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Backgrounds: Influenza vaccination could decrease the risk of major cardiac events in patients with hypertension. However, the vaccine’s effects on decreasing the risk of chronic kidney disease (CKD) development in such patients remain unclear. Methods: We retrospectively analysed the data of 37,117 patients with hypertension (≥55 years old) from the National Health Insurance Research Database during 1 January 2001 to 31 December 2012. After a 1:1 propensity score matching by the year of diagnosis, we divided the patients into vaccinated (n = 15,961) and unvaccinated groups (n = 21,156). Results: In vaccinated group, significantly higher prevalence of comorbidities such as diabetes, cerebrovascular disease, dyslipidemia, heart and liver disease were observed compared with unvaccinated group. After adjusting age, sex, comorbidities, medications (anti-hypertensive agents, metformin, aspirin and statin), level of urbanization and monthly incomes, significantly lower risk of CKD occurrence was observed among vaccinated patients in influenza season, non-influenza season and all season (Adjusted hazard ratio [aHR]: 0.39, 95% confidence level [C.I.]: 0.33–0.46; 0.38, 95% C.I.: 0.31–0.45; 0.38, 95% C.I.: 0.34–0.44, respectively). The risk of hemodialysis significantly decreased after vaccination (aHR: 0.40, 95% C.I.: 0.30–0.53; 0.42, 95% C.I.: 0.31–0.57; 0.41, 95% C.I.: 0.33–0.51, during influenza season, non-influenza season and all season). In sensitivity analysis, patients with different sex, elder and non-elder age, with or without comorbidities and with or without medications had significant decreased risk of CKD occurrence and underwent hemodialysis after vaccination. Moreover, the potential protective effect appeared to be dose-dependent. Conclusions: Influenza vaccination decreases the risk of CKD among patients with hypertension and also decrease the risk of receiving renal replacement therapy. Its potential protective effects are dose-dependent and persist during both influenza and noninfluenza seasons.

胸痛為臨床常見主述，在排除心因性問題後，常因病人合併胃灼熱感，診斷為胃食道逆流。然而本案例為一位36歲女性，因反覆進食後胸痛、胃灼熱及逆流等症狀，依醫囑斷續服用氫離子幫浦抑制劑（Proton Pump Inhibitor, PPI）治療胃食道逆流約一年仍未改善，直至夜間逆流咳嗽加劇，轉至本院消化內科求治，問診後發現合併有吞嚥困難及體重減輕情形，安排上消化道內視鏡排除食道腫瘤後，經食道攝影檢查確診為食道弛緩不能症（achalasia）。個案接受經口內視鏡肌層切開術治療、營養重建及心理諮商後，胸痛、逆流及吞嚥困難等症狀大幅改善，體重也從44 kg回復至50 kg，焦慮程度亦漸緩解。針對反覆出現與胃食道逆流相似症狀，或經藥物治療無效者，應進一步評估有無吞嚥困難，與胃食道逆流作鑑別診斷，避免病人因進食困難，造成營養不良併發症，以及長期睡眠困擾導致負向情緒感受，嚴重影響生活品質。 Chest pain as a relatively common clinical symptom especially when excluding ischemic heart dis­ease, patients are often diagnosed with gastroesophageal reflux disease due to acid regurgitation and a sensation of heartburn. A 36-year-old woman had had been intermittently treated with an oral proton pump inhibitor (PPI) under the impression of gastroesophageal reflux disease for approximately one year due to recurrent chest pain, heartburn, and a sensation of regurgitation. However, the symptoms deteriorated with exacerbation at night, which was an indication of poor response to the oral medi­cation. Thus, she was transferred to the Department of Gastroenterology for further examination and treatment. After detailed inquiry, the patient also suffered from progressive dysphagia with body weight loss, chest pain and regurgitation sensation. Therefore, an upper gastrointestinal panendoscopy was performed to exclude the presence of esophageal tumors. A diagnosis of esophageal achalasia was confirmed after an upper gastrointestinal examination series was conducted. After informing the patient, per-oral-endoscopic myotomy was performed. Nutritional supplementation and psychological consultation were also provided. The patient’s symptoms (e.g., chest pain, regurgitation, and dyspha­gia) improved significantly. Body weight increased from 44 kg to 50 kg, and her anxiety level was gradually reduced. For those who diagnosed with recurrent gastroesophageal reflux disease along with a poor response to oral medications, a detailed inquiry and a specific examination should be conduct­ed for other differential diagnoses, (e.g., achalasia) that may have long-term negative impact on the patient’s nutritional status, sleep disturbance, negative emotions, and quality of life &nbsp

Heart failure (HF) and cancer have similar risk factors. HMG-CoA reductase inhibitors, also known as statins, are chemoprotective agents against carcinogenesis. We aimed to evaluate the chemoprotective effects of statins against liver cancer in patients with HF. This cohort study enrolled patients with HF aged ≥20 years between 1 January 2001 and 31 December 2012 from the National Health Insurance Research Database in Taiwan. Each patient was followed to assess liver cancer risk. A total of 25,853 patients with HF were followed for a 12-year period; 7364 patients used statins and 18,489 did not. The liver cancer risk decreased in statin users versus non-users (adjusted hazard ratio (aHR) = 0.26, 95% confidence interval (CI): 0.20–0.33) in the entire cohort in the multivariate regression analysis. In addition, both lipophilic and hydrophilic statins reduced the liver cancer risk in patients with HF (aHR 0.34, 95% CI: 0.26–0.44 and aHR 0.42, 95% CI: 0.28–0.54, respectively). In the sensitivity analysis, statin users in all dose-stratified subgroups had a reduced liver cancer risk regardless of age, sex, comorbidity, or other concomitant drug use. In conclusion, statins may decrease liver cancer risk in patients with HF.

