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The standard treatment for early-stage lung cancer is complete tumor excision by limited resection of the lung. Pre-operative localization is used before video-assisted thoracoscopic surgery (VATS) to improve the accuracy of pulmonary nodule excision. However, lung atelectasis and hypoxia resulting from controlling apnea during the localization procedure may affect the localization accuracy. Pre-procedural pulmonary recruitment may improve respiratory mechanics and oxygenation during localization. In this study, we investigated the potential benefits of pre-localization pulmonary recruitment prior to pulmonary ground-glass nodule localization in a hybrid operating room. We hypothesized that pre-localization pulmonary recruitment would increase localization accuracy, improve oxygenation, and prevent the need for re-inflation during the localization procedure. We retrospectively enrolled patients with multiple pulmonary nodule localizations before surgical intervention in our hybrid operating room. We compared localization accuracies between patients who had undergone pre-procedure pulmonary recruitment and patients who had not. Saturation, re-inflation rate, apnea time, procedure-related pneumothorax, and procedure time were also recorded as secondary outcomes. Patients who had undergone pre-procedure recruitment had better saturation, shorter procedure time, and higher localization accuracy. The pre-procedure pulmonary recruitment maneuver was effective in increasing regional lung ventilation, leading to improved oxygenation and localization accuracy.

The standard treatment for early-stage lung cancer is complete tumor excision by limited resection of the lung. Preoperative localization is used before video-assisted thoracoscopic surgery (VATS) to improve the accuracy of pulmonary nodule excision. However, lung atelectasis and hypoxia resulting from controlling apnea during the localization procedure may affect the localization accuracy. Pre-procedural pulmonary recruitment may improve the respiratory mechanics and oxygenation during localization. In this study, we investigated the potential benefits of pre-localization pulmonary recruitment prior to pulmonary ground-glass nodule localization in a hybrid operating room. We hypothesized that pre-localization pulmonary recruitment would increase the localization accuracy, improve oxygenation, and prevent the need for re-inflation during the localization procedure. We retrospectively enrolled patients with multiple pulmonary nodule localizations before surgical intervention in our hybrid operating room. We compared the localization accuracy between patients who had undergone pre-procedure pulmonary recruitment and patients who had not. Saturation, re-inflation rate, apnea time, procedure-related pneumothorax, and procedure time were also recorded as secondary outcomes. The patients who had undergone pre-procedure recruitment had better saturation, shorter procedure time, and higher localization accuracy. The pre-procedure pulmonary recruitment maneuver was effective in increasing regional lung ventilation, leading to improved oxygenation and localization accuracy.

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.

Hepatocellular carcinoma (HCC) is a fatal cancer worldwide, and surgical resection remains the standard treatment. Postoperative opioid prescription has been believed to affect cancer recurrence through complex biological pathways. We conducted a retrospective cohort study using the Longitudinal Health Insurance Database of Taiwan to evaluate the relationship between postoperative opioid use and long-term surgical outcomes of patients with HCC. This study had a retrospective cohort design. In total, 812 patients older than 20 years who underwent hepatectomy because of HCC were included. The exposure group comprised patients who used opioids during hospitalization postoperatively. The comparison group included those who never used opioids during hospitalization postoperatively. A Cox proportional hazards model was used to evaluate the overall survival or recurrence-free survival rate between the opioid group and the nonopioid group. A total of 530 patients received opioids postoperatively and 282 patients did not. The hazard ratios of overall survival and recurrence-free survival were 1.10 (95% confidence interval [CI], 0.85-1.41) and 1.15 (95% CI, 0.91-1.46), respectively. Total postoperative opioids were converted into oral morphine milligram equivalents and then divided into 3 equal subgroups: low dose,40 mg; medium dose, 40 to 144 mg; and high dose, ≥145 mg. The hazard ratios of overall survival were 0.88 (95% CI, 0.63-1.24) for the low-dose group, 1.27 (95% CI, 0.92-1.74) for the medium-dose group, and 1.14 (95% CI, 0.83-1.58) for the high-dose group. Postoperative opioids do not affect overall and recurrence-free survival in patients undergoing hepatectomy or liver transplantation because of HCC. Cancer recurrence should not be a clinical concern regarding postoperative opioid prescription.

Jui-Wen Peng,1 Oswald Ndi Nfor,2 Chien-Chang Ho,3,4 Shu-Yi Hsu,2 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 Liaw, No. 110 Sec. 1 Jianguo N. Road, Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, 40201, Taiwan, Tel +886436097501, Fax +886423248179, Email Liawyp@csmu.edu.tw Ming-Chih Chou, No. 110 Sec. 1 Jianguo N. Road, Institute of Medicine, Chung Shan Medical University, Taichung, 40201, Taiwan, Tel +886424730022 ext. 11191, Fax +886423248130, Email juhan0223@yahoo.com.twPurpose: Stroke is a complex health condition caused by multiple risk factors. We investigated whether the Cytochrome P450 2C9 (CYP2C9) rs4918758 polymorphism and sex were independently and interactively associated with ischemic stroke risk among Taiwan Biobank (TWB) participants.Material and Methods: We analyzed TWB data pertaining to 9197 female and 8625 male individuals. Data collected between 2008 and 2015 were linked to medical records in the National Health Insurance Database (NHIRD). Based on multiple logistic regression analyses, we estimated odds ratios (OR) and 95% confidence intervals (CI) for ischemic stroke.Results: We found that 441 women and 468 men had ischemic stroke. There were no differences in the risk of ischemic stroke between individuals with the TC/CC genotype and those with the TT genotype [OR (95% CI) = 1.04 (0.90– 1.21)]. When compared to women, men had an OR of 1.03 (95% CI = 0.87– 1.22) for ischemic stroke. Based on further analysis, sex was found to interact with polymorphism rs4918758 (p for interaction = 0.0019). After categorizing by sex, men with TC/CC genotype showed significant ORs but not women [OR (95% CI) = 1.32 (1.07– 16.33) vs 0.83 (0.68– 1.00)]. Further stratification by genotype showed that in comparison with their female counterparts, men with the TT and TC/CC genotypes had ORs of 0.59 (95% CI = 0.44– 0.80) and 1.36 (95% CI = 1.10– 1.68), respectively.Conclusion: According to our study, the TT genotype of rs4918758 was associated with a reduced risk of ischemic stroke in Taiwanese men when compared to women, whereas the TC/CC genotype was associated with a greater risk.Keywords: stroke, genetic variant, sex, ischemic heart, gender

