Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 576
Filtrar
1.
J Mol Neurosci ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31925706

RESUMO

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease that preferentially affects central nerve system. Herein, we evaluated changes of CD40L and CD40 mRNA expressions in NMOSD and controls to explore their potential roles in development of NMOSD. The expressions of CD40L and CD40 mRNA in peripheral blood mononuclear cells (PBMCs) from patients with NMOSD and healthy controls were detected by quantitative real-time PCR (qPCR). Kruskal-Wallis tests were used to compare expression levels of CD40L and CD40 mRNA between groups, and Spearman correlation analysis was performed to evaluate correlation between mRNA expression levels and annual relapse rate (ARR) of NMOSD. A total of 71 patients with NMOSD and 42 gender- and age-matched healthy volunteers were recruited in our study. Compared with healthy controls, expression of CD40L mRNA was significantly decreased in untreated patients with NMOSD, and similar trends were observed also in CD40 mRNA expression although the difference was not significant. Other than that, immunosuppressants not only successfully increased CD40L and CD40 mRNA levels during remission of NMOSD, but also corrected the negative correlation between CD40L mRNA expression and annual relapse rate (ARR) of patients NMOSD. These results favored the long-term prognosis of NMOSD patients. Our results suggest that decreased expressions of CD40L mRNA may be involved in developing of NMOSD and the proper CD40L mRNA levels benefit to prevent attacks of NMOSD. Nevertheless, the relationship between protein and mRNA expressions of CD40L and their underlying roles in the pathogenesis of NMOSD remains to be further studied.

2.
J Investig Med ; 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31941664

RESUMO

This study aimed to explore the protective potential of influenza vaccination against occurrence of dementia in patients with chronic obstructive pulmonary disease (COPD), who are expected to be more vulnerable to influenza infection. This nationwide retrospective cohort study enrolled patients with COPD (aged ≥60 years) from 1 January 2001 to 31 December 2012 by using the Taiwan National Health Insurance Research Database. By applying time-dependent Cox proportional hazard model, we used multivariate analysis to calculate the adjusted HR (aHR) with 95% CI of dementia in relation to influenza vaccination among patients with COPD. Besides, patients were partitioned into four groups according to the vaccination number (unvaccinated, 1, 2-3 and ≥4 total vaccinations) to investigate the dose-response effect of vaccinations on the dementia incidence. This cohort study included 19 848 patients with COPD, and 45% of them received influenza vaccination. The aHR of dementia was 0.68 (95% CI: 0.62 to 0.74, p<0.001) comparing vaccinated patients with unvaccinated ones. Furthermore, there was a trend of dementia risk reduction with the vaccination number. For patients who received 2-3 vaccinations, the aHR was 0.81 (95% CI: 0.73 to 0.90), and for those received 4 vaccinations, the aHR was 0.44 (95% CI: 0.40 to 0.50), with p for trend <0.001. In conclusion, annual influenza vaccination can reduce the risk of dementia in patient with COPD in a dose-dependent manner.

3.
Int J Cardiol ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31955975

RESUMO

Some cohort studies showed the possibility of renin-angiotensin-aldosterone system (RAAS) blockade in preventing future osteoporotic fractures. The study aimed to evaluate the association between angiotensin converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), and future osteoporotic fracture in a hypertensive population. We queried the Taiwan Longitudinal Health Insurance Database between 2001 and 2012. We used propensity score matching and the total cohort was made up of 57,470 participants (28,735 matched-pairs using or not using RAAS blockers). The mean follow-up period was 6 years. The number of incident fractures was 3757. Hazard ratios (HRs) [95% confidence interval (CI)] of ACEIs and ARBs use with incident fractures were calculated. The incidence of future osteoporotic fracture was significantly lower in the ACEI and ARB user groups but not in the group using an ACEI plus ARB concomitantly, when compared with RAAS blocker nonusers. Comparing ACEI users with RAAS blocker non-users and ARB users with RAAS blocker non-users, the HRs for composite fractures were 0.70 (0.62-0.79) and 0.58 (0.51-0.65), respectively. Sensitivity analysis confirmed a lower incidence of future osteoporotic fracture in patients taking an ACEI for >55 cumulative defined daily doses (cDDDs) and those who received an ARB for >90 cDDDs. These results suggested a lower incidence of future osteoporotic fracture in a hypertensive population who were using an ACEI or ARB compared with RAAS blocker nonusers but not in the group taking an ACEI and ARB concomitantly.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31893997

