To explore the effects of herbal medicine among cancer patients in Taiwan: A cohort study.

BACKGROUND: Traditional Chinese medicine (TCM) is widely used by ethnic Chinese communities. TCM is covered by Taiwan's National Health Insurance (NHI) program. We evaluated the efficacy and outcomes of complementary Chinese herbal medicine (CHM) therapy in patients with cancer. METHODS: This population-based cohort study was conducted using the data of patients who received a cancer diagnosis between 2005 and 2015 in Taiwan. Eligible patients were divided into standard and complementary CHM therapy groups. The complementary CHM therapy group was further divided into low cumulative dosage (LCD), medium cumulative dosage (MCD), and high cumulative dosage (HCD) subgroups. Overall survival (OS), mortality risk, cancer recurrence, and metastasis were analyzed for all cancers and five major cancers (lung, liver, breast, colorectal, and oral cancers). RESULTS: We included 5707 patients with cancer (standard therapy, 4797 [84.1%]; complementary CHM therapy, 910 [15.9%]; LCD, 449 [7.9%]; MCD, 374 [6.6%], and HCD, 87 [1.5%]). For the LCD, MCD, and HCD subgroups, the mortality risk was 0.83, 0.64, and 0.45, and the 11-year OS, 5-year cumulative cancer recurrence, and 5-year cumulative cancer metastasis rates were 6.1 ± 0.2, 6.9 ± 0.2, and 8.2 ± 0.4 years; 39.2%, 31.5%, and 18.8%; and 39.5%, 32.8%, and 16.6%, respectively. The cumulative cancer recurrence and metastasis rates of the standard therapy group were 40.9% and 32.8%, respectively. The cumulative recurrence and metastasis rates of all cancers, lung cancer, and liver cancer and all cancers, colorectal cancer, and breast cancer, respectively, were significantly lower in the HCD subgroup than in the other subgroups and standard therapy group ( p < 0.05). CONCLUSION: Patients receiving complementary CHM therapy may have prolonged OS and reduced risks of mortality, recurrence, and metastasis. A dose-response relationship was noted between CHM therapy and mortality risk: increased dosage was associated with improved OS and reduced mortality risk.

Cluster Analysis of DSC MRI, Dynamic Contrast-Enhanced MRI, and DWI Parameters Associated with Prognosis in Patients with Glioblastoma after Removal of the Contrast-Enhancing Component: A Preliminary Study.

BACKGROUND AND PURPOSE: No report has been published on the use of DSC MR imaging, DCE MR imaging, and DWI parameters in combination to create a prognostic prediction model in glioblastoma patients. The aim of this study was to develop a machine learning-based model to find preoperative multiparametric MR imaging parameters associated with prognosis in patients with glioblastoma. Normalized CBV, volume transfer constant, and ADC of the nonenhancing T2 high-signal-intensity lesions were evaluated using K-means clustering. MATERIALS AND METHODS: A total of 142 patients with glioblastoma who underwent preoperative MR imaging and total resection were included in this retrospective study. From the normalized CBV, volume transfer constant, and ADC maps, the parametric data were sorted using the K-means clustering method. Patients were divided into training and test sets (ratio, 1:1), and the optimal number of clusters was determined using receiver operating characteristic analysis. Kaplan-Meier survival analysis and log-rank tests were performed to identify potential parametric predictors. A multivariate Cox proportional hazard model was conducted to adjust for clinical predictors. RESULTS: The nonenhancing T2 high-signal-intensity lesions were divided into 6 clusters. The cluster (class 4) with the relatively low normalized CBV and volume transfer constant value and the lowest ADC values was most associated with predicting glioblastoma prognosis. The optimal cutoff of the class 4 volume fraction of nonenhancing T2 high-signal-intensity lesions predicting 1-year progression-free survival was 9.70%, below which the cutoff was associated with longer progression-free survival. Two Kaplan-Meier curves based on the cutoff value showed a statistically significant difference (P = .037). When we adjusted for all clinical predictors, the cluster with the relatively low normalized CBV and volume transfer constant values and the lowest ADC value was an independent prognostic marker (hazard ratio, 3.04; P = .048). The multivariate Cox proportional hazard model showed a concordance index of 0.699 for progression-free survival. CONCLUSIONS: Our model showed that nonenhancing T2 high-signal-intensity lesions with the relatively low normalized CBV, low volume transfer constant values, and the lowest ADC values could serve as useful prognostic imaging markers for predicting survival outcomes in patients with glioblastoma.

