Search

To explore the complex genetic architecture of common diseases and traits, we conducted comprehensive PheWAS of ten diseases and 34 quantitative traits in the community-based Taiwan Biobank (TWB). We identified 995 significantly associated loci with 135 novel loci specific to Taiwanese population. Further analyses highlighted the genetic pleiotropy of loci related to complex disease and associated quantitative traits. Extensive analysis on glycaemic phenotypes (T2D, fasting glucose and HbA1c) was performed and identified 115 significant loci with four novel genetic variants (HACL1, RAD21, ASH1L and GAK). Transcriptomics data also strengthen the relevancy of the findings to metabolic disorders, thus contributing to better understanding of pathogenesis. In addition, genetic risk scores are constructed and validated for absolute risks prediction of T2D in Taiwanese population. In conclusion, our data-driven approach without a priori hypothesis is useful for novel gene discovery and validation on top of disease risk prediction for unique non-European population.

Background Poor oral health affects quality of life; oral health literacy studies are increasing as it plays an essential role in promoting oral health. However, little is known regarding the gender differences in oral health literacy and oral health-related quality of life (OHRQoL) among older adults. This study aimed to explore the gender differences in oral health literacy and OHRQoL among community-dwelling older adults in Taiwan. Methods A cross-sectional study design with convenience sampling was undertaken to recruit participants at two community service centres. Data were collected using a structured survey consisted of the demographic characteristics, instrumental activities of daily living, nutrition assessment, oral health literacy and OHRQoL. The logistic regression was used to examine the gender differences in the relationship between oral health literacy and OHRQoL. Results A total of 202 participants completed the survey. Of which 56.4% (n = 114) were female. Logistic regression analyses showed that after controlling for age, instrumental activities of daily living, nutrition, education level, and average monthly income, better oral health literacy was associated with better oral health quality of life (p = 0.006) in men. Conclusions The relationship between oral health literacy and OHRQoL was only significant for men. No significant relationship between women’s oral health literacy and their OHRQoL. However, good OHRQoL is an integral part of overall health, but it is affected by differences in oral health and the accessibility of healthcare services. We suggest that gender-specific oral health literacy education should be offered through community health-education programs.

Purpose: To establish an appropriate clinical protocol for early photoscreening in 12-to-24-month-old children at pediatric well-baby clinics. Methods: This prospective study included a total of 277 children aged 12–24 months who visited a pediatric well-baby clinic. All participants underwent: 1) inquiry of medical history; 2) photoscreening with PlusoptiX A12; and 3) comprehensive ophthalmologic examinations. The optimal referral cut-off point for PlusoptiX was determined by receiver operating characteristic analyses. A high-risk subgroup was defined as having a birth weight

Human oral squamous cell carcinoma (OSCC) has been one of the most common oral cancers owing to high percentage of betel nuts chewers, smokers, and alcohol consumption. With current treatment strategies in OSCC, more than half patients relapse and develop distant metastases with poor prognosis. To overcome the incident, OSCC poses a challenge in current therapies and treatments. Naringenin, a natural flavonoid, has been noted for antitumor effects on various types of cancers; however, the effects of naringenin on OSCC remain bias. In this study, naringenin demonstrated the potential multifunction in human OSCC cells not only leading to cell apoptosis, but also alternating the general function of autophagy, serving as pro-survival mechanism by inducing the endoplasmic reticulum (ER) stress signaling through intracellular reactive oxygen species (ROS) production. In the process of programmed cell death, naringenin induced apoptotic signaling through caspase-cascade, mitochondrial dysfunction, and ER stress by aberrance of Ca

This study aimed to determine the role of mitochondria-associated proteins (HtrA2, α-synuclein, and Park7) in attention deficit/hyperactivity disorder (ADHD). A total of 125 patients with ADHD (77.6% were males) and 66 healthy controls (66.7% were males) were recruited. We found that girls with ADHD demonstrated higher plasma HtrA2 level than control girls, and their HtrA2 levels were positively correlated with verbal comprehensive ability, and negatively correlated to behavior symptoms. Among boys, we observed no correlations between these mitochondrial proteins, neuropsychological findings, and clinical symptoms. Our findings suggest that an underlying gender-specific mitochondria pathway may influence with the pathophysiology of ADHD.

