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Objective This study aimed to evaluate the effects of 2 endoscopic spine surgeries on the biomechanical properties of normal and osteoporotic spines. Methods Based on computed tomography images of a healthy adult volunteer, 6 finite element models were created. After validating the normal intact model, a concentrated force of 400 N and a moment of 7.5 Nm were exerted on the upper surface of L3 to simulate 6 physiological activities of the spine. Five types of indices were used to assess the biomechanical properties of the 6 models, range of motion (ROM), maximum displacement value, intervertebral disc stress, maximum stress value, and articular protrusion stress, and by combining them with finite element stress cloud. Results In normal and osteoporotic spines, there was no meaningful change in ROM or disc stress in the 2 surgical models for the 6 motion states. Model N1 (osteoporotic percutaneous transforaminal endoscopic discectomy model) showed a decrease in maximum displacement value of 20.28% in right lateral bending. Model M2 (unilateral biportal endoscopic model) increased maximum displacement values of 16.88% and 17.82% during left and right lateral bending, respectively. The maximum stress value of L4–5 increased by 11.72% for model M2 during left rotation. In addition, using the same surgical approach, ROM, maximum displacement values, disc stress, and maximum stress values were more significant in the osteoporotic model than in the normal model. Conclusion In both normal and osteoporotic spines, both surgical approaches were less disruptive to the physiologic structure of the spine. Furthermore, using the same endoscopic spine surgery, normal spine biomechanical properties are superior to osteoporotic spines.

Abstract Background To date, the clinical equivalence between branded and generic medications remains debate and may sometimes be a reason why psychiatrists are hesitant to prescribe generic medications. Depression is recognized to exacerbate suicide risk globally and selective serotonin reuptake inhibitors, such as fluoxetine are common treatment options. Therefore, this study aimed to explores differences in suicidal risks between users of branded and generic fluoxetine in Taiwan. Methods This cohort study used Taiwan Longitudinal Health Insurance Database, encompassing 2 million individuals covered by National Health Insurance (NHI) program. The full cohort consisted of 32,298 fluoxetine new users. Then, 7,380 branded and 7,380 propensity score matched (PSM) generic fluoxetine new users were identified. The study further utilized Cox proportional hazards models to assess risk of 5-year suicidal ideation, suicide mortality, and all-cause mortality. Results The study revealed that the adjusted hazard ratios (HRs) for suicidal ideation, suicide mortality and all-cause mortality in branded users were 0.766 (95% CI, 0.497 − 1.181), 0.660 (95% CI, 0.447 − 0.975), and 0.942 (95% CI, 0.849 − 1.045), respectively, when compared with matched generic fluoxetine users. Stratified and sensitivity analyses showed the lower risk of suicide mortality in specific subgroups, such as male (adjusted HRs = 0.536, 95% CI = 0.306–0.939) and young branded users (adjusted HRs = 0.549, 95% CI = 0.334–0.904). Conclusion This study observed trends in the prevention effects of suicide-related risks. However, only suicide mortality was statistically significant, especially in males and those aged

Background/purpose: Oral submucous fibrosis (OSF) is a premalignant disorder that is associated with betel nut chewing. The purpose of the study was to establish the role of histone deacetylase (HDAC) 8, one of histone deacetylases, in the regulation of fibrotic conditions to provide a therapeutic potential for OSF. Materials and methods: First, we examined the expression of HDAC8 in fibrotic buccal mucosal fibroblasts (fBMFs) and OSF tissues. Markers of myofibroblasts and TGF-β signaling were conducted in fBMFs with HDAC8 knockdown were examined. Furthermore, epithelial–mesenchymal transition (EMT) markers, collagen gel contraction and migration ability were also examined in fBMFs transfected with sh-HDAC8. HDAC8 inhibitor was used to analyze the collagen gel contraction and wound healing ability in fBMFs. Results: We observed the mRNA expression of HDAC8 was significantly increased in fBMFs. Compared to normal tissues, the protein level of HDAC8 was upregulated in OSF. Next, mRNA and protein expression of HDAC8 was significantly decreased, accompanying downregulation of α-SMA and COL1A1 in fBMFs infected with sh-HDAC8. To determine the critical role of HDAC8 in OSF fibrogenesis, results revealed that TGF-β secretion and the expression of EMT transcription factor SNAIL and p-Smad were significantly decreased in HDAC8-knockdown fBMFs. We further demonstrated that collagen gel contraction and migration ability were significantly decreased in fBMFs transfected with sh-HDAC8. Last, results revealed that significantly reduced collagen gel contraction and wound healing ability in fBMFs with HDAC8 inhibitor treatment. Conclusion: We concluded that downregulation of HDAC8 alleviated the activities of myofibroblasts and TGF-β/Smad signaling pathway in OSF.