A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial☆.

BACKGROUND: Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC. PATIENTS AND METHODS: The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146). RESULTS: A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable. CONCLUSIONS: In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.

Dynamic Contrast-Enhanced MR Imaging of Nonenhancing T2 High-Signal-Intensity Lesions in Baseline and Posttreatment Glioblastoma: Temporal Change and Prognostic Value.

BACKGROUND AND PURPOSE: The prognostic value of dynamic contrast-enhanced MR imaging on nonenhancing T2 high-signal-intensity lesions in patients with glioblastoma has not been thoroughly elucidated to date. We evaluated the temporal change and prognostic value for progression-free survival of dynamic contrast-enhanced MR imaging-derived pharmacokinetic parameters on nonenhancing T2 high-signal-intensity lesions in patients with glioblastoma before and after standard treatment, including gross total surgical resection. MATERIALS AND METHODS: This retrospective study included 33 patients who were newly diagnosed with glioblastoma and treated with gross total surgical resection followed by concurrent chemoradiation therapy and adjuvant chemotherapy with temozolomide in a single institution. All patients underwent dynamic contrast-enhanced MR imaging before surgery as a baseline and after completion of maximal surgical resection and concurrent chemoradiation therapy. On the whole nonenhancing T2 high-signal-intensity lesion, dynamic contrast-enhanced MR imaging-derived pharmacokinetic parameters (volume transfer constant [K trans], volume of extravascular extracellular space [v e], and blood plasma volume [vp ]) were calculated. The Cox proportional hazards regression model analysis was performed to determine the histogram features or percentage changes of pharmacokinetic parameters related to progression-free survival. RESULTS: Baseline median K trans, baseline first quartile K trans, and posttreatment median K trans were significant independent variables, as determined by univariate analysis (P < .05). By multivariate Cox regression analysis including methylation status of O6-methylguanine-DNA methyltransferase, baseline median K trans was determined to be the significant independent variable and was negatively related to progression-free survival (hazard ratio = 1.48, P = .003). CONCLUSIONS: Baseline median K trans from nonenhancing T2 high-signal-intensity lesions could be a potential prognostic imaging biomarker in patients undergoing gross total surgical resection followed by standard therapy for glioblastoma.

Black TiO2 nanotubes: Efficient electrodes for triggering electric field-induced stimulation of stem cell growth.

TiO2 nanostructures represent a key platform for biomedical applications, due to the combination of biocompatibility and high surface area. Especially TiO2 nanotube layers have been widely investigated due to controllable nanotopographic effects as well as for electrodes in electrostimulation experiments. In the present work we produce Ar/H2-reduced 'black' TiO2 nanotube arrays with a strongly enhanced electrical conductivity and explore their interaction with mesenchymal stem cells when used as electrodes to apply electric fields (EF) across the cells. While we observe no significant change in cell adhesion and their focal contact formation on these high conductivity nanotubes, we do observe a rapid stem cell response when EF is engaged using the 'black' TiO2 nanotube arrays as electrodes. Compared to as-formed nanotube arrays, a faster stem cell growth was observed and a lower EF intensity caused an intracellular calcium level elevation. Our results indicate that the increased conductivity in TiO2 nanotubes significantly enhances the early stem cell response to minimal electric field stimuli. STATEMENT OF SIGNIFICANCE: The use of TiO2 nanostructures in biomedical applications is widely investigated, especially considering the nanostructured surface influence on the biomaterial-cell interactions. We have previously shown that an applied electric field (EF) on stem cells grown on TiO2 nanotubes leads to synergistic osteogenic stimulation in the absence of biochemical bone-inducing supplements. Here we report that black (i.e. highly conductive nanotubes obtained by reduction treatments) TiO2 nanotubes enable short-time EF effects on stem cells: we observe a faster stem cell growth and a significantly enhanced early stem cell response to minimal EF stimuli. The application of such nanostructures under electric field is promising for therapeutic interventions for bone regeneration and tissue engineering approaches.

