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Cervical cancer is a common gynecologic malignancy worldwide. It is the fourth for both incidence and mortality. For cervical cancer, imaging and pathology assessments are incorporated in the revised 2018 Federation of Gynecology and Obstetrics (FIGO) staging system. Uses of imaging techniques for the pre-treatment work-up of cervical cancer have been increasing. Among imaging techniques for the evaluation of cervical cancer, ultrasound is cheaper, faster and widely available than other imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI). Advanced technique in ultrasound, such as three-dimension (3D) ultrasound and color Doppler, have improved the clinical application of ultrasound in cervical cancer. Ultrasound may provide highly accurate information on detecting tumor presence and evaluating local tumor extent if performed by ultrasound-trained gynecologists; the experience of readers is also critical for correct pretreatment staging and assessment of response to treatment. Sonographic images could be useful to predict response of neoadjuvant chemotherapy, radiotherapy, chemotherapy and concurrent chemoradiotherapy in patients with cervical cancer. This review article attempted to present the most updated specific applications of ultrasound in cervical cancer.

Background Nasopharyngeal carcinoma (NPC) is one of the most common cancers in areas of Southeast Asia, such as Taiwan, and North Africa. The treatments of NPC, including radiotherapy and chemotherapy, were effective, but they also caused some severe side effects. Erianin, a natural product derived from Dendrobium, was proved to have anti-cancer effect in hepatoma, melanoma, non-small-cell lung carcinoma, myelogenous leukemia, breast cancer, and osteosarcoma. Hypothesis/Purpose According to previous research, we hypothesized that erianin inhibits cancer cell growth through apoptotic mechanisms. This study aimed to determine whether Erianin has an anti-NPC effect and what mechanisms were involved. Methods and Results The result showed that erianin significantly increased activation of apoptosis in NPC cell lines (NPC-039 and NPC-BM) and arrest the cell cycle obviously through mitochondrial membrane alternation, death receptors activation, and caspase-3, -8, -9 activation. Phosphorylated ERK1/2 was also decreased in erianin-treated NPC cell with dose-dependent manner, and the result was thought to promote apoptosis. Furthermore, the increased rate of apoptotic cells with erianin plus it’s inhibitors (U) was also revealed in this study. Conclusion In conclusion, this is the first research to identify the anti-NPC effect of erianin via the apoptosis mechanism. Erianin was a promising natural agent against nasopharyngeal carcinoma.

High-mobility group protein box 1 (HMGB1) is overexpressed and reported to be a prognostic factor in patients with non-small-cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutants play an important role in NSCLC progression. The aim of this study was to explore potential associations between genetic polymorphisms of HMGB1 and EGFR mutations in a cohort that included 280 patients with NSCLC, some of whom were smokers and others who never smoked. Four tagged single-nucleotide polymorphisms (SNPs) of HMGB1 were detected by a TaqMan-based real-time polymerase chain reaction (PCR) in patients. We found that after adjusting for other covariates, NSCLC patients who smoked and who respectively had CG, CT, and TC heterozygotes of HMGB1 rs2249825, rs1045411, and rs1360485, were at lower risk of developing mutant EGFR, compared to those patients with wild-type homozygotes. Moreover, significant inverse associations between the CG and CG + GG genotypes of HMGB1 rs2249825 and the EGFR hotspot mutation, an exon 19 in-frame deletion, were also observed among NSCLC patients. Within patients harboring mutant EGFR, HMGB1 rs1360485 C (TC + CC) allele carriers were at higher risk of developing poorly differentiated cancer types (odds ratio=5.493, 95% confidence interval: 1.130~26.696, p=0.019), compared to patients with TT homozygotes. Furthermore, we found that HMGB1 rs1360485 polymorphisms seemed to be related to susceptibility to developing poorly differentiated cancer linked to tobacco consumption in EGFR mutant patients. In conclusion, our results suggested that HMGB1 variants are significantly inversely associated with EGFR mutations among NSCLC patients who smoked. HMGB1 variants and tobacco consumption might contribute to the pathological development of NSCLC.

Previous studies have indicated that prenatal exposure to endocrine-disrupting chemicals (EDCs) can cause adverse neuropsychiatric disorders in children and adolescents. This study aimed to determine the association between the concentrations of prenatal EDCs and brain structure changes in teenagers by using MRI. We recruited 49 mother–child pairs during the third trimester of pregnancy, and collected and examined the concentration of EDCs—including phthalate esters, perfluorochemicals (PFCs), and heavy metals (lead, arsenic, cadmium, and mercury)—in maternal urine and/or serum. MRI voxel-based morphometry (VBM) and generalized q-sampling imaging (GQI) mapping—including generalized fractional anisotropy (GFA), normalized quantitative anisotropy (NQA), and the isotropic value of the orientation distribution function (ISO)—were obtained in teenagers 13–16 years of age in order to find the association between maternal EDC concentrations and possible brain structure alterations in the teenagers’ brains. We found that there are several specific vulnerable brain areas/structures associated with prenatal exposure to EDCs, including decreased focal brain volume, primarily in the frontal lobe, high frontoparietal lobe, temporooccipital lobe and cerebellum, and white matter structural alterations, which showed a negative association with GFA/NQA and a positive association with ISO, primarily in the corpus callosum, external and internal capsules, corona radiata, superior fronto-occipital fasciculus, and superior longitudinal fasciculus. Prenatal exposure to EDCs may be associated with specific brain structure alterations in teenagers.

Jui-Wen Peng,1 Oswald Ndi Nfor,2 Chien-Chang Ho,3,4 Shu-Yi Hsu,2 Chia-Chi Lung,2 Disline Manli Tantoh,2,5 Ming-Chih Chou,1 Yung-Po Liaw2,5 1Institute of Medicine, Chung Shan Medical University, Taichung, 40201, Taiwan; 2Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, 40201, Taiwan; 3Department of Physical Education, Fu-Jen Catholic University, New Taipei City, 24205, Taiwan; 4Research and Development Center for Physical Education, Health, and Information Technology, Fu Jen Catholic University, New Taipei, 24205, Taiwan; 5Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung City, 40201, TaiwanCorrespondence: Yung-Po LiawDepartment of Public Health and Institute of Public Health, Chung Shan Medical University, No. 110, Sec. 1 Jianguo N. Road, Taichung, 40201, TaiwanTel +886424730022 ext. 11838Fax +886423248179Email Liawyp@csmu.edu.twMing-Chih ChouInstitute of Medicine, Chung Shan Medical University, No. 110, Sec. 1 Jianguo N. Road, Taichung, 40201, TaiwanTel +886424730022 ext. 11191Fax +886423248130Email juhan0223@yahoo.com.twPurpose: Ischemic stroke accounts for approximately 85% of all strokes. Risk factors include atrial fibrillation, metabolic disorders, and genetic and lifestyle factors. There is limited evidence to support the association between atrial fibrillation and the risk of ischemic stroke based on genetic variants. We assessed the relationship between ischemic stroke and atrial fibrillation among participants in Taiwan Biobank (TWB) based on the rs2860905 variant of the cytochrome P450 Family 2 Subfamily C Member 9 (CYP2C9) gene.Materials and Methods: Using logistic regression analysis, we estimated the odds ratios (OR) and 95% confidence intervals (CI) for ischemic stroke among 17,726 biobank adults recruited from 2008 through 2015.Results: Of the eligible participants (n = 17,726), 906 were identified with ischemic stroke. Atrial fibrillation was positively associated with ischemic stroke (OR=3.70; 95% CI, 2.21– 6.20), whereas the rs2860905 variant was not. The OR for ischemic stroke among those with GA/AA genotype was 1.00 (95% CI, 0.82– 1.22) compared to those with the GG genotype. Based on the genotype-stratified analysis, the OR for ischemic stroke was 4.68 (95% CI, 2.70– 8.09) among individuals with GG genotype who had atrial fibrillation compared to those who did not.Conclusion: These results demonstrate that the GG genotype of the CYP2C9 rs2860905 variant appears to enhance the risk of ischemic stroke among adults in Taiwan. It could be essential to factor this genotype-specific contributor to ischemic stroke into clinical and experimental investigations of the disease in Taiwan.Keywords: genetic variation, risk prediction, stroke