Chronic kidney disease (CKD) is associated with malignancy, including colorectal cancer, via the potential mechanism of chronic inflammation status. This study aimed to determine whether influenza vaccines can reduce the risk of colorectal cancer in patients with CKD. Our cohort study enrolled 12,985 patients older than 55 years with a diagnosis of CKD in Taiwan from the National Health Insurance Research Database at any time from 1 January 2001 to 31 December 2012. Patients enrolled in the study were divided into a vaccinated and an unvaccinated group. In this study, 7490 and 5495 patients were unvaccinated and vaccinated, respectively. A propensity score was utilized to reduce bias and adjust the results. Cox proportional hazards regression was used to estimate the correlation between the influenza vaccine and colorectal cancer in patients with CKD. The results showed that the influenza vaccine exerted a protective effect against colorectal cancer in populations with CKD. The incidence rate of colon cancer in the vaccinated group was significantly lower than in the unvaccinated group, with an adjusted hazard rate (HR) of 0.38 (95% CI: 0.30–0.48, p < 0.05). After the propensity score was adjusted for Charlson comorbidity index, age, sex, dyslipidemia, hypertension, diabetes, monthly income, and level of urbanization, the dose-dependent effect was found, and it revealed adjusted HRs of 0.74 (95% CI: 0.54–1.00, p < 0.05), 0.41 (95% CI: 0.30–0.57, p < 0.001), 0.16 (95% CI: 0.11–0.25, p < 0.001) for one, two to three, and four or more vaccinations, respectively. In summary, the influenza vaccine was found to be associated with a reduced risk of colorectal cancer in CKD patients. This study highlights the potential chemopreventive effect of influenza vaccination among patients with CKD. Future studies are required to determine whether the aforementioned relationship is a causal one.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is estimated to be approximately about 25.24% of the population worldwide. NAFLD is a complex syndrome and is characterized by a simple benign hepatocyte steatosis to more severe steatohepatitis in the liver pathology. Phellinus linteus (PL) is traditionally used as a hepatoprotective supplement. Styrylpyrone-enriched extract (SPEE) obtained from the PL mycelia has been shown to have potential inhibition effects on high-fat- and high-fructose-diet-induced NAFLD. In the continuous study, we aimed to explore the inhibitory effects of SPEE on free fatty acid mixture O/P [oleic acid (OA): palmitic acid (PA); 2:1, molar ratio]-induced lipid accumulation in HepG2 cells. Results showed that SPEE presented the highest free radical scavenging ability on DPPH and ABTS, and reducing power on ferric ions, better than that of partitions obtained from n-hexane, n-butanol and distilled water. In free-fatty-acid-induced lipid accumulation in HepG2 cells, SPEE showed an inhibition effect on O/P-induced lipid accumulation of 27% at a dosage of 500 μg/mL. As compared to the O/P induction group, the antioxidant activities of superoxide dismutase, glutathione peroxidase and catalase were enhanced by 73%, 67% and 35%, respectively, in the SPEE group. In addition, the inflammatory factors (TNF-α, IL-6 and IL-1β) were significantly down-regulated by the SPEE treatment. The expressions of anti-adipogenic genes involved in hepatic lipid metabolism of 5’ adenosine monophosphate (AMP)-activated protein kinase (AMPK), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) were enhanced in the SPEE supplemented HepG2 cells. In the protein expression study, p-AMPK, SIRT1 and PGC1-α were significantly increased to 121, 72 and 62%, respectively, after the treatment of SPEE. Conclusively, the styrylpyrone-enriched extract SPEE can ameliorate lipid accumulation and decrease inflammation and oxidative stress through the activation of SIRT1/AMPK/PGC1-α pathways.

Background. Treating advanced colon cancer remains challenging in clinical settings because of the development of drug resistance and distant metastasis. Mechanisms underlying the metastasis of colon cancer are complex and unclear. Methods. Computational analysis was performed to determine genes associated with the exosomal long noncoding (lncRNA) plasmacytoma variant translocation 1 (PVT1)/vascular endothelial growth factor A (VEGFA) axis in patients with colon cancer. The biological importance of the exosomal lncRNA PVT1/VEGFA axis was examined in vitro by using HCT116 and LoVo cell lines and in vivo by using a patient-derived xenograft (PDX) mouse model through knockdown (by silencing of PVT1) and overexpression (by adding serum exosomes isolated from patients with distant metastasis (M-exo)). Results. The in silico analysis demonstrated that PVT1 overexpression was associated with poor prognosis and increased expression of metastatic markers such as VEGFA and epidermal growth factor receptor (EGFR). This finding was further validated in a small cohort of patients with colon cancer in whom increased PVT1 expression was correlated with colon cancer incidence, disease recurrence, and distant metastasis. M-exo were enriched with PVT1 and VEGFA, and both migratory and invasive abilities of colon cancer cell lines increased when they were cocultured with M-exo. The metastasis-promoting effect was accompanied by increased expression of Twist1, vimentin, and MMP2. M-exo promoted metastasis in PDX mice. In vitro silencing of PVT1 reduced colon tumorigenic properties including migratory, invasive, colony forming, and tumorsphere generation abilities. Further analysis revealed that PVT1, VEGFA, and EGFR interact with and are regulated by miR-152-3p. Increased miR-152-3p expression reduced tumorigenesis, where increased tumorigenesis was observed when miR-152-3p expression was downregulated. Conclusion. Exosomal PVT1 promotes colon cancer metastasis through its association with EGFR and VEGFA expression. miR-152-3p targets both PVT1 and VEGFA, and this regulatory pathway can be explored for drug development and as a prognostic biomarker.