This study explored the technology learning model of the elderly in a senior learning center under the impact of the COVID-19 pandemic. Many senior learning centers were closed during the pandemic, and many of them adopted the mode of online education. However, problems such as decreased motivation and a lack of peer interaction still exist. To solve these problems, this study used the easy-to-implement calligraphy AR approach and E-book approach to conduct a quasi-experiment on the elderly of a calligraphy course offered by a senior learning center. The results show a higher learning motivation among the elderly who use calligraphy AR. The learning effectiveness and technology acceptance of the elderly in the E-book learning group were higher than those in the calligraphy AR group. The elderly mentioned that the E-book learning approach is more user-friendly. In general, in the face of the COVID-19 pandemic affecting the suspension of classes in senior centers, education through the development of technology has stimulated the growth of education in advanced learning centers. Through this kind of scientific and technological learning method, it will bring a whole new experience to the elderly. It can improve the stress relief methods, mental health, and quality of life of the elderly during the COVID-19 emergency shutdown, and provide a novel calligraphy technique learning experience for the elderly. Therefore, we believe that the calligraphy AR learning approach and the calligraphy E-book learning approach are practical and may promote quality of life and mental health of the elderly during the emergency closures due to COVID-19, providing elderly attendees with a novel calligraphy technology learning experience.

Background Inhibiting TNF-α is an effective therapy for inflammatory diseases such as rheumatoid arthritis. However, systemic, nondiscriminatory neutralization of TNF-α is associated with considerable adverse effects. Methods Here, we developed a trimeric chimeric TNF receptor by linking an N-terminal mouse Acrp30 trimerization domain and an MMP-2/9 substrate sequence to the mouse extracellular domain of TNF receptor 2 followed by a C-terminal mouse tetranectin coiled-coil domain (mouse Acrp-MMP-TNFR-Tn). Results Here, we show that the Acrp30 trimerization domain inhibited the binding activity of TNFR, possibly by closing the binding site of the trimeric receptor. Cleavage of the substrate sequence by MMP-9, an enzyme highly expressed in inflammatory sites, restored the binding activity of the mouse TNF receptor. We also constructed a recombinant human chimeric TNF receptor (human Acrp-MMP-TNFR-Tn) in which an MMP-13 substrate sequence was used to link the human Acrp and the human TNF receptor 2. Human Acrp-MMP-TNFR-Tn showed reduced binding activity, and MMP-13 digestion recovered its binding activity with TNF-α. Conclusion Acrp-masked chimeric TNF receptors may be able to be used for inflammatory tissue-selective neutralization of TNF-α to reduce the adverse effects associated with systemic neutralization of TNF-α.

The objective of this retrospective review is to evaluate the ability of the Murray secretion scale to predict aspiration as determined by fiberoptic endoscopic evaluation of swallowing. Patients with dysphagia undergoing a fiberoptic endoscopic evaluation of swallowing study between January 2013 and November 2015 from a single, tertiary care institution were retrospectively reviewed. The Murray secretion scale and penetration aspiration scale on fiberoptic endoscopic evaluation of swallowing examination were determined. Spearman’s correlation analysis, sensitivity, specificity, predictive values, and relative risk evaluating the relationship between the Murray secretion scale and aspiration on fiberoptic endoscopic evaluation of swallowing were calculated. Subgroups of head and neck cancer patients, penetration group, and aspiration group were also analyzed. The mean age of the cases (N = 212) was 62.4 years. Eighty percent were male. There was a strong correlation between Murray secretion scale grade and penetration aspiration scale score (r = 0.785, p

Objective Cryptotanshinone (CPT) and dihydrotanshinone (DHT) are diterpenoid anthraquinone compounds extracted from traditional Chinese herbal medicine (TCM). Recent studies have shown that CPT regulates the signal transduction pathways via microRNA (miRNA) alterations. However, few studies have investigated the role of DHT in miRNA alterations affecting cell-signaling pathways. This study aimed to investigate the miRNA alterations and post-transcriptional regulation activities of DHT in comparison to CPT. Methods HepG2 and HT-29 cells were treated with DHT or CPT for 72 h. MiRNA, transcription factor encoding mRNA, and downstream gene expression were determined using real-time quantitative PCR. Protein expression was analyzed using western blotting. Results The results revealed that CPT and DHT targeted cell proliferation and apoptosis signaling pathways via miR-15a-5p, miR-27a-5p, miR-100−5p, and miR-200a-5p alterations.In silico target predictions showed that downregulation of epidermal growth factor receptor (EGFR) mRNA expression by DHT might also suppress the expression of STAT family proteins and lead to anti-proliferation effects. We also found that, compared to CPT, DHT might possess higher potency in cell growth regulation via multi-miRNA and transcription factor alterations. Conclusion This study revealed that CPT and DHT targeted cell proliferation and apoptosis signaling pathways via alterations in miRNAs and transcription factors. In addition, the findings of this study suggest that DHT is more potent than CPT in cancer chemopreventive activities. Therefore, DHT at a low dose is a TCM compound with less toxic side effects and may contribute to the development of natural medicine as a potential cancer chemopreventive agent.