Background DNA methylation of Cadherin 13 (CDH13), a tumor suppressor gene is associated with gene repression and carcinogenesis. We determined the relation of dietary fat and sex with CDH13 cg02263260 methylation in Taiwanese adults. Methods Data of 870 eligible participants (430 men and 440 women) between 30 and 70 years were obtained from the Taiwan Biobank (TWB) database. The association of dietary fat and sex with CDH13 cg02263260 methylation was determined using multiple linear regression. Results The association between sex and cg02263260 methylation was significant: beta-coefficient (β) = 0.00532; 95% confidence interval (CI) = 0.00195–0.00868. Moreover, the interaction between sex and dietary fat on cg02263260 methylation was significant (P-value = 0.0145). After stratification by sex, the association of dietary fat with cg02263260 methylation was significant only in women. Specifically, high dietary fat was positively associated with cg02263260 methylation in women (β = 0.00597; 95% CI = 0.00061–0.01133) and the test for trend was significant (P-value = 0.0283). Conclusion High fat intake was significantly associated with higher cg02263260 methylation in women and the test for trend was significant. These findings suggest that the association of fat intake and CDH13 cg02263260 might vary by sex and CDH13 cg02263260 methylation levels in women might increase as fat intake increases.

Human cervical cancer is the fourth most common malignancy among women worldwide, and it is expected to result in 460,000 deaths per year by 2040. Moreover, patients with cervical cancer often display drug resistance and severe side effects; therefore, the development of effective novel chemotherapeutic agents is important. In the present study, the effects of metformin, a first‑line therapeutic drug for type 2 diabetes mellitus, were evaluated in cervical cancer. Compared with the control group, metformin significantly inhibited cell viability and migration, and induced apoptosis and cell cycle arrest in human cervical cancer cell lines (CaSki and HeLa). Following metformin treatment, the protein expression levels of p‑AMP‑activated protein kinase (p‑AMPK), which promotes cell death, and the tumor suppressor protein p‑p53 were remarkably upregulated in CaSki and C33A cells compared with the control group. Furthermore, compared with the control group, metformin significantly suppressed the PI3K/AKT signaling pathway in CaSki, C33A and HeLa cells. Compound C (an AMPK inhibitor) significantly reversed the effects of metformin on CaSki, C33A and HeLa cell viability, and AMPK and p53 phosphorylation. The results of the present study suggested that metformin induced AMPK‑mediated apoptosis, thus metformin may serve as a chemotherapeutic agent for human cervical cancer.

Background and objectives: We aimed to evaluate the correlation between periodontal disease (PD) and following ocular diseases via the National Health Insurance Research Database in Taiwan. Materials and Methods: A retrospective cohort study was conducted. Subjects were regarded as having PD according to the diagnostic codes. For comparison, each subject with PD was matched to one non-PD individual from the database after exclusion. The main outcome was defined as the development of infectious keratitis, endophthalmitis, orbital cellulitis, lacrimal duct infection, uveitis and infectious scleritis. Cox proportional hazard regression was used to yield the adjusted hazard ratios (aHR) of ocular diseases between the study and control groups. Results: A total of 426,594 subjects were enrolled in both the study and control groups. In the multivariable analysis, significantly higher rates of infectious keratitis (aHR: 1.094, 95% CI: 1.030&ndash, 1.161), uveitis (aHR: 1.144, 95% CI: 1.074&ndash, 1.218) and infectious scleritis (aHR: 1.270, 95% CI: 1.114&ndash, 1.449) were found in the study group. Concerning the PD interval, infectious keratitis (aHR: 1.159, 95% CI: 1.041&ndash, 1.291) and infectious scleritis (aHR: 1.345, 95% CI: 1.055&ndash, 1.714) would significantly occur in PD patients with an interval shorter than two years, individuals with a PD interval that ranged from two to five years were under a higher risk of developing uveitis (aHR: 1.184, 95% CI: 1.065&ndash, 1.315) and infectious scleritis (aHR: 1.386, 95% CI: 1.125&ndash, 1.708), and the rate of uveitis (aHR: 1.149, 95% CI: 1.038&ndash, 1.272) was significantly higher if PD persisted more than five years. Conclusions: The presence of PD will significantly elevate the risk of developing infectious keratitis, uveitis and infectious scleritis.

Coronarin D (CD) is one of the main components of Hedychium coronarium rhizome, which has therapeutic potential by reducing cell proliferation in cancer cells. However, the mechanism of CD to 5-fluorouracil (5FU) oral cancer cell remain unclearly. This study discusses the CD to 5FU chemoresistance oral squamous cell carcinoma (OSCC) biochemical mechanisms and possibly pathways to inhibit multiplication in oral cancer. The effect of CD-treated 5FU-chemoresistance human oral cancer cell lines were subjected to MTT assay, cell cycle assay, DAPI assay, annexin-V/PI double staining assay and mitochondrial membrane potential measurement. Furthermore, western blotting was performed to assess the effect of CD on the expression levels of apoptosis related protein and MAPK signaling pathway. The results of the study evidenced that CD reduced viability of 5FU cancer cells in a dose- and time-dependent manner compared with control. The cytotoxic effect of CD lead to cell cycle arrest in the G2/M phase and induced apoptosis in both internal and external pathways. CD induces apoptosis by enhancing phosphorylation of JNK, further exploring the combination of CD and SP600125 reduced the overexpression of phosphate JNK levels. The mechanism of action of CD in 5FU on human oral cancer cells is reported for the first time and can hopeful to be a potential therapeutic agent for 5FU against human oral cancer cells.

Background and objectives: High-density lipoprotein cholesterol (HDL-C) is important for improving risk estimates of atherosclerotic cardiovascular disease. We investigated the effect of omnivore and diverse vegetarian diets in connection with exercise on HDL-C. Materials and Methods: Historical data of 9588 biobank participants (4025 exercisers and 5563 non-exercisers) aged 30&ndash, 70 years were categorized as omnivores (n = 8589), former vegetarians (n = 544), lacto-ovo vegetarians (n = 417), and strict vegetarians (n = 38). We used multiple linear regression for analyses. Results: HDL-C levels were higher in exercisers compared to non-exercisers. Compared with omnivores, strict vegetarians had decreased levels of HDL-C (&beta, = &minus, 5.705, p = 0.001) followed by lacto-ovo vegetarians (&beta, 3.900, p &lt, 0.001) and former vegetarians (&beta, 0.329, p = 0.475). The test for trend was significant (p &lt, 0.001). After categorization by exercise modalities, the &beta, value was &minus, 13.984 for strict vegetarians, &minus, 4.419 for lacto-ovo vegetarians, and &minus, 1.864 for former vegetarians, respectively (p &lt, 0.05). There was an interaction between diet and exercise (p = 0.009). Omnivores who exercised regularly had significantly higher HDL-C, whereas strict vegetarians who exercised regularly had significantly lower HDL-C. Conclusions: In summary, strict vegetarian diets in conjunction with regular exercise might not serve as healthful behaviors to be implemented in everyday life considering the negative impact on HDL-C.

