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Background and Aims: Endoscopic radiofrequency ablation (RFA) has shown good efficacy and safety in eradicating flat-type early esophageal squamous cell neoplasia (ESCN). However, post-RFA stricture is still a major concern, especially when treating ultralong-segment ESCNs. The aim of this study was to investigate the efficacy and safety of oral prednisolone to prevent post-RFA stricture., Methods: We prospectively enrolled 48 patients treated with balloon-type RFA who had Lugol-unstained or mosaic-like flat-type ESCNs with an expected treatment area of >10 cm. Oral prednisolone was started at a dose of 30 mg/day on the third day after RFA and continued for 4 weeks. The results were compared with an historical control group of 25 patients who received RFA without oral steroids. The primary endpoint was the frequency of post-RFA stricture. Secondary endpoints were the number of balloon dilation sessions and adverse event rate., Results: No significant differences were found in the worst pathology grade at baseline and length of unstained lesions between the 2 groups. The complete response rates after 1 session of RFA were 73% and 72%, respectively. Compared with the control group, the oral prednisolone group had a significantly lower stricture rate (4% [2/48 patients] vs 44% [11/25 patients]; P < .0001) and a lower number of balloon dilation sessions (median, 0 [range, 0-4] vs 6 [range, 0-10]). Two cases of asymptomatic candida esophagitis occurred in the study group, but no severe adverse effects., Conclusions: Oral prednisolone may offer a useful and safe preventive option for post-RFA stricture in ultralong ESCNs. (Clinical trial registration number: NCT05768282.)., Competing Interests: Disclosure All authors disclosed no financial relationships. Research support for this study was provided to Wen-Lun Wang, Ching-Tai Lee, Ying-Nan Tsai, and Ming-Hung Hsu by grants from the Ministry of Health and Welfare (MOHW111-TDU-B-221-114006), the Ministry of Science and Technology, Taiwan (MOST-110-2314-B-650-003), and E-Da Hospital (EDAHP110008, EDPJ105060, EDPJ106069, EDAHS111016, EDAHS111018, and EDAHS111019)., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background/aims: Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB), but biomarkers for post-treatment monitoring are limited. We investigated whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR)., Methods: This retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase > two times the upper limit of normal with recurrent viremia. We applied time-dependent Cox proportional hazard models to clarify the association between HBcrAg levels and subsequent CR., Results: The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.6% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5-40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7-67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1-62.4%). Time-varying HBcrAg level was a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.53 per log U/mL; 95% CI, 1.12-2.08) with adjustment for EOT HBsAg, EOT anti-HBe, EOT HBcrAg and time-varying HBsAg. During follow-up, HBcrAg <1,000 U/mL predicted a lower risk of CR (aHR, 0.41; 95% CI, 0.21-0.81)., Conclusion: Dynamic measurement of HBcrAg after NA cessation is predictive of subsequent CR and may be useful to guide post-treatment monitoring.

Objective: Chronic pelvic pain (CPP) is one of the most challenging conditions that physicians and patients face nowadays. This study aimed to assess the traditional Chinese medicine (TCM) body constitution profiles, demographic characteristics, and lifestyle of women suffering from CPP., Materials and Methods: This study included 378 female patients of reproductive potential from a single Obstetrics and Gynecology clinic in Taiwan. Data were collected using the Short Form 36 Health Survey Questionnaire (SF-36), the TCM Body Constitution Deviation (BCQ-44) Questionnaire, and the Behavior Rating Scale. The chi-squared test, the Kruskal-Wallis test, the Mann-Whitney U test, and Spearman's correlation were used to analyze the data., Results: TCM body composition deviation was correlated with the level of pain in patients with CPP. Moreover, the quality of life (QOL) of these patients was found to be affected by the level of pain. Additionally, the QOL was correlated with the TCM body composition deviation profile., Conclusion: The TCM BCQ-44 can be used in the medical practice to assess patients' health status and can also serve as a guide to address the risk factors for CPP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Treatment with oral anticoagulants (OACs) could prevent stroke in atrial fibrillation (AF), but side effects developed due to OACs may cause patients anxiety during decision making. This study aimed to investigate whether shared decision making (SDM) reduces anxiety and improves adherence to stroke prevention measures in patients with AF., Methods: A one-group pretest-posttest design using a questionnaire survey was applied at the outpatient cardiology clinic between July 2019 until September 2020. A Patient Decision Aid (PDA) tool was used for the completion of the questionnaire survey after health education and counseling. Ten questions were included for patients' recognition of SDM, and a 5-point scoring method was used, where "very much" was scored as 5 points, and "totally not" was scored as 1 point., Results: Fifty-two patients with AF were enrolled. In terms of patients' recognition of SDM, points of more than 4.17 out of 5 were noted, indicating recognition above the level of "very much." The patients' anxiety scores before SDM were 3.56 (1.2), with a decrease of 0.64 points (p < 0.001) to 2.92 (1.3) after SDM. After SDM, the number of patients who decided to take OAC increased from 76.9% to 88.5%, and the 15.4% answering "unclear" decreased to 1.9% (p = 0.006). The patients' anxiety levels after SDM were associated with gender (p = 0.025)., Conclusions: The approach using SDM enhanced our understanding of the pros and cons of OAC treatment and, in patients with AF, decreased anxiety about therapeutic decisions and increased willingness to accept treatment options., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article.

