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Hypercholesterolemia is a preventable risk factor for atherosclerosis and cardiovascular disease. However, the mechanisms whereby cis -palmitoleic acid ( c POA) and trans -palmitoleic acid ( t POA) promote cholesterol homeostasis and ameliorate hypercholesterolemia remain elusive. To investigate the effects of c POA and t POA on cholesterol metabolism and its mechanisms, we induced hypercholesterolemia in mice using a high-fat diet and then intragastrically administered c POA or t POA once daily for 4 weeks. t POA administration reduced serum cholesterol, low-density lipoprotein, high-density lipoprotein, and hepatic free cholesterol and total bile acids (TBAs). Conversely, c POA had no effect on these parameters except for TBAs. Histological examination of the liver, however, revealed that c POA ameliorated hepatic steatosis more effectively than t POA. t POA significantly reduced the expression of 3-hydroxy-3-methyl glutaryl coenzyme reductase (HMGCR), LXRα, and intestinal Niemann-Pick C1-Like 1 (NPC1L1) and increased cholesterol 7-alpha hydroxylase (CYP7A1) in the liver, whereas c POA reduced the expression of HMGCR and CYP7A1 in the liver and had no effect on intestinal NPC1L1. In summary, our results suggest that c POA and t POA reduce cholesterol synthesis by decreasing HMGCR levels. Furthermore, t POA, but not c POA, inhibited intestinal cholesterol absorption by downregulating NPC1L1. Both high-dose t POA and c POA may promote the conversion of cholesterol into bile acids by upregulating CYP7A1. t POA and c POA prevent hypercholesterolemia via distinct mechanisms., 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 © 2020 Huang, Hong, Bai, Tan, Yang, Sun, Yi and Wu.)

Physicians have a fiduciary duty to be honest and to act in the patients' best interest. There are times when these two duties conflict. Honesty is paramount in supporting the physician-patient relationship and loss of patient trust is devastating. Furthermore, even minor deception can suggest a return to the physician authoritarianism of the past century that has been decried by modern ethicists. Nonetheless, circumstances can arise in which good judgement may require less than complete honesty to avoid harm to the patient. If the benefit for the patient is large and the risk from deception is small, thoughtful application of minor deception could be designed to benefit patients. Of course, research is required to fully assess this strategy.

Background: Pyoderma gangrenosum (PG) is a rare autoinflammatory skin condition that causes tissue destruction and subsequent painful ulcers. To date, there are no core domains or instruments for assessing PG severity in clinical trials, and current treatment paradigms rely on outcome measurements that have not been well characterized in the literature., Objectives: To perform two systematic reviews that (i) identify the outcome measurement instruments used in PG clinical trials and their corresponding domains and (ii) identify any associated validation studies and evaluate their measurement properties and methodological quality., Methods: We systematically searched the MEDLINE and Embase databases for PG outcome measurement instruments. We also systematically searched for PG instrument validation studies. We evaluated the measurement properties and methodological quality of validation studies using the 2018 COSMIN Risk of Bias checklist., Results: In total, seven clinical trials were included. These studies utilized a total of 20 different instruments, including 11 physician-reported instruments, eight patient-reported instruments and one composite instrument. Among these, 85% of the instruments lacked any validation data. Of the remaining three validated instruments (speed of healing, physician global assessment and resolution of inflammation), methodological quality was not available for half of the COSMIN categories., Conclusions: We identified 17 non-validated outcome measurement instruments used in PG clinical trials. We conclude that PG validation studies are required for existing instruments, and new instruments need to be developed to inform the consensus process for the development of a core outcome set for PG. What is already known about this topic? Pyoderma gangrenosum (PG) is a rare autoinflammatory skin condition that has been characterized by multiple outcome measurement instruments in clinical trials. However, there is no consensus on the most validated and appropriate outcome measurement instruments. What does this study add? This study identifies and evaluates 20 unique outcome measurement instruments for PG in the literature. Of these 20, 17 lack any instrument validation data, highlighting the need for future studies. What are the clinical implications of this work? Despite the current use of several outcome measurement instruments, future studies should explore the validation surrounding these instruments, as no instruments can currently be recommended., (© 2020 British Association of Dermatologists.)

Open-air burning of rice straw (RS) on sites after harvesting produces tremendous amounts of air pollutants in Southeast Asia. Additionally, cooking oil smoke (COS) from high-temperature frying is classified as "Probably carcinogenic to humans" (Group 2A) by the International Agency for Research on Cancer. To mitigate the air pollution from COS, RS was recycled to prepare activated carbon (AC), which was used as a bed filter (BF) packing material for COS removal, and to our best knowledge, this study is the first one. Besides, a negative air ionizer (NAI) was firstly utilized to enhance the removal efficiency (η) of COS particles. Other biomass waste, including tea leaves (TL), wood dust (WD), rice hulls (RH), and coffee grounds (CG), were also used as packing materials for comparison. Specific surface area and pore volume of the packing materials were determined by nitrogen adsorption/desorption isothermal. Laser airborne particle counters and volatile organic compound (VOC) monitors (photoionization detector) were utilized for real-time recording of the particle and VOC concentration of COS. Economic assessments for the control of COS was also conducted. For submicron particles, the removal efficiency of the BFs ranged from 0 to 98% and the AC filter had the highest quality factor. The NAI remarkably enhanced the η value and filter quality factor. For the removal of particles larger than 2.5 μm, all BFs had η > 96%. The removal efficiency of volatile organic compounds (VOCs) (η VOC ) of the test BFs ranged from 18.22 to 90.8%. The AC filter had the largest pore volume (0.432 cm 3 /g) and surface area (877 m 2 /g) among all packing materials, causing this filter to have the highest η VOC and adsorption capacity (over 28.3 mg-VOCs/g-AC). The annual operating costs of the TL, WD, RH, CG, and AC filters were 319.4, 23.3, 29.1, 189.4, and 62.9 US$, respectively. Therefore, using RS to prepare an AC bed filter for the removal of COS is a practical and sustainable strategy for COS control.