RESUMO

BACKGROUND: The Hepatocyte Growth Factor Receptor (HGFR) c-Met is over-expressed and/or mutated in various human tumor types. Dysregulation of c-Met/HGF signaling pathway affects cell proliferation, survival and motility, leading to tumor growth, angiogenesis, and metastasis. Therefore, c-Met has become an attractive target for cancer therapy. OBJECTIVE: This study is aimed to evaluate a new series of 4-phenoxypyridine derivatives containing semicarbazones moiety for its cytotoxicity. METHODS: A series of novel 4-phenoxypyridines containing semicarbazone moieties were synthesized and evaluated for their in vitro cytotoxic activities against MKN45 and A549 cancer cell lines and some selected compounds were further examined for their inhibitory activity against c-Met kinase. In order to evaluate the mechanism of cytotoxic activity of compound 24, cell cycle analysis, Annexin V/PI staining assay, AO/EB assay, wound-healing assay and docking analysis with c-Met were performed. RESULTS: The results indicated that most of the compounds showed moderate to good antitumor activity. The compound 28 showed well cytotoxic activity against MKN45 and A549 cell lines with IC50 values of 0.25µM and 0.67µM, respectively. Compound 24 showed good activity on c-Met and its IC50 value was 0.093µM. CONCLUSION: Their preliminary structure-activity relationships (SARs) studies indicated that electron-withdrawing groups on the terminal phenyl rings are beneficial for improving the antitumor activity. Treatments of MKN45 cells with compound 24 resulted in cell cycle arrest in G2/M phase and induced apoptosis in a dose-dependent manner. In addition, AO/EB assays indicated 24 induced dose-dependent apoptosis of A549 and MKN45 cells. Wound-healing assay results indicated that compound 24 strongly inhibited A549 cell motility.

5.
Food Chem ; 311: 125966, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31862567

RESUMO

A hapten of sulfabenzamide was first synthesized to generate a monoclonal antibody that simultaneously recognized 32 sulfonamides. The computational simulation showed that the 3D conformation, molecular bend angle, molecular volume, electronic charge of core structure of these drugs all showed influences on the antibody binding. The antibody was combined with a heterologous enzyme-labeled hapten to develop a direct competitive chemiluminescence enzyme linked immunosorbent assay for determination of the 32 sulfonamides in chicken muscle sample. The CRs of the optimized method for these drugs were in the range of 7.3%-1778%, and the IC50 values were in the range of 0.038-11.2 ng/g. The limits of detection for detection of these drugs in chicken were in the range of 0.03-26 ng/g. Their recoveries from the standards fortified blank chicken samples were in the range of 60.8%-97.1%. Therefore, this method could be used as a useful tool for routine screening sulfonamides residues in meat.

6.
Life Sci ; 242: 117221, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31881224

RESUMO

AIMS: Endothelial cell (EC) tube formation is crucial for tumor angiogenesis, which becomes a target for chemotherapy. The anti-malaria agent dihydroartemisinin (DHA) inhibited tumor growth and angiogenesis. The aim of this study was to investigate the effects of DHA on EC tube formation and the underlying mechanisms. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured with different concentrations of DHA, and the tube formation was measured by in vitro angiogenesis assay. The protein levels of signal transducer and activator of transcription factor 3 (STAT3), phosphorylated STAT3 and fatty acid synthase (FASN) were detected by Western blotting. The gene expression of FASN was determined by real time-polymerase chain reaction (RT-PCR). The FASN siRNA and STAT3 (Y705D) vector were introduced into HUVECs by lipofectin transfection. KEY FINDINGS: DHA treatment inhibited tube formation, and the phosphorylation of STAT3 on Y705 of HUVECs. The expression of FASN was down-regulated by DHA and STAT3 inhibitor. The inhibitory effect of DHA on FASN expression in HUVECs was eliminated by co-treatment with the STAT3 inhibitor. Over-expression of STAT3 (Y705D) relieved the inhibitory effect of DHA on tube-formation and FASN expression. Under hypoxia condition, expression of FASN was up-regulated but inhibited by DHA treatment in HUVECs through suppression of STAT3 phosphorylation. SIGNIFICANCE: We demonstrate that DHA inhibits the protein level of FASN via attenuation of the Y705 phosphorylation of STAT3, and subsequently inhibits tube formation of HUVECs. Our results support the therapeutic potential of DHA on angiogenesis.