Background/purpose: 5-Fluorouracil (5FU) is a commonly used anticancer drug. However, the severe oral mucositis induced by 5FU in about 60–70% of patients was a major cause of discontinuous therapy. Since oral dysbiosis induced by 5FU was well correlated with severity of oral mucositis and Porphyromonas gingivalis (P.g.) was a keystone pathogen of dysbiosis. Thus, in this study, we aimed to explore the novel regimens of 5FU combined with phytopolyphenols (curcumin, green tea polyphenols) as well as ZnSO4 on antibacterial effects of cultured P.g. growth. In addition, similar regimens containing thioridazine (TRZ) were also tested for their antibacterial efficacy. Materials and methods: The synergistic (Combination Index (CI)

Abstract Background Pulmonary vein isolation (PVI) is a cornerstone therapy for paroxysmal atrial fibrillation (PAF). The variations in nonlinear heart rate variability (HRV) between patients with and without recurrences remain unclear. We aimed to characterize the nonlinear HRV before and after PVI in patients with and without recurrence. Methods Twenty‐five drug‐refractory PAF patients (56.0 ± 9.1 years old, 20 males) who received PVI were enrolled. Holter electrocardiography were performed before, 1–3, and 6–12 months after PVI. After 8.2 ± 2.5 months of follow‐ups after PVI, patients were divided into two groups: the recurrence (n = 8) and non‐recurrence (n = 17) groups. Linear and nonlinear HRV variables were analyzed, including the Poincaré Plot analysis and the Detrended Fluctuation Analysis (DFA). Results The non‐recurrence group, but not the recurrence group, had decreased high‐frequency component (HF), the root mean square of successive RR interval differences (RMSSD), and the Poincaré Plot index SD1 1–3 months after PVI and increased DFAslope2 6–12 months after PVI. The non‐recurrence group's LF/HF ratio and DFAslope1 decreased significantly 1–3 and 6–12 months after PVI, respectively, whereas there was no significant change in the recurrence group after PVI. Conclusions Significantly reduced vagal tone 1–3 months after PVI, increased long‐term fractal complexity 6–12 months after PVI, and decreased sympathetic tone as well as short‐term fractal complexity 1–3 and 6–12 months after PVI led to a better AF‐free survival after PVI. These findings suggest that neuromodulation and heart rate dynamics play crucial roles in AF recurrence following PVI.

Background/purpose: Porphyromonas gingivalis (P.g.) played a keystone pathogen not only in initiation and progression of periodontitis but also as a risk factor involved in systemic diseases (Alzheimer’s disease, cancers, diabetes, osteoporosis etc.). Developments of effective and safe drugs to inhibit P.g. growth are urgent. In this study, we aimed at approaching novel regimens so called (PTM) by combination of repurposing drugs including phytopolyphenols (P) (curcumin, tea polyphenols), targeting drugs (T) such as cisplatin or memantine and metal ions(M) (ZnSO4). Materials and methods: The synergistic (combination Index (CI)

Personalized medicine is a new medical concept to achieve patient-centered care. In dentistry, it is recognized for the customization of operative strategies and managements for oral diseases. Access cavity preparation in endodontic treatment is an irreversible procedure. Endodontic training will be more realistic by the implementation of clinical relevant 3D virtual reality technology. In this article, the authors first presented a personized case from a real patient to provide assess cavity preparation in haptic virtual reality dental simulator Simodont® (Nissin Dental Products Inc., Nieuw-Vennep, Netherlands). The practical framework to generate STL from cone beam computed tomography was demonstrated. A case of virtual tooth #26 access cavity preparation in Simodont® was established for trainee unlimited practices before performing the clinical procedure on a real patient. Taken together, access cavity preparation in a virtual environment using a 3D personized tooth may minimize procedural errors and facilitate clinical treatment outcome.

