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Background and aims Thrombomodulin (TM) is an endothelial cell membrane-bound anticoagulant protein expressed in normal arteries. After vascular injury, medial and neointimal smooth muscle cells (SMCs) exhibit large amounts of TM. The purpose of this study was to investigate the physiological significance of vascular SMC-bound TM. Methods The morphology, expression of phenotype markers and cell behaviors of cultured aortic SMCs after knockdown of TM were observed. Transgenic mice with SMC-specific TM deletion were generated, and carotid neointima formation was induced by carotid ligation. Results Cultured human aortic SMCs displayed a synthetic phenotype with a rhomboid-shaped morphology and expressed TM. TM knockdown induced a spindle-shaped change in morphology with an increased expression of contractile phenotype marker and decreased expression of synthetic phenotype marker. TM knockdown not only attenuated the proliferation of SMCs but also reduced tumor necrosis factor-α-induced nuclear factor-κB activation and interlukin-6 production. In a carotid artery ligation model, transgenic mice with SMC-specific TM deletion (SM22-cretg/TMflox/flox) had significantly less cellular proliferation in arterial walls compared with wild type mice (SM22-cretg/TM+/+). The neointima area and neointima/media area ratio were smaller in SM22-cretg/TMflox/flox mice at 4 weeks after ligation. Conclusions Our results indicate that vascular SMC-bound TM plays a role in changes of the SMC phenotype. It also influences SMC cell behavior and injury-induced neointima formation.

Advance care planning (ACP) and advance directives (ADs) ensure patient autonomy in end-of life care. The number of ADs made and followed in Taiwan is still lacking. This study aimed to determine the factors that influence the willingness to participate in ACP among outpatients in Taiwan. In this study, we conducted a cross-sectional survey based on convenient sampling methods. The questionnaire included questions about participants’ basic sociodemographic information, knowledge of ACP, and awareness of ACP. A total of 198 adults who were outpatients of a family medicine clinic in an affiliated hospital in Taiwan were recruited. The associations between each variable were evaluated using the χ2 test. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the logistic regression method to examine the influence of each variable on willingness to participate in ACP. Being happy and being a healthcare professional were positively correlated with ACP participation. A lack of ACP knowledge (OR = 0.30 in model A and OR = 0.42 in model C), valuing “Reducing families’ end-of-life decision-making burden” (OR = 2.53 in model B and OR = 2.65 in model C), and a “Belief in a good death” (OR = 4.02 in model B and OR = 4.10 in Model C) were the main factors affecting subjects’ willingness to participate in ACP. Knowing which factors influence willingness to participate in ACP helps in the promotion of ACP. Continuously educating both the general public and healthcare professionals strengthens knowledge about the right to autonomy, about its associated laws, and about the ACP process, and thus, programs should be created to provide this education. Additionally, taking into account the differences between cultures can be helpful.

BACKGROUND PCDH8 is a newly-discovered suppressor gene that is frequently inactivated by aberrant methylation in several human cancers, including prostate cancer. The identification of PCDH8 methylation can be used as a potential predictive biomarker. Prostate cancer patients with high Gleason score are considered as being at high risk for tumor recurrence and progression, and adjuvant therapy is often routinely performed in clinical practice. In the present study, we did not measure the methylation of PCDH8 in these patients. The main purpose of the present study was to evaluate the clinical significance of PCDH8 methylation in serum of prostate cancer patients with low Gleason score. MATERIAL AND METHODS PCDH8 methylation in serum samples of 117 patients and 47 controls was checked by methylation-specific PCR (MSP). Then, we correlated PCDH8 methylation status with the clinicopathological parameters of prostate cancer patients with low Gleason score and patient outcomes. RESULTS We found that PCDH8 was more frequently methylated in serum samples of patients with prostate cancer than in controls. PCDH8 methylation was correlated with advanced clinical stage (P=0.021), higher level of preoperative PSA (P=0.008), and positive lymph node metastasis (P=0.010). Moreover, patients with PCDH8 methylation had worse biochemical recurrence (BCR)-free survival (P