This study aimed to describe the landscape of Immune checkpoint inhibitors (ICIs)-related adverse events (AEs) in a predominantly Chinese cohort. We searched electronic datasets including PubMed, Web of Science and Embase to identify and recruit relevant trials up to September 2, 2019. Clinical trials focusing on ICIs in Chinese patients or a predominantly Chinese population were included. Incidences of treatment-related AEs (TRAEs) and immune-related AEs (irAEs) were pooled and compared. In total, we recruited 13 trials consisting of 1063 patients, with 922 (86.7%) receiving ICI monotherapy and 141 (13.3%) receiving combination of ICI with chemotherapy or anti-angiogenesis. The pooled incidence of any grade TRAEs, grade 1-2, grade 3-5 TRAEs, any grade irAEs, grade 1-2 irAEs and grade 3-5 irAEs in all 1063 patients were 84.1%, 63.3%, 20.9%, 43.3%, 40.0% and 3.0%, respectively. Moreover, 4.3% (44/1018) of patients experienced treatment discontinuation and only 8 (0.8%) patients experienced treatment-related death. Compared to ICI monotherapy, combination significantly increased grade 3-5 TRAEs (46.1% vs. 17.0%, P < 0.001) and grade 3-5 irAEs (7.1% vs. 2.0%, P = 0.015). By comparing the toxicity profiles between different ICIs, we found some drug-specific AEs such as reactive capillary haemangiomas for camrelizumab (58.6%), hyperglycemia for toripalimab (55.6%) and pyrexia for tislelizumab (54.3%). Additionally, nivolumab has the lowest incidence of any grade (64.1%) and grade 3-5 (11.8%) TRAEs. ICI-related AEs were generally mild and tolerable for a predominantly Chinese cohort. However, we should pay attention to the combination of ICI with chemotherapy as it could increase grade 3-5 TRAEs and irAEs.

Background/aim: Casticin, one of the active components of Vitex rotundifolia L., presents biological and pharmacological activities including inhibition of migration, invasion and induction of apoptosis in numerous human cancer cells in vitro. This study aimed to assess the effects of casticin on tumor growth in a human oral cancer SCC-4 cell xenograft mouse model in vivo., Materials and Methods: Twenty-four nude mice were injected subcutaneously with SCC-4 cells and when palpable tumors reached a volume of 100-120 mm 3 the mice were randomly divided into three groups. The control (0.1% dimethyl sulfoxide), casticin (0.2 mg/kg), and casticin (0.4 mg/kg) groups were intraperitoneally injected every two days for 18 days. Tumor volume and body weights were measured every two days., Results: Casticin significantly decreased tumor volume and weight in SCC-4 cell xenograft mice but there was no statistically significant difference between the body weights of control mice and mice treated with 0.2 mg/kg or 0.4 mg/kg casticin. Therefore, the growth of SCC-4 cells in athymic nude mice can be inhibited by casticin in vivo., Conclusion: These findings support further investigations in the potential use of casticin as an oral anti-cancer drug in the future., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Demethoxycurcumin (DMC), a derivate of curcumin from natural plants, exerts antitumor effects on various human cancer cells in vitro and in vivo. Nevertheless, no reports have disclosed whether DMC can affect the growth of human cervical cancer cells in vivo. Therefore we investigated the antitumor effects of DMC on a HeLa cell xenograft model in nude mice in this study., Materials and Methods: Twenty-four nude mice were subcutaneously injected with HeLa cells. All mice were randomly divided into control, low-dose DMC (30 mg/kg), and high-dose DMC (50 mg/kg) groups and individual mice were treated intraperitoneally accordingly every 2 days., Results: DMC significantly reduced tumor weights and volumes of HeLa cell xenografts in mice, indicating the suppression of growth of xenograft tumors., Conclusion: These effects and findings might provide evidence for investigating the potential use of DMC as an anti-cervical cancer drug in the future., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Leukemia is one of the major diseases causing cancer-related deaths in the young population, and its cure rate is unsatisfying with side effects on patients. Fluorouracil (5-FU) is currently used as an anticancer drug for leukemia patients. Casticin, a natural polymethoxyflavone, exerts anticancer activity against many human cancer cell lines in vitro, but no other reports show 5-FU combined with casticin increased the mouse leukemia cell apoptosis in vitro. Herein, the antileukemia activity of 5-FU combined with casticin in WEHI-3 mouse leukemia cells was investigated in vitro. Treatment of two-drug combination had a higher decrease in cell viability and a higher increase in apoptotic cell death, the level of DNA condensation, and the length of comet tail than that of 5-FU or casticin treatment alone in WEHI-3 cells. In addition, the two-drug combination has a greater production rate of reactive oxygen species but a lower level of Ca 2+ release and mitochondrial membrane potential (ΔΨ m ) than that of 5-FU alone. Combined drugs also induced higher caspase-3 and caspase-8 activities than that of casticin alone and higher caspase-9 activity than that of 5-FU or casticin alone at 48 hours treatment. Furthermore, 5-FU combined with casticin has a higher expression of Cu/Zn superoxide dismutase (SOD [Cu/Zn]) and lower catalase than that of 5-FU or casticin treatment alone. The combined treatment has higher levels of Bax, Endo G, and cytochrome C of proapoptotic proteins than that of casticin alone and induced lower levels of B-cell lymphoma 2 (BCL-2) and BCL-X of antiapoptotic proteins than that of 5-FU or casticin only. Furthermore, the combined treatment had a higher expression of cleaved poly (ADP-ribose) polymerase (PARP) than that of casticin only. Based on these findings, we may suggest that 5-FU combined with casticin treatment increased apoptotic cell death in WEHI-3 mouse leukemia cells that may undergo mitochondria and caspases signaling pathways in vitro., (© 2020 Wiley Periodicals, Inc.)

Problems with PM 2.5 pollution in the Pearl River Delta (PRD) have been significantly reduced since the Chinese government released a series of emission control policies including the strengthened controls in the 13 th Five-Year Plan. This study assessed the efficacy of emission control measures using the Community Multiscale Air Quality (CMAQ) model to provide data-driven support to government decision making, which is becoming increasingly important. This study aimed to quantitatively evaluate the integrated results of proposed policies for controlling PM 2.5 concentrations. Accordingly, the regional 2015 emission inventory was modified with recently released government data for the PRD, and scenarios for four dynamical emission-reduction policies (S1-S4) were explored. The results show that all four proposed control measures can help to reduce PM 2.5 concentrations throughout Hong Kong (HK), Macao, and the PRD economic zone (PRD EZ) by 2020. In all cases, reductions in PM 2.5 concentrations were larger over PRD EZ than over HK. For HK, the predicted annual concentrations of PM 2.5 were less than 20 μg/m 3 for S1-S3 and less than 15 μg/m 3 for S4. For Macao, the predicted annual concentrations of PM 2.5 were less than 25 μg/m 3 for S1 and less than 15 μg/m 3 up to S3. Regionally, HK had the lowest PM 2.5 levels, and the area around Foshan had the highest. Controlling the sources of air pollution (i.e., industry, transport, power production, and other sources) within PRD can get most of the PRD EZ region to below 35 μg/m 3 . Similar national air quality management efforts could reduce PM 2.5 levels to less than 25 μg/m 3 in the PRD EZ and less than 15 μg/m 3 in HK. Control measures in S1 led to significant improvement in Shenzhen and HK, but the S3 option brought the greatest improvement for PRD EZ and Macao. The S4 policy option led to substantial reductions, particularly for HK., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