7.
Nanoscale ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31799577

RESUMO

Tumor-associated macrophages (TAMs) are the most important components in the tumor immunosuppressive microenvironment, promoting tumor growth and metastasis. Although TAMs have become one of the hot topics of tumor immunotherapy, challenges still remain to achieve TAM-targeted re-polarization therapy. In this work, porous hollow iron oxide nanoparticles (PHNPs) were synthesized for loading a P13K γ small molecule inhibitor (3-methyladenine, 3-MA) and further modified by mannose to target TAMs. The delivery system named PHNPs@DPA-S-S-BSA-MA@3-MA showed good efficiency for targeting TAMs. The inflammatory factor NF-κB p65 of macrophages was activated by the combination of PHNPs and 3-MA, which synergistically switched TAMs to pro-inflammatory M1-type macrophages. As a result, it activated immune responses and inhibited tumor growth in vivo. The study provides an intracellular switch of the TAM phenotype for targeted TAM therapy.

8.
Oncol Lett ; 18(6): 6443-6450, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31807167

RESUMO

Desmoid tumors (DTs), derived from the abdomen, are a type of rare and aggressive borderline tumor exhibiting high recurrence and malignant potential. The aim of the present study was to investigate the clinicopathological and molecular characteristics of abdominal DT in a Chinese population and to provide clues for selecting the optimal treatment strategy for different types of abdominal DT. The clinicopathological data of 15 consecutive patients with DT was collected. Matched fresh-frozen tumor tissues and peripheral blood samples were used to detect mutations of adenomatous polyposis coli gene (APC), ß-catenin (CTNNB1) and MutY DNA glycosylase (MUTYH) using Sanger sequencing. Pearson's test was conducted to analyze the differences between sporadic DT and familial adenomatous polyposis (FAP) associated with DT. Time to progress (TTP) and overall survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. A review of the patient clinicopathological characteristics revealed that FAP-associated DT exhibited a higher rate of abdominal surgery history (P=0.011), with no significant differences in any other characteristics. Sequencing revealed that mutations in the APC, CTNNB1 and MUTYH genes were common in DT, and only one patient harbored no mutations in these genes. Survival analyses revealed that patients with FAP exhibited shorter TTP (P=0.030). Log-rank test demonstrated a tendency towards shorter TTP in the cases where an R2 resection was performed (P=0.072) and a tendency towards poor prognosis in the cases of DT associated with FAP (P=0.087). In conclusion, Abdominal DTs were prone to occur in patients with FAP with a history of abdominal surgery. Mutations in the APC, CTNNB1 and MUTYH genes were detected in patients with DTs. To the best of our knowledge, this is the first study of abdominal DT occurrence in patients with MUTYH-associated FAP. The prognosis of DT associated with FAP may be worse compared with that of sporadic DT.

9.
Bioanalysis ; 11(21): 1955-1965, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31829055

RESUMO

Aim: A novel single-stranded deaminated oligonucleotide metabolite resulting from a REVERSIR™ oligonucleotide was discovered and identified in monkey liver after subcutaneous administration. Results & methodology: REVERSIR-A and its metabolites were extracted from biological matrices by solid phase extraction and analyzed using LC coupled with high-resolution MS under negative ionization mode. A novel 9-mer metabolite of REVERSIR-A, resulting from deamination of the 3' terminal 2'-O-methyl-adenosine nucleotide to 2'-O-methyl-inosine, was discovered at significant levels in monkey liver. The metabolite's identity was confirmed by LC-MS/MS. Conclusion: This report describes the first observation of a long-chain deaminated metabolite of a single-stranded REVERSIR oligonucleotide in vivo in monkey liver.