Abstract Recent studies have revealed the significant role of the competing endogenous RNA (ceRNA) network in human diseases. However, systematic analysis of the ceRNA mechanism in chronic rhinosinusitis with nasal polyps (CRSwNP) is limited. In this study, we constructed a competitive endogenous RNA (ceRNA) network and identified a potential regulatory axis in CRSwNP based on bioinformatics analysis and experimental verification. We obtained lncRNA, miRNA, and mRNA expression profiles from the Gene Expression Omnibus. After analysis of CRSwNP patients and the control groups, we identified 565 DE-lncRNAs, 23 DE-miRNAs, and 1799 DE-mRNAs by the DESeq2 R package or limma R package. Enrichment analysis of 1799 DE-mRNAs showed that CRSwNP was associated with inflammation and immunity. Moreover, we identified 21 lncRNAs, 8 miRNAs and 8 mRNAs to construct the lncRNA-miRNA-mRNA ceRNA network. A potential MIAT/miR-125a/IRF4 axis was determined according to the degree and positive correlation between a lncRNA and its competitive endogenous mRNAs. The GSEA results suggested that IRF4 may be involved in immune cell infiltration. The validation of another dataset confirmed that MIAT and IRF4 were differentially expressed between the CRSwNP and control groups. The area under the ROC curve (AUC) of MIAT and IRF4 was 0.944. The CIBERSORT analysis revealed that eosinophils and M2 macrophages may be involved in the CRSwNP process. MIAT was correlated with dendritic cells and M2 macrophages, and IRF4 was correlated with dendritic cells. Finally, to validate the key genes, we performed in-silico validation using another dataset and experimental validation using immunohistochemistry, immunofluorescence, and Western blot. In summary, the constructed novel MIAT/miR-125a/IRF4 axis may play a critical role in the development and progression of CRSwNP. We believe that the ceRNA network and immune cell infiltration could offer further insight into novel molecular therapeutic targets for CRSwNP.

Background/purpose: The estimated prevalence of xerostomia (lack of saliva) ranges from 10% to 50% of the general population. The oral cavity provides a multivariant environmental habitat to over 700 species of bacteria and fungi. We hypothesized that xerostomia will alter the composition of oral microbiota. Material and methods: Nineteen xerostomia patients and 10 healthy normal volunteers were studied for the oral microbiota. Gingival plaques were collected and microbiota were detected using bacterial 16S ribosomal RNA and analyzed based on the levels of phylum and class. Results: In all cases, phyla of Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria, and Proteobacteria make up to 100% of oral microbiota at phylum level. Analyzing individual phylum, presence of Bacteroidetes in xerostomia patients and normal subjects were 23.12 ± 2.56% and 23.23 ± 2.58%, respectively. Mean percentage presence of Firmicutes phylum in xerostomia patients and normal subjects were 18.94 ± 1.83% and 14.06 ± 0.98%, respectively. Statistically significant difference was not observed between xerostomia patients and normal subjects in this study. Conclusion: These observations revealed obvious but not statistically significant changes in oral major microorganism phylum between xerostomia patients and normal subjects in this study. More samples are needed to verify the current results and to use oral microbiota as a tool in the diagnosis of xerostomia.

Background: Antimicrobial resistance is a public health problem that threatens the efficacy of antibiotics. Incorrect knowledge of antibiotics may lead to their inappropriate use, hinder their effectiveness, and cause antibiotic resistance. Population-based educational campaigns have been found to have either mixed or no effect on improving knowledge and appropriate antibiotic practices, suggesting the need for more targeted approaches in tailoring education for specific subpopulations. Women are the primary caregivers of their families and are more willing to contact healthcare providers. They had greater knowledge of antibiotics and better adherence to the completion of the antibiotic regimen. Therefore, they are suitable for prioritization in a campaign program.Objective: This study examined the knowledge and practices of female visitors to health centers in Malang, Indonesia with respect to antibiotic use.Methods: This cross-sectional study was conducted in Malang, Indonesia, in July and August 2018. Data were collected from 677 women. Multivariate logistic regression was performed to identify the potential factors associated with antibiotic knowledge, self-medication, and completion of antibiotic regimens.Results: Overall, 82.7% of respondents were aware that antibiotics are used against bacteria, while 38.4% reported self-medication with antibiotics and 51.7% reported completing antibiotic regimens. Women with higher education, previous antibiotic use experience, and very easy accessibility to primary doctors were more likely to have high antibiotic knowledge than those with primary education, no antibiotic use in the previous year, and easy/other level of accessibility to primary doctors. Subjects residing in urban areas and with less accessibility to primary doctors were more likely to self-medicate with antibiotics. Additionally, the completion of antibiotic regimens was positively associated with access to a primary care doctor and high antibiotic knowledge.Conclusion: IF Policymakers tend to reduce inappropriate antibiotic use among women. Priority advocates are recommended for urban residents who have experiences of antibiotic use in the previous year. It is therefore important to increase their awareness, particularly regarding diseases against which antibiotics are effective, and activities such as unnecessary use of antibiotics in healthy animals, which may affect their overall effectiveness among humans. More communication channels should be included in the overall scheme to improve the public awareness and accessibility of health professionals.

