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Background/purpose: Burning mouth syndrome (BMS) is defined as a chronic burning pain of the oral mucosa with no associated clinical signs or apparent extraneous cause. Limited epidemiologic data have been published. In this study, we probed the nationwide registered database to assess the prevalence of BMS in Taiwan. Materials and methods: A retrospective study was conducted to analyze the dental dataset compiled by the Taiwan's National Health Insurance Research Database from 2004 to 2013. The diagnosis of BMS was identified in accordance with the International Classification of Disease, Ninth revision. In addition, sex and age were analyzed by multivariate Poisson regression. Results: The prevalence of BMS revealed from 2.24 (per 104) to 3.11 (per 104) over past 10 year period. Female has higher risk of BMS than male (RR: 1.39; 95% CI: 1.37–1.41). The 50–59 years old group, 60–69 years old group, and >70 years old group had 1.55-, 2.06-, and 2.58-fold risk than 40–49 years old group for BMS (p

Objective Observe the influence of oral nutritional agents rich in soluble dietary (enteral nutritional suspension [TPF‐DM]) on intestinal flora of elderly male subjects with malnutrition. Method Seventy‐eight subjects with good nutrition were considered as the healthy control group. Twenty‐eight male subjects who had malnutrition and were older than 70 years were included and randomly divided into the short‐term (3 months) intervention group (n = 20) and the long‐term (12 months) group (n = 8). They were provided with enteral nutritional suspension (TPF‐DM) 500 mL/day or maximum tolerance dose, so as to observe the changes in nutrition‐related indexes and intestinal flora after the elderly take enteral nutritional suspension (TPF‐DM). Results (1) For elderly male subjects with malnutrition, their body weight, body mass index, hemoglobin, total protein, and albumin were significantly lower than the control group with favorable nutrition. (2) There were obvious differences in intestinal flora between healthy elderly male subjects and those with malnutrition. After the treatment of enteral nutritional suspension (TPF‐DM), intestinal flora of the malnourished elderly subjects showed recovery toward the healthy elderly subjects. The obvious gradient changes of the flora were mainly in the bacteroidetes, firmicutes, and proteobacteria phyla, and the relative abundance of CAG2 clusters in the malnourished group was higher than that in the healthy control group, and the relative abundance decreased after long‐term treatment, and the change approached the healthy control group. The relative abundance of CAG3 and CAG6 clusters in the malnourished group was lower than that in the healthy control group, and the relative abundance increased after long‐term treatment, and the change approached the healthy control group. Conclusion Malnutrition has obvious impact on intestinal flora of the elderly. Enteral nutritional suspension (TPF‐DM) not only prevents the further decline in the state of nutrition but also helps the recovery in intestinal flora of the elderly. Long‐term application can produce better effects., The relative abundance of CAG3 and CAG6 clusters in the malnourished group was lower than that in the healthy control group, and the relative abundance increased after long‐term treatment, and the change approached the healthy control group.

AIM: To evaluate the predictive value of islet autoantibodies for the diagnosis of autoimmune uveitis (AU), as well as to characterize the association bet ween islet autoantibodies and AU. METHODS: Totally 97 patients with AU and 100 healthy persons without any autoimmune diseases as the control group were recruited. Multiple serum islet autoantibodies were measured using commercial enzyme-linked immunosorbent assay kits (ELISA). A supplementary questionnaire was used to complement the subject's demographics and clinical features. The level of glucose concentrations and white blood cells were measured. Conditional logistic regression was performed to estimate odds ratios (ORs), and 95% confidence intervals (CIs) of AU according to islet autoantibodies and to evaluate the predictive value of islet autoantibodies for AU diagnosis. Autoantibodies subgroups and other variables were included into analysis. RESULTS: In AU patients, the prevalence of detecting at least one of the autoantibodies was 31.9% (31/97). The most frequent autoantibody was ZnT8A (30.9%), followed by GADA (11.3%), IA-2A (4.1%), ICA (2.1%) and IAA (2.1%). Islet autoantibodies were found to be correlated positively with AU diagnosis [OR (95%CI): 13.86 (3.28, 58.50), P

Background/purpose: Oct4, a key transcription factor, could reprogram human somatic fibroblasts into embryonic stem cell-like pluripotent cells. The exact mechanism of cyclosporine A (CsA)-induced gingival overgrowth is still unclear. The aim of this study was to investigate the effects of CsA on the expression of Oct4 in cultured human gingival fibroblasts (HGFs) in vitro. Materials and methods: The effects of CsA on HGFs were used to elucidate whether Oct4 expression could be induced by CsA by using quantitative real-time reverse transcription-polymerase chain reaction and western blot. Cell growth in CsA-treated HGFs with Oct4 lentiviral-mediated shRNAi knockdown was evaluated by tetrazolium bromide reduction assay. Results: CsA was found to upregulate Oct4 transcript in a dose-dependent manner (p