Objective In this study, patients with head and neck adenoid cystic carcinoma were investigated with respect to disease characteristics, treatments, and potentially prognostic variables. Materials and Methods Between January 1995 and December 2010, 29 patients with ACC of the head and neck treated at our institution were retrospectively reviewed. Results The 29 patients had a mean age of 54.7 years. Of the 29 patients, 4 (13.8%) underwent surgical resection only, 21 (72.4%) underwent surgery with radiotherapy, and 4 (13.8%) received postoperative chemoradiotherapy. Of 9 patients (31.0%) who experienced a recurrence within the follow-up period, 3 (10.3%) had local recurrence and 5 (17.2%) had distant metastasis; 1 (3.4%) patient had both local recurrence and distant metastatic spread. Conclusion ACC is a relatively rare tumor associated with long survival, even in metastatic settings. Despite aggressive therapy with surgery, radiotherapy, and chemo- therapy, a marked potential for local and distant recurrence still remains.

Aims Heart failure (HF) influences health‐related quality of life. However, the factors that contribute to health‐related quality of life remain unclear in Taiwan. We aim to identify the factors influencing health‐related quality of life in HF patients. Methods Hospitalized HF (N = 225) patients were included from April 2011 to April 2014. Health‐related quality of life was assessed by using the 36‐Item Short‐Form Health Survey (SF‐36) and the Minnesota Living with Heart Failure Questionnaire. A new cut‐off was conducted based on the combination of SF‐36 and Minnesota Living with Heart Failure questionnaire. Results There were significant differences between good and poor quality groups on age, gender, education levels, occupational classification caregiver, New York Heart Association classes, and the numbers of comorbidities. The logistic regression analysis showed that the number of comorbidities was more than three and New York Heart Association class IV were significantly associated with health‐related quality of life.

Rheumatoid arthritis (RA) is an autoimmune disease caused by genetic and environmental factors. Infection is proposed to contribute to the pathogenesis.1 Several viral and bacterial infections, including parvovirus B19, Chikungunya, hepatitis C, Epstein-Barr virus and Porphyromonas gingivalis , have been raised to be associated with RA.1 The mechanism of how infections affect RA remains undetermined, generally considered to be via molecular mimicry and cross-reactions between self-antigens and viral proteins.1 Furthermore, recent study postulates that RA may be the result of immunosenescence, meaning premature ageing of the immune system via various mechanisms including telomere shortening.2 A recent review article illustrates that the expression of human telomerase reverse transcriptase was influenced by human papillomavirus (HPV) E6/E7.3 Therefore, immunosenescence caused by telomere shortening may be another hypothetical mechanism in RA development followed by HPV infection. HPV infections have been found to be associated with autoimmune diseases including systemic lupus erythematosus and RA.4 5 …

Gallic acid (GA) possesses potential antitumoral activity on different types of malignancies. In this study, we aimed to explore the antitumoral effects of GA on triple-negative breast cancer (TNBC) cells, the breast cancer cells showing resistance to hormonal therapy or HER2 receptor targeting therapy. We observed that GA treatment significantly decreased the cell viability of human TNBC cell line MDA-MB-231 and HS578T in a dose-dependent manner. In addition, GA exerted a relative lower cytotoxicity on noncancer breast fibroblast MCF-10F. Next, we analyzed the changes of cell-cycle distribution in response to GA treatment and found that GA led to an increase of G0/G1 and sub-G1 phase ratio in MDA-MB-231 cells. We further explored the crucial mediators controlling cell cycle and inducing apoptotic signaling, and the findings showed that GA downregulated cyclin D1/CDK4 and cyclin E/CDK2, upregulated p21and p27, and induced activation of caspase-9 and caspase-3. In addition, we demonstrated that p38 mitogen-activated protein kinase was involved in the GA-mediated cell-cycle arrest and apoptosis. Collectively, our findings indicate that GA inhibits the cell viability of TNBC cells, which may attribute to the G1 phase arrest and cellular apoptosis via p38 mitogen-activated protein kinase/p21/p27 axis. Thus, we suggest that GA could be beneficial to TNBC treatment.

// Chun-Chi Chen 1, 2 , Shiow-Her Chiou 3 , Cheng-Lin Yang 4 , Kuan-Chih Chow 4 , Tze-Yi Lin 5 , Hui-Wen Chang 5 , Weir-Chiang You 6 , Hisu-Wen Huang 7 , Chien-Min Chen 7 , Nien-Cheng Chen 8 , Fen-Pi Chou 8 and Ming-Chih Chou 1, 9 1 Institute of Medicine, Chung-Shan Medical University, Taichung, Taiwan 2 Section of Urology, Department of Surgery, Changhua Christian Hospital, Chang-Hua, Taiwan 3 Graduate Institute of Microbiology and Public Health, National Chung Hsing University, Taichung, Taiwan 4 Graduate Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan 5 Department of Pathology, China Medical University Hospital, China Medical University, Taichung, Taiwan 6 Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan 7 Endemic Species Research Institute, Council of Agriculture, Executive Yuan, Chi-Chi, Taiwan 8 Institute of Biochemistry, Microbiology and Immunology, Chung-Shan Medical University, Taichung, Taiwan 9 Department of Family and Community Medicine, Chung-Shan Medical University Hospital, Chung-Shan Medical University, Taichung, Taiwan Correspondence to: Kuan-Chih Chow, email: kcchow@dragon.nchu.edu.tw Ming-Chih Chou, email: cs1601@csmu.edu.tw Keywords: prostate cancer, gelsolin, sortilin, CD37, tumor-infiltrated lymphocytes Received: January 13, 2017 Accepted: June 12, 2017 Published: August 23, 2017 ABSTRACT Loss of immunosurveillance is a major cause of cancer progression. Here, we demonstrate that gelsolin, a constituent of ejaculate, induces apoptosis of activated lymphocytes in prostate cancer. Gelsolin was highly expressed in prostate cancer cells, and was associated with tumor progression, recurrence, metastasis, and poor prognosis. In vitro , secreted gelsolin inactivated CD4 + T cells by binding to CD37, and induced apoptosis of activated CD8 + T lymphocytes by binding to Fas ligand during cell contact dependent on major histocompatibility complex I. Moreover, secreted gelsolin bound to sortilin, which in turn bound to Wiskott-Aldrich syndrome protein family member 3, thereby enhancing the endocytosis and intracellular transport of essential lipids needed to facilitate tumor growth and expansion. Under normal conditions, gelsolin is a seemingly harmless protein that prevents immune responses in female recipients. In disease states, however, this protein can inhibit immunosurveillance and promote cancer progression.