Background: Head and neck squamous cell carcinomas (HNSCCs) are derived from the mucosal linings of the upper aerodigestive tract, salivary glands, thyroid, oropharynx, larynx, and hypopharynx. The present study aimed to identify the novel genes and pathways underlying HNSCC. Despite the advances in HNSCC research, diagnosis, and treatment, its incidence continues to rise, and the mortality of advanced HNSCC is expected to increase by 50%. Therefore, there is an urgent need for effective biomarkers to predict HNSCC patients’ prognosis and provide guidance to the personalized treatment.Methods: Both HNSCC clinical and gene expression data were abstracted from The Cancer Genome Atlas (TCGA) database. Intersecting analysis was adopted between the gene expression matrix of HNSCC patients from TCGA database to extract TME-related genes. Differential gene expression analysis between HNSCC tissue samples and normal tissue samples was performed by R software. Then, HNSCC patients were categorized into clusters 1 and 2 via NMF. Next, TME-related prognosis genes (p < 0.05) were analyzed by univariate Cox regression analysis, LASSO Cox regression analysis, and multivariate Cox regression analysis. Finally, nine genes were selected to construct a prognostic risk model and a prognostic gene signature. We also established a nomogram using relevant clinical parameters and a risk score. The Kaplan–Meier curve, survival analysis, time-dependent receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and the concordance index (C-index) were carried out to assess the accuracy of the prognostic risk model and nomogram. Potential molecular mechanisms were revealed by gene set enrichment analysis (GSEA). Additionally, gene correlation analysis and immune cell correlation analysis were conducted for further enriching our results.Results: A novel HNSCC prognostic model was established based on the nine genes (GTSE1, LRRN4CL, CRYAB, SHOX2, ASNS, KRT23, ANGPT2, HOXA9, and CARD11). The value of area under the ROC curves (AUCs) (0.769, 0.841, and 0.816) in TCGA whole set showed that the model effectively predicted the 1-, 3-, and 5-year overall survival (OS). Results of the Cox regression assessment confirmed the nine-gene signature as a reliable independent prognostic factor in HNSCC patients. The prognostic nomogram developed using multivariate Cox regression analysis showed a superior C-index over other clinical signatures. Also, the calibration curve had a high level of concordance between estimated OS and the observed OS. This showed that its clinical net can precisely estimate the one-, three-, and five-year OS in HNSCC patients. The gene set enrichment analysis (GSEA) to some extent revealed the immune- and tumor-linked cascades.Conclusion: In conclusion, the TME-related nine-gene signature and nomogram can effectively improve the estimation of prognosis in patients with HNSCC.

Background/purpose: Oral submucous fibrosis (OSF) is an irreversible fibrosis disease and a potentially malignant disorder in the oral cavity. Various studies have shown that miR-21 was implicated in the fibrogenesis and carcinogenesis, but its functional role in the development of OSF has not been investigated. Methods: The expression levels of miR-21 in arecoline-stimulated normal buccal mucosal fibroblasts (BMFs) and OSF specimens were determined by qRT-PCR. Exogenous administration of TGF-β and its inhibitor (SB431542) were utilized to examine the involvement of TGF-β signaling in miR-21 alteration. Collagen gel contraction, transwell migration, and invasion assays were used to assess the myofibroblast activities. The relationship between α-SMA and miR-21 was calculated using the Pearson correlation coefficient. Results: MiR-21 expression was induced in BMFs by arecoline treatment in a dose-dependent manner. Our results showed that this upregulation was mediated by TGF-β signaling. Subsequently, we demonstrated that the administration of the miR-21 inhibitor suppressed the arecoline-induced myofibroblast characteristics, including a higher collagen gel contractility and cell motility, in normal BMFs. Furthermore, inhibition of miR-21 was sufficient to attenuate the myofibroblast features in fibrotic BMFs. Besides, we showed that the expression of miR-21 was aberrantly upregulated in the OSF tissues and there was a positive correlation between miR-21 and myofibroblast marker, α-SMA. Conclusion: MiR-21 overexpression in OSF may be due to the stimulation of areca nut, which was mediated by the TGF-β pathway. Our data suggested that the repression of miR-21 was a promising direction to palliate the development and progression of OSF.