ObjectiveTo confirm the diagnostic performance of computed tomography (CT)-based texture analysis (CTTA) and magnetic resonance imaging (MRI)-based texture analysis for grading cartilaginous tumors in long bones and to compare these findings to radiological features.Materials and MethodsTwenty-nine patients with enchondromas, 20 with low-grade chondrosarcomas and 16 with high-grade chondrosarcomas were included retrospectively. Clinical and radiological information and 9 histogram features extracted from CT, T1WI, and T2WI were evaluated. Binary logistic regression analysis was performed to determine predictive factors for grading cartilaginous tumors and to establish diagnostic models. Another 26 patients were included to validate each model. Receiver operating characteristic (ROC) curves were generated, and accuracy rate, sensitivity, specificity and positive/negative predictive values (PPV/NPV) were calculated.ResultsOn imaging, endosteal scalloping, cortical destruction and calcification shape were predictive for grading cartilaginous tumors. For texture analysis, variance, mean, perc.01%, perc.10%, perc.99% and kurtosis were extracted after multivariate analysis. To differentiate benign cartilaginous tumors from low-grade chondrosarcomas, the imaging features model reached the highest accuracy rate (83.7%) and AUC (0.841), with a sensitivity of 75% and specificity of 93.1%. The CTTA feature model best distinguished low-grade and high-grade chondrosarcomas, with accuracies of 71.9%, and 80% in the training and validation groups, respectively; T1-TA and T2-TA could not distinguish them well. We found that the imaging feature model best differentiated benign and malignant cartilaginous tumors, with an accuracy rate of 89.2%, followed by the T1-TA feature model (80.4%).ConclusionsThe imaging feature model and CTTA- or MRI-based texture analysis have the potential to differentiate cartilaginous tumors in long bones by grade. MRI-based texture analysis failed to grade chondrosarcomas.

Background/purpose: The disparate or irregular dental care was associated with acute clinical problems that may lead to care seeking for emergency visits. The aim of this study was to determine the time trends, demographics, and conditions of emergency dental (ED) visits in Taiwan. Methods: This cross-sectional study was conducted to analyze the insurance reimbursement of dental care services in National Health Insurance Research Database. The demographic characteristics and age-period effects of ED visits were estimated by multivariate Poisson regression. In addition, the top causes of ED visits were evaluated and stratified by traumatic and non-traumatic conditions. Results: The prevalence of ED visits were 3.18, 5.44, and 4.83 (per 10,000 persons) in 1997, 2002, and 2013, respectively. The primary diagnosis code for ED visits was 522 ‘pulp and periapical tissues’. Pulpitis (522.0), cellulitis (528.3), acute periodontitis (523.3), and caries (521.0) were the top 4 non-traumatic reasons for seeking ED visits. The top 3 traumatic conditions were open wound of internal structures of mouth without mention of complication (873.6), open wound of face without mention of complication (873.4), and loss of teeth due to trauma (525.1). The higher prevalence of ED visits were found in male (aRR = 1.50, 95% CI: 1.49–1.51), 6 y/o group (aRR = 1.56, 95% CI: 1.53–1.59), east region (aRR = 1.27, 95% CI: 1.25–1.29), and dependent coverage group (aRR = 1.16, 95% CI: 1.14–1.19). Conclusion: Taken together, these demographic data could serve as a reference for the authorities concerned to improve the current situation of ED in Taiwan. Keywords: Emergency dental visits, Taiwan, Nationwide population, National health insurance research database

Background The safety of hypoglycemic drugs should be paid more attention to in elderly patients with type 2 diabetes mellitus due to their concomitant diseases, physiological decline of liver and kidney function and cognitive decline. The aim of this study was to evaluate the efficacy and safety of DPP-4 inhibitors in elderly patients with type 2 diabetes mellitus. Methods From January 2010 to November 2018, 300 patients with type 2 diabetes mellitus who were over 60 years old were enrolled in the outpatient clinic of Geriatric Medical Center. Their medication records and follow-up medical records were used for retrospective analysis. The duration of treatment with DPP-4 inhibitors was more than 3 months. The changes of fasting blood glucose (GLU), glycosylated hemoglobin (HbA1C), body weight, body mass index (BMI) and liver and kidney function were compared before and after treatment. Results The average age of 300 patients (212 males and 88 females) was 73.7 ± 9.1 years old, BMI was 26.5 ± 2.8 kg/m2 and the duration of diabetes was 10.7 ± 8.2 years. The results of retrospective analysis showed that HbA1C decreased by 0.27% after treatment (P Conclusion After DPP-4 inhibitors were used in elderly patients with type 2 diabetes mellitus, the elevated glycosylated hemoglobin could be controlled with improved safety of liver and kidney, and might have the effect of weight loss.