Objectives To determine the association between usages of proton pump inhibitors (PPIs) and subsequent risk of pneumonia in dementia patients. Design Retrospective cohort study. Setting Taiwanese National Health Insurance Research Database. Participants The study cohort consisted of 786 dementia patients with new PPI usage and 786 matched dementia patients without PPI usage. Measurements The study endpoint was defined as the occurrence of pneumonia. The Cox proportional hazard model was used to estimate the pneumonia risk. Defined daily dose methodology was applied to evaluate the cumulative and dose-response relationships of PPI. Results Incidence of pneumonia was higher among patients with PPI usage (adjusted hazard ratio (HR) = 1.89; 95% CI = 1.51–2.37). Cox model analysis also demonstrated that age (adjusted HR = 1.05; 95% CI = 1.03–1.06), male gender (adjusted HR = 1.57; 95% CI = 1.25–1.98), underlying cerebrovascular disease (adjusted HR = 1.30; 95% CI = 1.04–1.62), chronic pulmonary disease (adjusted HR = 1.39; 95% CI = 1.09–1.76), congestive heart failure (adjusted HR = 1.54; 95% CI = 1.11–2.13), diabetes mellitus (adjusted HR = 1.54; 95% CI = 1.22–1.95), and usage of antipsychotics (adjusted HR = 1.29; 95% CI = 1.03–1.61) were independent risk factors for pneumonia. However, usage of cholinesterase inhibitors and histamine receptor-2 antagonists were shown to decrease pneumonia risk. Conclusion PPI usage in dementia patients is associated with an 89% increased risk of pneumonia.

Changes in concentrations of high-density lipoprotein cholesterol (HDL-C) are modified by several factors. We examined the relationship between aerobic exercise and HDL-C among different categories of body mass index (BMI) and waist-hip ratio (WHR) and the impact of rs1800588 variant in the hepatic lipase (LIPC) gene. We analyzed data from 6184 men and 8353 women aged 30&ndash, 70 years. Participants were grouped into two WHR categories: Normal (0 &lt, WHR &lt, 0.9 for men and 0 &lt, 0.8 for women) and abnormal (WHR &ge, 0.9 for men and WHR &ge, 0.8 for women). The BMI categories were: Underweight (BMI &lt, 18.5 kg/m2), normal weight (18.5 &le, BMI &lt, 24 kg/m2), overweight (24 &le, 27 kg/m2), and obese (BMI &ge, 27 kg/m2). Multivariate linear regression models were used to investigate associations between HDL-C and exercise. Aerobic exercise was significantly associated with higher HDL-C (&beta, = 1.18325, p &lt, 0.0001) when compared with no exercise. HDL-C was significantly lower in persons with abnormal compared to those with normal WHR (&beta, = &minus, 3.06689, 0.0001). Compared with normal weight, overweight and obese categories were associated with lower HDL-C, with &beta, values of &minus, 4.31095 and &minus, 6.44230, respectively (p &lt, 0.0001). Unlike rs1800588 CT and TT genotypes, associations between aerobic exercise and HDL were not significant among CC carriers no matter their BMI or WHR.

Education, sex, and the APOE-rs405509 variant are associated with Alzheimer&rsquo, s disease and cognitive performance. We investigated if the rs405509 TT, TG, and GG genotypes modulate the effect of sex and education on cognitive impairment in Taiwanese adults. Data on cognitive health (defined by Mini-Mental State Examination (MMSE) scores) and rs405509 were from Taiwan Biobank. Participants included 2105 men and 2027 women with a mean age of 64 years. Education below university level was significantly associated with lower MMSE scores. The odds ratios (ORs) were 1.82, 95% confidence interval (CI) 1.38&ndash, 2.41 for senior high school, 3.39, 95% CI 2.50&ndash, 4.59 for junior high school, and 11.94, 95% CI 9.91&ndash, 15.50 for elementary school and below (p-trend &lt, 0.05). The association between MMSE score and sex was significant only in the lowest educational group (elementary and below), with lower odds of having a low MMSE score in men compared to women (OR = 0.51, 95% CI 0.34&ndash, 0.77). After stratification by rs405509 genotypes, this association was significant only among TT genotype carriers (OR = 0.481, CI = 0.253&ndash, 0.915). In conclusion, a significant association between MMSE score and sex was observed in the lowest educational group, especially among carriers of rs405509 TT genotypes.

The effects of genetic variants on the interaction between hyperlipidemia and sex have not been investigated among gout patients in Taiwan. Using Taiwan Biobank and the National Health Insurance Research Database (NHIRD), we examined hyperlipidemia, sex, and their relationship with gout among Taiwanese adults with the human leukocyte antigen B (HLA-B) genetic variants. Hyperlipidemia was present in 1437 patients with gout. Sex and hyperlipidemia had significant associations on gout risk, with hyperlipidemia showing a relatively stronger effect. Gout was present in men, with an odds ratio (OR) of 1.945 (95% confidence interval (CI) 1.568&ndash, 2.411) compared to women, and in hyperlipidemic (OR = 4.032, 95% CI: 3.581&ndash, 4.540) compared to non-hyperlipidemic patients. The interaction of sex and hyperlipidemia was significant for rs2523608 GG (p = 0.0402) and rs4713518 AA (p = 0.0003) genotypes. After stratification, hyperlipidemia remained a risk factor in women (OR = 4.735, 95% CI: 3.375&ndash, 6.643) and men (OR = 3.640, 95% CI: 2.916&ndash, 4.544) with rs2523608 GG genotype. The odds ratio in hyperlipidemic women and men with rs4713518 AA genotype was 7.454 (95% CI 5.103&ndash, 10.888) and 3.585 (95% CI 2.854&ndash, 4.503), respectively. Our study indicates that hyperlipidemia-sex interactions exist for gout risk in Taiwanese adults with rs2523608 GG and rs4713518 AA genotypes.

The purpose of this study was to investigate whether individuals receiving influenza vaccines have a lower risk of pneumonia. A nationwide population-based case-control study was conducted using data from the National Health Insurance Research Database in Taiwan. We enrolled 7565 patients each in pneumonia and non-pneumonia groups after diagnosis of patients with chronic pulmonary disease, and these patients were individually age and sex matched in a 1:1 ratio. Using conditional logistic regression analysis, adjusted odds ratios (aORs) were estimated in patients who received influenza vaccination and those who had not previously had pneumonia. Moreover, we also analyzed the interval between vaccination and the onset of pneumonia and the number of vaccinations received by patients. This was compared with patients who never received influenza vaccination. Patients who had received influenza vaccination and had been vaccinated for two consecutive years (aOR = 0.85, confidence interval (CI) = 0.79&ndash, 0.93 and aOR = 0.75, CI = 0.67&ndash, 0.85, respectively) showed lower rates of pneumonia occurrence by 15&ndash, 25%. In conclusion, influenza vaccination significantly reduces the occurrence of pneumonia, especially in individuals who receive vaccination in consecutive years.

Elevated levels of high-density lipoprotein cholesterol (HDL-C) have been associated with a decreased risk of coronary heart disease (CHD). An active lifestyle is necessary in order to improve lipid HDL-C, including (but not limited to) physical exercise. Research on the association between badminton, an intermittent exercise, and HDL-C is limited. We investigated the impact of aerobic exercise and badminton on HDL-C levels in Taiwanese adults. The sociodemographic data of 7797 participants comprising 3559 men and 4238 women aged between 30 to 70 years were retrieved from the Taiwan Biobank. The participants were grouped into three exercise categories&mdash, no exercise, aerobic exercise, and badminton exercise. The HDL-C levels were compared using an analysis of variance (ANOVA). The multivariate linear regression models were used to determine the associations between HDL and exercise. Comparing the other two groups to the no-exercise group, the individuals who were engaged in aerobic and badminton exercise were significantly associated with a higher HDL-C (&beta, =1.3154, p &lt, 0.0001 and &beta, = 6.5954, p = 0.0027, respectively). Aerobic exercise and badminton were also associated with higher HDL-C levels among carriers of the lipoprotein lipase (LPL) rs328 genotypes. Aerobic exercise and regular badminton were associated with higher levels of HDL-C, with the badminton group being more significant.