Abstract Background Acute postoperative pain plays an important role in the perioperative neurocognitive disorders (PND). The pathogenesis of PND is still unknown, but it is generally believed that peripheral and central nervous system inflammation play an important role, and acute postoperative pain is also thought to aggravate postoperative inflammatory response. The aim of the present study is to explore the effect of acute postoperative pain on peripheral and central nervous system inflammation and related cognitive impairment behaviour in elderly rats after surgery. Methods Rats were assigned into four groups: control, surgery for internal fixation for tibial fracture, surgery with analgesia using intraperitoneal morphine, and morphine without surgery. Pain was assessed by the Subjective Pain Scale. The spatial memory of rats was assessed by the Morris water maze (delayed matching task) from the second day to the seventh day after surgery (POD2-POD7). In part of the rats, the pro-inflammatory cytokines TNF-α in plasma, the medial prefrontal cortex (mPFC), and the hippocampus were determined by ELISA on the POD2. The activation of microglia and the expression of c-Fos in the hippocampal CA1 regions and mPFC were detected by the immunohistochemical method on the POD2. Results Acute postoperative pain and spatial memory impairment occurred after operation, and postoperative analgesia could significantly improve the both parameters. Additionally, on the POD2, the levels of TNF-α in plasma, hippocampus and mPFC were significantly increased, while the activation of microglia cells and the expression c-Fos in the hippocampal CA1 regions and mPFC were significantly increased. And postoperative analgesia with morphine significantly inhibited the above reactions. Conclusion Our data suggest that acute postoperative pain increases the incidence of perioperative neurocognitive disorders. Peripheral and central nervous system inflammation may be involved in this cognitive impairment. And reducing the intensity of acute postoperative pain may be one of the main preventive strategies for PND.

Background: The skin sympathetic nerve activity (SKNA) is a new method to measure sympathetic nerve activity by using conventional ECG electrodes. We developed a novel approach to analyze the complexity of SKNA time series under different time scales and showed its prognostic significance in patients receiving critical care. Methods: This study measured SKNA in patients admitted to an intensive care unit (ICU). Each recording is 10-minute long with 10000Hz sampling rate. Multi-scale fluctuation analysis (MSFA) was developed to quantify the variation within each time scale after removing the linear trend. The prognostic value of SKNA was combined with traditional prognostics scoring system to improve the predictive values. Results: 155 patients were recruited. After 30 and 90 days, 30 and 48 patients expired. MSFA was significantly higher in survival group than mortality group for 30-day (0.487 ± 0.185 vs 0.401 ± 0.045, p = 0.018) and 90-day (0.499 ± 0.196 vs 0.414 ± 0.061, p = 0.001) follow-up. Sequential Organ Failure Assessment (SOFA) score was significantly lower in the survival group compared to the expired group for 30-day and 90-day (4.1 ± 2.9 vs. 5.5 ± 4.1, p = 0.032 and 3.9 ± 3.0 vs. 5.4 ± 3.5, p = 0.012). The Kaplan–Meier survival analysis showed MSFA lower than 0.401 (log-rank test:4.96, p = 0.03) or with SOFA score lower than 5 (log-rank test:5.49, p = 0.019) have a significantly higher mortality rate. A multivariate Cox regression model showed that the MSFA is an independent predictor for 30-day mortality (HR = 2.35, 1.08–5.09, p = 0.031) and 90-day mortality (HR = 1.96, 1.08–3.58, p = 0.027). Conclusion: MSFA was a significant prognostic predictor for critically ill patients. MSFA adding to SOFA score could help improve risk prediction.