Anthropogenic activities strongly affect greenhouse gases emissions in coastal wetland. In situ field study was conducted to explore the effects of anthropogenic activities on the N2O emissions, used static, manual stainless steel chambers in four seriously disturbed coastal wetlands (west side of the seawall, WSS; oil field existed, OF; Spartina alterniflora coastal marsh, SCM; and aquaculture pond, ACP) in the Yellow River estuary. Results showed that N2O emissions showed significant seasonal variation (p

Background/purpose: Temporomandibular disorder (TMD) is defined as various clinical signs and symptoms involving the masticatory muscles, the temporomandibular joint and associated structures. The aim of this study was to investigate the prevalence of diagnosed TMD in Taiwan using a National Health Insurance Research Database from 2004 to 2013. Materials and methods: A retrospective study was conducted to analyze the registered database compiled by the National Health Insurance from 2004 to 2013. The diagnosis of TMDs was identified in accordance with the International Classification of Disease, Ninth revision (ICD-9-CM 524.6). The relative risk of TMD from 2004 to 2013 after adjusting for year, age, and gender was evaluated by logistic regression analysis. Results: The prevalence of TMD increased significantly from 14 (per 104) to 26 (per 104) over the past 10 year period [odds ratio (OR), 1.07; 95% confidence interval (CI), 1.04–1.09]. The mean age with TMD from 2004 to 2013 was 52.31±17.15 years and 45.12±17.32 years, respectively. The female group had a higher risk of TMD than the male group (OR, 1.70; 95% CI, 1.49–1.94). Conclusion: Taken together, the estimated prevalence of TMD significantly increased from 2004 to 2013 in Taiwan. In addition, the risk for TMD was higher among women than among men. Keywords: health insurance database, nationwide population, prevalence, temporomandibular disorder

Purpose: Tumor-associated PD-L1 expression is predictive of clinical response to PD-1–directed immunotherapy. However, PD-L1–negative patients may also respond to PD-1 checkpoint blockade, suggesting that other PD-1 ligands may be relevant to the clinical activity of these therapies. The prevalence of PD-L2, the other known ligand of PD-1, and its relationship to response to anti-PD-1 therapy were evaluated. Experimental Design: PD-L2 expression was assessed in archival tumor tissue from seven indications using a novel immunohistochemical assay. In addition, relationships between clinical response and PD-L2 status were evaluated in tumor tissues from patients with head and neck squamous cell carcinoma (HNSCC) with recurrent or metastatic disease, treated with pembrolizumab. Results: PD-L2 expression was observed in all tumor types and present in stromal, tumor, and endothelial cells. The prevalence and distribution of PD-L2 correlated significantly with PD-L1 (P = 0.0012– Conclusions: Clinical response to pembrolizumab in patients with HNSCC may be related partly to blockade of PD-1/PD-L2 interactions. Therapy targeting both PD-1 ligands may provide clinical benefit in these patients. Clin Cancer Res; 23(12); 3158–67. ©2017 AACR.

Type VI Schatzker tibial plateau fractures are very complex intra-articular fractures that often occur after high-energy trauma, as the fracture pattern involves joint and metaphyseal-diaphyseal region.

Background Osteoarthritis (OA) is a degenerative joint disorder with limited long-lasting treatment options. Various steroid formulations on the market are effective but required frequent intra-articular (IA) injections due to short-term symptomatic relief. IA steroids have been shown to increase cartilage loss in knee and the rapid absorption into systemic circulation could cause adverse side effects, limiting their effectiveness [1]. To circumvent these issues, TLC599, a novel sustained-release liposome formulation of dexamethasone sodium phosphate (DSP) was developed to provide a sustained OA pain management over an extended period with reduced side effects and toxicity. TLC599 resulted in sustained presence in the synovial fluid without significant local and systemic side effects from OA treatments following IA injection. Objectives To evaluate pharmacokinetics (PK) and toxicokinetics (TK) of TLC599 following IA injection in dogs. Methods In two studies, the dexamethasone phosphate (DP) and dexamethasone (DEX) concentration was quantified and the PK/TK profile of TLC599 was evaluated in dogs following IA injection. DSP is the sodium salt form of DP and DEX is the active form of DSP. Study#8351851: TLC599 was administered as a single- or multiple-dose injection (once every 13 weeks for total of four times) at 18 mg/knee (36 mg/animal). Synovial fluid was collected at 2.5, 48, 96, 168 and 360 hours post-dose from 4 animals/time point, and plasma was collected at 0.25, 0.75, 1.25, 2, 4, 6, 24, 48, 96 and 168 hours post-dose from 8 animals/time point. Study#8388198: TLC599 was administered as a single-dose injection at 18 mg/knee. The synovial fluid was collected at 15, 30, 45, 90, and 120 days post-dose from 4 animals/time point. Results Study#8351851: Following a single-dose IA injection of TLC599, DP concentration declined gradually after 2.5 hr but remained detectable through 360 hr, demonstrating the prolonged local exposure in the joint (Figure 1). The PK parameters of DP and DEX in dog plasma were assessed in the multiple-dose group. The mean Cmax and AUC0-t values of DP and DEX were comparable between the first dose (Day 1) and the fourth dose (Day 274) (Table 1), indicating there was no accumulation of systemic exposure of DP and DEX following four repeated IA injections of TLC599. By evaluating the effect on cartilage, it was also shown that the local safety profiles were similar between multiple-dose and single-dose TLC599 injections. Study#8388198: Following a single-dose IA injection of TLC599, DP concentration declined after 15 days but remained at similar level from 30 days to 120 days post-dose. Overall, the prolonged 120-day residence time of TLC599 in synovial joint was observed (Figure 2). Conclusion TLC599, a novel extended-release liposome formulation of DSP, showed a long-lasting profile up to 120 days in synovial joint after a single IA injection in a preclinical dog study. In addition, no significant systemic exposure and accumulation of DP and DEX in dog plasma was observed following multiple-dose administration of TLC599. Animal studies indicate that TLC599 may be an effective and superior chronic treatment for OA. Reference [1] Zhang W, et al., OARSI recommendations for the management of hip and knee osteoarthritis, part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage 2008;16(2): 137-62 Acknowledgement The authors thank Yingfang Li, Jiunmin Lai, Ruixue Chen, Ph.D. and Carl Brown Ph.D. for reviewing support. Disclosure of Interests Tzung-Ju Wu Employee of: Current employee of Taiwan Liposome Company, Wan-Ni Yu Employee of: Current employee of Taiwan Liposome Company, Ming-Ju Wu Employee of: Current employee of Taiwan Liposome Company, Po-Chun Chang Employee of: Current employee of Taiwan Liposome Company, Sheue-Fang Shih Employee of: Current employee of Taiwan Liposome Company