Background Chylothorax is a rare condition among neonates, although it is considered clinically significant, as it is difficult to manage in these patients. In addition, the course of chylothorax varies widely. Therefore, we aimed to elucidate the clinical features and effect of prenatal therapy on the prognosis of congenital chylothorax in neonates. Methods We retrospectively reviewed the medical records of all infants with congenital chylothorax who were admitted to National Taiwan University Hospital, Taipei, Taiwan between January 2000 and December 2012. Their demographic characteristics, as well as their antenatal, perinatal, and postnatal information, were collected for our analysis of the mortality risk. Results We found 29 infants who were diagnosed with congenital chylothorax during the study period. The median gestational age at birth was 34 weeks (range, 28–41 weeks), and 71% of the infants presented with hydrops fetalis. Most cases of congenital chylothorax were bilateral (bilateral: 86.2%, unilateral: 13.79%), and the overall survival rate was 59.6%. Among the cases with a prenatal diagnosis at ≤ 34 weeks of gestation, infants who received prenatal therapy had a significantly higher survival rate, compared to infants who did not receive prenatal therapy (76.9% vs. 11%, respectively; p = 0.008). Conclusion We found that infants whose chylothorax was diagnosed ≤ 34 weeks of gestation, and who subsequently received prenatal therapy, experienced a better perinatal condition and exhibited improved postnatal outcomes.

Acne is a skin disease common in adolescents and increasingly common in the adult population. The major pathologic events of acne vulgaris include increased sebum production, retention hyperkeratosis, carrying commensal skin microbiota, and inflammation. In recent years, more than 10,000 compounds have been isolated and identified from marine organisms. The aim of this study was to discover the potential anti-acne activity of fraction 9 + 10 (SF-E) of Sinularia flexibilis extract and six cembrene diterpenoids. We found that the SF-E significantly reduced Cutibacterium acnes-induced edema in Wistar rat ears. The cembrene diterpenoids including 11-dehydrosinulariolide (SC-2), 3,4:8,11-bisepoxy-7-acetoxycembra-15(17)-en-1,12-olide (SC-7), and sinularin (SC-9) reduced nitric oxide (NO) production with 50% inhibitory concentration of 5.66 &plusmn, 0.19, 15.25 &plusmn, 0.25, and 3.85 &plusmn, 0.25 &mu, M, respectively, and inducible NO synthase expression in RAW 264.7 cells. Moreover, treatment with SC-2, SC-7, and SC-9 significantly suppressed lipopolysaccharide- and heat-killed C. acnes-induced expression of proteins involved in mitogen-activated protein kinase pathway in both RAW 264.7 and HaCaT cells. After treatment with SC-2, SC-7, and SC-9, over-proliferation of HaCaT cells was significantly terminated. In summary, SC-2, SC-7, and SC-9 showed anti-inflammatory effects in RAW 264.7 cells, suggesting that these cembrene diterpenoids obtained from S. flexibilis are natural marine products with potential anti-acne activities.

The aim of this study was to examine the metabolic parameters, including body mass index (BMI), homeostasis model assessment-estimated insulin resistance (HOMA-IR), homeostasis model assessment-estimated pancreatic β-cell function (HOMA-β), and lipid plasma level, in medicated patients with major depressive disorder (MDD) and to assess factors related to metabolic parameters in patients with MDD. 121 patients with MDD and 63 controls were recruited. The Hamilton Depression Rating Scale (HDRS), Wisconsin Card Sorting Test (WCST), Continuous Performance Test (CPT), and Finger-Tapping Test (FTT), were administered. BMI, HOMA-IR, and HOMA-β were calculated as modifiable metabolic parameters. The FTT results and BMI in depressed patients were significantly poorer and lower, respectively, than those of the controls. However, no significant differences were noted between MDD patients and controls included metabolic parameters and other neuropsychological tests. Among depressed patients, higher BMI is significantly related with lower education, no tobacco use, and male. The result demonstrated metabolic parameters could be neutral among medicated patients with MDD, particularly in non-elderly Asian individuals. The deficits of psychomotor speed could be more prominent than other cognitive alterations in patient with MDD.