Background Spontaneous heart rate fluctuations contain rich information related to health and illness in terms of physiological complexity, an accepted indicator of plasticity and adaptability. However, it is challenging to make inferences on complexity from shorter, more practical epochs of data. Distribution entropy (DistEn) is a recently introduced complexity measure that is designed specifically for shorter duration heartbeat recordings. We hypothesized that reduced DistEn predicted increased mortality in a large population cohort. Method and Results The prognostic value of DistEn was examined in 7631 middle‐older–aged UK Biobank participants who had 2‐minute resting ECGs conducted (mean age, 59.5 years; 60.4% women). During a median follow‐up period of 7.8 years, 451 (5.9%) participants died. In Cox proportional hazards models with adjustment for demographics, lifestyle factors, physical activity, cardiovascular risks, and comorbidities, for each 1‐SD decrease in DistEn, the risk increased by 36%, 56%, and 73% for all‐cause, cardiovascular, and respiratory disease–related mortality, respectively. These effect sizes were equivalent to the risk of death from being >5 years older, having been a former smoker, or having diabetes mellitus. Lower DistEn was most predictive of death in those

Background/Purpose: Emerging research findings suggest that long non-coding RNAs (lncRNAs) are key regulators to fibrosis formation. Nevertheless, the role of lncRNA GAS5-AS1 in the progression of precancerous oral submucous fibrosis (OSF) remains to be elucidated. Methods: Quantitative real-time PCR were used to examine the expression of GAS5-AS1 in OSF tissues. The activities of myofibroblasts, including collagen contractility and cell migration, as well as the marker α-smooth muscle actin (SMA) were assessed following overexpression of GAS5-AS1. Also, we analyzed the expression of Smad activity in order to gain insight into the downstream regulator. Results: The level of GAS5-AS1 was found significantly downregulated in the OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs). Ectopic expression of GAS5-AS1 significantly reduced the abilities of collagen gel contraction and migration in fBMFs or arecoline-treated BMFs. Moreover, we have shown that overexpression of GAS5-AS1 inhibited the expression of p-Smad and the marker of myofibroblasts. Conclusion: We showed the reduced expression of GAS5-AS1 in OSF tissues and demonstrated its effect on the myofibroblast activities and the level of p-Smad and α-SMA, indicating its potential contribution in OSF pathogenesis. Keywords: lncRNA GAS5-AS1, Myofibroblasts, Oral submucous fibrosis

Background/purpose: The prevalence of orofacial pain is high but the etiology of orofacial pain is not well understood. Because of clinical treatment is not so effective, it is urgent to explore novel regimens with more effective and less side effects for clinical application. Materials and methods: Male mice (ICR strain) were injected with capsaicin (10μg/5 μl) in vibrissa pad. Spontaneous orofacial pain in 20 min was recorded after receiving capsaicin to quantify the nociceptive level. Green tea polyphenols (GTP 60 mg/kg), memantine (Mem 10 mg/kg), and GTPm (GTP 30 mg/kg plus Mem 3 mg/kg) were dissolved in 2% carboxymethyl cellulose, which was orally administered to mice twice per day and five times per week consecutively for 2 weeks. TruScan photobeam tracking was used to record changes of behavior and locomotor activities. Results: GTPm by itself attenuated orofacial pain induced by capsaicin. Moreover, GTPm enhanced morphine analgesic effects, reduced morphine depressant side effects and delayed morphine tolerance. Along with this experiment, GTPm was tested on the hot plate (52 °C)-induced peripheral thermal pain. It was found that both memantine and GTPm reduced morphine-analgesia in hind paw thermal pain. Conclusion: In this study, GTP (60 mg/kg/day) orally administrated produced a significant analgesic effect on capsaicin–induced orofacial pain. Memantine combined with GTP synergistically not only reduced orofacial pain but also enhanced morphine analgesic effects. Thus, a new regimen of GTPm orally administered twice per day attenuated orofacial pain after consecutive 5 days.