Colorectal cancer (CRC) is a multifactorial malignancy, and its high incidence and mortality rate remain a global public health burden. Fibroblast growth factor receptor 4 (FGFR4) is a receptor tyrosine kinase that has been shown to play a key role in cancer development and prognosis via the activation of its downstream oncogenic signaling pathways. The present study aimed to explore the impact of FGFR4 gene polymorphisms on the risk and progression of CRC. Three FGFR4 single-nucleotide polymorphisms (SNPs), including rs1966265, rs351855, and rs7708357, were evaluated in 413 CRC cases and 413 gender- and age-matched cancer-free controls. We did not observe any significant association of three individual SNPs with the risk of CRC between the case and control group. However, while assessing the clinicopathological parameters, patients of rectal cancer possessing at least one minor allele of rs1966265 (AG and GG, AOR, 0.236, p = 0.046) or rs351855 (GA and AA, AOR, 0.191, p = 0.022) were found to develop less metastasis as compared to those who are homozygous for the major allele. Further analyses using the datasets from the Genotype-Tissue Expression (GTEx) Portal and The Cancer Genome Atlas (TCGA) revealed that rs351855 regulated FGFR4 expression in many human tissues, and increased FGFR4 levels were associated with the occurrence, advanced stage, and distal metastasis of colon adenocarcinoma. These data suggest that the amino acid change in combination with altered expression levels of FGFR4 due to genetic polymorphisms may affect CRC progression.

The treatment of cancer is an important issue in both developing and developed countries. Clinical use of ultrasound in cancer is not only for the diagnosis but also for the treatment. Focused ultrasound surgery (FUS) is a noninvasive technique. By using the combination of high-intensity focused ultrasound (HIFU) and imaging method, FUS has the potential to ablate tumor lesions precisely. The main mechanisms of HIFU ablation involve mechanical and thermal effects. Recent advances in HIFU have increased its popularity. Some promising results were achieved in managing various malignancies, including pancreas, prostate, liver, kidney, breast and bone. Other applications include brain tumor ablation and disruption of the blood-brain barrier. We aim at briefly outlining the clinical utility of FUS as a noninvasive technique for a variety of types of cancer treatment.

Background and objectives: Breast cancer is a common cancer in women and has been the fourth leading cause of death in Taiwanese women. Risk factors for breast cancer include family history of breast cancer, genetic factors, and not breastfeeding. Several studies have reported an association between repeated inflammation at a young age, especially among lactating women, and cancer, however, the number of studies about the association of mastitis and breast cancer in nonlactating women is still limited. Therefore, the aim of this study was to determine the relationship between mastitis in women aged &ge, 40 years and breast cancer. Materials and Methods: This was a retrospective cohort study design. The data source was the Longitudinal Health Insurance Database 2010 (LHID 2010), comprising data collected by Taiwan&rsquo, s National Health Insurance program. Cases of newly diagnosed mastitis in women aged &ge, 40 years (ICD-9-CM code = 611.0) were selected from the years 2010 to 2012. Women not diagnosed with mastitis were selected as the control group, and their data for the years 2009 to 2013 were obtained through the database. In addition, the non-mastitis group was matched 1:10 by age. Results: A total of 8634 participants were selected from the LHID 2010, which included 734 cases with mastitis and 7900 cases without mastitis. After adjustment for age, hypertension, hyperlipidemia, diabetes, hypothyroidism, and autoimmune diseases, the Cox proportional hazard model showed that patients with mastitis had a higher risk of breast cancer (aHR = 3.71, 95% CI = 1.9&ndash, 7.02) compared with the non-mastitis group. The Kaplan&ndash, Meier curve also showed that women with mastitis had a higher risk of developing breast cancer. Conclusions: This study confirmed that women with mastitis have a higher risk of developing breast cancer. Therefore, women aged &ge, 40 years could reduce breast cancer risk by taking precautions to prevent mammary gland infection and mastitis.

Elevated levels of high-density lipoprotein cholesterol (HDL-C) have been associated with a decreased risk of coronary heart disease (CHD). An active lifestyle is necessary to improve HDL-C, including (but not limited to) physical exercise. Research on the association between badminton, an intermittent exercise, and HDL-C is limited. We investigated the impact of aerobic exercise and badminton on HDL-C levels in Taiwanese adults. The sociodemographic data of 7543 participants, comprising 3472 men and 4071 women aged between 30 and 70 years, were retrieved from the Taiwan Biobank. The participants were grouped into three exercise categories&mdash, no exercise, aerobic exercise, and badminton exercise. The HDL-C levels were compared using an analysis of variance (ANOVA). Multivariate linear regression models were used to determine the associations between HDL and exercise. Comparing the other two groups to the no-exercise group, the individuals who were engaged in aerobic and badminton exercise were significantly associated with higher HDL-C levels (&beta, = 1.4077, p &lt, 0.0001 and &beta, = 5.6052, p = 0.0079, respectively). Aerobic exercise and badminton were also associated with higher HDL-C levels among carriers of the lipoprotein lipase (LPL) rs328 genotypes. Aerobic exercise and regular badminton were associated with higher levels of HDL-C, with the badminton group being more significant.

The incidence of oral cancer is increasing all over the world, with rates particularly high in Southeast Asian countries, such as Taiwan. Coronarin D (CD) has been confirmed to have anti-inflammatory, anti-bacterial effects, and anti-apoptotic effects in human hepatocellular carcinoma and nasopharyngeal carcinoma. The purpose of this study is to explore whether CD has a suppression effect on oral cancer cells and the mechanisms involved. The results of our study revealed the significantly decreased cancer cell viability and increased activation of apoptosis via increased loss of mitochondrial membrane potential, increased death receptors, leading to the activation of caspase-8, -9, -3. Moreover, the rate of apoptosis of cells treated with CD plus JNK inhibitors was decreased compared to CD-treated cells. This is the first study to demonstrate that CD induces apoptosis in human oral cancer cells and can be expected to be a promising anticancer agent for oral cancer treatment.

Osteosarcoma is the most frequent bone tumor, characterized by a high metastatic potential. However, the crosstalk between chemokine (C-C motif) ligand 3 (CCL3), which facilitates tumor progression and metastasis. Vascular endothelial growth factor-A (VEGF-A), an angiogenesis inducer and a highly specific mitogen for endothelial cells, has not been well explored in human osteosarcoma. Here we demonstrate the correlation of CCL3 and VEGF-A expressions, quantified by immunohistochemistry, with the tumor stage of human osteosarcoma tissues. Furthermore, CCL3 promotes VEGF-A expression in human osteosarcoma cells that subsequently induces human endothelial progenitor cell (EPC) migration and tube formation. Phosphorylation of JNK, ERK, and p38 was found after CCL3 stimulation. In addition, JNK, ERK, and p38 inhibitors also abolished CCL3-induced VEGF-A expression and angiogenesis. We noted that CCL3 reduces the expression of miR-374b and miR-374b mimic by reversing CCL3-promoted VEGF-A expression and angiogenesis in vitro and in vivo. This study shows that CCL3 promotes VEGF-A expression and angiogenesis in human osteosarcoma cells by down-regulating miR-374b expression via JNK, ERK, and p38 signaling pathways. Thus, CCL3 may be a new molecular therapeutic target in osteosarcoma angiogenesis and metastasis.