Utilization patterns of traditional medicine in Taiwan and South Korea by using national health insurance data in 2011.

BACKGROUND: The growing popularity of traditional medicine (TM) is reflected in the increasing trend for its use worldwide. Many people are turning to use TM as a complementary or integrative treatment. The aim of this study is to present the first nationwide report describing the use of TM in two countries (South Korea and Taiwan). MATERIALS AND METHODS: To present the TM utilization patterns between South Korea and Taiwan, we analyzed data from the National Health Insurance cohorts in each country, each of which has approximately one million inhabitants. RESULTS: In total, 261,478 (25.5%) of 1,025,340 people in South Korea and 260,529 (26.8%) of 970,866 people in Taiwan used TM services at least once under the National Health Insurance in 2011. Using multivariable logistic regression, TM users in South Korea were significantly more likely to be female, 61-80 years of age and individuals with a high income, and those in Taiwan were significantly more likely to be female, 21-40 years of age and individuals with a middle income. The two countries showed similar utilization patterns in visit seasons. People visited TM clinics more frequently than TM hospitals in both countries. The most common TM treatment in South Korea was acupuncture, whereas in Taiwan, various powdered Chinese herbal preparations were the most commonly used treatment. The most common diseases for people seeking TM services were musculoskeletal system and connective tissue diseases in South Korea and Symptoms, signs, and ill-defined conditions in Taiwan. CONCLUSION: According to the National Health Insurance database, about one fourth of the NHI beneficiaries of South Korea and Taiwan had TM use in 2011. Different TM utilization patterns existed between South Korea and Taiwan, which might be due to the differences in insurance coverage between the two countries.

Population-based comparison of traditional medicine use in adult patients with allergic rhinitis between South Korea and Taiwan.

BACKGROUND: As the number of people seeking to use traditional medicine to treat common diseases is increasing worldwide, the quantity of information that needs to be analyzed is also increasing. Traditional medicine is commonly used in South Korea and Taiwan for treating allergic rhinitis and is covered by the National Health Insurance in both countries. To date, there has been no nationwide comparison of traditional medicine used to treat patients with allergic rhinitis between these two countries. METHODS: This study analyzed the National Health Insurance cohort database in 2011 from South Korea and Taiwan to compare the utilization pattern of traditional medicine in adult patients with allergic rhinitis. RESULTS: During 2011, there were significantly more adult patients with allergic rhinitis using traditional medicine in Taiwan (9898/54,555, 18.1%) than in South Korea (533/11,761, 0.5%). Users of traditional medicine from both countries were more prevalent among women, the younger population aged 20-39 years, and among people who visited traditional medicine clinics more frequently than hospitals. The most common traditional medicine treatment modality for allergic rhinitis was acupuncture in South Korea, while powdered herbal preparations was most commonly used in Taiwan. Xiaoqinglong-tang (Socheongryongtong-tang) was the most commonly used herbal preparation in South Korea, while Xinyi-san (Sinyi-san) was the most commonly prescribed herbal preparation in Taiwan. CONCLUSION: An analysis of the National Health Insurance database of South Korea and Taiwan revealed different utilization patterns of traditional medicine in adult patients with allergic rhinitis between the two countries. We believe these phenomena are due to the difference in the national healthcare systems in both countries.

Cystatin C-Based Equation for Predicting the Glomerular Filtration Rate in Kidney Transplant Recipients.