To find out the role of hsa-miR-570-3p targeting CD274 in triple negative breast cancer (TNBC) via PI3K/AKT/mTOR signaling pathway. Hsa-miR-570-3p and CD274 expressions in 175 TNBC patients were detected by qRT-PCR and immunohistochemistry respectively. The human TNBC cell lines (MDA-MB-468 and MDA-MB-231) were used to verify the targeting relationship between hsa-miR-570-3p and CD274 via dual-luciferase reporter gene assay. Then, MDA-MB-468 and MDA-MB-231 cells were divided into Blank, miR-NC, miR-570-3p mimics, NC siRNA, CD274 siRNA, and miR-570-3p inhibitors + CD274 siRNA groups. Next, the biological activities of cells were detected by MTT, Cell-Light EdU, Annexin-V-FITC/PI, wound healing and Transwell invasion assays. Western blotting was conducted to detect protein expressions.MiR-570-3p expression was lower in tumor tissues than that in adjacent normal tissues, which was more obvious in CD274-positive TNBC patients, which targeted CD274 in TNBC cell lines. MiR-570-3p inhibited cell proliferation, invasion and migration, but induced cell apoptosis accompanying the upregulation of apoptotic proteins and downregulation of anti-apoptotic protein. CD274 siRNA had the similar results of miR-570-3p mimics, which could be reversed by miR-570-3p inhibitors. Besides, both miR-570-3p mimics and CD274 siRNA blocked PI3K/AKT/mTOR signaling pathway in TNBC cell lines. Hsa-miR-570-3p was downregulated and CD274 was upregulated in TNBC patients. Besides, hsa-miR-570-3p targeted CD274 to inhibit cell proliferation, invasion, migration, and induce cell apoptosis, which may be related to the suppression of PI3K/AKT/mTOR pathway., (© 2020 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)

Background: Intraoperative hypotension is associated with increased morbidity and mortality after surgery. We hypothesized that intraoperative hypotension might also be associated with worse long-term survival after cancer surgery. Herein, we analyzed the correlation between intraoperative hyper-/hypotension and overall survival after lung cancer surgery., Methods: In this retrospective cohort study, 676 patients who received lung cancer surgery between January 1, 2006 and December 31, 2009 were reviewed. Intraoperative hyper- and hypotension were defined according to their correlation with long-term survival. The primary endpoint was overall survival. The association between episodes of intraoperative hyper-/hypotension and overall survival was analyzed with multivariable Cox proportional hazard models., Results: Long-term follow-ups were completed in 515 patients with a median duration of 5.2 years. The estimated 5-year survival rates were 66.5, 61.3, 56.5, and 41.2% in patients with only hypertension (systolic blood pressure > 140 mmHg for ≥5 min), with both hyper- and hypotension (systolic blood pressure < 100 mmHg for ≥5 min), with neither hyper- nor hypotension, and with only hypotension during surgery, respectively. After adjusting confounding factors, intraoperative hypotension was significantly associated with shortened overall survival (compared with patients with only intraoperative hypertension, those with both hyper- and hypotension: hazard ratio [HR]1.033, 95% confidence interval [CI] 0.709 to 1.507, p = 0.864; those with neither hyper- nor hypotension: HR 0.952, 95% CI 0.608 to 1.489, p = 0.829; those with only hypotension: HR 1.736, 95% CI 1.218 to 2.475, p = 0.002)., Conclusions: For patients undergoing lung cancer surgery, intraoperative hypotension, but not hypertension, was associated with shortened overall survival.

Background: The population of the U.S. is becoming more diverse every year. The field of dermatology is not following the same trend., Objective: To assess the promotion of diversity in the field of dermatology by analyzing publications focused on diversity, compared to other specialties., Methods: The PubMed database was systematically searched to identify publications focused on diversity from January 2008 to July 2019. The search criteria were as follows: dermatology/radiology/ophthalmology/ anesthesiology/orthopedic surgery/family medicine/ internal medicine/general surgery AND diversity/ diverse/racial/race/ethnic/ethnicity/cultural/culture/competency/competence. Comparisons were made using single-factor ANOVA and two-group t-tests. A qualitative analysis was performed for publications in the field of dermatology., Results: From January 2016 to July 2019, there were 25 publications focused on diversity in dermatology (Mean=6.25, SD=2.06), compared to 6 in radiology (Mean=1.50, SD=1.29, P=0.01), two in ophthalmology (Mean=0.50, SD=0.58, P=0.01), two in anesthesiology (Mean=0.50, SD=1.00, P=0.01), 12 in orthopedic surgery (Mean=3.00, SD=1.41, P=0.04), 23 in family medicine (Mean=5.75, SD=2.22, P=0.75), 9 in internal medicine (Mean=2.25, SD=1.71, P=0.02), and 7 in general surgery (Mean=1.75, SD=0.50, P=0.02)., Conclusions: Although the field of dermatology has suffered from a lack of racial/ethnic diversity, efforts to promote diversity via increased publications in the last four years have been stronger in dermatology compared to many other fields.

Here, we describe the recent progress toward construction of 1-azabicyclic structures using a domino hydroformylation double cyclization strategy of an amide bearing the trisubstituted alkene functionality. The method provides a rapid and atom-economic access to alkaloid structures under mild conditions, especially for quinolizidine and pyrrolidine-fused azepane skeletons with yields up to 82% and good diastereoselectivity. Subsequent oxidative cleavage conditions are developed for the synthesis of Dendrobatid alkaloid epi-epiquinamide., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

The effects of two-drug combination, all-trans retinoic acid (ATRA) and bisdemethoxycurcumin (BDMC), on apoptosis induction of liver cancer cells were investigated in human liver Hep 3B cells. Two-drug combination caused a more effective decrease in cell viability and in induction of S phase arrest, DNA damage, and cell apoptosis than that of ATRA or BDMC only. Also, the two-drug combination caused more cells to undergo significantly increased ROS productions when compared to that of ATRA or BDMC only. Results of Western blotting demonstrated that two-drug combination increased expressions of Fas, pro-apoptotic proteins, and active form of caspase-3 and -9, but decreased that of anti-apoptotic proteins and XIAP than that of ATRA or BDMC only in Hep 3B cells. In conclusion, ATRA combined with BDMC enhance cell apoptosis and associated protein expression in Hep 3B cells. PRACTICAL APPLICATIONS: Bisdemethoxycurcumin (BDMC) derived from natural plants, turmeric (Curcuma longa), which had been used for Asia food for thousands of years. All-trans retinoid acid (ATRA) is currently used as a primary treatment for patients with acute promyelocytic leukemia. In previous study, ATRA and BDMC were reported to have anti-inflammatory and anticancer effects. Our results showed that treatment of ATRA combined with BDMC showed more effectively apoptosis than that of ATRA or BDMC only in Hep 3B cells. The findings also provided possible pathways concerning the induction of liver cancer cell apoptosis. We conclude that ATRA combined with BDMC may be potent anticancer agents or adjuvants for liver cancer therapy in the future., (© 2019 Wiley Periodicals, Inc.)