To determine the effects of co-ingesting caffeine (CAF) and carbohydrate (CHO) on high-intensity intermittent sprints (HIS) performance and physiological responses. Twelve active males underwent 4 interventions at least 7 days apart in a randomized, double-blind, placebo-controlled, balanced trial. A meal contained 65 % CHO was provided 2 h before the HIS test. Participants ingested the placebo (PLA) or CAF (6 mg kg−1 BW) 1 h before taking an HIS test, and ingested a PLA or CHO solution (0.8 g kg−1 BW) before undergoing the testing protocol. The HIS protocol comprised ten sets of 5 × 4-s sprints on a cycle ergometer with a 2-min recovery between each set. There was no significant difference between peak power output and mean power output between trials (p > 0.05). Compared with PLA, CAF + CHO resulted in a 5.2 % reduction in total work, corresponding to a 24.7–25.7 % increase in fatigue at the end stage of the HIS. The administration of CAF + CHO supplementation also resulted in an 11.1 % increase in blood lactate, and elevated blood glucose concentrations throughout HIS testing compared with PLA (p

Vitis thunbergii Sieb. et Zucc. var. taiwaniana Lu (VT) is an indigenous plant in Taiwan that is traditionally used for promoting joint health. In this study, we used in vitro primary human chondrocytes (PHCs) and two in vivo animal models to evaluate the anti-inflammatory effects of VT on arthritis. Results showed that the water extract of the stems and roots from VT (VT-SR) was rich in flavones and phenols with 1.1 mg/g of resveratrol, 6.7 mg/g of hopeaphenol, and 5.1 mg/g of (+)-ɛ-viniferin. VT-SR significantly scavenged DPPH radicals and inhibited prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-induced PHCs without exhibiting significant cytotoxicity. In in vivo models, the VT-SR (500 mg/kg) significantly decreased serum PGE2 and knee 2-(18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) levels in LPS-induced acute inflammatory arthritis in rabbits. In addition, dietary supplementation with VT-SR for 28 days significantly alleviated type II collagenase-induced rat osteoarthritis with improvements in weight bearing and range of motion tests. In conclusion, our results suggest that the VT-SR is a good candidate for developing dietary supplements to prevent joint deterioration and inhibit inflammation.

Following human papilloma virus (HPV) infection, recurrent respiratory papillomatosis (RRP) develops secondary to dysfunction of innate and adaptive immune responses. Diabetes mellitus (DM) is a common medical disorder; these patients are considered to be relatively immunocompromised. It is hypothesized that comorbid DM occurs more frequently than expected in a cohort of adult RRP patients and that RRP patients with DM have more severe disease than those without DM.Retrospective cohort study.Tertiary care laryngology practice, 5-year period.Adult-onset RRP patients from 2007 to 2012 at the University of Washington were reviewed. The gender, age of onset of RRP, number of interventions, pathology, presence or absence of DM, and calculated anatomic Derkay severity score were recorded.Eighty-four adult RRP patients were characterized; 64 male (76%) and 20 female (24%). Six of 84 patients (7.1%) had DM; this prevalence was not higher than an age-matched general population. The number of interventions required for disease control did not significantly differ (P = .13) between adult RRP patients with DM (avg 2.6/yr, median 2.3/year) and those without DM (avg 1.9/yr, median 1.3/yr). There was no significant difference in anatomic Derkay score at the time of intervention (P = .26) or presence of dysplasia in biopsy specimens (P = .49) between RRP patients with and without DM.In this large series of adult RRP patients, DM does not appear to have a higher prevalence than that seen in age-matched controls, nor do RRP patients with DM appear to have more severe disease.

Acne is a common skin condition with sebum overproduction, hyperkeratosis, Propionibacterium acnes (P. acnes) and Staphylococcus aureus, and inflammation. Punica granatum (pomegranate) is well-known for its anti-inflammatory effects; however, few studies have discussed the anti-acne effects of pomegranate. In this study, we found that pomegranate extract (PG-E) significantly reduced P. acnes-induced edema in Wistar rat ears. Therefore, an evaluation platform using multiple pathogenic mechanisms of acne was established to explore the anti-acne effects of pomegranate. Results showed that PG-E inhibited bacterial growth and lipase activity. Through a bioguided-fractionation-isolation system, four hydrolysable tannins, punicalagin (1), punicalin (2), strictinin A (3), and granatin B (4), were isolated. Compounds 1 and 2 had greater anti-bacterial activities and anti-testosterone-induced HaCaT proliferative effects than the others. Compounds 1, 3, and 4 displayed lipase inhibitory effects. Compound 4 decreased cyclooxygenase-2 expression and downregulated prostaglandin E2 production in heat-killed P. acnes-treated RAW 246.7 cells. In conclusion, PG-E is abundant in hydrolysable tannins that display multiple anti-acne capacities, including anti-bacterial, anti-lipase, anti-keratinocyte proliferation, and anti-inflammatory actions. Hence, PG-E has great potential in the application of anti-acne and skin-care products, and punicalagin (1), the most effective component in PG-E, can be employed as a quality control marker.