Background: It is unclear whether women with psoriasis who receive adequate management or achieve better control of their psoriasis before and during pregnancy could eliminate the negative effects. Objectives: The objective of this study was to investigate the association between physician visits for psoriasis and adverse pregnancy outcomes. Methods: This study used the National Health Insurance database and Birth Certificate Application in Taiwan. This research further categorized the study subjects into mothers with mild/severe psoriasis who visited physicians for psoriasis before delivery, mothers with mild/severe psoriasis who did not visit a physician for psoriasis before delivery, and mothers without psoriasis. Logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the occurrence of adverse pregnancy outcomes, including maternal and neonatal outcomes. Results: 3,339 mothers with severe psoriasis, 41,296 mothers with mild psoriasis, and 2,017,271 mothers without psoriasis were included in this study. The mothers with mild/severe psoriasis demonstrated a significantly higher risk of labor complications and maternal risk factors. After adjusting for confounders, mothers with severe psoriasis who did not visit a physician for psoriasis demonstrated significantly higher odds of labor complications (OR: 1.217), maternal risk factors (OR: 1.507), having low‑birth weight infants (OR: 1.236), etc., than mothers without psoriasis. Conclusion: This study demonstrated that mothers with psoriasis had a higher risk of adverse pregnancy outcomes. In addition, seeking medical care for psoriasis, particularly for women with severe psoriasis, appeared to exert a protective effect against adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer (OC) is the second most common gynecological malignancy and has a high mortality rate. The current chemotherapeutic drugs have the disadvantages of drug resistance and side effects. Myricetin, a kind of natural compound, has the advantages of easy extraction, low price, and fewer side effects. Multiple studies have demonstrated the anti-cancer properties of myricetin. However, its impact on OC is still unknown and needs further investigation. Therefore, this study aimed to elucidate the mechanism by which myricetin suppresses transforming growth factor-β (TGF-β) -induced epithelialto-mesenchymal transition (EMT) in OC through in vivo and in vitro experiments. Methods: In vitro experiments were conducted to evaluate the effects of myricetin on cell proliferation and apoptosis using CCK8 assay, plate clonal formation assay, and flow cytometry. Western blot was employed to evaluate the expression levels of caspase-3, PARP, and the MAPK/ERK and PI3K/AKT signaling pathways. Wound healing, transwell, western blot and immunofluorescence assay were used to detect TGF-β-induced cell migration, invasion, EMT and the levels of Smad3, MAPK/ERK, PI3K/AKT signaling pathways. Additionally, a mouse xenograft model was established to verify the effects of myricetin on OC in vivo. Results: Myricetin inhibited OC proliferation through MAPK/ERK and PI3K/AKT signaling pathways. Flow cytometry and western blot analyses demonstrated that myricetin promoted apoptosis by increasing the expression of cleaved-PARP and cleaved-caspase-3 and the ratio of Bax/Bcl-2 in OC. Furthermore, myricetin suppressed the TGF-β-induced migration and invasion by transwell and wound healing assays. Mechanistically, western blot indicated that myricetin reversed TGF-β-induced metastasis through Smad3, MAPK/ERK and PI3K/AKT signaling pathway. In vivo, myricetin significantly repressed OC progression and liver and lung metastasis. Conclusion: Myricetin exhibited inhibitory effects on OC progression and metastasis both in vivo and in vitro. And it also reversed TGF-β-induced EMT through the classical and non-classical Smad signaling pathways. [ABSTRACT FROM AUTHOR]

Background/purpose: Oral submucous fibrosis (OSF) is a potentially malignant disorder of oral squamous cell carcinoma (SCC). In this study, we obtained the genetic expression signatures of OSF and SCC by microarray analysis. Materials and methods: Five patients with clinically evident OSF, five patients with SCC who also had existing OSF, and four normal volunteers who did not have a history of chewing betel quids were recruited. Biopsy specimens were obtained with an approved Institutional Review Board protocol. Total RNA from OSF or SCC was isolated and hybridized to a Human Oligo 1A (V2) Microarray (G4110B) chip against normal control RNA that was pooled from the four healthy volunteers. Results: We found similar, but distinct genetic expression signatures for OSF and SCC. At the hierarchical clustering analysis, 24 known genes (23 upregulated and 1 downregulated) in OSF were differentially expressed consistently in all participants. Among the genes, XRCC5 was cloned and transfected into oral cancer GNM cells. The results demonstrated that the overexpression of XRCC5 increased the resistance of GNM cells to low-density X-ray irradiation and promoted the cell growth rate. Conclusion: The distinct but similar genetic expression signatures seen in OSF and SCC suggested that this expression may be used as a supplemental diagnostic tool in pathology practice. This preliminary study showed that the XRCC5 gene promoted GNM cell growth and conferred resistance to low-density X-ray irradiation. Further studies on the effect of XRCC5 in oral cancer cells are in progress.