Akt is frequently hyperactivated in human cancers and is targeted for cancer therapy. However, the physiological consequences of systemic Akt isoform inhibition were not fully explored. We showed that while combined Akt1 and Akt3 deletion in adult mice is tolerated, combined Akt1 and Akt2 deletion induced rapid mortality. Akt2(-/-) mice survived hepatic Akt1 deletion but all developed spontaneous hepatocellular carcinoma (HCC), which is associated with FoxO-dependent liver injury and inflammation. The gene expression signature of HCC-bearing livers is similar to aggressive human HCC. Consistently, neither Akt1(-/-) nor Akt2(-/-) mice are resistant to diethylnitrosamine-induced hepatocarcinogenesis, and Akt2(-/-) mice display a high incidence of lung metastasis. Thus, in contrast to other cancers, hepatic Akt inhibition induces liver injury that could promote HCC.

The present study aimed to investigate the effects of glycogen synthase kinase-3β (GSK-3β) on the expression levels of receptor activator of nuclear factor (NF)-κB (RANK), RANK ligand (RANKL) and NF-κB in the renal tissues of rats modeling diabetic nephropathy (DN). The rats were allocated at random into three groups, as follows: Normal control group (NC), the DN model group (DNM group) and the DN model lithium chloride (LiCl) intervention group (DNI group). Urinary proteins were examined by staining with the Coomassie Brilliant Blue dye for 24 h. Histochemical analyses of kidney tissue sections were conducted using hematoxylin and eosin staining, after which the kidney pathology of the rats was observed. In addition, the mRNA and protein expression levels of GSK-3β, RANK, RANKL and NF-κB in the renal tissues were detected using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, respectively. As compared with the NC group, the level of urinary protein was significantly increased in the DNM group (P

Background & Aim Establishment of a potency assay in the manufacturing of clinical grade mesenchymal stromal cells (MSCs) has been a challenge due to the issues of variability in starting cellular material, complex mechanisms of action, and lack of reference cells or materials. Indoleamine 2, 3-dioxygenase (IDO) is one of the most important factors for human MSC-mediated immunosuppression. IDO is expressed in IFN-γ-licensed MSC, but not in resting MSC in vitro. This intracellular enzyme catalyzes tryptophan degradation toward kynurenine and depletion of tryptophan suppresses T cells proliferation. Methods, Results & Conclusion In this study, we have developed a flow cytometry-based IDO assay for quantitatively measuring the IDO expression level per cell, the IPBV (Intracellular Protein Binding Value) of the cells represents the relative quantity of IDO expressed in the MSC. IPBV is defined as the number of anti-IDO fluorescent antibody molecules bound to intracellular IDO and standardized by fluorescence intensity of beads. Two kinds of in-house quality control reference cells were running in parallel with product to ensure that the assay is performing as expected and the level of IDO expression. Validation of the quantitative IDO assay, including accuracy, precision, specificity, linearity, range and robustness, were presented in this study. Moreover, we presented the application of the quantitative IDO assay for analysis of MSC product stability, comparability, and compatibility in the manufacturing of clinical grade MSC-based product- RegStem® ASC. In this study, we demonstrated the flow cytometry-based quantitative MSC IDO assay correlates with MSC's inhibition of autologous T cells proliferation, as well as the correlation with preliminary clinical effects in the phase I autologous MSC-based clinical trial for the treatment of Osteoarthritis. As the results, we believe that our novel flow cytometry-based quantitative IDO assay can be a potential potency assay candidate for advanced phase clinical trial of MSCs products.