Background: Hepatocellular carcinoma (HCC) remains an aggressive malignancy with a poor prognosis and a leading cause of cancer-related mortality globally. Cumulative evidence suggests critical roles for endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in chronic liver diseases. However, the role of ER stress in HCC pathogenesis, aggressiveness and therapy response remains unclear and understudied. Objectives: Against this background, the present study evaluated the therapeutic efficacy and feasibility of notopterol (NOT), a furanocoumarin and principal component of Notopterygium incisum, in the modulation of ER stress and cancer stemness, and the subsequent effect on liver oncogenicity. Methods: An array of biomolecular methods including Western blot, drug cytotoxicity, cell motility, immunofluorescence, colony and tumorsphere formation, flow-cytometric mitochondrial function, GSH/GSSG ratio, and tumor xenograft ex vivo assays were used in the study. Results: Herein, we demonstrated that NOT significantly suppresses the viability, migration, and invasion capacity of the human HCC HepJ5 and Mahlavu cell lines by disrupting ATF4 expression, inhibiting JAK2 activation, and downregulating the GPX1 and SOD1 expression in vitro. NOT also markedly suppressed the expression of vimentin (VIM), snail, b-catenin, and N-cadherin in the HCC cells, dose-dependently. Treatment with NOT significantly attenuated cancer stem cells (CSCs)-like phenotypes, namely colony and tumorsphere formation, with the concomitant downregulation of stemness markers OCT4, SOX2, CD133, and upregulated PARP-1 cleavage, dose-dependently. We also demonstrated that NOT anticancer activity was strongly associated with increased cellular reactive oxidative stress (ROS) but, conversely, reduced mitochondrial membrane potential and function in the HepJ5 and Mahlavu cells in vitro. Our tumor xenograft studies showed that compared with sorafenib, NOT elicited greater tumor growth suppression without adverse changes in mice body weights. Compared with the untreated control and sorafenib-treated mice, NOT-treated mice exhibited markedly greater apoptosis ex vivo, and this was associated with the co-suppression of stemness and drug-resistance markers OCT4, SOX2, ALDH1, and the upregulation of endoplasmic reticulum stress and oxidative stress factors PERK and CHOP. Conclusions: In summary, we demonstrated for the first time that NOT exhibits strong anticancer activity via the suppression of cancer stemness, enhanced endoplasmic reticulum stress and increased oxidative stress thus projecting NOT as a potentially effective therapeutic agent against HCC.

The aim of this research was to analyse football tournaments, UEFA Euro 2021 and Copa America 2021, to provide statistical measurement to predict which teams were likely to be qualified to the next round in the knockout stage. The research method used to collect six key variables statistics including total attempts, on target, possession, passes attempted, passing accuracy, and corners taken from 79 matches in UEFA Euro 2021 and Copa America 2021. The data were analysed by the grey relational analysis (GRA). The results were as follows: first, this study presented variables related to goals scored and offense correlated on goals scored. Second, this study proposed a GRA model that provides an efficient way to predict match outcomes. Third, the GRA model will perform better than the FIFA world ranking when more teams participated and the world ranking were tight.

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Until recently, sorafenib has been the only treatment approved by the U.S. Food and Drug Administration for patients with advanced hepatocellular carcinoma (HCC). Some patients, however, exhibit resistance to this treatment and subsequently experience cancer progression, recurrence, or death. Therefore, identifying a new alternative treatment for patients with little or no response to sorafenib treatment is vital. In this study, we explored the therapeutic potential and underlying molecular mechanism of antrocinol ((3aS,4R,6aS,10aR)-4-(hydroxymethyl)-7,7-dimethyldecahydro-1H-naphtho[1,8a-c]furan-1-one) in patients with HCC. The results indicated that antrocinol was more therapeutically effective than antrocin, Stivarga, and sorafenib against HCC cell lines. Antrocinol also substantially suppressed the expression of KRAS-GTP, p-MEK1/2, p-ERK1/2, and p-AKT in the Huh7 cell line. Additionally, antrocinol-induced apoptosis in the Huh7 cell line, inhibited the formation of tumorspheres, and suppressed the expression of cancer stem cell markers CD133, KLF4, CD44, OCT4, SOX2, and c-Myc. Animal studies revealed that antrocinol alone considerably suppressed tumor growth in nonobese diabetic/severe combined immunodeficient mice inoculated with Huh7 tumorspheres. It also synergistically enhanced the anticancer effect of sorafenib, resulting in enhanced suppression of tumor growth (p 0.001) and tumorsphere formation (p 0.001). In tumor samples resected from mice treated with antrocinol alone or in combination with sorafenib, immunohistochemical analysis revealed an increase in BAX expression and a decrease in ERK and AKT protein expression. To the best of our knowledge, this is the first report of the anti-HCC activity of antrocinol. With its higher therapeutic efficacy than that of sorafenib, antrocinol is a candidate drug for patients with HCC who demonstrate little or no response to sorafenib treatment.