Guan-Cheng Huang,1–3 Shih-Yu Chen,4 Po-Wei Tsai,5 Jerome G Ganzon,5 Chia-Jung Lee,6 Her-Shyong Shiah,7 Ching-Chiung Wang4,5 1School of Medicine, College of Medicine, Taipei Medical University, Taipei, 2Division of Hematology and Oncology, Department of Internal Medicine, Yuan’s General Hospital, 3Department of Leisure and Recreation Industry Management, College of Humanities and Management, Fooyin University, Kaohsiung, 4Graduate Institute of Pharmacognosy, College of Pharmacy, 5School of Pharmacy, College of Pharmacy, 6PhD Program for Clinical Drug Discovery of Chinese Herbal Medicine, College of Pharmacy, Taipei Medical University, 7Division of Hematology and Oncology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan Abstract: Dang-Gui-Bu-Xue-Tang (DBT), a combination of Angelicae Sinensis Radix and Astragali Radix, is a widely used herbal decoction in traditional Chinese medicine primarily to promote or invigorate the “blood”. In this study, we explored this ancient formulation and provide evidence of its blood-toning properties. We used the improvement iron uptake as promote or invigorate the “blood” indicator. Ferritin formation of Caco-2 cells in vitro assay and diet-induced anemia (DIA) in rat model were used to prove its improvement iron uptake and ameliorating effects. Finally, the iron–DBT interactions were measured by iron-bind­ing assay. We first demonstrated DBT increased uptake of ferrous iron through the biosynthesis of ferritin by Caco-2 cells and determined which complementary treatment would provide optimum results. Thereafter, effects of the treatment on improving the bioavailability of absorbed iron in the form of hemoglobin (Hb) were established using a DIA-animal model. The results showed that DBT slightly improved Hb levels compared with the baseline Hb and pretreatment with DBT for 2 hours prior to supplementation with ferrous sulfate provided the greatest gain in Hb levels in DIA rats. However, DBT and ferrous sulfate were co-treated with Caco-2 cell or DIA rats, the ferritin formation and Hb levels both were decreased. In iron-bind­ing assay, the DBT extract influenced the free Fe(II) type in the FeSO4 solution. Therefore, we suggest that complementary treatment with DBT and iron supplementation can have a strong ameliorating effect on iron-deficiency anemia in clinical settings, but needs a 2-hour interval of DBT administration prior to ferrous sulfate treatment. Keywords: Dang-Gui-Bu-Xue-Tang, ferulic acid, iron uptake, ferritin, iron-deficiency anemia, herb–drug interaction

Cantharidin, an active component in mylabris, is used in traditional Chinese medicine (TCM) to treat scabies and hepatoma, but accompanied by hemorrhagic cystitis. Evidence shows that cantharidin induces human bladder carcinoma cell death through COX-2 overexpression in vitro. In TCM, Scutellaria baicalensis is usually used to cure mylabris-induced hematuria. This work was undertaken to determine the mechanisms of cantharidin-induced rat hemorrhagic cystitis and explore the uroprotective effect of S. baicalensis. In vitro results showed cantharidin could induce cytotoxicity through prostaglandin (PG)E2 overproduction of T24 cells. Boiling-water extract of S. baicalensis (SB-WE) could significantly inhibit PGE2 production and COX-2 expression in lipo-polysaccharide-induced RAW 264.7 cells, indicating obvious anti-inflammatory abilities. In vivo results indicated that cantharidin caused rat hemorrhagic cystitis with hematuria via c-Fos and COX-2 overexpression. SB-WE was given orally to cantharidin-treated rats, whereby hematuria level, elevated PGE2 and COX-2 protein overexpression were significantly and dose-dependently inhibited by SB-WE. The anti-inflammatory components of SB-WE are baicalin and wogonin, whose contents were 200.95 ± 2.00 and 31.93 ± 0.26 μg/mg, respectively. In conclusion, cantharidin induces rat cystitis through c-Fos and COX-2 over-expression and S. baicalensis can prevent the resulting hematuria because of its anti-inflammatory effects.