Casticin was obtained from natural plants, and it has been shown to exert biological functions; however, no report concerns the induction of DNA damage and repair in human lung cancer cells. The objective of this study was to investigate the effects and molecular mechanism of casticin on DNA damage and repair in human lung cancer A549 cells. Cell viability was determined by flow cytometric assay. The DNA damage was evaluated by 4',6-diamidino-2-phenylindole (DAPI) staining and electrophoresis which included comet assay and DNA gel electrophoresis. The protein levels associated with DNA damage and repair were analyzed by western blotting. The expression and translocation of p-H2A.X were observed by confocal laser microscopy. Casticin reduced total viable cell number and induced DNA condensation, fragmentation, and damage in A549 cells. Furthermore, casticin increased p-ATM at 6 h and increased p-ATR and BRCA1 at 6-24 h treatment but decreased p-ATM at 24-48 h, as well as decreased p-ATR and BRCA1 at 48 h. Furthermore, casticin decreased p-p53 at 6-24 h but increased at 48 h. Casticin increased p-H2A.X and MDC1 at 6-48 h treatment. In addition, casticin increased PARP (cleavage) at 6, 24, and 48 h treatment, DNA-PKcs and MGMT at 48 h in A549 cells. Casticin induced the expressions and nuclear translocation of p-H2AX in A549 cells by confocal laser microscopy. Casticin reduced cell number through DNA damage and condensation in human lung cancer A549 cells.

Background: There are still oral cancer patients without surgery. To improve the survival, it is necessary to know the causes of the oral cancer patients without surgery., Methods: 23,217 patients with a newly-diagnosed oral cancer in Taiwan Cancer Registry (TCR) database between 2011 and 2015 were enrolled. Data from TCR database named "Reason for No Surgery of Primary Site" were extracted for analysis of the causes of those without surgery. Overall survival plots were presented using the Kaplan-Meier method with log-rank test., Results: 3263 (14%) patients did not received surgery. Among them, there were 720 patients (group 3) without surgery although surgery was advised, 154 patients (group 2) because of poor condition or death before surgery, and 2389 patients (group 1) because of other causes. Twenty-four percent of the patients with surgery were treated one month and more after diagnosis. The 5-year overall survival rates were 68.7%, 25.2%, 9.1% and 17.3% for surgery group, group 3, 2 and 1, respectively (p < 0.001). The mean age of the patients with and without surgery were 54.8 and 59.3, respectively (p < 0.01). Female patients were commoner in group 3 (p < 0.01). The patients without surgery was commoner in the middle (15.7%) and southern (14.8%) than in Northern Taiwan (12.1%). All groups without surgery had more advanced stage and lower BMI (p < 0.01)., Conclusion: One-sevenths of patients were not treated surgically because of refusal, poor condition, older age, low BMI, and advanced stage. It is necessary to encourage the patients to undergo surgery with shortening the diagnosis-to-treatment interval., (Copyright © 2019 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Cantharidin (CTD), a sesquiterpenoid bioactive substance, has been reported to exhibit anticancer activity against various types of cancer cells. The aim of the present study was to investigate the apoptosis effects and the underlying mechanisms of CTD on osteosarcoma U-2 OS cells. Results showed that CTD induced cell morphologic changes, reduced total viable cells, induced DNA damage, and G 2 /M phase arrest. CTD increased the production of reactive oxygen species and Ca 2+ , and elevated the activities of caspase-3 and -9, but decreased the level of mitochondrial membrane potential. Furthermore, CTD increased the ROS- and ER stress-associated protein expressions and increased the levels of pro-apoptosis-associated proteins, but decreased that of anti-apoptosis-associated proteins. Based on these observations, we suggested that CTD decreased cell number through G 2 /M phase arrest and the induction of cell apoptosis in U-2 OS cells and CTD could be a potential candidate for osteosarcoma treatments.

Deoxynivalenol (DON) is one of the mycotoxins most frequently encountering in cereal-based foods throughout the world. Saccharomyces cerevisiae was used to alleviate porcine jejunal epithelia cell (IPEC-J2) injury induced by DON in this study. The results indicated that cell viability and proliferation rates were significantly decreased when DON concentrations were increased from 0 to 64 µM after 24 h incubation (p < 0.05). The longer incubation time and higher DON concentrations would cause more serious effects on cell viability. S. cerevisiae could significantly degrade DON and decrease lactic dehydrogenase (LDH) release in the cells induced by DON (p < 0.05). DON (4 µM) could increase necrotic and apoptotic cell rates as well as decrease viable cell rates, compared with the control group (p < 0.05). However, S. cerevisiae addition in the DON group could decrease necrotic, late apoptotic and early apoptotic cell rates by 38.05%, 46.37% and 44.78% respectively, increase viable cell rates by 2.35%, compared with the single DON group (p < 0.05). In addition, S. cerevisiae addition could up-regulate mRNA abundances of IL-6, IL-8 and IL-10 in IPEC-J2 cells (p < 0.05), but down-regulate mRNA abundances of tight junction proteins (TJP-1) and occludin by 36.13% and 50.18% at 1 µM of DON (p < 0.05). It could be concluded that S. cerevisiae was able to alleviate IPEC-J2 cell damage exposed to DON.

Lupeol, one of the common components from the fruits and natural foods, has been reported to exert antitumor activities in many human cancer cell lines; however, its effects on osteosarcoma cell metastasis were not elucidated. In the present study, lupeol at 10-25 μM induced cell morphological changes and decreased total viable cell number in U-2 OS cells. Lupeol (5-15 μM) suppressed cell mobility, migration, and invasion by wound healing and transwell chamber assays, respectively. Lupeol inhibited the activities of MMP-2 and -9 in U-2 OS cells by gelatin zymography assay. Lupeol significantly decreased PI3K, pAKT, β-catenin, and increased GSK3β. Furthermore, lupeol decreased the expressions of Ras, p-Raf-1, p-p38, and β-catenin. Lupeol also decreased uPA, MMP-2, MMP-9, and N-cadherin but increased VE-cadherin in U-2 OS cells. Based on these observations, we suggest that lupeol can be used in anti-metastasis of human osteosarcoma cells in the future.