Reduced nuclear p27 expression is associated with a poor outcome in various cancers, including non-small cell lung cancer (NSCLC). Cytoplasmic p27 expression was shown to be associated with an unfavorable response to chemotherapy and poor outcomes in some carcinomas, but it has not been well studied in NSCLC. Herein, p27 expression in 219 tumors surgically resected from NSCLC patients was evaluated by immunohistochemistry (IHC). The most common of p27 immunostaining in lung tumors was observed in the cytoplasm (N-/C+, 32 %), followed by negative (N-/C-, 29 %), nucleus (N+/C-, 24 %), and nucleus plus cytoplasm (N+/C+, 15 %). Kaplan-Meier and Cox regression models showed that p27 N-/C+ tumors exhibited the worst overall survival (OS) and relapse-free survival (RFS) among the four categories of tumors. Among 135 of 219 patients who received cisplatin-based chemotherapy, p27 N-/C+ tumors most commonly showed an unfavorable response to cisplatin-based chemotherapy, followed by p27 N-/C- tumors when p27 N+/C- tumors were used as a reference. IHC analysis for phosphorylated extracellular signal-regulated kinase (p-ERK) and Bcl-2 expression in the lung tumors was performed to test whether ERK activation could enhance p27 nuclear export and the expression of Bcl-2 to test whether ERK activation could enhance p27 nuclear export and Bcl-2 expression. The data showed that p-ERK expression was positively correlated with cytoplasmic p27 (N-/C+) and Bcl-2 expression in the lung tumors. Patients with high Bcl-2-expressing tumors treated with cisplatin-based chemotherapy showed unfavorable predictive values in a subset of this study population. Therefore, we suggest that cytoplasmic p27 (N-/C+) via ERK-activated Bcl-2 expression may predict an unfavorable response to cisplatin-based chemotherapy and poor outcomes in NSCLC.

MicroRNA (miR)-184 has been reported to have a dual role in human cancers. However, the role of miR-184 in non-small cell lung cancer (NSCLC) remains unclear. Wild-type or mutant CDC25A promoters were constructed by PCR and site-directed mutagenesis to verify whether miR-184 could inhibit CDC25A expression at post-transcription level. Boyden chamber assay was used to assess whether miR-184 could modulate cell invasiveness via targeting CDC25A and c-Myc. We utilized 124 tumors from NSCLC patients to determine miR-184, miR-21, PDCD4 mRNA, c-Myc mRNA, and CDC25A mRNA expression levels by means of real-time PCR analysis. The prognostic value of CDC25A, c-Myc, and miR-184 on overall survival (OS) and relapse-free survival (RFS) was evaluated by Kaplan–Meier and Cox regression analysis. MiR-184 suppressed CDC25A expression by enhancing the instability of its mRNA as a result of miR-184 binding to its coding region. An increase in CDC25A expression by means of a reduction in miR-184 promotes cell invasiveness. Moreover, a concomitant increase in CDC25A and c-Myc expression as a result of decreased miR-184 via the miR-21-mediated PDCD4 reduction is responsible for cell invasiveness. Among patients, miR-184 expression in lung tumors was found to correlate negatively with CDC25A mRNA, c-Myc mRNA, and miR-21 expression, but was positively related to PDCD4 mRNA expression. High-miR-184, High-CDC25A, or high-c-Myc mRNA tumors exhibited shorter OS and RFS periods than their counterparts. The worst OS and RFS were observed in low-miR-184/high-CDC25A/high-c-Myc tumors, followed by low-miR-184 /high-CDC25A, low-miR-184/high-c-Myc, high-c-Myc, and high-CDC25A tumors. MiR-184 as a tumor suppressor miR inhibits cell proliferation and invasion capability via targeting CDC25A and c-Myc. Low miR-184 level may predict worse prognosis in NSCLC patients.

Objectives Urothelial cell carcinoma (UCC) of the urinary bladder is a major malignancy of the genitourinary tract. Etiological factors, such as the environment, ethnicity, genetics, and diet, contribute to UCC carcinogenesis. WNT1-inducible signaling pathway protein 1 (WISP1), also known as CCN4, a cysteine-rich protein belonging to the Cyr61, CTGF, Nov (CCN) family of matricellular proteins, has many developmental functions and might be involved in carcinogenesis. This study investigated WISP1 single-nucleotide polymorphisms to evaluate UCC susceptibility and clinicopathological characteristics. Materials and methods Real-time polymerase chain reaction was used to analyze 4 single-nucleotide polymorphisms of WISP1 in 369 patients with UCC and 738 controls without cancer. Results The results showed that in 128 women with UCC who carried WISP1 rs2929973 (AG + GG) variants had a higher risk of developing an advanced muscle-invasive tumor stage (pT2–pT4, P = 0.007) and a large tumor (T1–T4, P = 0.030). Further analyses revealed that a correlation between the expressions of WISP1 and invasive tumor and large tumor size in urothelial carcinoma was observed in the TCGA (The Cancer Genome Atlas) dataset. Conclusions Our results indicated that patients with UCC carrying rs2977530 genetic variants (AG + GG) have a higher risk of developing a more invasive tumor stage and a large tumor. WISP1 polymorphisms may serve as a marker or a therapeutic target in UCC.

Pneumocytoma, former known as sclerosing hemangioma, is a rare and benign tumor in lung which derived from primitive respiratory epithelium. It’s usually a single tumor, size from 0.3–7 cm (70% of patient

Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Human WW domain-containing oxidoreductase (WWOX) gene has been identified as a tumor suppressor gene in multiple cancers. We hypothesize that genetic variations in WWOX are associated with HCC risk. Methodology/principal findings Five single-nucleotide polymorphisms (SNPs) of the WWOX gene were evaluated from 708 normal controls and 354 patients with HCC. We identified a significant association between a WWOX single nucleotide polymorphism (SNP), rs73569323, and decreased risk of HCC. After adjustment for potential confounders, patients with at least one T allele at rs11545028 of WWOX may have a significantly smaller tumor size, reduced levels of α-fetoprotein and alanine aminotransferase (ALT). Moreover, the A allele at SNP rs12918952 in WWOX conferred higher risk of vascular invasion. Additional in silico analysis also suggests that WWOX rs12918952 polymorphism tends to affect WWOX expression, which in turn contributes to tumor vascular invasion. Conclusions In conclusion, genetic variations in WWOX may be a significant predictor of early HCC occurrence and a reliable biomarker for disease progression.