In order to shield the electronic circuits on a transparent polyimide (PI) substrate, an anti-reflection (AR) layer was deposited on a PI film via DC reactive magnetron sputtering. The effects of sputtering power and thickness of AR layer on the optical property and adhesion strength of the PI were investigated. The composition of the AR layer influences the bonding between layers. Sufficient thickness of the AR layer is essential to strengthen the adhesion between the PI and copper (Cu) layers. The sputtered AR layer on the PI also improves the barrier property for water vapor. The AR layer-sputtered PI substrates remain transparent and exhibit high peel strength to the Cu layer, suggesting their potential applications as reliable transparent substrates for modern electronic devices., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Previous studies that compared the postoperative health-related quality of life (HRQoL) outcomes after receiving laparoscopic resection (LR) or open resection (OR) in patients with colorectal cancer (CRC) have different conclusions., Aim: To explore the medium-term effect of postoperative HRQoL in such patients., Methods: This study randomized 567 patients undergoing non-metastatic CRC surgery managed by one surgeon to the LR or OR groups. HRQoL was assessed during the preoperative period and 3, 6, and 12 mo postoperative using a modified version of the 36-Item Short Form (SF-36) Health Survey questionnaire, emphasizing eight specific items., Results: This cohort randomly assigned 541 patients to receive LR ( n = 296) or OR ( n = 245) surgical procedures. More episodes of postoperative urinary tract infection ( P < 0.001), wound infection ( P < 0.001), and pneumonia ( P = 0.048) were encountered in the OR group. The results demonstrated that the LR group subjectively gained mildly better general health ( P = 0.045), moderately better physical activity ( P = 0.006), and significantly better social function recovery ( P = 0.0001) 3 mo postoperatively. Only the aspect of social function recovery was claimed at 6 mo, with a significant advantage in the LR group ( P = 0.001). No clinical difference was found in HRQoL during the 12 mo., Conclusion: Our results demonstrated that LR resulted in better outcomes, including intra-operative blood loss, surgery-related complications, course of recovery, and especially some health domains of HRQoL at least within 6 mo postoperatively. Patients should undergo LR if there is no contraindication., Competing Interests: Conflict-of-interest statement: All authors declare that we have no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Parameters of DC-reactive magnetron sputtering are optimized to deposit anti-reflection (AR) layers on transparent polyimide (PI) substrates, followed by the deposition of the conductive copper layer, to fabricate practically reliable composite films as advanced flexible circuits. When the deposition thickness is controlled and the gas composition during sputtering is adjusted, the resultant AR layer-coated PI film exhibits low reflectance and reveals improved adhesion strength to the copper layer. The adhesion reliability tests confirm that the peel strength between the PI film and the deposited layers could be further improved after thermal processing due to the formation of a worm-like morphology for better mechanical interlocking with layers. The facile sputtering process successfully fabricates a reliable substrate material with low reflectance and sufficient adhesion strength to copper for application as flexible printed circuits., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Purpose: Weight reduction decreases gastroesophageal reflux disease (GERD), but laparoscopic sleeve gastrectomy (LSG) that damages the structure of the stomach may worsen GERD. We aimed to elucidate the factors associated with increased severity of erosive esophagitis (EE) at 1 year after LSG., Materials and Methods: Data on patients who underwent LSG between February 2007 and March 2016 were reviewed. Endoscopic findings and anthropometric data before and after surgery were recorded. The severity of EE was assessed according to the Los Angeles classification; severe EE was defined as grade C or D esophagitis., Results: Totally, 316 patients were enrolled. Before LSG, 96 patients (30.4%) had grade A or B EE. One year after LSG, 215 patients (68%) had EE, including 136 (43%) with grade A, 62 (19.6%) with grade B, and 17 (5.4%) with grade C or D EE. One-hundred and twenty-seven of 220 patients (57.7%) without EE before LSG developed de novo EE following LSG. The incidence of severe EE after LSG in patients without pre-operative EE, grade A EE, or grade B EE at baseline was 3.2%, 6.8%, and 50%, respectively. Independent factors for an increased severity of EE after LSG were male gender (OR = 2.55, 95% CI = 1.52-4.28) and post-operative hiatal hernia (OR = 3.17, 95% CI = 1.66-6.06)., Conclusion: The prevalence and severity of EE increased after LSG. Male gender and post-operative hiatal hernia are independent factors for an increased severity of EE after LSG. The incidence of severe EE after LSG is low for patients without pre-operative EE or grade A EE at baseline., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: This study aimed to investigate whether the use of levonorgestrel intrauterine devices (LNG-IUD) in the perspective of traditional Chinese medicine (TCM) can improve the body constitution deviations and quality of life (QoL) in patients with chronic pelvic pain (CPP) and heavy menstrual bleeding (HMB)., Materials and Methods: To understand the TCM body constitution differences between patients, patients with CPP from a gynecology clinic were first compared to a healthy control group from the Academia Sinica Taiwan Biobank (TWB). Patients with CPP were also compared with patients with pelvic diseases from the TWB. Patients with CPP and HMB, some who under LNG-IUD treatment, underwent tests for physical consistency. After 6-8 months, the TCM body constitution and QoL of patients who received LNG-IUD treatment were reanalyzed. The questionnaires used included the Self-Assessment Chart of Menstrual Bleeding, the Taiwanese version of the Pictorial Blood Loss Assessment Chart, the TCM Body Constitution Questionnaire, the 6-point Behavior Rating Scale, and the Taiwanese version of the Short Form-36 Health Survey. All data were analyzed using Wilcoxon's signed-rank test in SAS 9.4 software., Results: In total, 2932 healthy women and 724 women with pelvic diseases were present in the TWB project. Moreover, 376 patients with CPP were admitted to a gynecology clinic, of whom 42 received LNG-IUD treatment. After LNG-IUD treatment, the primary endpoint was regarded as an improvement in Yang-Xu (lack of energy), Yin-Xu (lack of material), and phlegm stasis (accumulation of pathological products). These findings indicated an improvement in menstrual blood loss, pelvic pain, physical functioning, physical problems, body pain, general health, and emotional problems (p < 0.05)., Conclusion: LNG-IUD treatment improves body constitution deviations in TCM and QoL in patients with CPP and HMB. Our results provide a valuable reference for the use of modern medicine and TCM in treating CPP and HMB., Competing Interests: Declaration of competing interest None., (Copyright © 2022. Published by Elsevier B.V.)

Endoscopic resection or esophagectomy has becoming the standard treatment for superficial esophageal squamous cell carcinomas (SESCC), but some patients may develop disease progression or second primary cancers after the therapies. Neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), and platelet to lymphocyte ratio (PLR) reflect the balance between pro-cancer inflammatory and anti-cancer immune responses, however their roles in SESCC are still unknown. We consecutively enrolled patients with newly diagnosed SESCC (clinical stage Tis or T1N0M0) who were treated at our institute. Pre-treatment NLR, LMR and PLR were assessed and then correlated with clinical factors and long-term survival. A total of 156 patients were enrolled (152 males, 4 females; median age: 52.2 years), of whom 104 received endoscopic resection and 52 were treated with esophagectomy or chemoradiation.. During a mean follow-up period of 60.1 months, seventeen patients died of ESCCs, and 45 died of second primary cancers. The 5-year ESCC-specific survival and 5-year overall survival rate were 86% and 57%, respectively. LMR (P < 0.05) and NLR (P < 0.05), but not PLR were significantly correlated with overall survival. Receiver operating characteristic curve analysis showed optimal LMR and NLR cut-off values of 4 and 2.5, respectively, to predict a poor prognosis. Patients with a high NLR or low LMR tended to have longer tumor length, larger circumferential extension, and presence of second primary cancers. Multivariate Cox regression analysis showed that presence of second primary cancers (HR: 5.05, 95%CI: 2.75-9.28), low LMR (HR: 2.56, 95%CI: 1.09-6.03) were independent risk factors for poor survival. A low pre-treatment LMR may be a non-invasive pretreatment predictor of poor prognosis to guide the surveillance program, suggesting that anti-cancer immunity may play a role in the early events of esophageal squamous cancer., (© 2022. The Author(s).)