Activation of mitogen-activated protein kinase (MAPK) and PI3K signaling confers resistance against sorafenib, a mainstay treatment for advanced hepatocellular carcinoma (HCC). Antrocin and ovatodiolide constitute as the most potent secondary metabolites isolated from Antrodia camphorata and Anisomeles indica, respectively. Both natural compounds have recently gained a lot of attention due to their putative inhibition of MAPK and PI3K signaling in various solid cancers. However, whether their combination is effective in HCC remains unknown. Here, we investigated their effect, alone or in various combinations, on MAPK and PI3K signaling pathways in HCC cells. An array of in vitro study were used to investigate anticancer and stemness effects to treat HCC, such as cytotoxicity, drug combination index, migration, invasion, colony formation, and tumor sphere formation. Drug effect in vivo was evaluated using mouse xenograft models. In this study, antrocin and ovatodiolide synergistically inhibited the SNU387, Hep3B, Mahlavu, and Huh7 cell lines. Sequential combination treatment of Huh7 and Mahlavu with ovatodiolide followed by antrocin resulted stronger cytotoxic effect than did treatment with antrocin followed by ovatodiolide, their simultaneous administration, antrocin alone, or ovatodiolide alone. In the Huh7 and Mahlavu cell lines, ovatodiolide→antrocin significantly suppressed colony formation and proliferation as well as markedly downregulated ERK1/2, Akt, and mTOR expression. Inhibition of ERK1/2 and Akt/mTOR signaling by ovatodiolide→antrocin suppressed ribosomal biogenesis, autophagy, and cancer stem cell-like phenotypes and promoted apoptosis in Huh7 and Mahlavu cells. The sorafenib-resistant clone of Huh7 was effectively inhibited by synergistic combination of both compound in vitro. Eventually, the ovatodiolide→antrocin combination synergistically suppressed the growth of HCC xenografts. Taken together, our findings suggested that ovatodiolide→antrocin combination may represent potential therapeutic approach for patients with advanced HCC.

The KRAS mutation is one of the leading driver mutations in colorectal cancer (CRC), and it is usually associated with poor prognosis and drug resistance. Therapies targeting the epidermal growth factor receptor (EFGR) are widely used for end-stage CRC. However, patients with KRAS mutant genes cannot benefit from this therapy because of Ras signaling activation by KRAS mutant genes. Our previous study revealed the anti-proliferative effect of 4-acetyl-antroquinonol B (4-AAQB) on CRC cells, but whether the drug is effective in KRAS-mutant CRC remains unknown. We screened CRC cell lines harboring the KRAS mutation, namely G12A, G12C, G12V and G13D, with one wild type cell line as the control, SW1463 and Caco-2 cell lines were used for further experiments. Sulforhodamine B assays, together with the clonogenicity and invasion assay, revealed that KRAS-mutant SW1463 cells were resistant to cetuximab, however, 4-AAQB treatment effectively resensitized CRC cells to cetuximab through the reduction of colony formation, invasion, and tumorsphere generation and of oncogenic KRAS signaling cascade of CRC cells. Thus, inducing cells with 4-AAQB before cetuximab therapy could resensitize KRAS-mutant, but not wild-type, cells to cetuximab. Therefore, we hypothesized that 4-AAQB can inhibit KRAS. In silico analysis of the publicly available GEO (GSE66548) dataset of KRAS-mutated versus KRAS wild-type CRC patients confirmed that miR-193a-3p was significantly downregulated in the former compared with the latter patient population. Overexpression of miR-193a-3p considerably reduced the oncogenicity of both CRC cells. Furthermore, KRAS is a key target of miR-193a-3p. In vivo treatment with the combination of 4-AAQB and cetuximab significantly reduced the tumor burden of a xenograft mice model through the reduction of the expression of oncogenic markers (EGFR) and p-MEK, p-ERK, and c-RAF/p-c-RAF signaling, with the simultaneous induction of miR-193a-3p expression in the plasma. In summary, our findings provide strong evidence regarding the therapeutic effect of 4-AAQB on KRAS-mutant CRC cells. Furthermore, 4-AAQB effectively inhibits Ras singling in CRC cells, through which KRAS-mutant CRC can be resensitized to cetuximab.

BACKGROUND Foreign body impaction in the upper gastrointestinal (UGI) tract is considered an emergency worldwide. This article reports our experience in the endoscopic management of foreign bodies in the UGI tract of adults. METHODS A retrospective chart review was conducted on adult patients (aged >18 years) who received endoscopic management of foreign bodies in the UGI tract at Shuang Ho Hospital between November 2008 and November 2016. RESULTS A total of 280 patients (male/female: 107/178; mean age: 56 years) were included. Fish bones were the most common ingested foreign bodies (n = 162; 56.8%), and the esophagus was the most common lodgment site (n = 222; 77.9%). The presence of symptoms indicated that the ingested foreign bodies were lodged in the hypopharynx or esophagus rather than in the stomach or duodenum (p < 0.01). The detection rate of ingested foreign bodies in the UGI tract through plain radiography was 53% (122/230). The average "door-to-scope" was 5.9 hours, and 99.2% of the patients received endoscopic management of the ingested foreign bodies within 24 hours. The complication rate was relatively low (n = 14; 4.9%). No patient received surgical intervention or died of endoscopic management. CONCLUSION Endoscopic management is a safe and highly effective procedure for extracting ingested foreign bodies. Rapid endoscopic intervention should be provided to reduce the risk of complications.