Summary Akt is frequently activated in human cancers. However, it is unknown whether systemic inhibition of a single Akt isoform could regress cancer progression in cancers that are not driven by Akt activation. We systemically deleted Akt1 after tumor onset in p53 −/− mice, which develop tumors independently of Akt activation. Systemic Akt1 deletion regresses thymic lymphoma in p53 −/− mice emulating p53 restoration. Furthermore, pharmacological inhibition of Akt selectively kills thymic lymphoma cells and not primary thymocytes. Mechanistically, Akt1 inhibition in p53 −/− thymic lymphoma inhibits Skp2 expression and induces FasL, which is the primary cause of cell death. Skp2 exerts resistance to cell death by antagonizing the induction of FasL and reducing FAS expression, which is linked to cyclin D1 expression. The results established a paradigm whereby systemic Akt1 inhibition is sufficient to regress tumors that are not driven by Akt activation and a mechanism of cell survival by Skp2.

Deer bone has been used as a health-enhancing food as well as an antiaging agent in traditional Oriental medicine. Recently, the water extract of deer bone (DBE) showed a neuroprotective action against glutamate or Aβ1–42-induced cell death of mouse hippocampal cells by exerting antioxidant activity through the suppression of MAP kinases. The present study is to examine whether DBE improves memory impairment induced by scopolamine. DBE (50, 100 or 200 mg/kg) was administered orally to mice for 14 days, and then scopolamine (2 mg/kg, i.p.) was administered together with DBE for another 7 days. Memory performance was evaluated in the Morris water maze (MWM) test and passive avoidance test. Also, brain acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activity, biomarkers of oxidative stress and the loss of neuronal cells in the hippocampus, was evaluated by histological examinations. Administration of DBE significantly restored memory impairments induced by scopolamine in the MWM test (escape latency and number of crossing platform area), and in the passive avoidance test. Treatment with DBE inhibited the AChE activity and increased the ChAT activity in the brain of memory-impaired mice induced by scopolamine. Additionally, the administration of DBE significantly prevented the increase of lipid peroxidation and the decrease of glutathione level in the brain of mice treated with scopolamine. Also, the DBE treatment restored the activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase to control the level. Furthermore, scopolamine-induced oxidative damage of neurons in hippocampal CA1 and CA3 regions were prevented by DBE treatment. It is suggested that DBE may be useful for memory improvement through the regulation of cholinergic marker enzyme activities and the suppression of oxidative damage of neurons in the brain of mice treated with scopolamine.

Objective. By observing the needle-knife of KOA rabbit morphology, knee joint cartilage p-FAK, p-PI3K, Aggrecan gene, and protein expression, to study the effect of needle-knife to promote cartilage cell synthesis metabolism mechanism. Method. 49 male New Zealand rabbits, randomly divided into normal group (Z), model group (M), model-inhibitors (MP), needle-knife group (D), needle-knife inhibitors group (DP), electroacupuncture group (E), and electroacupuncture inhibitors (EP). RT-PCR and Western Blot were used to test each animal cartilage p-FAK, p-PI3K, and Aggrecan gene and protein expression level. Results. Compared with N group, p-FAK and p-PI3K protein and mRNA expression of M group, D group, and E group increased (P < 0.05), while the protein and mRNA expression of Aggrecan reduced (P < 0.05). Compared with M group, p-FAK, p-PI3K, Aggrecan protein, and mRNA of E and D group increased (P < 0.05). Compared with E group, p-FAK, p-PI3K, Aggrecan protein, and mRNA expression of D group increased (P < 0.05); after adding inhibitors, p-FAK, p-PI3K, Aggrecan protein, and mRNA expression reduced (P < 0.05). Conclusion. Needle-knife therapy can promote the repairment of cartilage cells by activating FAK-PI3K signaling pathways, promoting the synthesis of cartilage cell metabolism.

This study consisted of a site- and age-specific investigation linking children's blood lead level (BLL) to environmental exposures in a historic mining site in south China. A total of 151 children, aged 3–7 years, were included in this study. The geometric mean (GM) BLL was 8.22 μg/dl, indicating an elevated BLL. The Integrated Exposure Uptake Bio-Kinetic (IEUBK) model has proven useful at many sites for study of routes of exposure. Application of the IEUBK model to these children indicated that the GM difference between observed and predicted BLL levels was only 1.07 μg/dl. It was found that the key environmental exposure pathway was soil/dust intake, which contributed 86.3% to the total risk. Younger children had higher BLL than did older children. Therefore, of the various low risk-high benefit solutions, interventions for the children living near the site should be focused on the dust removal and soil remediation. Implementation of the China Eco-village Construction Plan and China New Rural Reconstruction Movement of the government may be a better solution.