Pacemaker cells can be differentiated from stem cells or transdifferentiated from quiescent mature cardiac cells via genetic manipulation. Here we show that the exposure of rat quiescent ventricular cardiomyocytes to a silk-fibroin hydrogel activates the direct conversion of the quiescent cardiomyocytes to pacemaker cardiomyocytes by inducing the ectopic expression of the vascular endothelial cell-adhesion glycoprotein cadherin. The silk-fibroin-induced pacemaker cells exhibited functional and morphological features of genuine sinoatrial-node cardiomyocytes in vitro, and pacemaker cells generated via the injection of silk fibroin in the left ventricles of rats functioned as a surrogate in situ sinoatrial node. Biomaterials with suitable surface structure, mechanics and biochemistry could facilitate the scalable production of biological pacemakers for human use., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The mechanisms underlying angiotensin receptor-neprilysin inhibitor (ARNi) suppression of ventricular arrhythmia (VA) are unclear. This study aimed to investigate the mechanism of ARNi-related suppression of VA in a heart failure (HF) model., Methods: New Zealand white rabbits (n = 6 per group) were assigned to normal, HF [4 weeks of left ascending artery (LAD) ligation], angiotensin receptor blocker (ARB, valsartan at 27 mg/kg/day for 3 weeks after 1 week of LAD ligation), and ARNi (sacubitril at 34 mg/kg/day and valsartan at 27 mg/kg/day for 3 weeks after 1 week of LAD ligation) groups. Experiments involving echocardiogram, optical mapping, histological of trichrome stain and immunostain, and flow cytometry were performed., Results: HF group had larger left ventricular (LV) internal dimensions in diastole and systole, and lower LV ejection fraction and fractional shortening than normal, ARB, and ARNi groups. HF group had a prolonged action potential duration (APD) and decreased conduction velocity (CV), which was mitigated in ARB and ARNi groups. HF group had a prolonged QRS duration, QT and QTc intervals, which was reversed in ARB and ARNi groups. HF group had a steeper maximum slope of APD restitutions, which was attenuated in normal, ARB, and ARNi groups. HF group had increased number of phase singularities (PSs) and VA inducibility than normal, ARB, and ARNi groups. A higher content of fibrosis was found in HF group than that in normal, ARB, and ARNi groups. Compared to ARB group, ARNi had a lower context of fibrosis. HF group had more peripheral blood CD4 + and CD8 + cells count than normal, ARB, and ARNi group., Conclusions: In a rabbit model of ischemic HF, ventricular arrhythmogenesis could be suppressed by ARNi treatment. This appears to be mediated by reversing changes in the APD, CV, maximum slope of the APDR, PSs, fibrosis, and inflammation., (Copyright © 2021. Published by Elsevier Ltd.)

Purpose: Ventricular arrhythmia (VA) is related to inflammatory activity. Rhodiola crenulate (RC) and its main active component, salidroside, have been reported as anti-inflammatory agents. The aim of this study was to demonstrate the effect of RC and salidroside in preventing VA via the inhibition of IL-17 in an ischemic heart failure (HF) model., Methods: Rabbit HF models were established by coronary artery ligation for 4 weeks. These rabbits were treated with RC (125, 250, 500 mg/kg) and salidroside (9.5 mg/kg) once every 2 days for 4 weeks. WBC, serum biochemistry, ECG, and the expression of CD4 + T cells were measured every 2 weeks. The mRNA and protein expressions of IL-17 were measured by real time-PCR, ELISA, and Western blotting after RC and salidroside treatment for 4 weeks. Open-chest epicardial catheter stimulation was performed for VA provocation., Results: After RC and salidroside treatment in HF left ventricle, (1) the levels of WBC and CD4 + T cells decreased, (2) the expression of IL-17 and its downstream target genes, IL-6, TNF-α, IL-1β, IL-8, and CCL20, reduced, (3) the level of NLRP3 inflammasome was decreased, (4) fibrosis and collagen production were significantly downregulated, (5) p38 MAPK and ERK1/2 phosphorylation were attenuated, (6) the inducibility of VA was decreased, and (7) the levels of Kir2.1, Nav1.5, NCX, PLB, SERCA2a and RyR were up-regulated., Conclusions: RC inhibited the expression of IL-17 and its downstream target genes that were mediated by activation of several MAPKs, which decreased the levels of fibrosis and apoptosis and suppressed VA., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The mechanism of Interleukin-17 (IL-17) induced ventricular arrhythmia (VA) remains unclear. This study aimed to investigate the effect of intracellular calcium (Ca i ) handling and VA susceptibility by IL-17. Methods: The electrophysiological properties of isolated perfused rabbit hearts under IL-17 (20 ng/ml, N = 6) and the IL-17 with neutralizer (0.4 μg/ml, N = 6) were evaluated using an optical mapping system. The action potential duration (APD) and Ca i transient duration (Ca i TD) were examined, and semiquantitative reverse transcriptase-polymerase chain reaction analysis of ion channels was performed. Results: There were longer APD 80 , Ca i TD 80 and increased thresholds of APD and Ca i TD alternans, the maximum slope of APD restitution and induction of VA threshold in IL-17 group compared with those in IL-17 neutralizer and baseline groups. During ventricular fibrillation, the number of phase singularities and dominant frequency were both significantly greater in IL-17 group than in baseline group. The mRNA expressions of the Na + /Ca 2+ exchanger, phospholamban, and ryanodine receptor Ca 2+ release channel were upregulated, and the subunit of L-type Ca 2+ current and sarcoplasmic reticulum Ca 2+ -ATPase 2a were significantly reduced in IL-17 group compared to baseline and IL-17 neutralizer group. Conclusions: IL-17 enhanced Ca i TD and APD alternans through disturbances in calcium handling, which may increase VA susceptibility., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tsai, Hsiao, Lin, Chan, Hsieh, Tang, Lee, Huang, Li, Chao, Higa, Wu, Chang and Chen.)