Aim of the study This study examined the modulating effects of Clematis chinensis Osbeck (Ranunculaeae) on pro-inflammatory and degradative mediators associated with inflammatory arthritis. Materials and methods Primary human chondrocytes (PHC) were stimulated with IL-1β or lipopolysaccharide (LPS) to induce the enhanced release of prostaglandin E 2 (PGE 2 ), metalloproteinase (MMP-3 and -13), and cyclooxygenase-2 (COX-2) protein expression. The 18 F-FDG microPET imaging system was used to evaluate the anti-arthritic effects of Clematis chinensis in vivo . Results The acetone extracted Clematis chinensis (CC6) contained the most total saponins compared to other solvent's extracts and showed significant and dose-dependent inhibitory effects on PGE 2 , MMP-3, -13, and COX-2 productions by LPS-stimulated PHC. Furthermore, CC6 also exerted inhibitory effects on 2- 18 F-fluoro-2-deoxy- d -glucose ( 18 F-FDG) uptake when assessed by positron emission tomography (PET) uptake in the joints and serum PGE 2 of rabbits with knee joints injected with LPS. Conclusion The results suggest the significant chondroprotective effects of Clematis chinensis are through its anti-inflammatory and MMPs inhibitory abilities. Meanwhile, we established a new analysis method to evaluate the Chinese herbal anti-arthritic effects.

Killian-Jamieson diverticulum (KJD) is a rare cervical esophageal abnormality. Transcervical approach has been the main treatment modality to prevent recurrent laryngeal nerve (RLN) injury. We presented two cases of patients confirmed with KJD and were managed successfully under rigid endoscope. The new technique and idea were described in detail. Under rigid laryngoscope, the septum between the true esophagus lumen and diverticulum can be exposed clearly. A microscope equipped with CO2 LASER system offered precise and focused point cutting energy to the septum. Several efforts were applied to prevent RLN injury in the cases descriptions. We use transnasal esophagoscope and eating assessment tool (EAT-10) for anatomic and functional result evaluation. Much improved symptoms of dysphagia and intact RLN function were observed. Under the assist of rigid laryngoscope and point-cutting CO2 LASER, KJD diverticulotomy could be performed safely with little complication for patients refusing transcervical route.

Objective.Kawasaki disease (KD) is an acute febrile vasculitic syndrome in children. CD40 ligand (CD40L) has been implicated in certain types of vasculitis. We proposed that CD40L expression might be correlated with coronary artery lesions in KD.Methods.Blood samples were collected from 43 patients with KD before intravenous immunoglobulin (IVIG) treatment and 3 days afterward. Forty-three age-matched febrile children with various diseases were studied in parallel as controls. CD40L expression on T-cells and platelets were detected by flow cytometry, and soluble CD40L (sCD40L) levels were measured by enzyme-linked immunosorbent assay.Results.We found that CD40L expression on CD4+ T-cells was significantly higher in patients with KD than in the febrile control (FC) group (28.69 ± 1.17% vs 4.37 ± 0.36%). CD40L expression decreased significantly 3 days after IVIG administration (28.69 ± 1.17% vs 13.53 ± 0.55%). CD40L expression on platelets from patients with KD was also significantly higher than in the FC group (8.20 ± 0.41% vs 1.26 ± 0.12%) and decreased after IVIG therapy. sCD40L levels were also significantly higher in KD patients with those of FC (9.69 ± 0.45 ng/mL vs 2.25 ± 0.19 ng/mL) but were not affected by IVIG treatment 3 days afterward (9.69 ± 0.45 ng/mL vs 9.03 ± 0.32 ng/mL). More interesting, we found that in KD patients, CD40L expression on CD4+ T-cells and platelets but not on CD8+ T-cells or sCD40L was correlated with the occurrence of coronary artery lesions.Conclusions.CD40L might play a role in the immunopathogenesis of KD. IVIG therapy might downregulate CD40L expression, resulting in decrease of CD40L-mediated vascular damage in KD. This implicates that modulation of CD40L expression may benefit to treat KD vasculitis.

Objective: To assess nitric oxide (NO) production and different displays of NO synthase (NOS) isoforms in patients with Kawasaki disease (KD) before and after intravenous immunoglobulin (IVIG) treatment. Study design: Blood and urine samples were collected from patients with KD before IVIG treatment and 3 days afterward. Age-matched febrile patients with various diseases served as control patients. Plasma NOx (NO3- + NO2-) levels were measured as NO production. Real-time reverse transcriptase–polymerase chain reaction and immunohistochemical staining were used to detect differential NOS isoform expression in mononuclear leukocytes (MNCs). Results: Patients with KD (n = 40) had higher levels of NOx than the non-KD febrile control patients. The elevated NOx levels in patients with KD were significantly associated with the occurrence of coronary artery dilation (>3 mm). These elevated NOx levels significantly decreased after IVIG treatment (157.8 ± 15.9 μmol/L vs 57.0 ± 4.27 μmol/L, P