Background Oral submucous fibrosis (OSF) is a one of the well-recognized oral potentially malignant disorders. In this study, we investigated the malignant transformation of OSF in a Taiwanese population. Methods A retrospective cohort study was analyzed from Taiwan's National Health Insurance Research Database. A comparison cohort that was randomly frequency-matched with the OSF cohort according to age, sex, and index year. Oral leukoplakia (OL) was further stratified to evaluate for the possible synergistic effects for OSF-associated malignant transformation. Results In this cohort, 71 (9.13%) of 778 cases of OSF were observed to transform into oral cancer. The malignant transformation rate was 29.26-fold in the OSF cohort than in the comparison cohort after adjustment (95% confidence intervals 20.55-41.67). To further stratify with oral leukoplakia (OL), OSF with OL (52.46; 95% confidence intervals 20.99-42.42) had higher risk of malignant transformation rate than OSF alone (29.84; 95% confidence intervals 20.99-42.42). The Kaplan-Meier plot revealed the rate free of malignant transformation was significant over the 13 years follow-up period (log-rank test, p

Oral submucous fibrosis (OSF) has been regarded as a precancerous condition. Research examining the prevalence of OSF could be the first step in preventing or reducing malignant transformation. In this study, we probed a nationwide registered database to assess the prevalence, gender distribution, age, income, and urbanization status of OSF patients in Taiwan. Methods: A retrospective study was conducted to analyze the registered database compiled by the National Health Insurance provided by the Ministry of Health and Welfare, Taiwan. We identified dental visit patients diagnosed with OSF during the period between January 1, 1996 and December 31, 2013. In addition, demographic characteristics were analyzed by multivariate Poisson regression. Results: The prevalence of OSF increased significantly from 8.3 (per 105) in 1996 to 16.2 (per 105) in 2013 (p < 0.0001). Men had a significantly higher OSF prevalence than women (p < 0.001). The mean age of patients with OSF increased from 1996 to 2013. Individuals living in rural areas had a higher risk of OSF compared with those living in urban areas [relative risk (RR), 1.10; 95% confidence interval (CI), 1.07–1.13]. The higher income group had a lower risk of OSF compared with the lower income group (RR, 0.76; 95% CI, 0.73–0.80). Conclusion: This large-scale government-centered survey demonstrates that the prevalence of OSF in Taiwan significantly increased from 1996 to 2013. The prevalence was higher among men than among women.

AimsThe probabilistic approach is widely adopted for breast fine needle aspiration cytology. However, a definite cytological diagnosis is not always possible for C3 (atypia) cases, which poses a management dilemma as this represents a mixed category of benign and malignant cases. It would be beneficial to be able to predict malignancy based on specific cytological features in C3 aspirates.MethodsA comprehensive panel of cytological features (including quantitative, cytomorphological and background features) in a large cohort of C3 breast aspirates with subsequent histological excisions was evaluated to identify relevant morphological criteria predicting the risk of subsequent malignancy.ResultsA total of 229 C3 specimens with histological follow-up were included. Malignant outcome was found in 30.1% of specimens and the majority were invasive cancers. Features that showed a significant association with malignant outcome included older age (p=0.001), lower percentage of epithelial cell clusters and high percentage of single cells (p=0.002), cribriform architecture in cell clusters (p=0.034), presence of intracellular mucin (p=0.027), increased cell clusters without myoepithelial cells (p=0.048), diminished fibromyxoid stromal fragments (p=0.001), reduced bipolar nuclei (p=0.021) and the presence of necrosis (p=0.023). Except for the percentages of single cells and cell clusters without myoepithelial cells, all other features were shown to be independent risk predictors in multivariate analysis.ConclusionsC3 aspirates were associated with a significant probability of histological malignancy. Certain quantitative, cytomorphological and background features were potentially helpful in predicting the risk of a malignant outcome. The prediction could be clinically useful in the management of C3 cases.

The Selenium-Polysaccharides from Rich selenium Chemical explicitly defined the Edible Fungus (Se-EF) in Boiling water extraction by alcohol precipitation, analysis indicated that the there were main ingredient comprises xylose, dextrose, rhamnose, galactose, and arabinose. First investigate lipids Metabolic and lipoprotein lipase (LPL) activated in the selenium-rich -EF rich in cholesterol and prospects by feeding rich foods (PRD). The purpose of this study is to explore the prospect 1st fed cholesterol-enriched diet (PRD) of KM mice selenium -EF on cholesterol metabolism and lipoprotein lipase (LPL) activated of antioxidant capacity. In addition, studies of the relationship between atherosclerosis and total antioxidant capacity index (AI) and LPL activity (TAC). The results showed that selenium polysaccharide significantly reduce TC serum total cholesterol and LDL-C concentrations comparatively in with the CK control groups. Furthermore, orally administered of polysaccharide selenium notable enhance pay, lipoprotein lipase activity and reduce MDA levels, and artificial intelligence. These results indicate that the beneficial affects of selenium on -EF hypercholesterolemia precautions. In addition, oral administration of polysaccharide selenium notable enhance TAC and LPL activity in the meantime reduce MDA levels, the same as AI. These results indicate that Se-EF has a beneficial effect on the prevention of hyperlipidemia. These results indicate that the beneficial affects of selenium on -EF hypercholesterolemia precautions.