Background: It is unclear whether tenofovir disoproxil fumarate and entecavir differ in their association with risk of hepatocellular carcinoma in patients with chronic hepatitis B, and previous meta-analyses have shown conflicting conclusions with substantial heterogeneity. We aimed to analyse the updated data and elucidate the source of heterogeneity., Methods: We searched PubMed, Embase, Web of Science, and the Cochrane library for relevant studies with time-to-event data for incident hepatocellular carcinoma occurring in patients with chronic hepatitis B who received tenofovir disoproxil fumarate or entecavir monotherapy with follow-up of at least 1 year. Studies published between Jan 1, 2006, and April 17, 2020, and abstracts from international conferences in 2018 and 2019 were included. We pooled covariate adjusted hazard ratios (HRs) for hepatocellular carcinoma using a random-effects model, assessed heterogeneity among included studies using the I 2 statistic and Cochran's Q test, and identified the source of heterogeneity using prespecified subgroup analyses. This study is registered with PROSPERO, ID CRD42020176513., Findings: 31 studies involving 119 053 patients were analysed. The 5-year cumulative incidence of hepatocellular carcinoma was 5·97% (95% CI 5·81-6·13, 28 studies) for entecavir and 3·06% (2·86-3·26, 13 studies) for tenofovir disoproxil fumarate in studies with unmatched populations (p<0·0001). For all eight studies matched by propensity score, the 5-year cumulative incidence was 3·44% (95% CI 3·08-3·80) for entecavir and 3·39% (2·94-3·83) for tenofovir disoproxil fumarate (p=0·87). Analysis of 14 comparative studies with covariate adjustment found that tenofovir disoproxil fumarate and entecavir had similar risk of hepatocellular carcinoma (primary outcome); adjusted HR 0·88, 95% CI 0·73-1·07; p=0·20), although heterogeneity was significant (I 2 =56·4%, p=0·0038). In a subgroup analysis for hospital-based clinical cohorts, there was no difference in hepatocellular carcinoma incidence between the two regimens (adjusted HR 1·03, 95% CI 0·88-1·21; I 2 =0%). However, tenofovir disoproxil fumarate was associated with a lower risk of hepatocellular carcinoma compared with entecavir in administrative database research (adjusted HR 0·67, 0·59-0·76; I 2 =0%)., Interpretation: Our study found no significant difference between tenofovir disoproxil fumarate and entecavir in their association with incident hepatocellular carcinoma. We suggest that treatment should be guided by patient tolerability and affordability rather than whether one drug is more effective than the other., Funding: Supported in part by E-DA Hospital (EDAHP 106008; EDAHP 103046)., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: Diabetes mellitus (DM) is a risk factor for pancreatic cancer but its prognostic impact remains controversial. We aimed to investigate the association between long-standing DM and the risk of mortality., Methods: This population-based cohort study analyzed data from the national healthcare database in Taiwan. We identified all patients diagnosed with pancreatic cancer and excluded those who were diagnosed with DM with-in 2 years of the cancer diagnosis. Eligible patients were grouped into long-standing DM (>2 years) and nondiabetic controls, and were compared for overall survival using a Cox proportional hazard model. Sensitivity tests stratified by cancer stages (as indicated by specific treatment) were performed., Results: Patients with long-standing DM were significantly older (mean age, 71.38 years versus 66.0 years; P<.0001) and had a higher Charlson comorbidity index (9.53 versus 6.78; P<.0001) and diabetes comorbidity severity index (2.38 versus 0.82; P<.0001) compared with the non-DM controls. Although the unadjusted analysis showed a higher risk of mortality in the patients with long-term DM (crude hazard ratio &lsqb;HR], 1.26; 95% confidence interval &lsqb;CI], 1.20 to 1.33; P<.0001), the association became insignificant after adjustment for age, sex, and comorbidity index (adjusted HR, 1.01; 95% CI, 0.95 to 1.06, P = .84). Subgroup analyses also showed no association between long-term DM and mortality in various subgroups stratified by cancer treatment., Conclusion: After adjusting for associated comorbidities and complications, long-standing DM per se was not an independent prognostic factor for overall survival in this nationwide population-based cohort with pancreatic cancer., Abbreviations: CCI = Charlson Comorbidity Index; CI = confidence interval; DCSI = Diabetes Complication Severity Index; DM = diabetes mellitus; HR = hazard ratio; ICD = International Classification of Diseases; NHIRD = National Health Insurance Research Database; RCIPD = Registry for Catastrophic Illness Patient Database., (© 2020 American Association of Clinical Endocrinologists. Published by Elsevier, Inc. All rights reserved.)

How long esophageal screening should be performed for, and on which sub-groups of head and neck cancer (HNC) survivors, remains uncertain. This retrospective study analyzed data from the Taiwan National Health Insurance Research Database from 1999 to 2013. A total of 68,131 newly- diagnosed HNC patients were enrolled. Subjects who received esophageal endoscopic screening within 6 months after their diagnosis date of index HNC were identified. The incidence trends of secondary primary EC were analyzed using a Cochran-Armitage trend test. Among the 9,707 patients who received index esophageal endoscopy screening, 101 (1.0%) cases of synchronous EC were diagnosed. The 5- and 10-year cumulative incidence rates of metachronous ECs were 1.4% and 2.7%, respectively in those with an initial negative index endoscopic finding. Patients with oropharynx or hypopharynx cancers were at significantly higher risk of developing metachronous ECs compared with those with oral or larynx cancers (10-year incidence rate: 3.3% vs. 0.9%, respectively; hazard ratio: 2.15; 95% confidence intervals: 1.57-2.96). Metachronous EC continues to develop in patients with HNC even at 10-years after treatment for primary HNC. HNC patients, especially those with oropharynx or hypopharynx cancer, may require long-term endoscopic surveillance.

Longitudinal epidemiological studies are considered the gold standard for understanding craniofacial morphologic development, but participant recruitment and retention can be challenging. This study describes strategies used to recruit and maintain a high level of participation in a longitudinal study involving annual three-dimensional (3D) craniofacial soft-tissue imaging from healthy Taiwanese Chinese elementary school students aged 6 to 12 years. The key aspects for project delineation, implementation, and the initial three-year practical experiment are portrayed in an integrated multistep workflow: ethics- and grant-related issues; contact, approval, and engagement from partners of the project (school stakeholders and parents); a didactic approach to recruit the students; research staff composition with task design; three station-based data collection days with two educative activities (oral hygiene and psychosocial interaction stations) and one 3D craniofacial imaging activity; and reinforcement tactics to sustain the longitudinal annual participation after the first enrollment. Randomly selected students and teachers answered an experience satisfaction questionnaire (five-point Likert scale ranging from one to five) designed to assist in understanding what they think about the data collection day. Measures of frequency (percentage) and central tendency (mean) were adopted for descriptive analysis. Six of seven contacted schools accepted participation in the project. All parents who attended the explanatory meetings agreed to join the project. A cohort of 676 students (336 girls) participated at baseline enrollment, with a follow-up rate of 96% in the second data collection. The average questionnaire-related scores were 4.2 ± 0.7 and 4.4 ± 0.6 for teachers and students, respectively. These 3D craniofacial norms will benefit multidisciplinary teams managing cleft-craniofacial deformities in the globally distributed ethnic Chinese population, particularly useful for phenotypic variation characterization, conducting quantitative morphologic comparisons, and therapeutic planning and outcome assessment. The described pathway model will assist other groups to establish their own age-, sex-, and ethnic-specific normative databases., Competing Interests: The authors declare no conflicts of interest.

Background: Telomere length is a biologic aging marker. This study investigated leukocyte telomere length (LTL) as a new biomarker to predict recurrence after paroxysmal atrial fibrillation (PAF) ablation.Methods and Results:A total of 131 participants (26 healthy individuals and 105 symptomatic PAF patients) were enrolled. PAF patients (54.1±10.8 years) who received catheter ablation therapy were divided into 2 groups: recurrent AF (n=25) and no recurrent AF after catheter ablation (n=80). Peripheral blood mononuclear cells were collected from all subjects to measure LTL. Under 50 years old, LTL in healthy individuals (n=17) was longer than in PAF patients (n=31; 7.34±0.58 kbp vs. 6.44±0.91 kbp, P=0.01). In PAF patients, LTL was positively correlated with left atrial bipolar voltage (R=0.497, P<0.001), and negatively correlated with biatrial scar area (R=-0.570, P<0.001) and left atrial diameter (R=-0.214, P=0.028). LTL was shorter in the patients with recurrent AF than in those without recurrent AF after catheter ablation (5.68±0.82 kbp vs. 6.66±0.71 kbp; P<0.001). On receiver operating characteristic curve analysis, LTL cut-off <6.14 kbp had a specificity of 0.68 and sensitivity of 0.79 to predict recurrent AF after catheter ablation., Conclusions: Young PAF patients (≤50 years) had shorter LTL. Shorter LTL was associated with a degenerative atrial substrate and recurrence after catheter ablation in younger PAF patients.

