selected 0.25-1.0 μM for inhibiting studies. Ouabain inhibited cell migration, invasion and the enzymatic activities of MMP-2, and also affected the expression of metastasis-associated protein in U-2 OS cells. The cDNA microarray assay indicated that CDH1, TGFBR3, SHC3 and MAP2K6 metastasis-related genes were increased, but CCND1, JUN, CDKN1A, TGFB1, 2 and 3, SMAD4, MMP13, MMP2 and FN1 genes were decreased. These findings provide more information regarding ouabain inhibited cell migration and invasion and associated gene expressions in U-2 OS cells after exposed to ouabain.

Cell-free DNA (cfDNA) screening for fetal trisomy 21, 18, and 13 is now widely used in clinical practice. However, false-positives and false-negatives did occur1,2. Actually, the majority of fetal cfDNA in maternal blood is from placental trophoblasts.

This study showed an improvement in how functional groups activate on to the polymer surface by using the pen-type plasma treatment. These functional groups will graft on to the original polymer bonds and activate the surfaces of polymer products such as synthetic fabrics, films, and plastics. This research discussed the modifications of the hydrophilicity and conductivity in Polyamide 6 woven fabrics prior to and following the surface plasma treatment. First, without considering any processing, such as calendering, fabrics with the same denier but different numbers of filament were compared after the plasma treatment. The analysis of the experiment verifies that after the plasma treatment, the finer the filament the fiber has, the better improvements are obtained in the surface properties, such as hydrophilicity and surface resistivity. Next, after including the factor of calendering, the experiment also confirmed that the Polyamide 6 fabric processed with calendering exhibits better modification affects than those without it. In addition, the hydrophilicity modification result increases with irradiation time for fabrics treated with pen-type plasma, where the hydrophilicity modification benefit improves by 20–30%. Moreover, fabrics coated with poly-3, 4-ethylenedioxythiophene (PEDOT) are tested by washing. It has been confirmed that the washing resistance of the conductivity benefit appears to improve with the number of calendering times and irradiation time. The spectra show formation of COOH-groups (3300–2400 cm−1), after impregnated acrylic acid process, and also show formation of O–H (alcohol) groups (3650–3200 cm−1), after PEDOT coating.

The plasma treating process used to adjust the functional groups and modifying surface properties and mechanical behavior is a very important treatment method. Many researches have shown the results, especially in the versatility of polymer material fields. In this study, a pen-type radio frequency plasma system was used to modify the surface of various organic materials, such as polyester, polypropylene, and polyamide 6. Because of the short distance between two stainless steel electrodes, argon has been selected to trigger the plasma. The Taguchi method was used to decide the optimal combinations of the experimental parameters such as argon gas flow amount, plasma irradiation power and time, and the distance between the plasma torch and the organic fabric samples. The L9 orthogonal arrays were also used to analyze the nine combinations of samples and achieve the optimal results for improving the hydrophilic ability of polyester, polypropylene, and polyamide 6. Then, the analysis of three different types...

Past studies have shown that most of the inertial profiler's verification procedures are conducted through repeated profile measurements on test sections with known profiles. The evaluation takes account of errors from the profiler equipment (accelerometers, laser distance sensors, and displacement measuring sensors), analytical software (signal processing and IRI computations), and operator's variables (tracking footprint and moving speed). In this study, a new method is presented to set aside the error factor of operator variables and concentrate only on errors of profiler instrumentation and analysis software. An experimental design was conducted at the Fatigue and Durability Test Laboratory of the Automotive Research and Testing Center (ARTC). Using a servo‐hydraulic loading tester with indiscriminate sinusoidal vertical displacement frequencies and amplitude levels, the facility simulates several levels of roughness for different pavement test sections. This apparatus compiled sinusoidal ver...