BACKGROUND: Precise monitoring of the glomerular filtration rate (GFR) is needed to estimate the allograft function in kidney transplant recipients (KTRs). The GFR is widely estimated with the use of formulas based on serum cystatin C (SCys) and serum creatinine (SCr) levels. We compared the efficacy of SCys-based equations with that of SCr-based equations to predict the allograft function. METHODS: We calculated the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI Cr), CKD-EPI creatinine-cystatin C (CKD-EPI Cr/Cys), and CKD-EPI cystatin C (CKD-EP ICys) equations in 70 KTRs. The measured GFR (mGFR) was defined as the GFR estimated by technetium-99m-diethylene triamine pentaacetic acid (99mTc-DTPA) clearance. The accuracy and precision of the equations were compared with the mGFR. The performance characteristics of SCr and SCys were analyzed with the use of receiver operating characteristic (ROC) curves to ascertain the sensitivity and specificity at the cutoff value of <45 mL/min/1.73 m2 DTPA. RESULTS: Overall, MDRD and CKD-EPICys did not show significant differences from mGFR (P = .05 and P = .077, respectively), whereas CKD-EPI Cr and CKD-EPI Cr/Cys significantly underestimated mGFR (P < .001 and P = .005, respectively). In the subgroup of patients with mGFR <45 mL/min/1.73 m2, CKD-EPI Cys showed little bias (P = .122), whereas MDRD significantly underestimated mGFR (P = .037). The area under the ROC curve for predicting mGFR <45 mL/min/1.73 m2 was 0.80 for SCys, which was better than that for SCr at 0.763. CONCLUSIONS: Cystatin C-based equations showed better predictive performance of the allograft function than creatinine-based equations for the KTRs, including patients with lower GFR. Cystatin C level might be a good alternate measurement to monitor the allograft function.

Scientific publications in gastroenterology and hepatology in Taiwan: An analysis of Web of Science from 1993 to 2013.

BACKGROUND: Scientific publications are important for evaluating the achievements of a medical specialty or discipline. Gastroenterology and Hepatology is a medical specialty in great demand in Taiwan, therefore, this study aimed to analyze the Gastroenterology and Hepatology publications from 1993 to 2013 in Taiwan, using the Web of Science (WoS) database. METHODS: Scientific publications from departments/institutes of gastroenterology and hepatology were retrieved and analyzed from the WoS database, which included articles published in the Science Citation Index Expanded and Social Science Citation Index journals from 1993 to 2013. RESULTS: Among 229,030 articles published from departments/institutes of gastroenterology and hepatology worldwide during 1993-2013, 5061 (2.21%) were published in Taiwan, ranking the country 13th in the world. In total, 4759 articles from Taiwan were selected for further analysis, excluding meeting abstracts and corrections. During these two decades, the number of gastroenterology and hepatology publications increased rapidly. There were 440 articles published during 1993-1997, 646 articles during 1998-2002, 1211 articles during 2003-2007, and up to 2462 articles during 2008-2013. However, the mean number of articles cited decreased from 25.35 to 27.25 to 20.64 to 7.28, and the mean impact factor of publishing journals decreased from 5.0 to 4.20 to 4.13 to 4.03 during 1993-1997, 1998-2002, 2003-2007, and 2008-2013, respectively. Most of those publications belong to the subject category gastroenterology and hepatology (2346 articles, 49.30%), followed by surgery (677 articles, 14.23%), medicine, general and internal (358 articles, 7.52%), oncology (316 articles, 6.64%), and pharmacology pharmacy (286 articles, 6.01%). The Journal of Gastroenterology and Hepatology published the most papers (326 articles, 6.9%), followed by World Journal of Gastroenterology (201 articles, 4.2%), Hepato-Gastroenterology (165 articles, 3.5%), Gastrointestinal Endoscopy (159 articles, 3.3%), and Hepatology (146 articles, 3.1%). CONCLUSION: Scientific publications from departments/institutes of gastroenterology and hepatology in Taiwan increased rapidly from 1993 to 2013. However, there were decreasing trends in the number of articles cited and journal impact factors.

Foxp3 is a key downstream regulator of p53-mediated cellular senescence.