Background: Pulse diagnosis researches acquiring pulse waves from the wrist radial artery has not yet addressed the issue of whether this information is affected by differences in the hemodynamic characteristics of pressure waves derived from different locations. This study aimed to clarify whether the blood dynamic states are identical with regard to the "three positions and nine indicators" ((Equation is included in full-text article.)) listed in traditional Chinese medicine (TCM)., Methods: A total of 37 participants of CAD group and 20 participants of healthy group were recruited, and pressure pulse waves were measured at 18 locations on both hands. A multivariate analysis (MANOVA) was performed with a "randomized block design" using SPSS 22.0 and R 3.4.1 to examine the time-domain parameters that represented certain hemodynamic characteristics., Results: In CAD group, the results showed significant differences (p < 0.05) among the h1, h2, h3, h1/t, and h3/h1 measurements of the pulse waves using different indicators at the same position; the h1, h2, h3, and h1/t measurements of the pulse waves at different positions using the indicator "Superficial"; and the h1, h2, h3, h1/t, and h3/h1 measurements of the pulse waves at different positions using the indicator "Medium". In healthy group, the results showed significant differences (p < 0.05) among the h1, h2, h3, and h1/t measurements of the pulse waves using different indicators at the same position; the h1, h2, and h1/t measurements of the pulse waves at different positions using the same indicator., Conclusion: Because of the differences in the hemodynamic characteristics among the different positions and indicators, the article might provide a new opinion for future pulse diagnosis investigations to carefully consider the measurement location to ensure the completeness of the information.

Background: We aimed to investigate the impact of interleukin (IL)-17 on ventricular remodeling and the genesis of ventricular arrhythmia (VA) in an ischemic heart failure (HF) model. The expression of the proinflammatory cytokine IL-17 is upregulated during myocardial ischemia and plays a fundamental role in post-infarct inflammation. However, the influence of IL-17 on the genesis of VA has not yet been studied., Methods and Results: The level of inflammation and Th17 cell (CD4 + IL-17 + ) expression in the rabbit model of ischemic HF were studied by flow cytometry, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA). The effect of IL-17 on VA induction following acute and chronic administration of IL-17 was determined using electrophysiological techniques and optical mapping. The expression of IL-17 target genes and related cytokines and chemokines in vivo and in vitro were measured using qPCR, ELISA, and immunoblotting. Th17 cells were markedly increased in the ischemic HF rabbit model. IL-17 directly induced VA in vivo and in vitro in a dose-dependent manner. IL-17 decreased conduction velocity, lengthened action potential duration, and increased the slope of the left ventricle (LV) restitution curve. IL-17 treatment led to fibrosis, collagen production and apoptosis in the LV. Furthermore, increased IL-17 signaling activated mitogen-activated protein kinase and increased the expression of downstream target genes, IL-6, TNF, CCL20, and CXCL1. An anti-IL-17 neutralizing antibody abolished the effects of IL-17., Conclusions: The expression of IL-17 and its downstream target genes may play fundamental roles in inducing VA in ischemic HF., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: This study aimed to clarify whether it is appropriate to choose any measurement location for pulse diagnosis research., Methods: A total of 37 subjects were recruited and measured for pulse pressure waves at 18 locations (9 per hand of "three positions and nine indicators"). These data were Fourier-transformed to the frequency spectrum, and the harmonics of C0-C10 of each location were obtained. Box plots of the harmonics were generated using SPSS v.22.0 and R v.3.4.1. Data were compared with multivariate analysis of variance (MANOVA) with a randomized block design., Results: The results showed that certain harmonics were different at different positions and different indicators; the harmonics of the same indicator at different positions (except for C8 and C10) and those of different indicators for the same position (except for C4 and C5) were significantly different (p<0.05)., Conclusions: In future researches of pulse diagnosis, due to the significant differences between positions and indicators, it is recommended that the measurement position should be carefully chosen instead of choosing any measurement location to ensure the integrity of the acquired information for further analyzing physiological or pathological status.

Aims: MicroRNAs (miRNAs) have been implicated in cardiac diseases. This study aimed to characterize the circulating miRNAs in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and correlate the miRNAs with the clinical outcomes of ARVC., Methods and Results: This study included 62 patients with ventricular arrhythmia (VA): 28 patients (45%) had definite ARVC, 11 (18%) had borderline or possible ARVC, and 23 (37%) had idiopathic ventricular tachycardia (VT). In addition, 33 age- and sex-matched healthy subjects were enrolled as normal control subjects. The expression of selected miRNAs was analysed in all study subjects. The clinical outcomes of patients with definite ARVC after catheter ablation were further investigated. On the basis of the miRNA polymerase chain reaction array, we selected 11 miRNAs for analysis of their expression in the plasma of all subjects. Definite ARVC patients had significantly higher expression of circulating miR-144-3p, 145-5p, 185-5p, and 494 than the three other groups. Out of 25 definite ARVC patients who underwent radiofrequency catheter ablation, recurrent VA occurred in 8 patients (32%) during the follow-up period (45 ± 20 months). Definite ARVC patients with recurrent VA had a higher level of circulating miR-494 than did those without recurrence. Receiver operating characteristic analysis showed miR-494 to be a predictive factor of recurrent VA (area under the curve: 0.832)., Conclusion: Plasma levels of miR-144-3p, 145-5p, 185-5p, and 494 were significantly elevated in definite ARVC patients with VA. An increased plasma level of miR-494 was associated with the recurrence of VA after ablation in definite ARVC patients.