In recent years much attention has been focused on the pharmaceutical relevance of bioflavonoids, especially hesperidin and its aglycon hesperetin in terms of their antioxidant and anti-inflammatory actions. However, the bioactivity of their metabolites, the real molecules in vivo hesperetin glucuronides/sulfates produced after ingestion, has been poorly understood. Thus, the study using an ex vivo approach is aimed to compare the antioxidant and anti-inflammatory activities of hesperidin/hesperetin or hesperetin metabolites derived from hesperetin-administered rat serum. We found that hesperetin metabolites (2.5-20 μM) showed higher antioxidant activity against various oxidative systems, including superoxide anion scavenging, reducing power, and metal chelating effects, than that of hesperidin or hesperetin. The data also showed that pretreatment of hesperetin metabolites (1-10 μM) within the range of physiological concentrations, compared to hesperetin, significantly inhibited nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production, as evidenced by the inhibition of their precursors, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein levels without appreciable cytotoxicity on LPS-activated RAW264.7 macrophages or A7r5 smooth muscle cells. Concomitantly, hesperetin metabolites dose-dependently inhibited LPS-induced intracellular reactive oxygen species (ROS). Furthermore, hesperetin metabolites significantly downregulate LPS-induced nuclear factor-κB (NF-κB) activation followed by the suppression of inhibitor-κB (I-κB) degradation and phosphorylation of c-Jun N-terminal kinase1/2 (JNK1/2) and p38 MAPKs after challenge with LPS. Hesperetin metabolites ex vivo showed potent antioxidant and anti-inflammatory activity in comparison with hesperidin/hesperetin.

Objective: To observe the expression of osteopontin (OPN) in hepatocytes of rats fed with corn baked by burning coal from fluorosis areas and a deficiency of calcium/protein intake following fluorosis. Methods: A total of 48 Wistar rats as objects were randomly assorted into four groups: dose-free fluorine group, which were mainly fed with fluorine-free corn (56% structurally), dose-free fluorine with biased dietary group, which were fed with lower contents of protein (119.41 g/kg) and calcium (0.68 g/kg), high-dose fluorine group (fluorine contents: 104.2 mg/kg), and high-dose fluorine with biased dietary group. After 180 days of cultivation, the contents of fluorine in the bones of rats were tested for the assessment of construction of fluorosis animal model. And the expression of OPN in hepatocytes of rats in different groups was detected with immunohistochemistry and reverse transcription polymerase chain reaction. Results: The present study validated the result that OPN was overexpressed in hepatocytes following fluorosis after oral intake of burning coal-baked corn. OPN was expressed most significantly in high fluorine with biased dietary group, and the high-fluorine group ranked the second most; and dose-free fluorine with biased dietary group ranked the third. The dose-free fluorine group expressed the least OPN. Conclusion: Overexpression of OPN in hepatocytes following fluorosis after excess fluorine intake was involved in liver damage process, which was enhanced by deficiency of calcium and protein intake. The results also demonstrated that the development of fluorosis in Guizhou province was correlated with local baking staple corn as a way of excess intake of fluorine and deficiency of calcium/protein intake.

Rationale: Lymphoepithelioma-like cholangiocarcinoma (LEL-CC) is a rare variant of intrahepatic cholangiocarcinoma (ICC), which is characterized by the better outcome than normal ICC. There is no report about the treatment for the metastasis of the LEL-CC. Here, we describe a rare case of LEL-CC of the liver and report the treatment for metastasis of it. Patient concerns: A 38-year-old woman with a chronic hepatitis B infection was referred to the department of liver surgery in our hospital with a mass in the liver. Diagnoses: A past ultrasound examination had revealed a 28 mm × 16 mm nodular lesion in the right posterior lobe of the liver in May 2013. She had undergone partial resection of the thyroid gland for papillary carcinoma 1 year earlier. Intervention: Suspicious of the metastasis from thyroid cancer, she underwent surgery with liver segmentectomy. The pathologic diagnosis of the lesion was LEL-CC. After surgery, she regularly got checked in our hospital, and in the 6 months after surgery, there was enlargement of lymph node before the inferior vena cava in CT. The doctor did not detect the enlargement of the lymph node until June 2017. The PET-CT was done in June of 2017, which showed the lymph node was hypermetabolic. Outcomes: The patient got her second surgery for lymph node three years after the first surgery, which was proved that the lymph node was metastasis from LEL-CC. The patient was free from recurrence 9 months after surgery. Lessons: We report the first case of surgery for metastasis from LEL-CC in the liver that was diagnosed 3 years after hepatectomy. Our findings suggest that surgery could be an effective way of treating lymph node metastasis of LEL-CC and early PET-CT can help to identify metastasis.