Nasopharyngeal carcinoma (NPC) is one of the most aggressive malignant tumors of the head and neck. Xanthohumol (Xn) is a compound extracted in a high concentration from the hard resin of hops (Humulus lupulus L.), the basic raw material of beer. This study investigated the apoptotic effect and anticancer properties of Xn in human NPC cell lines. Our study demonstrated that at the concentration 40 μM, Xn significantly reduced cell viability and promoted cell cycle arrest in the G2/M phase in two cell lines. The results indicated that Xn induced apoptosis in NPC cell lines through annexin V/propidium iodide staining, chromatin condensation, and apoptosis-related pathways. Xn upregulated the expression of apoptosis-related proteins, namely DR5, cleaved RIP, caspase-3, caspase-8, caspase-9, PARP, Bim, and Bak, and it downregulated the expression of Bcl-2. Xn upregulated the c-Jun N-terminal kinase (JNK) in the mitogen-activated protein kinase (MAPK), and the inhibition of JNK clearly resulted in decreasing expression of Xn-activated cleaved caspase-3 and PARP. Our research provides sufficient evidence to confirm that Xn induces the MAPK JNK pathway to promote apoptosis of NPC and is expected to become a safe and acceptable treatment option for human NPC.

Antivascular endothelial growth factor (anti-VEGF) therapy has been a standard treatment for patients with metastatic colorectal cancer. However, the risk of thromboembolic events and cardiovascular events associated with this therapy remains controversial. We assessed whether anti-VEGF therapy increases the risk of thromboembolic events or major adverse cardiovascular events (MACEs) in patients with colorectal cancer based on real-world evidence. This retrospective cohort study was designed using linked 2009–2016 nationwide databases, including the Taiwan Cancer Registry, the National Health Insurance Research Database, and Taiwan’s National Death Index. In total, 189,708 patients newly diagnosed as having advanced colorectal cancer from 2009 to 2016 were identified and categorized into the anti-VEGF and comparator groups through age, sex, clinical stage, and diagnosis date (within 180 days) matching. Propensity score matching was further performed to balance the baseline characteristics between the two groups. The Kaplan–Meier method was used to create the cumulative incidence curves of thromboembolic events and MACEs, and log-rank tests were used to compare the differences in Kaplan–Meier curves. Competing hazard ratios (HRs) for thromboembolic events and MACEs were estimated using the Fine–Gray method when considering the competing event of death. Statistical analysis was performed using two-tailed tests with a significance level of 0.05. In total, 4635 patients were included in both the anti-VEGF group and comparator group. The risk of thromboembolic events and MACEs did not differ significantly between the two groups. After propensity score matching, the adjusted HR for MACEs or thromboembolic events was 1.040, which for MACEs was 0.989, and that for thromboembolic events was 1.028. The competing HR for MACEs or thromboembolic events was 0.921, which for MACEs, was 0.862, and that for thromboembolic events was 0.908. In conclusion, patients with advanced colorectal cancer who received anti-VEGF therapy did not exhibit significantly higher risks of thromboembolic events and MACEs than those without anti-VEGF therapy. Our study provides real-world evidence regarding the safety of anti-VEGF therapy in Asian patients with advanced colorectal 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

Additional file 1: Association between dietary fat and cg02263260 methylation in Taiwanese adults based on menopausal status and adjustments for ADIPOQ cg16126291 methylation.

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.

This study investigates the development of glaucoma in subjects with surgery-indicated chronic rhinosinusitis (CRS) by the use of the National Health Insurance Research Database in Taiwan. Individuals that received the functional endoscopic sinus surgery (FESS) with a diagnostic code of CRS were regarded as surgery-indicated CRS and enrolled in the study group. Four non-CRS patients were age- and gender-matched to each patient in the study group. The exclusion criteria included legal blindness, ocular tumor, history of eyeball removal, and previous glaucoma. The outcome was regarded as the development of glaucoma, and conditional logistic regression was used for the statistical analysis, which involved multiple potential risk factors in the multivariate model. A total of 6506 patients with surgery-indicated CRS that received FESS and another 26,024 non-CRS individuals were enrolled after exclusion. The age and gender distributions were identical between the two groups due to matching. There were 108 and 294 glaucoma events in the study group and control group, respectively, during the follow-up period, and the study group had a significantly higher adjusted hazard ratio (1.291, 95% confidential interval: 1.031&ndash, 1.615). The cumulative probability analysis also revealed a correlation between the occurrence of glaucoma and the CRS disease interval. In the subgroup analysis, the chance of developing open-angle glaucoma and normal-tension glaucoma was significantly higher in the study group than in the control group. In conclusion, the existence of surgery-indicated CRS is a significant risk factor for the development of glaucoma, which correlated with the disease interval.

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.

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.

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.