Neratinib is a tyrosine kinase inhibitor that was FDA-approved for extended adjuvant treatment in adults with human epidermal growth factor receptors-2 (HER-2) positive breast cancer in 2017. Due to the novelty of the drug, there are no current reports in the literature of adverse cutaneous effects associated with neratinib therapy. We present a case of a woman on neratinib for HER-2 positive infiltrating ductal carcinoma of the right breast who presented to the dermatology clinic with changes to the fingernails, acne, and a rash on the face. Physical examination revealed erythema, induration, and some serum crust along the lateral nail folds of the right fourth and left third digits as well as monomorphic acneiform papules and pustules on the face. The timeline of the patient's paronychia and acneiform rash were consistent with a diagnosis of neratinib-associated skin changes. The patient was prescribed doxycycline to control the acneiform eruption. For the nails, she used mupirocin ointment as well as Listerine soaks. She experienced great improvement on this regimen at her 3-month follow-up visit. This case highlights similar cutaneous side effects to epidermal growth factor receptor (EGFR) inhibitors with a newer agent, neratinib, that have not been documented in the literature.

Introduction: Gemcitabine is a chemotherapeutic agent used to treat several solid organ malignancies. The most common cutaneous toxicities are a mild erythematous rash and pruritus, which are often attributed to infectious etiologies. However, certain clinical characteristics may favor a drug-related reaction. Clinicians should recognize these phenomena to avoid potentially unnecessary antibiotic treatment or withdrawal of chemotherapeutic agents., Objective: We aim to report a case of gemcitabine-related acute lipodermatosclerosis-like eruption, add to the evolving classification of this condition, and highlight developing literature on gemcitabine that may explain this toxicity., Case: Dermatology was consulted for presumed cellulitis in a 62-year-old female with pancreatic carcinoma. The patient presented to the emergency department five days after her first dose of gemcitabine with erythema in both lower extremities. A diagnosis of gemcitabine-related acute lipodermatosclerosis was made and the patient was started on topical triamcinolone., Conclusion: It is important to recognize gemcitabine-related acute lipodermatosclerosis in order to avoid unnecessary antibiotic use and disruptions in chemotherapy.

Background: A reliable and valid observational gait assessment intended to guide clinical intervention for gait deficits in older adults has not been proposed. A quick gait classification method which tailors clinical management for different patterns of gait dysfunction may be useful for clinicians with limited access to apply computer-assisted gait analyses., Research Question: This work aims to establish reliability and validity of the Treatment-Based Gait Pattern Classification (TBGPC) that can be used to quickly identify and classify mobility problems of older males, and possibly target interventions for specific gait deficits in clinical settings., Method: Videotapes of 116 older male veterans referred for mobility problems were analyzed in this cross-sectional study. The TBGPC defined by movement control (consistent, inconsistent) and postural biomechanical factors (usual, flexed, extended, crouched) was validated by comparing means of individual items of the Modified Gait Abnormality Rating Scale (GARS-M) across groups., Results: Kappas for interrater reliability of the TBGPC movement control and biomechanical components were 0.59 and 0.75, respectively; for intrarater reliability, 0.82 and 0.72, respectively. Both movement control and biomechanical components were validated. All GARS-M items were different between older males with consistent and inconsistent gait. Within the consistent and inconsistent group, hip ROM was one of the most differentiating GARS-M item between older males with usual and flexed gait and flexed and crouched group. Total GARS-M score and guardedness were two differentiating factors between the usual and crouched group., Significance: Gait patterns of older males were reliably recognized and validated by mean differences in abnormal characteristics of gait across patterns. The TBGPC may be useful to quickly identify and classify mobility problems of older males and to guide clinical intervention., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Cis- and trans-palmitoleic acids (Cis-POA and trans-POA) are isomers of palmitoleic acid, a monounsaturated fatty acid which affects glucose and lipid metabolism, and reduces insulin resistance. Trans-POA is used as a biomarker for indicating the risk of type II diabetes and coronary heart disease, but no methods of analysis or distinguishing between cis-POA and trans-POA have yet been reported., Method: An accurate and precise HPLC method was developed to determine cis- and trans-POA simultaneously, and compared with results from a GC method. Cis- and trans-POA were analyzed by HPLC on a reverse-phase BDS-C18 column, equilibrated and eluted with acetonitrile (A) and water (B). In the established and validated GC method used for comparison, potassium hydroxide ester exchange was chosen to derivatize the cis- and trans-POA, before being determined., Results: The calibration curves for cis- and trans-POA were linear over the range 0.05 to 500 μg/mL. The HPLC method exhibited good sensitivity, precision and accuracy. The limits of detection (LOD) for cis- and trans-POA were 0.2 and 0.05 μg/mL, respectively. The method successfully determined cis- and trans-POA in fish oil. For the GC method, the contents of cis-POA quantified were similar to those from the HPLC method, but the contents of trans-POA revealed significant variation between the two methods., Conclusions: After a comprehensive consideration of the characteristics of the saponification and methyl esterification methods which have been tested and verified, the HPLC method was found to be suitable for determining cis- and trans-POA contents in fish oil. It was also suggested that in natural fish oil, cis-POA may be in the glyceride state, and trans-POA almost completely in the free acid form. In comparison with the GC method, the HPLC method provided a simpler process and faster analyses for identifying and determining cis- and trans-POA. The study has also provided technical support for studying the pharmacological differences and relationship between structure and activity of cis- and trans-POA. This could help physicians to analyze patients' samples more quickly in 10 min and therefore provide a more rapid diagnosis of problems relating to the risk of type II diabetes and coronary heart disease.