Data hiding techniques for steganography, which embed secret data in multimedia imperceptibly, are useful for protecting information security. By taking advantage of the popularity of MIDI files on the Internet, a new data hiding method via MIDI files is proposed, which modifies the velocities of musical note sequences to embed secret data. Initially, musical note sequences with monotonic pitches, each consisting of at least three consecutive notes with pitches either entirely non-decreasing or entirely non-increasing, are found from an input MIDI file. Next, for each of such musical note sequences, a reference velocity is generated for each non-end note in the sequence by a linear interpolation scheme. Then, a number of data bits are embedded into each non-end note by adding the decimal value of the bits to or subtracting the value from the corresponding reference velocity value to yield a new velocity for the note. The new velocity value does not differ much from the original one and fits the velocity trend in the musical note sequence, so that the resulting stego-MIDI file does not yield abnormal note strengths and the musical expression is kept. Moreover, a melody humanization scheme is proposed for modifying the velocity values in strength-invariant MIDI channels to create data embeddability without producing unreasonable melodies. The original MIDI file size is also kept unchanged after data embedding, avoiding attracting attentions from hackers. Experimental results show the feasibility of the proposed method. Also, a comparison with five other methods show that the method has the merit of reducing the resulting melody distortion or file-size change while yielding a reasonable secret-bit embedding rate.

Background: The assessment of symptoms distress is an important strategy for symptoms management and treatment of patients with liver cirrhosis (LC); however, appropriate instruments are limited. Objective: The objective of this study was to validate a symptoms distress scale (SDS) by confirming the appropriateness of each item using item response theory. Methods: A cross-sectional and convenience sampling was conducted to recruit eligible cirrhotic outpatients from the gastroenterology outpatient department of a single medical university hospital. In total, 163 patients with LC completed the 21-itemSDS. A graded response model with two-parameter (discrimination and difficulty) estimation was used for data analysis. Results: The item response theory model identified the validity of the SDS and found that most of the items in the SDS represented a high level of symptoms distress; moreover, three items of bruising, drowsiness, and dark urine were reported in cirrhotic patients with severe symptom distress. Four items comprising bodily pain, right upper quadrant pain, muscle cramps, and change in appearance can be appropriately represented in cirrhotic patients with mild symptoms distress. Moreover, the amount of test information in the SDS was >0.70, indicating acceptable reliability. Discussion: Items of the SDS can be useful for assessing different levels of symptoms distress; however, using the scale to assess mild symptoms distress in populations with LC should be done with great caution

BACKGROUND AND AIM The need for all-oral hepatitis C virus (HCV) treatments with higher response rates, improved tolerability, and lower pill burden compared with interferon-inclusive regimen has led to the development of new direct-acting antiviral agents. Ravidasvir (RDV) is a second-generation, pan-genotypic NS5A inhibitor with high barrier to resistance. The aim of this phase 2 study (EVEREST study) was to assess the efficacy and safety of interferon-free, 12-week RDV plus ritonavir-boosted danoprevir (DNVr) and ribavirin (RBV) regimen for treatment-naive Asian HCV genotype 1 (GT1) patients without cirrhosis. METHODS A total of 38 treatment-naive, non-cirrhotic adult HCV GT1 patients were enrolled in this multicenter, open-label, single-arm phase 2 study (NCT03020095). All patients received a combination of RDV 200 mg once daily (q.d.) plus DNVr 100 mg/100 mg twice daily (b.i.d.) and oral RBV 1000/1200 mg/day (body weight

The objectives of this study were to survey the frequency of engaging in a health-promoting lifestyle in patients with liver cirrhosis, and examine the mediating effects of a health-promoting lifestyle on relationships of symptoms and psychological distress with the quality of life (QOL). A cross-sectional study was conducted to recruit 148 cirrhotic outpatients from the gastroenterology outpatient department of one medical university hospital. All study participants completed self-administered questionnaires comprising a multidimensional symptoms scale, Hospital Anxiety and Depression Scale, short-form Chinese health-promoting lifestyle profile, and the Taiwanese version of the Short-Form 36. Hierarchical linear regression and mediation models were used to evaluate the effect of a health-promoting lifestyle on the QOL. Results showed these cirrhotic outpatients reported low frequencies of health-promoting behaviors in their daily activities and had poor mental health but superior physical health. The hierarchical linear regression model found that depression, anxiety, and a health-promoting lifestyle were significant determinants of mental health. The mediation analysis further identified that a health-promoting lifestyle acted as a significant mediator which ameliorated the effects of depression and anxiety on the mental health aspect of the QOL. A health-promoting lifestyle can improve the mental health of the QOL. Healthcare professionals can develop effective health-promoting interventions to manage and improve the mental health of cirrhotic patients.

Solder joints with Cu/Sn-Ag/Cu structure and bump height of 15 μm have been used to investigate the electromigration phenomenon at different temperatures and current densities. Moreover, the grain orientation was analyzed using electron backscatter diffraction. It was found that the anisotropic properties of tin affected the formation rate of Cu-Sn intermetallic compounds (IMCs), and that the angle between the electron flow direction and tin grain orientation played an important role in the formation of Cu6Sn5 IMC. With changes in angle, the diffusion rate of copper atoms in tin also varied. When the c-axis of tin was parallel to the electron flux, copper atoms diffused rapidly, resulting in fast formation of Cu-Sn IMCs. On the other hand, if the angle between the c-axis of the grain and the electron flow direction was large, the tin grains were more resistant to Cu diffusion during current stressing, leading to a very slow IMC formation rate.