Temporomandibular joint disorder (TMD) is a general term for diseases of the temporomandibular joint and orofacial muscles. In this study, we tested whether laser acupuncture was effective for the treatment of TMD. Methods: Twenty patients with TMD were treated with diode K-Laser (wavelength 800 nm, energy density 100.5 J/cm2) once a week at four acupuncture points including three standard ipsilateral local points (ST6, ST7, Ashi point) and one contralateral distal point (LI4). A 10-cm visual analogue scale (0 no pain and 10 the most severe pain) was used for measuring the pain intensity before and after the treatment. Results: Seventeen out of 20 patients (85%) showed various degrees of pain relief after laser acupuncture treatment. The average pain score was 6.3 ± 1.6 before treatment and 2.5 ± 2.2 after treatment. Significant pain relief after laser acupuncture treatment was achieved (p = 0.0003, Wilcoxon signed rank test). The 17 patients showed an average pain relief of 63 ± 31%. There were six patients who showed no TMD symptoms after an average of four treatments of laser acupuncture. The other 11 patients showed partial relief of TMD symptoms after treatment. Although the pain was still present, it was less and was acceptable. No side effects were reported in any patients during or after laser acupuncture treatments. Conclusion: Laser acupuncture may be an alternative treatment modality for TMD because it is non-invasive, results in partial or total relief of pain, and has no side effects.

Background: Melanoma is considered as one of the most aggressive and deadliest cancers and current targeted therapies of melanoma often suffer limited efficacy or drug resistance. Discovery of novel multikinase inhibitors as anti-melanoma drug candidates is still needed. Methods: In this investigation, we assessed the in vitro and in vivo anti-melanoma activities of SC-535, which is a novel small molecule multikinase inhibitor discovered by us recently. We analyzed inhibitory effects of SC-535 on various melanoma cell lines and human umbilical vascular endothelial cells (HUVEC) in vitro. Tumor xenografts in athymic mice were used to examine the in vivo activity of SC-535. Results: SC-535 could efficiently inhibit vascular endothelial growth factor receptor (VEGFR) 1/2/3, B-RAF, and C-RAF kinases. It showed significant antiangiogenic potencies both in vitro and in vivo and considerable anti-proliferative ability against several melanoma cell lines. Oral administration of SC-535 resulted in dose-dependent suppression of tumor growth in WM2664 and C32 xenograft mouse models. Studies of mechanisms of action indicated that SC-535 suppressed the tumor angiogenesis and induced G2/M phase cell cycle arrest in human melanoma cells. SC-535 possesses favorable pharmacokinetic properties. Conclusion: All of these results support SC-535 as a potential candidate for clinical studies in patients with melanoma.

Background: Metabolic syndrome (MetS), associated with the risk of cardiovascular disease and stroke, resulted in subsequent functional decline among aging population. It would be of interest to investigate the characteristics and related health behaviors of MetS among community-dwelling elderly. Methods: During 2007–2010, we selected the elderly who underwent the annual health checkup and screen in Taipei Veterans General Hospital and did not have MetS in their first year of participation as the study population. After a mean of 2.8 years' follow-up, the elderly were categorized into new-developed MetS patients and non-MetS patients according to Adult Treatment Panel III diagnostic criteria of MetS. Health behaviors were collected using a questionnaire and the laboratory data were analyzed. Results: A total of 888 community-dwelling elderly were enrolled. Of those participants, 206 (23.2%) developed MetS (new-developed MetS group) and 682 (76.8%) did not develop MetS (non-MetS group). Presence of higher initial MetS score, hyperuricemia, and proteinuria, and lack of exercise were associated with new-developed MetS in the elderly. Proteinuria and initial MetS score of two patients were significantly related to the development of MetS in the Cox regression analysis (hazard ratio 2.530 and 4.728, respectively). Other health behaviors such as smoking, alcohol drinking, teeth brushing, vegetable intake, and milk intake were not correlated significantly with the development of MetS. Conclusion: For the community-dwelling elderly, proteinuria and initial MetS score of two participants were correlated to the occurrence of MetS. A stricter control of risk factors of MetS in these elderly is necessary.

Nevoid basal cell carcinoma syndrome (also named Gorlin-Goltz syndrome) is a rare disease. Commonly seen features include multiple odontogenic keratocysts (OKCs), nevus-like basal cell carcinoma, and bifid ribs. Genetic alterations of the PTCH1 gene are associated with the disease. Herein, we report the case of a 15-year-old girl who presented with multiple OKCs, a bifid rib, ectopic calcification of the falx cer-ebri, and an arachnoid cyst of the cerebrum. No basal cell carcinoma was identified. In addition, a search for genetic alterations was performed on the patient. We identified a genetic mutation of C→T in exon 12 (c.1686 bp) and a G→C mutation in intron 13 (g.91665 bp) of the PTCH1 gene. Although a similar mutation in exon 12 was reported in a literature search, the mutation in intron 13 has not previously been reported. The patient has continued to be followed-up almost 3 years after the surgery with no recurrence of the OKCs or development of basal cell carcinoma.