Photo-activated therapy is a non-invasive and promising medical technology for the treatment of cancers. Herein, we present Ce6-HA-CIS phototherapeutic nanohybrids composed of Cu-In-S (CIS) heterostructured nanorod (HS-rod), chlorin e6 (Ce6), and hyaluronic acid (HA) for the use in targeted photodynamic/photothermal therapy (PDT/PTT). In the Ce6-HA-CIS nanohybrids, the CIS HS-rod was investigated as a PTT agent to convert light into thermal energy, with Ce6 acting as a PDT agent to generate singlet oxygen ( 1 O 2 ). HA encapsulated the surface of the CIS HS-rod and aided the hydrophobic CIS HS-rod in achieving aqueous solubility. HA also acts as a tumor-specific targeting vector of cancer cells bearing the cluster determinant 44 receptor. Under light irradiation, the fabricated Ce6-HA-CIS nanohybrids exhibited high photothermal conversion efficiency, good photo-stability, and satisfactory photodynamic activity. In vitro and in vivo experiments demonstrated that Ce6-HA-CIS showed low cytotoxicity and synergistic photodynamic and photothermal cancer cell killing effects as compared to PTT or PDT agents alone. Therefore, these phototherapeutic nanohybrids may enhance cancer therapy in future clinical applications., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A combination therapy of multiple drugs including isoniazid, rifampicin, ethambutol and pyrazinamide has been proven to be an effective option for the vast majority of tuberculosis (TB) patients. However, various adverse drug reactions (ADRs) limit its merit, with anti-TB drug-induced hepatotoxicity (ATDH) being a common and sometimes severe ADR. This study aimed to investigate the association between polymorphisms in two nuclear receptor genes, pregnane X receptor (PXR) and constitutive androstane receptor (CAR), and the risk of ATDH in a Chinese population. Subjects with or without hepatotoxicity during anti-TB treatment were recruited. DNA was extracted from peripheral blood and genotypes of the selected single nucleotide polymorphisms (SNPs) were determined by using the improved multiplex ligation detection reaction technique. Three genetic models (additive, dominant, and recessive) as well as haplotype, SNP-SNP interaction analyses were used to evaluate the genetic risk of ATDH. A total of 502 subjects (203 ATDH and 299 non-ATDH) were enrolled. The results showed that the minor allele of rs7643645 and the H0010001 haplotype in PXR were associated with decreased risk of ATDH, suggesting that drug-metabolizing enzymes regulated by PXR are involved in the pathogenesis of ATDH. More studies are required to verify this result.

Previous research showed N 1 -(quinolin-2-ylmethy) butane-1, 4-diamine (QMA), a polyamine analogue, was efficacious in the prevention of oxidative injury in models of cerebral ischemia. The present study manifested that pretreatment with QMA attenuated ischemic damage accompanying up regulation of Nuclear factor erythroid 2‑related factor (Nrf2), Heme oxygenase‑1 (HO‑1), p-ERK and p-Akt in cerebral cortex tissues of middle cerebral artery occlusion (MCAO) rats and oxygen-glucose deprivation (OGD)-treated PC12 cells. Further more, treatment with LY294002 (specific PI3K inhibitor), PD98059 (specific ERK inhibitor), brusatol (specific Nrf2 inhibitor) and SnPP (specific HO-1 inhibitor) deprived almost all the effects of QMA in MCAO rats and OGD-treated PC12 cells. These data suggested that the protective actions of QMA on the cerebral ischemia may be related to activation of endogenous cytoprotective mechanism via ERK and Akt activated Nrf2/HO-1 signaling pathway., (Copyright © 2018 Elsevier B.V. All rights reserved.)

New Findings: What is the central question of this study? What is the role of the long non-coding RNA X-inactive specific transcript (XIST), which is up-regulated in injured podocytes and membranous nephropathy, in the pathogenesis of membranous nephropathy? What is the main finding and its importance? XIST was up-regulated in kidney tissue with membranous nephropathy and in injured podocytes. Down-regulation of XIST inhibited podocyte apoptosis. XIST negatively regulated miR-217, and miR-217 modulated Toll-like receptor 4. Inhibition of XIST suppressed podocyte apoptosis induced by angiotensin II via miR-217., Abstract: Membranous nephropathy is often characterized by glomerular podocyte injury. Up-regulation of the long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) has been verified in membranous nephropathy and in injured podocytes. Here the role of XIST in podocyte injury and membranous nephropathy was explored. Quantitative real-time PCR and western blot were performed to detect the expression of XIST and miR-217, and Toll-like receptor 4 (TLR4) protein, respectively. Podocyte apoptosis was evaluated with flow cytometry. Interaction between XIST and miR-217 was analysed by RNA immunoprecipitation and RNA pull-down assay. A dual luciferase reporter assay was used to examine the interplay between miR-217 and TLR4. Up-regulation of the lncRNA XIST and angiotensin II (Ang II) and kidney and podocyte injury were indicated in kidney tissue of patients with membranous nephropathy. Increase of XIST and apoptosis were induced by Ang II in podocytes. Down-regulation of XIST reversed podocyte apoptosis induced by Ang II. MiR-217 was negatively regulated by XIST. MiR-217 controlled TLR4 by targeting its 3'-untranslated region. XIST modulated TLR4 through miR-217 and inhibition of XIST reduced podocyte apoptosis induced by Ang II via regulating miR-217. Down-regulation of XIST ameliorates podocyte apoptosis via the miR-217-TLR4 pathway, which may improve membranous nephropathy., (© 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.)

Levallois approaches are one of the best known variants of prepared-core technologies, and are an important hallmark of stone technologies developed around 300,000 years ago in Africa and west Eurasia 1,2 . Existing archaeological evidence suggests that the stone technology of east Asian hominins lacked a Levallois component during the late Middle Pleistocene epoch and it is not until the Late Pleistocene (around 40,000-30,000 years ago) that this technology spread into east Asia in association with a dispersal of modern humans. Here we present evidence of Levallois technology from the lithic assemblage of the Guanyindong Cave site in southwest China, dated to approximately 170,000-80,000 years ago. To our knowledge, this is the earliest evidence of Levallois technology in east Asia. Our findings thus challenge the existing model of the origin and spread of Levallois technologies in east Asia and its links to a Late Pleistocene dispersal of modern humans.

The aim of this study was to investigate the effects of bufalin on human nasopharyngeal carcinoma NPC-TW 076 cells in vitro. Bufalin is a cardiotonic steroid and a key active ingredient of the Chinese medicine ChanSu. The extracts of Chansu are used for various cancer treatments in China. In the present study, bufalin induced cell morphological changes, decreased total cell viability and induced G 2 /M phase arrest of cell cycle in NPC-TW 076 cells. Results also indicated that bufalin induced chromatin condensation (cell apoptosis) and DNA damage by DAPI staining and comet assay, respectively. The induced apoptotic cell death was further confirmed by annexin-V/PI staining assay. In addition, bufalin also increased ROS and Ca 2 + production and decreased the levels of Δ Ψ m . Furthermore, the alterations of ROS, ER stress and apoptosis associated protein expressions were investigated by Western blotting. Results demonstrated that bufalin increased the expressions of ROS associated proteins, including SOD (Cu/Zn), SOD2 (Mn) and GST but decreased that of catalase. Bufalin increased ER stress associated proteins (GRP78, IRE-1 α , IRE-1 β , caspase-4, ATF-6 α , Calpain 1, and GADD153). Bufalin increased the pro-apoptotic proteins Bax, and apoptotic associated proteins (cytochrome c, caspase-3, -8 and -9, AIF and Endo G) but reduced anti-apoptotic protein Bcl-2 in NPC-TW 076 cells. Furthermore, bufalin elevated the expressions of TRAIL-pathway associated proteins (TRAIL, DR4, DR5, and FADD). Based on these findings, we suggest bufalin induced apoptotic cell death via caspase-dependent, mitochondria-dependent and TRAIL pathways in human nasopharyngeal carcinoma NPC-TW 076 cells.