Purpose To compare post-operative complication rates between inpatient and outpatient endoscopic airway surgery in patients with laryngotracheal stenosis. Secondary objectives included characterization of a cohort of patients with this disease. Methods Retrospective review of patients with laryngotracheal stenosis in a tertiary care laryngology practice over a 5-year period. Results Ninety-one patients underwent 223 endoscopic airway surgeries. Of 114 outpatient interventions, 1 patient (0.8%) sought emergent medical care following discharge for respiratory distress. Of 109 procedures resulting in admission, no patients required transfer to a higher level of care, endotracheal intubation or placement of a surgical airway. There was no statistically significant difference in complication rates between patients treated as outpatients or inpatients (p = 0.33, chi square). There were no cardiopulmonary events. There were no pneumothoraces despite frequent use of jet ventilation. The most common etiologic category was idiopathic (58%), followed by granulomatosis with polyangiitis (16%) and history of tracheotomy (12%). Most patients with idiopathic disease were female (p Conclusion Patients undergoing endoscopic surgery for airway stenosis rarely have post-operative complications, and outpatient surgery appears to be a safe alternative to post-operative admission and observation.

Glaucoma is an irreversible ocular disease that may lead to progressive visual field loss and eventually to blindness with inadequately controlled intraocular pressure (IOP). Latanoprost is one of the most potent ocular hypotensive compounds, the current first-line therapy in glaucoma. However, the daily instillation required for efficacy and undesirable side-effects are major causes of treatment adherence failure and persistence in glaucoma therapy. In the present study, we developed an injectable thermosensitive chitosan/gelatin/glycerol phosphate (C/G/GP) hydrogel as a sustained-release system of latanoprost for glaucoma treatment. The latanoprost-loaded C/G/GP hydrogel can gel within 1min at 37°C. The results show a sustained release of latanoprost from C/G/GP hydrogel in vitro and in vivo. The latanoprost-loaded C/G/GP hydrogel showed a good in vitro and in vivo biocompatibility. A rabbit model of glaucoma was established by intravitreal injection of triamcinolone acetonide. After a single subconjunctival injection of latanoprost-loaded C/G/GP hydrogel, IOP was significantly decreased within 8days and then remained at a normal level. The results of the study suggest that latanoprost-loaded C/G/GP hydrogel may have a potential application in glaucoma therapy.

To examine the effects of a Chinese medical herb complex formula, Kuan-Sin-Yin (KSY) decoction, on hepatitis B virus (HBV) carriers.Of 86 HBV carriers, 57 who met the inclusion criteria completed this study from February 2011 to December 2011 in Taipei City Hospital, Taiwan. The participants were randomly assigned to one of two groups: the KSY group (n=29) and a control group (n=28) that received KSY diluted 16 times. The participants took one packet of decoction per day after dinner for 6 weeks. The major outcome measurements were the percentage reduction in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the log of the HBV DNA level. The other measurements included seroconversion of hepatitis B e antigen and responses to the World Health Organization Quality of Life-Brief Version (WHOQOL-BREF) and Short-Form-12. The measurements were collected before the first treatment and 6 weeks later.In the KSY group, AST and ALT levels decreased significantly and the score on the physical component of WHOQOL-BREF increased significantly. However, in the control group, there was no significant change after 6 weeks of treatment. Only the KSY group had a significant percentage reduction in ALT (change, -25.2% versus -0.74% in the control group) after 6 weeks of treatment. No major adverse effects occurred after 6 weeks of treatment.KSY significantly improved ALT levels. The study suggests that a longer-term study testing the efficacy of KSY in a larger sample is warranted.

Indomethacin is used as an anti-inflammatory drug and a nonselective cyclooxygenase inhibitor. When indomethacin in methanol was photo-irradiated with an Hg lamp, methyl ester, ethyl ester, and gamma-lactone derivatives of indomethacin were produced. In the present study, we found that the methyl ester derivative of indomethacin (M-IN) could more potently inhibit prostaglandin E(2) (PGE(2)) and nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX 2) protein expression from lipopolysaccharide (LPS)-stimulated RAW 264.7 cells than indomethacin, similar to the effect of a non-steroidal anti-inflammatory drugs (NSAID). On the other hand, the results showed that M-IN with an IC(50) value maintained at 36.9 microg/ml for 12 h exhibited stronger cytotoxicity than ethyl ester, gamma-lactone derivatives of indomethacin, and indomethacin in promyelocytic leukemia HL-60 cells. Moreover, a series of biochemical analyses determined that M-IN caused apoptotic bodies, DNA fragmentation, and enhanced PARP and pro-caspase 3 degradation in HL-60 cells. These above results indicate that the photosynthesized product, M-IN, had stronger anti-inflammatory effects in LPS-stimulated RAW 264.7 cells and cytotoxicity effects in HL-60 cells than the parent drug, indomethacin.