The downstream events and target genes of p53 in the process of senescence are not fully understood. Here, we report a novel function of the forkhead transcription factor Foxp3, which is a key player in mediating T-cell inhibitory functions, in p53-mediated cellular senescence. The overexpression of Foxp3 in mouse embryonic fibroblasts (MEFs) accelerates senescence, whereas Foxp3 knockdown leads to escape from p53-mediated senescence in p53-expressing MEFs. Consistent with these results, Foxp3 expression resulted in the induction of senescence in epithelial cancer cells, including MCF7 and HCT116 cells. Foxp3 overexpression also increased the intracellular levels of reactive oxygen species (ROS). The ROS inhibitor N-acetyl-l-cysteine rescued cells from Foxp3-expression-induced senescence. Furthermore, the elevated ROS levels that accompanied Foxp3 overexpression were paralleled by an increase in p21 expression. Knockdown of p21 in Foxp3-expressing MEFs abrogated the Foxp3-dependent increase in ROS levels, indicating that Foxp3 acts through the induction of p21 and the subsequent ROS elevation to trigger senescence. Collectively, these results suggest that Foxp3 is a downstream target of p53 that is sufficient to induce p21 expression, ROS production and p53-mediated senescence.

Epac2a-null mice exhibit obesity-prone nature more susceptible to leptin resistance.

BACKGROUND: The exchange protein directly activated by cAMP (Epac), which is primarily involved in cAMP signaling, has been known to be essential for controlling body energy metabolism. Epac has two isoforms: Epac1 and Epac2. The function of Epac1 on obesity was unveiled using Epac1 knockout (KO) mice. However, the role of Epac2 in obesity remains unclear. METHODS: To evaluate the role of Epac2 in obesity, we used Epac2a KO mice, which is dominantly expressed in neurons and endocrine tissues. Physiological factors related to obesity were analyzed: body weight, fat mass, food intake, plasma leptin and adiponectin levels, energy expenditure, glucose tolerance, and insulin and leptin resistance. To determine the mechanism of Epac2a, mice received exogenous leptin and then hypothalamic leptin signaling was analyzed. RESULTS: Epac2a KO mice appeared to have normal glucose tolerance and insulin sensitivity until 12 weeks of age, but an early onset increase of plasma leptin levels and decrease of plasma adiponectin levels compared with wild-type mice. Acute leptin injection revealed impaired hypothalamic leptin signaling in KO mice. Consistently, KO mice fed a high-fat diet (HFD) were significantly obese, presenting greater food intake and lower energy expenditure. HFD-fed KO mice were also characterized by greater impairment of hypothalamic leptin signaling and by weaker leptin-induced decrease in food consumption compared with HFD-fed wild-type mice. In wild-type mice, acute exogenous leptin injection or chronic HFD feeding tended to induce hypothalamic Epac2a expression. CONCLUSIONS: Considering that HFD is an inducer of hypothalamic leptin resistance and that Epac2a functions in pancreatic beta cells during demands of greater work load, hypothalamic Epac2a may have a role in facilitating leptin signaling, at least in response to higher metabolic demands. Thus, our data indicate that Epac2a is critical for preventing obesity and thus Epac2a activators may be used to manage obesity and obesity-mediated metabolic disorders.

A Carcinoid Tumor of the Esophagus Treated with Endoscopic Ablation Therapy.

Esophageal carcinoids are exceedingly rare and only a few limited cases have been reported. Because knowledge about esophageal carcinoid is based primarily on case reports, the treatment of choice has not been settled. We report here on a localized carcinoid tumor in the esophagogastric junction. As our initial biopsy was nearly equal for the excision, we only performed coagulation ablation therapy instead of a wide excision which is traditionally recommended. The patient is free of recurrence so far during 50-month follow-up. Our report suggests that esophageal carcinoids may be not particularly associated with a poor prognosis.

Proteolytic degradation and potential role of onconeural protein cdr2 in neurodegeneration.