Casticin, derived from Fructus Viticis, has anticancer properties in many human cancer cells, however, there is no report to show that casticin promotes immune responses and affects the survival rate of leukemia mice in vivo. The aim of this study is to evaluate the effects of casticin on immune responses and the survival rate of WEHI-3 cells generated in leukemia mice in vivo. Animals were divided into six groups: normal control mice, leukemia control mice, mice treated with ATRA (all-trans retinoic acid), and casticin (0.1, 0.2, and 0.4 mg/kg) treated mice. All animals were treated for 14 days and then measured for body weights, total survival rate, cell markers, the weights of liver and spleen, phagocytosis of spleen cells, NK cell activities and cell proliferation. Results show that casticin did not affect animal appearances, however, it increased body weights and decreased the weights of liver at 0.2 mg/kg and 0.4 mg/kg treatment. Casticin also decreased spleen weight at 0.2 mg/kg and 0.4 mg/kg treatment, increased CD3 at 0.1, 0.2 and 0.4 mg/kg doses and increased CD19 at 0.2 mg/kg treatment but decreased CD11b and Mac-3 at 0.1, 0.2 and 0.4 mg/kg treatment. Casticin (0.1, 0.2 and 0.4 mg/kg) increased macrophage phagocytosis from PBMC (peripheral blood mononuclear cell) and peritoneal cavity. Furthermore, casticin increased NK cells' cytotoxic activity and promoted T cell proliferation at 0.1-0.4 mg/kg treatment with or without concanavalin A (Con A) stimulation, but only increased B cell proliferation at 0.1 mg/kg treatment. Based on these observations, casticin could be used as promoted immune responses in leukemia mice in vivo.

Background: A 2017 New York Times (NYT) article questioning the appropriateness of skin cancer treatment modality by dermatology providers stimulated discussion among the public pertaining to ethics in the current state of dermatologic practice., Objective: The purpose of this study is to characterize issues raised by the comments on the NYT article, discuss strategies to address these concerns, and encourage reflection on ethics in dermatologic care., Materials and Methods: A qualitative analysis was performed on the 309 comments on the NYT article. General themes were identified, resulting in the inclusion of 222 comments. These comments were reviewed and characterized by the type of commenter, his or her stance on health care, and what issues they raised., Results: Providers interested in "profit over patient" was the most common theme, followed by mistrust of APPs, health care system interested in "profit over patient," inadequate supervision by advanced practice providers (APPs), finding the "right" provider, support for coordinated APP and physician care, support for APP credentials, and finally inappropriate elderly care., Conclusion: The NYT article raises the concern of identifying quality care and choosing the "right provider"-one who successfully balances the various incentives affecting skin cancer management including appropriate usage of APPs.

Aim of Study: To further evaluate the influence of glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) null genotypes on bladder cancer risk, we conducted a meta-analysis in the Chinese population., Materials and Methods: PubMed and Chinese databases were electronically searched through April 2016., Results: Nine studies were included for our meta-analysis, involving 1646 bladder cancer cases and 1938 controls. In general, our findings indicated that a significant association existed between GSTM1-null genotype and the risk of bladder cancer in the studied Chinese population (odds ratio = 1.56, 95% confidence interval: 1.36-1.79). However, no significant association between GSTT1 polymorphism and bladder cancer was found. After stratification of the subgroup analyses by source of controls and geographical areas, a substantially elevated risk was revealed between GSTM1-null genotype and bladder cancer in the population-based studies and those conducted in South China and North China., Conclusion: Our meta-analysis suggested that GSTM1-null genotype is associated with an increased bladder cancer risk in the Chinese individuals., Competing Interests: None

Eosinophilic fasciitis is an uncommon connective tissue disorder that affects patients of all ages, resulting in significant morbidity. Systemic corticosteroids can induce remission of disease. However, there is no universally accepted treatment ladder for eosinophilic fasciitis. This case series evaluates treatment efficacy in patients with eosinophilic fasciitis seen at Wake Forest University Department of Dermatology outpatient clinics. Patient charts were screened using ICD-9 diagnosis code 710.9 (unspecified diffuse connective tissue disease) to identify patients with eosinophilic fasciitis (n=10) seen at our institution. Patients were treated for an average 24 months with a combination of methotrexate and prednisone therapy, unless one or both were contraindicated, with each medication tapered conservatively to prevent disease flares. Alternate treatments included mycophenolate mofetil with prednisone, azathioprine with prednisone, prednisone monotherapy, and methotrexate monotherapy. Disease remission off therapy and on low-dose therapy was 66 and 70%, respectively. Our first-line therapy of concomitant methotrexate and prednisone is well-tolerated and effective for managing patients with eosinophilic fasciitis. Our study was limited to cases seen at a single academic institution., Competing Interests: Disclosure and potential conflicts of interest: Dr Jorizzo serves as a consultant for Amgen and LEO. Dr Huang serves as a consultant for AbbVie Incorporated. No other disclosures were reported. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors are available for download at http://www.drugsincontext.com/wp-content/uploads/2018/08/dic.212529-COI.pdf

Many studies have demonstrated that berberine inhibited the cell migration and invasion in human cancer cell lines. However, the exact molecular mechanism of berberine inhibiting the cell migration and invasion of human melanoma A375.S2 and A375.S2/PLX (PLX4032 induced resistant A375.S2) skin cancer cells remains unknown. In this study, we investigated the anti-metastasis mechanisms of berberine in human melanoma cancer A375.S2 cells and A375.S2/PLX resistant cells in vitro. Berberine at low concentrations (0, 1, 1.5 and 2 μM) induced cell morphological changes and reduced the viable cell number and inhibited the mobility, migration, and invasion of A375.S2 cells that were assayed by wound healing and transwell filter. The gelatin zymography assay showed that berberine slightly inhibited MMP-9 activity in A375.S2 cells. Results from western blotting indicated that berberine inhibited the expression of MMP-1, MMP-13, E-cadherin, N-cadherin, RhoA, ROCK1, SOS-1, GRB2, Ras, p-ERK1/2, p-c-Jun, p-FAK, p-AKT, NF-κB, and uPA after 24 h of treatment, but increased the PKC and PI3K in A375.S2 cells. PLX4032 is an inhibitor of the BRAFV600E mutation and used for the treatment of cancer cells harboring activated BRAF mutations. Berberine decrease cell number and inhibited the cell mobility in the resistant A375.S2 (A375.S2/PLX, PLX4032 generated resistant A375.S2 cells). Based on these observations, we suggest that the potential of berberine as an anti-metastatic agent in melanoma that deserves to be investigated in more detail, including in vivo studies in future.