The objective of the study was to evaluate the impact of a program based on the Teaching Personal and Social Responsibility (TPSR) on the variables of responsibility, basic psychology needs, motivation, satisfaction with life and the intention to be physically active, as well as the differences of gender. The participants were 85 students (experimental group n = 35, 17 girls and control group n = 50, 28 girls). The students of the experimental group received the TPSR for 8 months within the physical education subject. The findings indicated an improvement in the experimental group in terms of personal responsibility and in the case of female students, in basic psychological needs and intrinsic motivation. In conclusion, the TPSR program can be integrated into the physical education curriculum in order to improve the personal responsibility of students and fulfill their motivation and satisfaction of basic psychological needs.

Early detection is important for improving the survival rate of patients with gastric cancer (GC). Serum tumor markers have been widely used for detecting GC. However, their clinical values remain controversial. This study aims to investigate the role of serum cancer antigen 72-4 (CA72-4) in the diagnosis of GC in a healthy population. A total of 7757 adults who underwent upper gastrointestinal endoscopy and serum CA72-4 level measurement in multicenters in Taiwan from January 2006 to August 2016 were recruited in this retrospective study. Risk factors for GC, serum tumor markers, and esophagogastroduodenoscopy (EGD) findings were evaluated. High serum levels of CA72-4 were found in 7.2% of healthy adults. CA72-4 level showed lower sensitivity (33.3%) but higher specificity (92.8%), however, the positive predictive value was quite low (0.18%). After adjustment of clinical risk factors for GC using EGD findings, gastric ulcer (adjusted odds ratio (aOR) = 2.11), gastric polyps (aOR = 1.42), and atrophic gastritis (aOR = 1.27) were significantly associated with high serum CA72-4 levels. Furthermore, both age (OR = 1.01) and Helicobacter pylori infection (OR = 1.44) exhibited a significant association with high serum CA72-4 levels. These results indicate that routine screening of CA72-4 levels for diagnosing GC in asymptomatic patients may be ineffective due to low sensitivity and low positive predictive value. The clinical utility of EGD findings along with serum CA72-4 level for screening healthy individuals with GC is warranted.

Oral antiviral therapy may reduce the disease progression of chronic hepatitis B (CHB) patients. We aimed to further investigate the efficacy of long-term entecavir therapy in reduction of the risk of hepatocellular carcinoma (HCC), cirrhotic events and mortality in a large group of CHB-related cirrhosis patients.The C-TEAM (Cirrhosis-Taiwanese EntecAvir Multicenter) study was a nationwide, multicenter, retrospective-prospective cohort study in Taiwan. We enrolled treatment-naïve patients with CHB-related cirrhosis and baseline HBV-DNA≥2000 IU/mL receiving long-term entecavir therapy and compared the development of HCC, cirrhotic events and mortality with that of a historical untreated cohort.In total, 1315 entecavir-treated and 503 untreated patients with cirrhosis were enrolled, with median treatment and follow-up durations of 4 and 6 years respectively. Compared with the untreated cohort, entecavir therapy was associated with a 60% HCC risk reduction [hazard ratio (HR): 0.40, 95% confidence interval (CI): 0.28-0.57]. Additionally, an older age, the male gender, HBeAg positivity, alpha-fetoprotein (AFP)≥7 ng/mL before therapy were independent predictors of HCC development. Further analysis showed that entecavir therapy significantly reduced risks of variceal bleeding, spontaneous bacterial peritonitis, and liver-related and all-cause mortality. These findings were confirmed by propensity score-matched cohorts in sensitivity analysis. In patients under entecavir therapy, an older age, the male gender, HBeAg positivity, AFP level ≥7 ng/mL before therapy, and 1-year virological response were predictive of HCC development.Four-year entecavir therapy significantly reduces the risk of HCC, cirrhotic events and mortality in patients with CHB-related cirrhosis.

Glucose transporters (GLUTs) are required for glucose uptake in malignant cells, and they can be used as molecular targets for cancer therapy. An RT-PCR analysis was performed to investigate the mRNA levels of 14 subtypes of GLUTs in human colorectal cancer (COLO 205 and HT-29) and normal (FHC) cells. RT-PCR (n = 27) was used to assess the differences in paired tissue samples (tumor vs normal) isolated from colorectal cancer patients. GLUT2 was detected in all tested cells. The average GLUT2 mRNA level in 12 of 27 (44.4%) cases was 2.4-fold higher in tumor compared to normal tissues (*, p = 0.027). Higher GLUT2 mRNA expression was preferentially detected in advanced-stage tumors (stage 0 vs 3 = 16.38-fold, 95% CI = 9.22-26.54-fold; *, p = 0.029). The apple polyphenol phloretin (Ph) and siRNA methods were used to inhibit GLUT2 protein expression. Ph (0-100 μM, for 24 h) induced COLO 205 cell growth cycle arrest in a p53-dependent manner, which was confirmed by pretreatment of the cells with a p53-specific dominant negative expression vector. Hepatocyte nuclear factor 6 (HNF6), which was previously reported to be a transcription factor that activates GLUT2 and p53, was also induced by Ph (0-100 μM, for 24 h). The antitumor effect of Ph (25 mg/kg or DMSO twice a week for 6 weeks) was demonstrated in vivo using BALB/c nude mice bearing COLO 205 tumor xenografts. In conclusion, targeting GLUT2 could potentially suppress colorectal tumor cell invasiveness.