Cerebellar degeneration-related protein 2 (cdr2) is expressed in the central nervous system, and its ectopic expression in tumor cells of patients with gynecological malignancies elicits immune responses by cdr2-specific autoantibodies and T lymphocytes, leading to neurological symptoms. However, little is known about the regulation and function of cdr2 in neurodegenerative diseases. Because we found that cdr2 is highly expressed in the midbrain, we investigated the role of cdr2 in experimental models of Parkinson's disease (PD). We found that cdr2 levels were significantly reduced after stereotaxic injection of 1-methyl-4-phenylpyridinium (MPP(+)) into the striatum. cdr2 levels were also decreased in the brains of post-mortem PD patients. Using primary cultures of mesencephalic neurons and MN9D cells, we confirmed that MPP(+) reduces cdr2 in tyrosine hydroxylase-positive dopaminergic neuronal cells. The MPP(+)-induced decrease of cdr2 was primarily caused by calpain- and ubiquitin proteasome system-mediated degradation, and cotreatment with pharmacological inhibitors of these enzymes or overexpression of calcium-binding protein rendered cells less vulnerable to MPP(+)-mediated cytotoxicity. Consequently, overexpression of cdr2 rescued cells from MPP(+)-induced cytotoxicity, whereas knockdown of cdr2 accelerated toxicity. Collectively, our findings provide insights into the novel regulatory mechanism and potentially protective role of onconeural protein during dopaminergic neurodegeneration.

How different is the care of terminal pancreatic cancer patients in inpatient palliative care units and acute hospital wards? A nationwide population-based study.

BACKGROUND: Inpatient palliative care is important for patients with terminal pancreatic cancer. However, the differences between inpatient palliative care and acute hospital care for inpatients with pancreatic cancer have not been explored in a population-based study. METHODS: This population-based nationwide study was conducted using data from the Taiwan National Health Insurance database to analyze the differences between inpatient palliative care and acute hospital care for inpatients with pancreatic cancer. We identified 854 patients with terminal pancreatic cancer, who had received in-hospital end-of-life care between January 2003 and December 2006. These patients were then sub-divided and matched 1:1 (using propensity score matching) according to whether they received inpatient palliative care (n = 276) or acute hospital care (n = 276). These groups were subsequently compared to evaluate any differences in the use of aggressive procedures, prescribed medications, and medical costs. RESULTS: Inpatient palliative care was typically provided by family physicians (39%) and oncologists (25%), while acute hospital care was typically provided by oncologists (29%) and gastroenterologists (24%). The inpatient palliative care group used natural opium alkaloids significantly more frequently than the acute hospital care group (84.4% vs. 56.5%, respectively; P < 0.001). The inpatient palliative care group also had shorter hospital stays (10.6 ± 11.1 days vs. 20.6 ± 16.3 days, respectively; P < 0.001), fewer aggressive procedures, and lower medical costs (both, P < 0.005). CONCLUSIONS: Compared to patients in acute hospital wards, patients with pancreatic cancer in inpatient palliative care units received more frequent pain control treatments, underwent fewer aggressive procedures, and incurred lower medical costs. Therefore, inpatient palliative care should be considered a viable option for patients with terminal pancreatic cancer.

Hospice palliative care article publications: An analysis of the Web of Science database from 1993 to 2013.