CXCL3 and its receptor CXCR2 were considered to play particularly important roles in the progression of malignancies. However, the investigations about CXCL3/CXCR2 axis in prostate cancer have been poorly involved. Herein we firstly reported our studies on the expression and biological roles of CXCL3 and CXCR2 in prostate cancer. Expression levels of CXCL3 and CXCR2 in prostate cancer cell lines (PC-3, DU145 and LNCaP), immortalized prostate stromal cell line (WPMY-1) and immortalized prostate epithelial cell line (RWPE-1) were investigated by RT-PCR, ELISA and western blot, whereas expression levels of CXCL3 in a prostate tissue microarray were detected by immunohistochemistry. Cell counting kit-8 and transwell assays were, respectively, utilized to determine the effects of exogenous CXCL3 on the cell proliferation and migration. We further examined whether CXCL3 could regulate the expression of genes correlated with prostate tumorigenesis by RT- PCR. Elevated expression of CXCR2 was detected in DU145, LNCaP and RWPE-1. Moreover, high-level CXCL3 can be secreted by PC-3 and RWPE-1, and CXCL3 protein expression level in tissue microarray is concordant with prostate cancer metastasis. Exogenous CXCL3 does not contribute to proliferation, but has a significant effect on migration of prostate cancer cells and RWPE-1. Finally, our data showed that exogenous CXCL3 can regulate the expression of genes including ERK, TP73, NUMB, BAX and NDRG3. Our findings suggest that CXCL3 and its receptor CXCR2 are overexpressed in prostate cancer cells, prostate epithelial cells and prostate cancer tissues, which may play multiple roles in prostate cancer progression and metastasis.

Objective To investigate the clinical significance of cadherin 13 ( CDH13) gene promoter methylation in the serum of patients with prostate cancer. Methods This prospective study examined the methylation status of CDH13 in serum samples obtained from patients with primary prostate cancer and age-matched control subjects, using methylation-specific polymerase chain reaction. Associations between methylation status of CDH13 and various clinicopathological features and patient survival were evaluated. Results A total of 98 patients with prostate cancer and 47 control subjects were enrolled in the study. CDH13 promoter methylation was detected in 44 out of 98 (44.9%) patients with prostate cancer; no methylation was found in control subjects. Methylation of CDH13 was significantly associated with an increased Gleason score, an advanced tumour stage, and a high prostate-specific antigen level. CDH13 methylation was associated with a worse survival outcome and a relative risk of death of 6.132 (95% confidence interval: 3.160, 12.187). Conclusions Promoter methylation of CDH13 occurred frequently in the serum of patients with prostate cancer, was associated with an increased risk of death, and may become a useful independent predictor of a poor prognosis.

Objective To investigate the clinical significance of protocadherin 17 ( PCDH17) promoter methylation in bladder cancer. Methods Methylation-specific polymerase chain reaction was used to examine the promoter methylation status of PCDH17 in tumour tissue specimens obtained from patients with bladder cancer, and in normal bladder epithelial tissue specimens obtained from age- and sex-matched controls. The correlations between methylation status and demographic and clinicopathological parameters, and disease outcome, were assessed. Results Methylation of the PCDH17 promoter was detected in 77/115 (67.0%) patients with bladder cancer and 0/43 (0%) of the controls. Methylation was significantly associated with high cancer grade (G3), advanced cancer stage (T2–T4), large tumour diameter (> 3 cm) and tumour recurrence. Methylation was also associated with significantly shorter survival time compared with unmethylated PCDH17 in patients with bladder cancer, and was an independent predictor of overall survival. Conclusions PCDH17 promoter methylation is closely associated with bladder cancer malignancy and may be used as an independent predictor of clinical outcomes in patients with bladder cancer.

This paper examines the relationships among core competence, unobservable human capital, and organizational performance conduct at an airport shopping center making use of personal interviews and secondary data. Factor analysis and hierarchical models are used to explore the relationship between performance and competence among employees. The findings suggest that the variables of core competences are positively correlated with organizational performance. Viewed from the perspective of job position, the management and non-management core competences of employees have different effects on organizational performances. The core competences of non-management, provide the greatest contribution to the performance of the shopping center while those for management are irrelevant.