Background: Myocardial infarction increases the risk of heart failure (HF) and atrial fibrillation. Renal denervation (RDN) might suppress the development of atrial remodeling. This study aimed to elucidate the molecular mechanism of RDN in the suppression of atrial fibrillation in a HF model after myocardial infarction., Methods and Results: HF rabbits were created 4 weeks after coronary ligation. Rabbits were classified into 3 groups: normal control (n=10), HF (n=10), and HF-RDN (n=6). Surgical and chemical RDN were approached through midabdominal incisions in HF-RDN. Left anterior descending coronary artery in HF and HF-RDN was ligated to create myocardial infarction. After electrophysiological study, the rabbits were euthanized and the left atrial appendage was harvested for real-time polymerase chain reaction analysis and Trichrome stain. Left atrial dimension and left ventricular mass were smaller in HF-RDN by echocardiography compared with HF. Attenuated atrial fibrosis and tyrosine hydroxylase levels were observed in HF-RDN compared with HF. The mRNA expressions of Cav1.2, Nav1.5, Kir2.1, KvLQT1, phosphoinositide 3-kinase, AKT, and endothelial nitric oxide synthase in HF-RDN were significantly higher compared with HF. The effective refractory period and action potential duration of HF-RDN were significantly shorter compared with HF. Decreased atrial fibrillation inducibility was noted in HF-RDN compared with HF (50% versus 100%, P <0.05)., Conclusions: RDN reversed atrial electrical and structural remodeling, and suppressed the atrial fibrillation inducibility in an ischemic HF model. The beneficial effect of RDN may be related to prevention of the downregulation of the phosphoinositide 3-kinase/AKT/endothelial nitric oxide synthase signaling pathway., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Postoperative leak is a serious complication of bariatric surgery and often results in significant morbidity and mortality. Stent placement is a less invasive alternative to surgery for the treatment of bariatric surgical leak. We evaluated the efficacy and complications of covered self-expandable metal stents (SEMS) in the treatment of post-bariatric surgical leak. We retrospectively reviewed patients who underwent stent placement for leak after bariatric surgery. Leak was diagnosed by upper gastrointestinal series or was visualized during the endoscopy. We examined the timing of stent placement, size of the leak, stent migration and its complications, total stent treatment duration, and treatment outcome. Between January 2011 and April 2015, seven patients underwent covered SEMS placement for leak after bariatric surgery, including laparoscopic sleeve gastrectomy (LSG) (n = 5) and laparoscopic loop duodenojejunal bypass with sleeve gastrectomy (LDJB-SG) (n = 2). A stent was placed in one patient for infection control and bridging to revisional surgery. Among the other six patients, one patient who received stent placement one year after leak diagnosis failed to achieve leak closure, and five patients with early stent placement achieved leak closure. Three patients with small leak achieved leak closure more quickly. Stent migration was found in six patients, and associated ulcers occurred in five patients. We conclude that stenting is effective in the management of staple-line leaks following LSG and LDJB-SG. Stent migration and associated ulcers are common after stent placement. Early stent removal can be achieved in patients with small leaks., (Copyright © 2017. Published by Elsevier Taiwan.)

Introduction: Rhodiola, a popular plant in Tibet, has been proven to decrease arrhythmia. The aim of this study was to elucidate the molecular mechanism and electrophysiological properties of rhodiola in the suppression of atrial fibrillation., Methods: This study consisted of 3 groups as follows: Group 1: normal control rabbits (n = 5); Group 2: rabbits with heart failure (HF) created by coronary ligation and who received 2 weeks of water orally as a placebo (n = 5); and Group 3: rabbits with HF who received 2 weeks of a rhodiola 270 mg/kg/day treatment orally (n = 5). The monophasic action potential, histology, and real-time polymerase chain reaction (RT-PCR) analysis of ionic channels and PI3K/AKT/eNOS were examined., Results: Compared with the HF group, attenuated atrial fibrosis (35.4 ± 17.4% vs. 16.9 ± 8.4%, P = 0.05) and improved left ventricular (LV) ejection fraction (51.6 ± 3.4% vs. 68.0 ± 0.5%, P = 0.001) were observed in the rhodiola group. The rhodiola group had a shorter ERP (85.3 ± 6.8 vs. 94.3 ± 1.2, P = 0.002), APD90 (89.3 ± 1.5 vs. 112.7 ± 0.7, P < 0.001) in the left atrium (LA), and decreased AF inducibility (0.90 ± 0.04 vs. 0.42 ± 0.04, P < 0.001) compared with the HF group. The mRNA expressions of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, and SERCA2a in the HF LA were up-regulated after rhodiola treatment. The rhodiola-treated HF LA demonstrated higher mRNA expression of PI3K-AKT compared with the HF group., Conclusions: Rhodiola reversed LA electrical remodeling, attenuated atrial fibrosis and suppressed AF in rabbits with HF. The beneficial electrophysiological effect of rhodiola may be related to upregulation of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, SERCA2a, and activation of PI3K/AKT signaling., (© 2016 Wiley Periodicals, Inc.)

Pediatric high-grade gliomas (pHGGs) are aggressive brain tumors affecting children, and outcomes have remained dismal, even with access to new multimodal therapies. In this study, we compared the miRNomes and transcriptomes of pediatric low- (pLGGs) and high-grade gliomas (pHGGs) using small RNA sequencing (smRNA-Seq) and gene expression microarray, respectively. Through integrated bioinformatics analyses and experimental validation, we identified miR-137 and miR-6500-3p as significantly downregulated in pHGGs. miR-137 or miR-6500-3p overexpression reduced cell proliferation in two pHGG cell lines, SF188 and UW479. CENPE, KIF14 and NCAPG levels were significantly higher in pHGGs than pLGGs, and were direct targets of miR-137 or miR-6500-3p. Furthermore, knockdown of CENPE, KIF14 or NCAPG combined with temozolomide treatment resulted in a combined suppressive effect on pHGG cell proliferation. In summary, our results identify novel mRNA/miRNA interactions that contribute to pediatric glioma malignancy and represent potential targets for the development of new therapeutic strategies.

Activation of N-methyl-D-aspartate (NMDA) receptor can facilitate the extinction of various maladaptive memories. Sodium benzoate (NaB) has been known to enhance a naturally occurring full agonist on the glycine binding site of the NMDA receptor. This study aimed to test whether systemic NaB treatment can affect the extinction of a cocaine-supported memory, the cocaine-induced conditioned place preference (CPP). Following the establishment of the cocaine (10 mg/kg/conditioning × 3)-induced CPP, an extinction protocol, consisting of two consecutive extinction training bouts at an 8-h interval, was used. NaB (500 mg/kg) or an equivalent volume of saline was given immediately following each extinction training bout to test the modulating effect of NaB on the maintenance of cocaine-induced CPP. Moreover, NaB was bilaterally micro-infused into the medial prefrontal cortex (mPFC) to validate the involvement of this brain region in mediating systemic NaB treatment-produced effect on cocaine-induced CPP. Systemic (500 mg/kg) and intra-mPFC (10 μg/side) NaB treatment significantly decreased subsequent cocaine-induced CPP magnitude, although the NaB treatment or the extinction training alone did not affect such CPP magnitude. It was of importance to note that systemic or intra-mPFC NaB delivery did not affect mouse locomotor activity in the retests. These results, taken together, suggest that NaB treatment in combination with the extinction training may facilitate the extinction of the cocaine-supported memory. Moreover, systemic NaB treatment exerts such effects, at least in part, via its effect in the mPFC.

The novel ambipolar hosts of o-CbzBz and o-DiCbzBz contain carbazole and benzimidazole through an ortho-connection. The orthogonal conformations cause the triplet state to be confined at the carbazole units to secure efficient energy transfer. The phosphorescent organic light-emitting diodes (PhOLEDs) show a high current efficiency, power efficiency, and low efficiency roll-off. o-DiCbzBz can be used as a host for sky-blue, green, and orange-red PhOLEDs, giving 57.5, 78.4, and 60.3 cd/A, respectively.