In this study, the mechanisms by which pu-erh tea extract (PETE) attenuates nicotine-induced foam cell formation were investigated. Monocytes were purified from healthy individuals using commercial antibodies coated with magnetic beads. We found that the nicotine-induced (1-10 μM) expression of oxidized low-density lipoprotein receptors (ox-LDLRs) and α9-nAchRs in monocytes was significantly attenuated by 24 h of PETE (10 μg/mL; ∗, p0.05) cotreatment. Nicotine (1 μM for 24 h) significantly induced the expression of the surface adhesion molecule ICAM-1 and the monocyte integrin adhesion molecule (CD11b) by human umbilical vein endothelial cells (HUVECs) and triggered monocytes to differentiate into macrophages via interactions with the endothelium. After treatment with nicotine (0.1-10 μM for 24 h), the HUVECs released chemotactic factors (IL-8) to attract monocytes into the tunica intima of the artery, and the monocytes then transformed into foam cells. We demonstrated that PETE treatment (1 μg/mL for 24 h; ∗, p0.05) significantly attenuates nicotine-induced (1 μM) monocyte migration toward HUVECs and foam cell formation. This study suggests that tea components effectively attenuate the initial step (foam cell formation) of nicotine-induced atherosclerosis in circulating monocytes.

To assess whether drinking tea can effectively prevent smoking-induced atherosclerosis, a clinical trial ex vivo study was performed. The volunteers were randomly allocated to two groups (n = 55 per group) that received either Pu-erh tea powder or a cellulose placebo (0.5 g/capsule, T.I.D.) for two months. The circulating monocytes were isolated from the tested individuals after 0, 1, and 2 months of tea-capsule administration. We found that monocytes displaying high α9-nicotinic-acetylcholine-receptor (α9-nAchR) expression that were isolated from heavy smokers before consuming tea capsules tended to form foam cells in response to nicotine (1 µL for 24 h, *P

This paper investigates the current-enhanced surface diffusion of solder along the side walls of Cu pillars. Two solder joints, Cu pillar/10-µm-solder/Ni and Cu pillar/Ni/10-µm-solder/Ni, were subjected to a 1.2 × 104 A/cm2 current density at 125 °C for various amounts of time. The Sn atoms may diffuse to the Cu pillars side walls and form Cu6Sn5 intermetallic compounds (IMCs). Because the Sn atoms are drawn from the solder joints, serious voids are formed in these joints. Side diffusion is more serious for the Cu pillar/Ni/10-µm-solder/Ni joints than the Cu pillar/10-µm-solder/Ni joints because, instead of forming Ni3Sn4 IMCs, the Sn atoms prefer diffusing into the Cu side walls to form Cu6Sn5 IMCs. This Sn side diffusion accelerates the depletion of solder in the joints and thus may be a serious reliability issue for solder joints with a reduced solder height.

α-L-fucosidase 1 (FUCA1) is a lysosomal enzyme that catalyzes the hydrolytic cleavage of the terminal fucose residue in breast cancer cells. FUCA1 mRNA levels were detected by real-time PCR, and there was a greater than 139-fold increase in FUCA1 mRNA expression in breast tumor samples compared with normal breast tissue samples (*P = 0.005, n = 236). Higher FUCA1 mRNA expression was preferentially detected in early-stage tumors (stage 0 to 2) compared with advanced-stage tumors (stage 3 to 4) (stage 0-1 versus stage 3, *P = 0.015; stage 0-1 versus stage 4, *P = 0.024). FUCA1 protein levels were higher in advanced-stage tumors concomitant with decreased fucosylated Lewis-x antigen expression, as evidenced using the immunohistochemical staining H-score method (*P < 0.001). Statistical analysis revealed that lower FUCA1 levels significantly predicted an inferior overall survival rate among triple-negative breast cancer (TNBC) patients compared with non-TNBC patients (*P = 0.009). Two stable FUCA1 siRNA knock-down MDA-MB-231 cell lines were established, and the results suggest that transient FUCA inhibition creates a selective pressure that triggers the metastasis of primary tumor cells, as detected by wound healing and invasion assays (*P < 0.01). The results suggest that FUCA1 may be a potential prognostic molecular target for clinical use, especially in TNBC patients.

The need for all-oral hepatitis C virus (HCV) treatments with higher response rates, improved tolerability, and lower pill burden compared with interferon-inclusive regimen has led to the development of new direct-acting antiviral agents. Ravidasvir (RDV) is a second-generation, pan-genotypic NS5A inhibitor with high barrier to resistance. The aim of this phase 2 study (EVEREST study) was to assess the efficacy and safety of interferon-free, 12-week RDV plus ritonavir-boosted danoprevir (DNVr) and ribavirin (RBV) regimen for treatment-naïve Asian HCV genotype 1 (GT1) patients without cirrhosis.A total of 38 treatment-naïve, non-cirrhotic adult HCV GT1 patients were enrolled in this multicenter, open-label, single-arm phase 2 study (NCT03020095). All patients received a combination of RDV 200 mg once daily (q.d.) plus DNVr 100 mg/100 mg twice daily (b.i.d.) and oral RBV 1000/1200 mg/day (body weight 75/≥ 75 kg) for 12 weeks. The primary endpoint was the rate of sustained virologic response 12 weeks after the end of treatment (SVR12).Of 38 patients, all (100%) achieved SVR12. During the study, no treatment-related serious adverse events, no patients discontinued treatment due to adverse events, and no deaths were reported. Six of 37 (16%) patients with available sequences had HCV NS5A resistance-associated variants at baseline. All patients (6/6) with baseline NS5A resistance-associated variants achieved SVR12.Twelve-week RDV and DNVr in combination with RBV for 12 weeks achieves the SVR12 rate of 100% in treatment-naïve non-cirrhotic Asian patients with HCV GT1 infection. This interferon-free regimen is also safe and well tolerated.