BACKGROUND: Academic publications are important for developing a medical specialty or discipline and improvements of quality of care. As hospice palliative care medicine is a rapidly growing medical specialty in Taiwan, this study aimed to analyze the hospice palliative care-related publications from 1993 through 2013 both worldwide and in Taiwan, by using the Web of Science database. METHODS: Academic articles published with topics including "hospice", "palliative care", "end of life care", and "terminal care" were retrieved and analyzed from the Web of Science database, which includes documents published in Science Citation Index-Expanded and Social Science Citation Indexed journals from 1993 to 2013. Compound annual growth rates (CAGRs) were calculated to evaluate the trends of publications. RESULTS: There were a total of 27,788 documents published worldwide during the years 1993 to 2013. The top five most prolific countries/areas with published documents were the United States (11,419 documents, 41.09%), England (3620 documents, 13.03%), Canada (2428 documents, 8.74%), Germany (1598 documents, 5.75%), and Australia (1580 documents, 5.69%). Three hundred and ten documents (1.12%) were published from Taiwan, which ranks second among Asian countries (after Japan, with 594 documents, 2.14%) and 16(th) in the world. During this 21-year period, the number of hospice palliative care-related article publications increased rapidly. The worldwide CAGR for hospice palliative care publications during 1993 through 2013 was 12.9%. As for Taiwan, the CAGR for publications during 1999 through 2013 was 19.4%. The majority of these documents were submitted from universities or hospitals affiliated to universities. CONCLUSION: The number of hospice palliative care-related publications increased rapidly from 1993 to 2013 in the world and in Taiwan; however, the number of publications from Taiwan is still far below those published in several other countries. Further research is needed to identify and try to reduce the barriers to hospice palliative care research and publication in Taiwan.

A randomised, double-blind, placebo-controlled multi-centre phase III trial of XELIRI/FOLFIRI plus simvastatin for patients with metastatic colorectal cancer.

BACKGROUND: The purpose of this randomised phase III trial was to evaluate whether the addition of simvastatin, a synthetic 3-hydroxy-3methyglutaryl coenzyme A reductase inhibitor, to XELIRI/FOLFIRI chemotherapy regimens confers a clinical benefit to patients with previously treated metastatic colorectal cancer. METHODS: We undertook a double-blind, placebo-controlled phase III trial of 269 patients previously treated for metastatic colorectal cancer and enrolled in 5 centres in South Korea. Patients were randomly assigned (1:1) to one of the following groups: FOLFIRI/XELIRI plus simvastatin (40 mg) or FOLFIRI/XELIRI plus placebo. The FOLFIRI regimen consisted of irinotecan at 180 mg m(-2) as a 90-min infusion, leucovorin at 200 mg m(-2) as a 2-h infusion, and a bolus injection of 5-FU 400 mg m(-2) followed by a 46-h continuous infusion of 5-FU at 2400 mg m(-2). The XELIRI regimen consisted of irinotecan at 250 mg m(-2) as a 90-min infusion with capecitabine 1000 mg m(-2) twice daily for 14 days. The primary end point was progression-free survival (PFS). Secondary end points included response rate, duration of response, overall survival (OS), time to progression, and toxicity. RESULTS: Between April 2010 and July 2013, 269 patients were enrolled and assigned to treatment groups (134 simvastatin, 135 placebo). The median PFS was 5.9 months (95% CI, 4.5-7.3) in the XELIRI/FOLFIRI plus simvastatin group and 7.0 months (95% CI, 5.4-8.6) in the XELIRI/FOLFIRI plus placebo group (P=0.937). No significant difference was observed between the two groups with respect to OS (median, 15.9 months (simvastatin) vs 19.9 months (placebo), P=0.826). Grade⩾3 nausea and anorexia were noted slightly more often in patients in the simvastatin arm compared with with the placebo arm (4.5% vs 0.7%, 3.0% vs 0%, respectively). CONCLUSIONS: The addition of 40 mg simvastatin to the XELIRI/FOLFIRI regimens did not improve PFS in patients with previously treated metastatic colorectal cancer nor did it increase toxicity.

Functional regulation of FoxO1 in neural stem cell differentiation.

Forkhead transcription factor family O (FoxO) maintains adult stem cell reserves by supporting their long-term proliferative potential. MicroRNAs (miRs) regulate neuronal stem/progenitor cell (NSPC) proliferation and differentiation during neural development by controlling the expression of a specific set of target genes. In the neurogenic subventricular zone, FoxO1 is specifically expressed in NSPCs and is no longer detected during the transition to neuroblast stage, forming an inverse correlation with miR-9 expression. The 3'-untranslated region of FoxO1 contains a conserved target sequence of miR-9 and FoxO1 expression is coordinated in concert with miR-9 during neuronal differentiation. Our study demonstrates that FoxO1 contributes to NSPC fate decision through its cooperation with the Notch signaling pathway.