MiR-21 has been associated with poor prognosis in colon adenocarcinomas. However, in our preliminary data, the prognostic value of miR-21 levels was observed only in adenomatous polyposis coli (APC)-mutated tumours, not in APC-wild-type tumours. We explored whether β-catenin nuclear translocation was synergistically promoted by miR-21 in APC-mutated cells but not in APC-wild-type cells. We enrolled 165 colorectal tumour to determine APC mutation, miR-21 levels and nuclear β-catenin expression by direct sequencing, real-time PCR and immunohistochemistry. Overall survival and relapse-free survival were analysed by Kaplan-Meier and Cox regression models. The mechanistic action of β-catenin nuclear translocation modulated by miR-21 and its effect on cell invasion were evaluated in a cell model. Positive nuclear β-catenin expression was more commonly occurred in APC-mutated tumours than in APC-wild-type tumours. High miR-21 levels were relatively more common in tumours with positive nuclear β-catenin expression than in those with negative nuclear β-catenin expression. APC-mutated tumours with high miR-21 levels had shorter overall survival and relapse-free survival periods compared with others. However, the prognostic value of miR-21 levels was not observed in APC-wild-type tumours. Phosphorylation of β-catenin at Ser552 via the miR-21-mediated PTEN/AKT axis plays a critical role in β-catenin nuclear translocation in APC-mutated cells but not in APC-wild-type cells. Moreover, nuclear β-catenin expression increased by miR-21 is responsible for the capability of invasiveness. In summary, nuclear translocation of β-catenin increased by miR-21 promotes tumour malignancy and a poor outcome in APC-mutated patients but not in APC-wild-type colorectal cancer.

Background: Our study aimed to assess the endometrial cancer risk after tamoxifen adjuvant treatment for female breast cancer patients in Taiwan. Materials and Methods: A total of 74,280 breast cancer patients between January 1997 and December 2004 were included in the study; 39,411 received tamoxifen treatment and 34,869 did not. Tamoxifen-associated endometrial cancer was defined as endometrial cancer that occurred in patients at least 6-month after the diagnosis of breast cancer, who underwent tamoxifen treatment. Results: A total of 222 patients developed endometrial cancer, and of these,153 (69 %) were seen in patients with tamoxifen treatment, and 69 (31%) were seen in patients without the use of tamoxifen. The incidence of endometrial cancer was 0.388% (153/39,411) in patients with tamoxifen treatment, while was 0.198% (69/34,869) in patients without tamoxifen treatment. Logistic regression analysis demonstrated that tamoxifen use and age over 35 years were significantly correlated with development of endometrial cancer (p

This study investigated the association of statin use with sepsis risk in patients with dementia. This retrospective cohort study was conducted in Taiwan by using data from the National Health Insurance Research Database. We identified and enrolled 308 patients with newly diagnosed dementia who used statin after dementia diagnosis. These patients were individually propensity score matched (1:1) according to age, sex, hypertension, hyperlipidemia, diabetes, cerebrovascular disease, renal disease, liver disease, asthma, malignancy, parkinsonism, and dementia drugs used (donepezil, rivastigmine, galantamine, and memantine) with 251 controls (statin non-users). A Cox proportional hazard model was used to estimate the adjusted hazard ratio for sepsis in statin users and non-users. After adjustment for other confounding factors, the incidence of sepsis in statin users was 1.42-fold higher than that in non-users (95% confidence interval = 0.81&ndash, 2.5). In conclusion, our analysis showed no positive association of sepsis with statin use in patients with dementia.

Fractional exhaled nitric oxide (FeNO) measurement is an important noninvasive tool for evaluating eosinophilic inflammation of the airways. However, measurement of online FeNO in elderly people may not be possible if they are unable to perform the expiratory maneuver. The offline FeNO test is an alternative method that obviates the need for the expiratory maneuver. Adult asthma patients were enrolled and assigned to one of two age groups: group 1, aged >65 years old (n = 29), and group 2, control group, aged 20-65 years old (n = 27). Online and offline FeNO measurements were performed for all patients. There were no significant differences in pulmonary function parameters (forced expiratory volume in 1 second [FEV1], percentage of predicted FEV1, and FEV1/forced vital capacity [FVC]) between the two groups but group 1 had significantly lower Asthma Control Test scores. There was a high correlation between online and offline FeNO levels (r = 0.908; p < 0.001). There was significantly higher mean FeNO level, regardless of online or offline measurements, in patients with poorly controlled asthma. Offline FeNO measurement was found to be a simple and convenient method of measuring FeNO in elderly patients and can be used as an objective guide for further management of eosinophilic inflammatory airway disease in this population.

Background: The direct impact of medical expenses on breast cancer incidence and mortality rate has not been sufficiently addressed. The purpose of this study is to investigate the potential correlation between the incidence and mortality rate of breast cancer and the medical expenses in Taiwan. Materials and Methods: Breast cancer cases were identified from the National Health Insurance Research Database (NHIRD) with corresponding to International Classification of Diseases, and the Ninth Revision (ICD-9) code 174, 1740-1749, 175, 1750 and 1759 from January 1999 to December 2006. Age-specific incidences were estimated by population data obtained from the Department of Statistics, Ministry of the Interior. Medical expenses, including outpatient and inpatient services, were also retrieved from the NHIRD. Results: The incidence increased from 20.06 per 100,000 in 1999 to 30.34 per 100,000 in 2006; the total expenses increased from 1,449,333,521 in 1999 to 4,350,400,592 Taiwan dollars in 2006. The age-standardized mortality rate for female breast cancer remained essentially unchanged, while the age-standardized incidence increased steadily (except 2002-2003). Among the top 20 coexisting ICD-9 codes for expenses, four are directly on cancers, while 16 are on other diseases or symptoms, which are not necessarily caused by breast cancer. Conclusions: Significantly increased medical expenditure on breast cancer failed to bring down its mortality and incidence rate. The finding has implications for healthcare policy planners in proposing strategies for breast cancer control and allocating the resources.

Background The aim of this study was to investigate the differential plasma levels of lipocalin 2 (LCN2) and its complex with MMP-9 (where MMP is matrix metalloproteinase) before and after antibiotic treatment in hospitalized adult patients with community-acquired pneumonia (CAP). Method Plasma LCN2 and LCN2/MMP-9 complex levels were measured in 61 adult patients with CAP and 60 healthy controls using commercial enzyme-linked immunosorbent assay (ELISA). Results A decrease in the number of white blood cells (WBCs) and neutrophils and decreases in the levels of C-reactive protein (CRP), LCN2, and LCN2/MMP-9 complex were observed after antibiotic treatment. The plasma level of LCN2, but not that of CRP, was correlated with the severity of CAP based on the Pneumonia Severity Index (PSI; r = 0.333, P = 0.009), confusion, urea, respiratory rate and blood pressure (CURB)-65 (r = 0.288, P = 0.024), and Acute Physiology And Chronic Health Evaluation II (APACHE II) scores (r = 0.328, P = 0.010). LCN2 levels were also significantly correlated with LCN2/MMP-9 levels and the numbers of WBCs or neutrophils. Conclusions Plasma levels of LCN2 and the LCN2/MMP-9 complex can act as adjuvant diagnostic biomarkers for CAP. Plasma LCN2 might play a further role in the clinical assessment of the severity of CAP, which could potentially guide the development of future treatment strategies.