The aims of this trial were to compare the attendant complications and postoperative voiding function of the Monarc and suprapubic arc (Sparc) suburethral sling procedures. This is the first article in English literature to compare different suburethral sling procedures using prosthesis of the same material and the same weave. Sixty women with urodynamic stress incontinence alone or combined with pelvic prolapse less than International Continence Society stage II were randomly allocated to either the Monarc or Sparc group. A comparison of the peri- and postoperative results comprising complications and symptoms of voiding function revealed no significant differences between the two groups in a follow‐up ranged from 6 to 14 months (median, 9 months). However, the nonsignificant increase in tendency of inadvertent vaginal perforation and disability/pain of thigh (Monarc 12.9 vs Sparc 0.0%, p=0.112 and Monarc 12.9 vs Sparc 0.0%, p=0.112, respectively) has clinical significance. Based on the analyses of the comparison of Blaivas obstruction nomograms, postoperative voiding function was not significantly different between the two surgical groups. We concluded that Monarc and Sparc suburethral taping proved to be equally safe and posed no remarkable impact on voiding function in a short term postoperative follow up. However, intraoperative urethrocystoscopy is recommended for safety in both the Monarc and Sparc procedures.

Triflamp, a metalloproteinase isolated from Trimeresurus flavo-viridis, inhibits heterotypic adhesion between platelets and neutrophils. Coincubation studies demonstrate that direct interaction of triflamp with neutrophils is sufficient to inhibit the formation of neutrophil-platelet complexes. Its anti-adhesive effect is in a concentration- and incubation time-dependent manner. Triflamp reduces the expression of P-selectin glycoprotein ligand-1 (PSGL-1) on neutrophils and glycoprotein (GP) Ibalpha on platelets as probed by flow cytometry and Western blot. Moreover, triflamp disrupts P-selectin-mediated adhesion by cleaving PSGL-1 from the neutrophil surface. There are obvious differences regarding PSGL-1 proteolysis by triflamp and cathepsin G. Besides the NH2-terminus of PSGL-1, other sites are truncated by triflamp. The inhibitory effect of triflamp on PSGL-1 expression was prevented by pretreatment with a metalloproteinase inhibitor, phenanthroline. However, triflamp-treated platelets fully keep the ability for binding to PAF- or fMLP-stimulated neutrophils. Our results indicate that degradation of platelet GPIb alpha by triflamp does not interfere with neutrophil-platelet adhesion. Its effect on neutrophil PSGL-1 appears to be a critical factor for its inhibition on neutrophil-platelet interaction.

SummaryThe biologically active components fromViperidae venoms specifically affect cell-matrix interactions, and have been utilized for developing anti-adhesive therapy as anti-thrombotic and antiangiogenic agents. Utilizing platelet aggregometry coupled with flow cytometry, we found that a metalloproteinase isolated from Trimeresurus flavoviridis, termed triflamp, inhibited heterotypic adhesion between platelets and neutrophils in whole blood samples. Triflamp is a monomeric glycoprotein with a molecular weight of ∼28 kDa. Triflamp has a N-terminal amino acid sequence homologous to other venom metalloproteinases isolated from T. flavoviridis. The enzymatic activity of triflamp was inhibited by EDTA and phenanthroline but not by PMSF. Moreover, triflamp is a pure α-fibrinogenase. Studies aimed at determining the nature of triflamp in affecting platelets or neutrophils revealed a selective inhibitory activity to glycoprotein (GP) Ibα.-dependent platelet aggregation and PSGL-1-dependent neutrophil homotypic aggregation, indicating that its effects are rather specific. As judged by Western blotting, GPIbα. on platelets and PSGL-1 on neutrophils are the substrates of triflamp. In conclusion, we suggest the novel role of venom metalloproteinase from Viperidae affecting the blood cell-cell interactions, thus offering a potential approach for further exploration of anti-inflammatory agents.

A 1-month-old baby girl, weighted 3100 g, was noted to have Grade III/VI continuous murmur 1 day after birth. Echocardiogram revealed a large coronary fistula from the right coronary artery to the right ventricle (RV) with large aneurysmal dilatation of RV ( Panels A – C , black arrows; …