Surfactant toxicity in a case of (4-chloro-2-methylphenoxy) acetic acid herbicide intoxication.

OBJECTIVE: Self-poisoning with (4-chloro-2-methylphenoxy) acetic acid (MCPA) is a common reason for presentation to hospitals, especially in some Asian countries. We encountered a case of a 76-year-old woman who experienced unconsciousness, shock and respiratory failure after ingesting 100 mL MCPA herbicide. We determined whether the surfactant in the formulation was the chemical responsible for the toxic symptom in this patient. DESIGN: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability and lactate dehydrogenase (LDH) cytotoxicity assays were performed on human brain neuroblastoma SK-N-SH cells. The expressions of 84 genes in 9 categories that are implicated in cellular damage pathways were quantified using an RT(2) Profiler™ PCR array on a human neuronal cell line challenged with polyoxyethylene tridecyl ether (PTE). SETTING: Pesticide intoxication institute in university hospital. INTERVENTIONS: Extracorporeal elimination with intravenous lipid emulsion. MEASUREMENTS: Cell viability and gene expression. MAIN RESULTS: In the MTT assay, MCPA only minimally decreased cell viability even at concentrations as high as 1 mM. Cells treated with 1-methoxy-2-propanol, dimethylamine and polypropylene glycol exhibited minimal decreases in viability, whilst the viability of cells challenged with PTE decreased dramatically; only 15.5% of cells survived after exposure to 1 µM PTE. Similarly, the results of the LDH cytotoxicity assay showed that MCPA had very low cytotoxicity, whilst cells treated with PTE showed incomparably higher LDH levels (p < 0.0001). PTE up-regulated the expressions of genes implicated in various cell damage pathways, particularly genes involved in the inflammatory pathway. CONCLUSIONS: The surfactant PTE was likely the chemical responsible for the toxic symptom in our patient.

Family medicine publications in Taiwan: an analysis of the Web of Science database from 1993 to 2012.

BACKGROUND: Academic publications are important for developing a medical specialty or discipline. Since family medicine is a rapidly growing medical specialty in Taiwan, this study aimed to analyze family medicine publications from 1993 to 2012 in Taiwan using the Web of Science database. METHODS: Published academic articles submitted from departments/institutes of family medicine were retrieved and analyzed from the Web of Science database, which includes articles published in the Science Citation Index-Expanded and Social Science Citation Indexed journals from 1993 to 2012. RESULTS: Among 33,073 published articles submitted from the departments/institutes of family medicine worldwide during the years 1993-2012, 1552 articles (4.69%) were submitted from Taiwan, ranking fourth in the world after the USA, Canada, and Sweden. In total, 1409 articles from Taiwan, excluding meeting abstracts and corrections, were selected for further analyses. During these two decades, family medicine publications increased rapidly. There were 60 articles published during 1993-1997, 180 articles during 1998-2002, 334 articles during 2003-2007, and up to 836 articles during 2008-2012. However, the mean citation number of articles decreased from 19.0 to 17.7, 15.1, and 3.8, and the mean impact factor of published journals decreased from 3.41 to 3.15, 2.78 and 2.82 during the periods 1993-1997, 1998-2002, 2003-2007, and 2008-2012, respectively. Most articles belonged to the subject category of the Medicine, General and Internal category (194 articles, 13.8%), followed by Public Environmental Occupational Health (144 articles, 10.2%), Oncology (126 articles, 9.2%), Endocrinology Metabolism (111 articles, 7.9%), Geriatrics Gerontology (99 articles, 7.0%), and the Gastroenterology Hepatology category (85 articles, 6.0%). However, only six articles (0.4%) were published in the Primary Health Care category. CONCLUSION: Publications from departments/institutes of family medicine in Taiwan increased rapidly from 1993 to 2012. However, the trends of decreased citation number of articles and journal impact factor, as well as the small amount of articles published in the Primary Health Care Category, deserve further attention and effort.