Background: MicroRNAs (miRNAs) have emerged as master regulators of angiogenesis and other cancer-related events. Discovering new angiogenesis-regulating microRNAs (angiomiRs) will eventually help in developing new therapeutic strategies for tumor angiogenesis and cardiovascular diseases. Kaposi's sarcoma (KS), which is induced by the etiological infectious agent KS-associated herpesvirus (KSHV), is a peculiar neoplasm that expresses both blood and lymphatic endothelial markers and possesses extensive neovasculature. Using KSHV and its proteins as baits will be an efficient way to discover new angiomiRs in endothelial cells. Kaposin B is one of the latent viral genes and is expressed in all KSHV tumor cells. Since Kaposin B is a nuclear protein with no DNA-binding domain, it may regulate gene expression by incorporating itself into a transcription complex., Results: We demonstrated that c-Myc and Kaposin B form a transcription complex and bind to the miR-221/-222 promoter, thereby affecting their expression and anti-angiogenic ability. By small RNA sequencing (smRNA-Seq), we revealed that 72.1% (173/240) of Kaposin B up-regulated and 46.5% (113/243) of Kaposin B down-regulated known miRNAs were regulated by c-Myc. We also found that 77 novel miRNA were up-regulated and 28 novel miRNAs were down-regulated in cells expressing both c-Myc and Kaposin B compared with cells expressing Kaposin B only. The result was confirmed by RNA-IP-seq data., Conclusions: Our study identifies known and novel c-Myc-regulated microRNAs and reveals that a c-Myc-oriented program is coordinated by Kaposin B in KSHV-infected cells.

Background: Isolate CH-1 of Rhizoctonia solani Kühn was commonly used in our studies of the pathogenicity and genetics of this pathogen. During the preparation of homokaryons through protoplast regeneration and tuft formation, a defective homokaryon was detected and a new variant was obtained., Results: When tuft formation was used to identify the karyotic nature of single protoplast regenerants (SPRs) of Rhizoctonia solani AG1-IC isolate CH-1, one homokaryon type designated as A type and the parental heterokaryon designated as AB type were obtained. The homokaryon B type was not found. Various approaches were used to obtain SPRs, including from fast or slow growing protoplast regenerants, and from regenerants of protoplasts released from mycelia grown in different nutrient broths or at different temperatures. Without exception, all these SPRs were either homokaryon A or heterokaryon AB. Moreover, the SPRs obtained from different generations of SPRs, and from different generations of SPRs treated with lytic enzymes 3 to 4 times also were invariably either homokaryon A or heterokaryon AB. When single hyphal isolates were obtained from the tuft resulting from the pairing between homokaryon A and heterokaryon AB, only the heterokaryon and a variant were obtained. The variant did not form tuft when paired with parental heterokaryon AB or homokaryon A. Its protoplast regenerants gave rise to heterokaryon AB, homokaryon A and the variant, indicating that it is a new kind of heterokaryon., Conclusion: Inability to obtain homokaryon B despite numerous attempts suggests that the B type nuclei are probably defective and are dependent on A type nuclei for their multiplication. This is the first report of a heterokaryotic R. solani strain carrying a defective type of nuclei. A new variant which is a new kind of heterokaryon was obtained from the tuft resulting from the paring between the homokaryon A and the parental heterokaryon AB.

Background: This study aimed to investigate the mechanism by which colchicine suppresses atrial fibrillation (AF) in a rabbit heart failure (HF) model., Methods and Results: HF was induced by coronary ligation. Using the Langendorff perfusion system, monophasic action potentials were recorded in the left atrial appendage (LAA) of normal rabbits (n=6) and HF rabbits (n=6) treated with colchicine (100 μM) followed by colchicine (100 μM) plus paclitaxel (5 μM). Collagen content and mRNA and protein expression of ion channels through the PI3K/AKT/eNOS signaling pathway were evaluated in LAA of normal rabbits (n=6) and HF rabbits treated with vehicle (n=6) or colchicine (n=6) intraperitoneal injection for 2 days. Colchicine decreased action potential duration (74.1±2.6 vs 91.8±3.3 ms, P<0.001), effective refractory period, and maximum slope of the restitution curve in HF LAA. However, these effects were reversed by paclitaxel. The incidence of early afterdepolarizations, delayed afterdepolarizations, and AF inducibility was significantly lower after colchicine perfusion than at baseline or after colchicine plus paclitaxel perfusion. Cardiac function increased and LA fibrosis decreased after colchicine treatment. mRNA and protein expression of Kir2.1, Kv1.4, Kv1.5, Kv7.1, Cav1.2, and SERCA2a were upregulated after colchicine treatment, as was mRNA expression of PI3K, AKT, and eNOS., Conclusion: Colchicine regulates ion channel gene expression and activates the PI3K/AKT/eNOS signaling pathway in HF rabbits, which may reverse atrial remodeling and suppress AF., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

This study was undertaken to assess sex differences and the modulating effects of gonad intactness and the estrous phase on basal and the stressor-decreased cell proliferation and early differentiation in Balb/C mouse dentate gyrus (DG). Besides, we compared the stress-reversing effects exerted by the presence of male and female Balb/C mouse odors in stressed male and female mouse DG in this regard. Female mice had lower baselines in the number of newly proliferated cells and neuroblasts than male mice. Although the stressor induced decreases in the number of newly proliferative cells and neuroblasts in both male and female DG, an obvious decrease in neuronal lineage commitment was observed in female DG. Moreover, ovariectomy induced decreases in baselines in the number of proliferative cells and neuroblasts but did not affect the stressor-induced decrease in neuronal lineage commitment in female DG. Interestingly, pro-estrous mice exhibited the stressor-decreased neuronal lineage commitment, while estrous and diestrous mice did not display such a decrease. Furthermore, orchidectomy did not affect basal or the stressor-decreased newly proliferative cells or neuroblasts in male DG. Finally, male odors were less effective than female odors in abolishing the stressor-decreased neuronal lineage commitment in female mice, while male and female odors were comparable in reversing the stressor-decreased newly proliferated cells and neuroblasts in male mice. The protective effects of mouse odors' company in the stressed male mouse DG were associated with local BDNF and NGF replenishment. Taken together, sexual differences in baselines in the number of newly proliferative cells, neuroblasts, and the sensitivity to stress-altered neuronal lineage commitment in the DG could be, in part, due to gonadal hormone differences between the two sexes. Mouse odors may reverse stressor-decreased newly proliferative cells and neuroblasts in male, but not in female, mouse DG by restoring BDNF and NGF levels., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

We have developed an on-line sequential photocatalyst-assisted digestion and vaporization device (SPADVD), which operates through the nano-TiO2-catalyzed photo-oxidation and reduction of selenium (Se) species, for coupling between anion exchange chromatography (LC) and inductively coupled plasma mass spectrometry (ICP-MS) systems to provide a simple and sensitive hyphenated method for the speciation analysis of Se species without the need for conventional chemical digestion and vaporization techniques. Because our proposed on-line SPADVD allows both organic and inorganic Se species in the column effluent to be converted on-line into volatile Se products, which are then measured directly through ICP-MS, the complexity of the procedure and the probability of contamination arising from the use of additional chemicals are both low. Under the optimized conditions for SPADVD - using 1g of nano-TiO2 per liter, at pH 3, and illuminating for 80 s - we found that Se(IV), Se(VI), and selenomethionine (SeMet) were all converted quantitatively into volatile Se products. In addition, because the digestion and vaporization efficiencies of all the tested selenicals were improved when using our proposed on-line LC/SPADVD/ICP-MS system, the detection limits for Se(IV), Se(VI), and SeMet were all in the nanogram-per-liter range (based on 3σ). A series of validation experiments - analysis of neat and spiked extracted samples - indicated that our proposed methods could be applied satisfactorily to the speciation analysis of organic and inorganic Se species in the extracts of Se-enriched supplements., (Copyright © 2013. Published by Elsevier B.V.)