PurposeThe purpose of this paper is to investigate whether value‐creating activities and intellectual capital (IC) accumulation are affected by different business models.Design/methodology/approachField visitations and interview‐based questionnaires are used for data collection. This study uses the structural equation model to examine Taiwanese original equipment manufacturers (OEMs) and original brand manufacturers (OBMs) in China.FindingsEmpirical results show that Taiwanese OEMs and OBMs adopt different combinations of value‐creating activities, which results in differences in IC accumulation. Taiwanese OEMs have engaged in manufacturing and innovation activities, and have created process and innovation capitals. By contrast, Taiwanese OBMs have developed their marketing channels, human resources, innovation centres, and social networks, and have accumulated their human, customer, process and innovation capitals.Practical implicationsTaiwanese OEMs have cultural advantages and have built productive infrastructure in China. Therefore, these enterprises should transform their business models into OBMs to enhance their market performance. Foreign investors could leverage the experiences and IC of Taiwanese enterprises to make their investments run more smoothly.Originality/valueThis paper contributes to the existing literature by investigating relationships among business models, value‐creating activities, and IC. This study also provides useful guidance for enterprises considering investing in China and for academics researching in this area.

Objective: To investigate the clinical and prognostic significance of protocadherin-10 (PCDH10) promoter methylation in serum-derived DNA from patients with bladder cancer. Methods: PCDH10 promoter methylation status was determined using methylation-specific polymerase chain reaction of DNA extracted from serum of patients with bladder cancer, and age- and sex-matched controls. Clinical and pathological details of bladder cancer were recorded. Results: PCDH10 promoter methylation was detected in 59/117 (50.4%) of patients with bladder cancer, and none of 37 (0%) controls. Methylation was significantly associated with advanced stage (T2 - T4), high grade (G3), tumour recurrence and larger tumour size (> 3 cm). In addition, methylation was associated with significantly worse survival and was an independent predictor of overall survival. Conclusion: Serum-based analysis of PCDH10 promoter methylation may represent a useful noninvasive biomarker of malignant behaviour and outcome in bladder cancer.

OBJECTIVES: The role and clinical significance of fragile histidine triad ( FHIT) gene in the pathogenesis of bladder urothelial carcinoma (UC) and the potential of Fhit protein as a prognostic biomarker for UC were investigated. METHODS: FHIT expression was determined according to semiquantitative immunohistochemical staining for Fhit protein levels in normal bladder and bladder UC tissues. Associations between FHIT expression, clinicopathological features and survival were evaluated. RESULTS: This study evaluated 42 cases of normal bladder and 125 cases of bladder UC; bladder UC cases had a median follow-up of 53.5 months. Immunohistochemistry showed that 95.2% of normal cases and 47.2% of bladder UC cases, respectively, were positive for Fhit protein; this difference was statistically significant. There was a significant association between negative FHIT expression in bladder UC and advanced tumour stage, high pathological grade, large tumour size, tumour recurrence and reduced survival time, but no association with age, gender, tumour number or tumour shape. CONCLUSIONS: The FHIT gene may have an important role in the pathogenesis of bladder UC and was expressed at lower levels in bladder UC compared with normal bladder tissue. Using Fhit protein as a biomarker could provide important information about patient prognosis.

Objective: A sensitive mutation detection method called co-amplification at lower denaturation temperature-polymerase chain reaction (COLD-PCR) was applied to improve the detection frequencies of expressive mutations in the H-ras gene, including exons 1 and 2, in a group of Chinese patients diagnosed with bladder cancer. Materials and Methods: The expressive mutations in the H-ras gene in 86 fresh tissues of human bladder cancer were identified by COLD-PCR or conventional PCR, followed by direct sequencing. Results: A high frequency of silent mutations of 29.1% (25 of 86) in exon 1 (c.81T>C, H27H) and activating mutations of 8.1% (7 of 86) were detected by COLD-PCR, yielding a 36% improvement in mutation detection compared with conventional PCR. No significant association was shown between activating mutations and clinicopathologic parameters, but the frequencies of silent mutations in recurrent tumors were higher than those in primary tumors (p = 0.034). Conclusions: COLD-PCR is a highly sensitive, reliable, and convenient clinical assay for mutation detection. The adoption of the method is straightforward and requires no additional reagents or instruments. Silent mutations might be important genomic alterations in bladder cancer, and play a role in bladder cancer recurrence.