The present study included a total of 111 consecutive patients who had undergone coronary computed tomography (CT) angiography, using a first-generation dual-source CT with automatic tube potential selection and tube current modulation. Body weight (BW) and body mass index (BMI) were recorded prior to CT examinations. Image noise and attenuation of the proximal ascending aorta (AA) and descending aorta (DA) at the middle level of the left ventricle were measured. Correlations between BW, BMI and objective image quality were evaluated using linear regression. In addition, two subgroups based on BMI (BMI ≤25 and >25 kg/m 2 ) were analyzed. Subjective image quality, image noise, the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR) were all compared between those. The image noise of the AA increased with the BW and BMI (BW: r=0.453, P<0.001; BMI: r=0.545, P<0.001). The CNR and SNR of the AA were inversely correlated with BW and BMI, respectively. The image noise of the DA and the CNR and SNR of the DA exhibited a similar association to those with the BW or BMI. The BMI >25 kg/m 2 group had a significant increase in image noise (33.1±6.9 vs. 27.8±4.0 HU, P<0.05) and a significant reduction in CNR and SNR, when compared with those in the BMI ≤25 kg/m 2 group (CNR: 18.9±4.3 vs. 16.1±3.7, P<0.05; SNR: 16.0±3.8 vs. 13.6±3.2, P<0.05). Patients with a BMI of ≤25 kg/m 2 had more coronary artery segments scored as excellent, compared with patients with a BMI of >25 kg/m 2 (P=0.02). In conclusion, this method is not able to achieve a consistent objective image quality across the entire patient population. The impact of BW and BMI on objective image quality was not completely eliminated. BMI-based adjustment of the tube potential may achieve a more consistent image quality compared to automatic tube potential selection, particularly in patients with a larger body habitus.

Background: many people living with dementia remain underdiagnosed and unrecognised. Screening strategies are important for early detection., Objective: to examine whether the Lawton's Instrumental Activities of Daily Living (IADL) scale, compared with other cognitive screening tools-the Mini-Mental State Examination (MMSE), and the Ascertain Dementia 8-item Informant Questionnaire (AD8)-can identify older (≥ 65 years) adults with dementia., Design: population-based cross-sectional observational study., Setting: all 19 counties in Taiwan., Participants: community-dwelling older adults (n = 10,340; mean age 74.87 ± 6.03)., Methods: all participants underwent a structured in-person interview. Dementia was identified using National Institute on Aging-Alzheimer's Association core clinical criteria for all-cause dementia. Receiver operator characteristic curves were used to determine the discriminant abilities of the IADL scale, MMSE and AD8 to differentiate participants with and without dementia., Results: we identified 917 (8.9%) participants with dementia, and 9,423 (91.1%) participants without. The discriminant abilities of the MMSE, AD8 and IADL scale (cutoff score: 6/7; area under curve = 0.925; sensitivity = 89%; specificity = 81%; positive likelihood ratio = 4.75; accuracy = 0.82) were comparable. Combining IADL with AD8 scores significantly improved overall accuracy: specificity = 93%; positive likelihood ratio = 11.74; accuracy = 0.92., Conclusions: our findings support using IADL scale to screen older community-dwelling residents for dementia: it has discriminant power comparable to that of the AD8 and MMSE. Combining the IADL and the AD8 improves specificity., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Gefitinib has been used for cancer patients and curcumin (CUR), demethoxycurcumin (DMC), or bisdemethoxycurcumin (BDMC) also shown to induce cancer cell apoptosis. However, no report shows the combination of gefitinib with, CUR, DMC, or BDMC induce cell apoptosis and autophagy in human oral cancer cells. In this study, we investigated the effects of gefitinib with or without CUR, DMC, or BDMC co-treatment on the cell viability, apoptotic cell death, autophagy, mitochondria membrane potential (MMP), and caspase-3 activities by flow cytometry assay and autophagy by acridine orange (AO) staining in human oral cancer SAS cells. Results indicated that gefitinib co-treated with CUR, DMC, or BDMC decreased total viable cell number through the induction of cell apoptosis and autophagy and decreased the levels of MMP and increased caspase-3 activities in SAS cells. Western blotting indicated that gefitinib combined with CUR, DMC, or BDMC led to decrease Bcl-2 protein expression which is an antiapoptotic protein and to increase ATG5, Beclin 1, p62/SQSTM1, and LC3 expression that associated with cell autophagy in SAS cells. Gefitinib combined with CUR and DMC led to significantly reduce the tumor weights and volumes in SAS cell xenograft nude mice but did not affect the total body weights. Based on those observations, we suggest that the combination of gefitinib with CUR, DMC, and BDMC can be a potential anticancer agent for human oral cancer in future., (© 2018 Wiley Periodicals, Inc.)

Background: Surgical resection is the main treatment for patients with non-small-cell lung cancer (NSCLC), but patients' long-term outcome is still challenging. The purpose of this study was to identify predictors of long-term survival in patients after lung cancer surgery., Methods: Patients who underwent surgery for NSCLC from January 1, 2006, to December 31, 2009, were enrolled into this retrospective cohort study. The primary outcome was the survival length after surgery. Predictors of long-term survival were screened with the multivariable Cox proportional hazard model., Results: Postoperative follow-up was completed in 588 patients with a median follow-up duration of 5.2 years (interquartile range, 2.0-6.8). Two hundred ninety-one patients (49.5%) survived at the end of follow-up with median survival duration of 64.3 months (interquartile range, 28.5-81.6). The overall survival rates were 90.8%, 70.0%, and 57.1% at the end of the first, third, and fifth year after surgery, respectively. Limited resection (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.08-1.98; P = .013) and large tumor size (HR, 1.29; 95% CI, 1.17-1.42; P < .001) were associated with short survival; whereas high body mass index grade (HR, 0.82; 95% CI, 0.69-0.97; P = .021), highly differentiated tumor (HR, 0.59; 95% CI, 0.37-0.93; P = .024), dissection of mediastinal lymph node during surgery (HR, 0.45; 95% CI, 0.30-0.67; P < .001), and perioperative use of dexamethasone (HR, 0.70; 95% CI, 0.54-0.90; P = .006) were associated with long survival. No association was found between perioperative use of flurbiprofen axetil and long survival (HR, 0.80; 95% CI, 0.62-1.03; P = .086). However, combined administration of dexamethasone and flurbiprofen axetil was associated with longer survival (compared to no use of both: adjusted HR, 0.57; 95% CI, 0.38-0.84; P = .005)., Conclusions: Certain factors in particular perioperative dexamethasone and flurbiprofen axetil therapy may improve patients' long-term survival after surgery for NSCLC. Given the small sample size, these findings should be interpreted with caution, and randomized clinical trials are needed for further clarification.