Cellular FLICE (FADD-like interleukin-1-beta-converting enzyme)-inhibitory protein (c-FLIP) inhibits death receptor-induced apoptosis by binding to FADD (Fas-associated death domain protein) and pro-caspase-8. c-FLIP has also been shown to transmit activation signals and to enhance interleukin (IL)-2 production. However, c-FLIP-mediated T cell activation is difficult to detect in most cells. We found that in DO11.10 T cells, c-FLIP expression led to inhibition of IL-2 production, in contrast to the readily detectable c-FLIP-induced activation in Jurkat cells. A direct comparison revealed that distinct signal pathways were regulated by c-FLIP in Jurkat cells and DO11.10 cells. We investigated whether constitutively activated phosphatidylinositide 3-kinase (PI3K) in Jurkat cells stimulated c-FLIP. Inhibition of PI3K in Jurkat cells abrogated a c-FLIP-mediated increase in IL-2 production. In addition, c-FLIP coordinated with active PI3K for ERK activation. Furthermore, introduction of PTEN back into Jurkat cells eliminated the stimulatory effect of c-FLIP on IL-2 production and ERK activation. Our results suggest that priming with PI3K promotes the coupling of c-FLIP to T cell activation.

Periodontitis is one of the most prevalent oral diseases. In this study, we probed the nationwide registered database to assess the time trends of prevalence of periodontitis in Taiwan.A retrospective study was conducted to analyze the registered database compiled by the National Health Insurance provided by the Department of Health, Taiwan, from 1997 to December 2013.We found that the prevalence of periodontitis significantly increased from 11.5% in 1997 to 19.59% in 2013 (P for trend 65 years old decreased markedly. The proportion of individuals with periodontitis in age groups

The aim of this paper was to explore the long-term effects and pain relief mechanism of acupuncture knife on third lumbar vertebrae (L3) transverse process syndrome. Forty SD rats were randomized into control, model, electroacupuncture (EA), and acupuncture knife (AK) group. Except control rats, other rats were subjected to an operation to emulate L3transverse process syndrome. Fourteen days after the operation, EA and AK rats were given electroacupuncture and acupuncture knife treatments, respectively. Fifty-six days after the operation, enzyme-linked immunosorbent assay was used to measure substance P (SP), 5-hydroxytryptamine (5-HT), interleukin-1β(IL-1β), interleukin-10 (IL-10), tumor necrosis factor-α(TNF-α), and transforming growth factor-β(TGF-β) in peripheral blood. The tail flick test was used to observe pain threshold. We found that rats with the simulation operation had significantly higher levels of SP, 5-HT, IL-1, IL-10, TNF-α, and TGF-β, while the AK rats had lower levels. In addition, the pain threshold of AK rats was similar to that of control rats. AK pretreatment could alleviate pain through modulating inflammatory response.

Fetal hamster ovaries were cultured for up to 16 days in the presence or absence of various dosages of insulin to evaluate the induction of folliculogenesis in vitro. In the absence of insulin, a few primordial follicle-like structures appeared by the 4th day, and distinct primary follicles (stage 1) appeared by the 12th day of culture. The organelles in the oocytes and adjacent granulosa cells developed along with follicular growth. Moreover, gap junctions between the oocyte and somatic cell plasma membrane also developed as early as 8 days in culture. In the presence of 0.2 microg/ml insulin, primary follicles developed after 8 days, and approximately 4% secondary follicles with 2-3 layers of granulosa cells appeared after 16 days of culture. However, higher dosages (> 0.2 microg/ml) of insulin retarded primary follicle formation and induced the formation of primordial follicles with larger oocytes. An increased number of larger oocytes with a few granulosa cells accumulated at the periphery of the ovary. The results indicate that although primordial and primary follicles can develop after 12 days in vitro in the absence of exogenous insulin, the latter is required for timely progression of follicular development through primary and secondary stages.

Maternal exposure to environmental tobacco smoke (ETS) has been reported to be associated with children's neurobehavioral development but there was no studies investigating the genetic susceptibilities to maternal ETS exposure on children's neurodevelopment. The aim of the study was to explore the modification effect of metabolic gene polymorphisms to cord blood cotinine on children's neurodevelopment at the 2 years of age. This study is one investigation of the Taiwan Birth Panel Study and a total of 145 pregnant women and their neonates were recruited between April 2004 and January 2005. We interviewed them by a structured questionnaire after delivery and collected umbilical cord blood at birth. Cotinine in umbilical cord blood as an indicator of environmental tobacco smoke was analyzed by using HPLC–MS/MS and the detection limited of this method was 0.05 ng/mL. Four metabolic genes, CYP1A1 MspI, CYP1A1 Ile462Val, GSTT1 and GSTM1 were identified. The Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT) was used for assessing children's neurodevelopment at the 2 years of age accompanying with the measurement of Home Observation for Measurement of the Environment scale. We used multiple linear regression models to estimate the effects of cord blood cotinine and gene modification. Cotinine levels were significantly negatively associated with developmental quotients (DQs) of the whole test, and cognitive, language, fine-motor and social subtests of the CDIIT. Lower cognitive and language DQs were found in exposed group with absent type of GSTT1. In addition, the lowest scores in fine-motor and whole test DQs were detected in exposed group with CYP1A1 Ile462Val variant type and GSTT1 absent type. It can be concluded that CYP1A1 Ile462Val and GSTT1 metabolic genes can modify the effect of cord blood cotinine on early child neurodevelopment especially for language and fine motor development.