Aim Peritoneal dialysis (PD) is an alternative treatment for elderly patients with end-stage renal disease (ESRD). In Taiwan, non-professional personnel are employed to provide assisted care for elderly patients. Whether assisted care is appropriate for elderly patients is unknown. The aim of this paper is to evaluate the outcomes of assisted care in a single centre. Methods This is a retrospective cohort study in a single medical centre. The outcomes were derived from the assessment of patient survival, technique survival and peritonitis incidence between self-care patients and assisted-care patients. Results From 1984 to 2010, there were 138 elderly PD patients at Taichung Veterans General Hospital, of which 70% were assisted-care patients and 30% self-care patients. The mean duration of PD survival was 49.2 months in self-care patients, which was significantly longer than the 17.0 months of assisted-care patients (P

Cyclosporine (CsA) nephrotoxicity shows characteristic tubular vacuolization (TV) which is endoplasmic reticulum (ER) in origin. However, the cellular events of CsA-induced TV and CsA-induced ER remained unclear. The aim of the present study was to study the nature of TV and the correlation to ER stress. Using proximal tubule NRK-52E cells in vitro and an in vivo model of acute CsA nephrotoxicity, we confirmed that CsA-induced TV was ER in origin and potentially reversible. Our results showed that CsA-induced ER stress and involved ER integrated stress response-related proteins (Bip/Grp78, ATF6, IRE1 and CHOP) but not cytoplasmic ER stress-related chaperones (HSP70, HSP40, HSP27, HSP90 and HSP60). Importantly, Bip/Grp78 was overexpressed on the membrane of TV and suppression of Bip/Grp78 blocked TV formation. In addition, suppression of Bip/Grp78-enhanced CsA-induced cell death and CsA-induced TV formation and Bip/Grp78 overexpression had a characteristic striped pattern in the tubulointerstitium. In summary, we demonstrate that CsA-induced TV was a potentially reversible process in which Bip/Grp78 overexpression is essential for TV formation. It is possible that Bip/Grp78 expression and TV formation may be involved in cellular defense mechanism against CsA nephrotoxicity.

Osteosarcoma is characterized by a high malignant and metastatic potential. Interleukin-6 (IL-6) is a multifunctional cytokine that is associated with the disease status and outcomes of cancers. However, the effect of IL-6 on migration activity in human osteosarcoma cells is mostly unknown. Here we found that IL-6 increased the migration and expression of intercellular adhesion molecule-1 (ICAM-1) in human osteosarcoma cells. Transfection of cells with ICAM-1 siRNA reduced IL-6-mediated cell migration. We also found that expression of IL-6 was significantly greater in human osteosarcoma tissues than in normal bone. The integrin-linked kinase (ILK)/Akt/AP-1 pathway was activated after IL-6 treatment, and IL-6-induced expression of ICAM-1 and migration activity was inhibited by the specific inhibitor and siRNA of ILK, Akt, and AP-1 cascades. In addition, over-expression of IL-6 shRNA inhibited the migratory ability and ICAM-1 expression in osteosarcoma cells. Taken together, these results indicate that IL-6 and IL-6 receptor interaction occurs through ILK and Akt, which in turn activates AP-1, resulting in the activations of ICAM-1 and contributing the migration of human osteosarcoma cells.

To determine expression levels of urokinase-type plasminogen activator (uPA), soluble urokinase-type plasminogen activator receptor (suPAR), plasminogen activator inhibitor-1 (PAI-1) in plasma and to identify gene polymorphisms specific to patients with pelvic inflammatory disease (PID) and healthy controls.Enzyme-linked immunosorbent assay and polymerase chain reaction-restriction fragment length polymorphism were used to measure plasma levels and polymorphisms in uPA, suPAR, and PAI-1 among seventy healthy controls and 64 PID patients before and after they received routine treatment protocols.The levels of plasma uPA (ng/ml) and soluble suPAR (pg/ml) were significantly increased in PID patients (uPA: 0.57±0.03; suPAR: 1372.04±68.20) when compared to that in normal controls (uPA: 0.55±0.06, p=0.002; suPAR: 1192.46±51.98, p=0.04); moreover, suPAR decreased significantly after treatment when compared to levels noted in the same patients (1220.06±58.14; p=0.003) after they received treatment. The increased expression of suPAR was significantly correlated with WBC counts (r=0.382, p=0.002, n=64) in blood as well as the plasma levels of CRP (r=0.441, p0.0001, n=64) and uPA (r=0.426, p0.0001, n=64) of PID patients prior to receiving treatment.Increased plasma suPAR could be a biological marker for the diagnosis of PID and may reflect a new focus in targeted therapy for pelvic inflammatory disease.

Oral cancer is a common cancer with poor prognosis. We evaluated the expression of PBK/TOPK (PDZ-binding kinase/T-LAK cell-originated protein kinase) and its prognostic significance in oral cancer. PBK/TOPK expression was measured by immunohistochemical staining of samples from 287 patients with oral cancer. The association between PBK/TOPK expression and clinicopathological features was analyzed. The prognostic value of PBK/TOPK for overall survival was determined by Kaplan-Meier analysis and Cox proportional hazard models. A high PBK/TOPK expression level was correlated with long overall survival. The prognostic role of PBK/TOPK expression was significant in young patients (p < 0.05), patients with smoking habits (p < 0.05), and late stage disease (p < 0.05). Our results suggest that PBK/TOPK expression is enhanced in oral cancer. High PBK/TOPK expression, either alone or in subgroups according to clinicopathological features, may serve as a favorable prognostic marker for patients with oral cancer.

Aim: Serum levels of soluble intracellular cell adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM) and monocyte chemotactic protein 1 (MCP-1), are elevated in patients with peripheral artery disease (PAD). However, the levels of these cell adhesion molecules in patients undergoing haemodialysis (HD) are unclear. Method: A total of 112 HD patients were included and PAD was diagnosed using the ankle-brachial index and Doppler ultrasound. Serum levels of sICAM-1, sVCAM-1 and MCP-1 were assayed using enzyme linked immunosorbent assay. Results: Out of 106 HD patients, 31 (27.7%) were diagnosed with PAD. After adjusting for risk factors, higher serum levels of sVCAM-1 and sICAM-1 were associated with PAD in HD patients, with an odds ratio of 5.3 (95% CI 3.3–65.5) and 2.7 (95% CI 1.2–21.8) respectively. Using sVCAM-1 and sICAM-1 for diagnosis of PAD in HD patients, sVCAM-1 had a sensitivity of 72.4% and specificity of 62.3% for sVCAM-1 and sICAM-1 had a sensitivity of 89.3% and a specificity of 40%. MCP-1 was not associated with PAD in HD patients. In addition, the fistula of HD patients with PAD had a lower A-V access flow. Conclusion: sVCAM-1 and sICAM-1 was associated with higher risk of PAD in HD patients. Moreover, HD patients with PAD had a lower blood flow and lower A-V access flow. Our results showed that sVCAM-1 and sICAM-1 may be used as screening markers for PAD in HD patients.

Aims and objectives. To assess the effects of respiratory training on lung function, activity tolerance and quality of life in patients with chronic obstructive pulmonary disease. Background. For patients with chronic obstructive pulmonary disease, pulmonary rehabilitation can increase activity tolerance and improve their psychological state by relieving dyspnoea and promoting their quality of life. Design. A randomised clinical trial was conducted in a local hospital. Methods. Patients with chronic obstructive pulmonary disease were randomly assigned to intervention (n = 20) and control groups (n = 20). Spirometry, six-minute walking distance and quality of life were used to assess the efficacy of respiratory training programme. Results. Significant improvement in lung function, including forced vital capacity (p = 0·037), forced expiratory volume in one-second (p = 0·006) and per cent predicted forced expiratory volume in one-second (p = 0·008) in the intervention group. Regarding efficacy of the training programme for patients with chronic obstructive pulmonary disease, in forced expiratory volume in one-second (p = 0·024) and per cent predicted forced expiratory volume in one-second (p = 0·035), six-minute walking distance significantly increased. In addition, there were significant improvements for symptoms (p = 0·018), impact (p