This paper reexamines the relationship between ownership and firm performance. Using an unbalanced panel data in the emerging Taiwan market, we adopt a simultaneous equations framework to explore the persistence of the relationship across the life cycle of firms over time. Empirical results suggest that firm performance is a function of institutional ownership, especially in the mature stage. Through dynamic specification, evidence appears to account for lack of persistence of the impacts of ownership on performance over time. To alleviate a potential simultaneity issue, we construct a lagged specification to examine the sensitivity of our results. Consequently, the main results are found to be robust.

Patients with end-stage head and neck cancer suffer from many physical and psychological symptoms, however, there have been relatively few studies looking at end-of-life symptoms in the head and neck cancer population. The objective of this study was to describe the symptom patterns of patients with terminal head and neck cancer in the palliative care unit.A retrospective chart review of 94 patients with terminal head and neck cancer admitted to a palliative care unit between May 2006 and December 2008 was performed. Demographic data, performance status, primary tumor site, time from diagnosis to first hospice admission, survival time after admission, medication for pain control, and main symptoms at the time of admission were examined.The mean time from diagnosis to first hospice admission was 33.1 ± 51.6 months. The mean survival time in the hospice was 21.9 ± 18.9 days. In this study, the most common symptom experienced was weight loss, followed by pain, cough, dysphagia, feeding difficulties, and communication difficulties. A statistically significant association of communication difficulties was found with presence or absence of a tracheostomy (p 0.001). Change of morphine dosage after hospice care is related to the site location of head and neck cancer. Levels of education seem to be related to the increasing use of morphine (p = 0.025). Change of morphine dosage was statistically correlated with survival time after hospice admission (p 0.001)Numerous symptoms at the end of life highlight the complexity of head and neck cancer patients that may necessitate early hospice referral for symptom control.

H-cadherin (CDH13; also known as T-cadherin), which functions as a tumour suppressor, is frequently silenced by promoter methylation in human cancers including bladder transitional cell carcinoma (TCC). This study investigated the clinical significance of methylation of the CDH13 gene promoter in serum from patients with bladder TCC. Methylation status of CDH13 in serum samples from 127 patients with primary bladder TCC and 41 healthy volunteers (controls) was examined by methylation-specific polymerase chain reaction. CDH13 methylation was found in 39 patients with bladder TCC (30.7%) but in no controls. CDH13 methylation was significantly associated with advanced tumour stage, high-grade tumour, large tumour size, tumour recurrence and poor prognosis. The results suggested that CDH13 methylation in serum may be a potential predictive biomarker for malignancy in bladder TCC, and an independent pre-therapeutic predictor of outcome. Demonstration of CDH13 methylation in serum may facilitate in the prediction of which patients require more aggressive additional post-operative systemic therapy.

PurposeThe purpose of this paper is to investigate value‐relevant information provided by intellectual capital (IC) beyond financial performance under different life‐cycle stages.Design/methodology/approachThe life‐cycle classification method and the residual income model are used to examine the information technology industry.FindingsThe empirical results show that the value‐relevant information provided by IC under the growth, maturing, and stagnant stages can be ranked in order (from high to low) of custom, innovation, process, and human capital. Specifically, the empirical results indicate that overall IC provided the most value‐relevant information in the stagnant stage and the lowest value‐relevant information in the growth stage.Research limitations/implicationsThis paper reveals that evaluating the company market value merely by financial performance involves a number of limitations, thereby requiring IC to supplement the process. The internet downturn in the mid‐2000s might have likewise affected the categorization of life‐cycle stages and the value‐relevant information provided by intellectual capital during the “bubble” period.Practical implicationsManagers and investors should not merely focus on financial performance as the main value‐relevant information, but a thorough review of IC in different life‐cycle stages should be made in order to avoid making incorrect decisions.Originality/valueThis paper contributes to the existing literature by exploring customer, process, innovation, and human capital which, significantly, have different value‐relevant information in different life‐cycle stages.

Background To investigate the association between metabolic syndrome, including its factors, and gallstone disease (GSD) in a Taiwanese population. Methods We conducted a cross-sectional study during 2011 ~ 2012. A total of 12050 subjects who completed a questionnaire and underwent physical examination, laboratory tests and abdominal ultrasonography formed the study population. Results The prevalences of metabolic syndrome and gallstone disease were 24.09% and 6.16%. In an age- and sex-adjusted logistic regression model, metabolic syndrome was associated with gallstone disease (OR = 1.61; P