Tagitinin C, a major sesquiterpenoid, was isolated from the leaves of Tithonia diversifolia. The high morbidity and mortality rate of hepatoma in Taiwan motivated our interest in the investigation of tagitinin C's mechanism against the human hepatocellular carcinoma. The methanolic extract of leaves of T. diversifolia (TDM) and tagitinin C were found to have cytotoxic activities against human hepatoma Hep-G2 cells in the MTT assay with IC(50) values of 40.0 ± 2.0 and 2.0 ± 0.1 μg/mL, respectively. This compound induced population increase in the sub-G(1) phase and S phase arrest. Treatment with tagitinin C isolated from TDM resulted in activation of both caspase 3 and caspase 8 which suggested that the antiproliferative effect of this compound was caspase-dependent apoptosis. Magnetic resonance techniques indicated that the tumorigenisity of xenografts derived from Hep-G2 cells was retarded by the delivery of tagitinin C (15 μg/mouse/day) relative to the control counterparts.

miRNAs have emerged as master regulators of cancer-related events. miRNA dysregulation also occurs in Kaposi sarcoma (KS). Exploring the roles of KS-associated miRNAs should help to identify novel angiogenesis and lymphangiogenesis pathways. In the present study, we show that Kaposi sarcoma-associated herpesvirus (KSHV), the etiological agent of KS, induces global miRNA changes in lymphatic endothelial cells (LECs). Specifically, the miR-221/miR-222 cluster is down-regulated, whereas miR-31 is up-regulated. Both latent nuclear antigen (LANA) and Kaposin B repress the expression of the miR-221/miR-222 cluster, which results in an increase of endothelial cell (EC) migration. In contrast, miR-31 stimulates EC migration, so depletion of miR-31 in KSHV-transformed ECs reduces cell motility. Analysis of the putative miRNA targets among KSHV-affected genes showed that ETS2 and ETS1 are the downstream targets of miR-221 and miR-222, respectively. FAT4 is one of the direct targets of miR-31. Overexpression of ETS1 or ETS2 alone is sufficient to induce EC migration, whereas a reduction in FAT4 enhances EC motility. Our results show that KSHV regulates multiple miRNA-mRNA networks to enhance EC motility, which eventually contributes to KS progression by promoting the spread of malignant KS progenitor cells. Targeting KSHV-regulated miRNAs or genes might allow the development of novel therapeutic strategies that induce angiogenesis or allow the treatment of pathogenic (lymph)angiogenesis.

The Tithonia diversifolia methanolic extract (TDM), which showed antiproliferative activity against human glioblastoma U373 cells, with an IC50 value of 59.2±3.7 μg mL(-1), was passed through silica gel chromatography and successively eluted with different percentages of EtOAc/hexane. The 10-60% EtOAc/hexane subfractions, which exhibited a comparatively higher antiproliferative activity, were isolated, and then structural identification was proceeded with 1H nuclear magnetic resonance. The isolated compound was tagitinin C, a kind of sesquiterpenoid. The IC50 value was 6.1±0.1 μg mL(-1) in U373 treated with tagitinin C. In flow cytometric analysis and inhibition of pan-caspase, the results showed that the anti-glioblastoma effect was apoptosis-independent. In PARP, p-p38, ULK1, and LC3-II expression, the anti-glioblastoma induced by tagitinin C was likely via autophagy. In the ULK1 siRNA transfection experiment, autophagy blockade counteracted the suppression induced by tagitinin C. The result suggested that tagitinin C induces U373 cell death dependent upon autophagy under certain conditions.

Changes in Ca(2+) content and flux, and the development of skin chloride cells in embryos and larvae of tilapia, Oreochromis mossambicus, were studied. Tilapia embryos hatched within 96h at an ambient temperature of 26-28°C. Total body Ca(2+) content was maintained at a constant level, about 4-8 nmol per individual, during embryonic development. However, a rapid increase in body Ca(2+) level was observed after hatching, 12.8 to 575.3 nmol per individual from day 1 to day 10 after hatching. A significant influx and efflux of Ca(2+) occurred during development, with the average influx rate for Ca(2+) increasing from 5.9 pmol mg(-1) h(-1) at 48h postfertilization to 47.8 pmol mg(-1) h(-1) at 1 day posthatching. The skin was proposed as the main site for Ca(2+) influx before the development of gills, and the increased Ca(2+) influx may be ascribed to gradual differentiation of skin surface and chloride cells during embryonic development. Ca(2+) efflux was 16-56 pmol mg(-1) h(-1) in 1-day-old larvae. The resulting net influx of Ca(2+), 10-12 pmol mg(-1) h(-1), accounted for the increased Ca(2+) content after hatching. When comparing the measured and estimated ratios of efflux and influx, active transport was suggested to be involved in the uptake of Ca(2+). Chloride cells, which may be responsible for the active uptake of Ca(2+), started to differentiate in the skin of embryos 48h after fertilization, and the density of chloride cells increased following the development. A possibility of active transport for Ca(2+) in early developmental stages of tilapia is suggested.

This paper describes depuration processes of copper and zinc in green oysters (Crassostrea gigas) and in blue mussels (Mytilus smarangdium) collected from an environment with heavy copper contamination, and then transferred to natural clean seawater. Results show that the total loss of copper content per oyster is an exponential function of exposure time for the first 6 days with a depuration rate of 351 microg g(-1) day(-1) and then levels off. During this exponential decrease period approximately 67% of the copper accumulated in green oysters was depurated. However, when the copper contents in the oysters decreased from 2225 +/- 111 microg g(-1) to 344 +/- 18.7 microg g(-1) the depuration rates decreased from 245 microg g(-1) day(-1) to 0.08 microg g(-1) day(-1). This means that green oysters had a 16-fold higher copper depuration rate (351 microg g(-1) day(-1)) than normal oysters (21.5 microg g(-1) day(-1)) for the first 6 days. However, the depuration of accumulated copper and zinc by the mussels was a fast process in natural clean seawater. About 91% of the accumulated copper was lost during the first 6-day period; copper contents declined from 20.2 +/- 3.41 microg g(-1) to 1.80 +/- 0.21 microg g(-1). Only 36% of the accumulated zinc was lost during a depuration period of 6 days. Calculations show that the biological half-lives of copper in green and normal oysters were 11.6 and 25.1 days, respectively. The biological half-lives of zinc in green and normal oysters were 16.7 and 30.1 days, respectively. In spite of the relatively low initial copper content in blue mussels being 20.2 +/- 3.41 microg g(-1), the biological half-life is only 6.40 days. From these results it is important to emphasise that the fastest turnover rate is for copper in blue mussels. However, zinc is more retentive in blue mussels than copper.