Background and Aim Chronic hepatitis C (CHC) infection is a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Pegylated interferon (PEG-IFN) plus ribavirin (RBV) combination therapy remains the standard of care for CHC genotype 1 in many Asian countries, and single nucleotide polymorphism or genotype of the interleukin-28B (IL28B) gene is associated with the development of sustained virologic response (SVR). The predictive value of IL28B genotype for retreatment outcomes of patients with CHC was only partly clarified and deserves further investigation. Methods A total of 75 CHC genotype 1 Taiwanese patients who relapsed after 24-week PEG-IFN/RBV combination therapy and received retreatment with a 48-week PEG-IFN/RBV therapy were consecutively enrolled since November 2009. The associations among IL28B rs8099917 genotype, virologic kinetics, and treatment outcomes were evaluated. Results Rapid virologic response (RVR) at week 4, end-of-treatment virologic response (EOT-VR) and SVR was 37%, 73%, and 52%, respectively. Relapse rate was 29%. None of patients had rs8099917 GG genotype. Patients with TT genotype (n = 54, 72%) had higher rates of RVR (50% vs 5%, P = 0.0002), end-of-treatment virologic response (85% vs 43%, P = 0.0001), and SVR (67% vs 14%, P = 0.0001) than those with GT genotype (n = 21, 28%). Combination of IL28B TT genotype and achieving RVR had 85% positive and 90% negative predictive values of SVR. Conclusions About half of the Taiwanese CHC relapsers to a previous 24-week combination therapy achieve SVR after retreatment for 48 weeks. IL28B genotype influences on-treatment viral kinetics and SVR rate in these retreated patients. Baseline IL28B genotype and RVR can serve as early predictors for treatment success.

Compared with the extensive research on logistics network infrastructures (LNIs) in the developed world, empirical research is still scarce in China. In this paper the theory of LNIs is firstly overviewed. Then a new evaluation index system for LNIs is set up which contains factors that reflect the economic development level, transportation accessibility and turnover volume of freight traffic. An empirical study is carried out by using data envelopment analysis (DEA) and principal component analysis (PCA) approach to classify LNIs into 4 clusters for 25 cities in the Yangtze River Delta Region of China. According to the characteristics of the 4 clusters, suggestions are proposed for improving their LNIs. Finally, after comparing different LNIs of 25 cities in the Yangtze River Delta Region of China, this paper proposes that different LNIs including hub, central distribution center or cross docking center, regional distribution center or distribution center should be built reasonably in order to meet the customer’s requirement in the four different cluster cities.

Background:Accumulating data have found that adiponectin is involved in development of breast cancer (BC). However, these results were inconsistent.Method:A systematic search in PubMed, Embase, ISI Web of Science, and Chinese National Knowledge Infrastructure databases were conducted up to O

A ZnSe MSM photodiode and an InGaP/GaAs HBT have been integrated successfully on a GaAs substrate by use of the selective-area epitaxy technique. The optical and electrical characterizations of the integrated photoreceiver as well as individual components used in this device structure were estimated. Photocurrent induced from the metal-semiconductor-metal (MSM) photodiode was amplified linearly by a common-emitter circuit composed of a HBT. A current amplification ratio and a voltage amplification sensitivity of the integrated device measured in this work were 20.8 and -29.6 mV/mu W, respectively. The result does not only demonstrate the high sensitivity monolithic photoreceiver but indicates the potential of the selective-area epitaxy technique in the development of WBG-based short wavelength integrated devices.

In this paper we present an automatic facial expression recognition system that utilizes a semantic-based learning algorithm using the analytical hierarchy process (AHP). All the automatic facial expression recognition methods are similar in that they first extract some low-level features from the images or video, then these features are used as inputs into a classification system, and the outcome is one of the preselected emotion categories. Although the effectiveness of low-level features in automatic facial expression recognition systems has been widely studied, the success is shadowed by the innate discrepancy between the machine and human perception to the image. The gap between low-level visual features and high-level semantics should be bridged in a proper way in order to construct a seamless automatic facial expression system satisfying the user perception. For this purpose, we use the AHP to provide a systematical way to evaluate the fitness of a semantic description for interpreting the emotion of a face image. A semantic-based learning algorithm is also proposed to adapt the weights of low-level visual features for automatic facial expression recognition. The weights are chosen such that the discrepancy between the facial expression recognition results obtained in terms of low-level features and high-level semantic description is small. In the recognition phase, only the low-level features are used to classify the emotion of an input face image. The proposed semantic learning scheme provides a way to bridge the gap between the high-level semantic concept and the low-level features for automatic facial expression recognition. Experimental results show that the performance of the proposed method is excellent when it is compared with that of traditional facial expression recognition methods.