10.
Bioanalysis ; 11(21): 1967-1980, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31829056

RESUMO

Aim: Advancements in RNA interference therapeutics have triggered development of improved bioanalytical methods for oligonucleotide metabolite profiling and high-throughput quantification in biological matrices. Results & methodology: HPLC coupled with high-resolution mass spectrometry (LC-HRMS) methods were developed to investigate the metabolism of a REVERSIR™ molecule in vivo. Plasma and tissue samples were extracted using solid-phase extraction followed by LC-HRMS analysis for metabolite profiling and quantification. The method was qualified from 10 to 5000 ng/ml (plasma) and 100 to 50000 ng/g (liver and kidney). In rat liver, intra and interday accuracy ranged from 80.9 to 118.5% and 88.4 to 111.9%, respectively, with acceptable precision (<20% CV). Conclusion: The LC-HRMS method can be applied for metabolite profiling and quantification of oligonucleotides in biological matrices.

11.
Retina ; 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31860522

RESUMO

PURPOSE: To report the surgical outcomes of primary rhegmatogenous retinal detachment (RRD) repaired by 27-gauge pars plana vitrectomy combined with Healaflow patch and air tamponade. METHODS: In an initial vitro experiment, we observed and compared the dissolution and displacement of the dispersion spots of 0.05-mL Healaflow and sodium hyaluronate. We then performed a prospective, interventional cohort study on 38 eyes in 37 consecutive patients with primary rhegmatogenous retinal detachment. All eyes underwent pars plana vitrectomy combined with Healaflow patch and air tamponade; the postoperative period did not involve prone positioning. The primary and final anatomical attachment rate, best-corrected visual acuity, and intraoperative and postoperative complications were evaluated. RESULTS: In the in vitro experiment, the viscoelastic Healaflow remained adherent with no change in the size of the area; however, the control dissolved completely in the balance solution. The patient study included 16 women (43.2%) and 21 men (56.8%) (mean age, 59.5 ± 9.5 years; mean follow-up period, 8.9 ± 3.8 months). A single break was present in 21 (55.3%) and 2 to 5 breaks in 17 cases (44.8%). The macula was involved in 25 (65.8%) and attached in 13 cases (34.2%) intraoperatively. Initial reattachment was achieved in 37 (97.4%) and final reattachment in 38 cases (100%). In one case (2.6%), the macula redetached because of failure of the chorioretinal scar to develop around the treated break. Mean preoperative and postoperative best-corrected visual acuities were 1.02 ± 0.82 logarithm of the minimum angle of resolution (median Snellen acuity: 20/125, range: 20/20,000-20/20) and 0.23 ± 0.17 logarithm of the minimum angle of resolution (median Snellen acuity: 20/32, range: 20/100-20/20), respectively (P < 0.001). Intraocular pressure was elevated transiently in 28 eyes (73.7%). There were no other intraoperative complications or postoperative scleral incision leakage. CONCLUSION: A 27-gauge pars plana vitrectomy combined with Healaflow patch, and air tamponade results in a high reattachment rate in the treatment of rhegmatogenous retinal detachment. Thus, patients can benefit from early visual recovery and less complications.

12.
J Cancer ; 10(24): 6057-6064, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31762815

RESUMO

Aims: Dihydroartemisinin (DHA), a derivative of artemisinin, suppresses angiogenesis by regulating endothelial cell phenotypes. In this study, we investigated the effect of DHA on endothelial cell autophagy and the underlying mechanisms. Methods: Human umbilical vein endothelial cells (HUVECs) were treated with DHA. Formation of autophagosomes in HUVECs was observed by fluorescence microscope after pcDNA3.1-green fluorescent protein (GFP)-microtubule-associated protein 1 light chain 3 (LC3) plasmids transfection. Dichlorofluorescein diacetate (DCFH-DA) staining was used to detect intracellular reactive oxygen species (ROS). Western blot was performed to detect the protein levels of LC3, p62, beclin 1, autophagy-related protein (Atg) 5, p-Akt (protein kinase B), p-mTOR (mammalian target of rapamycin), p-4E-BP1 (eukaryotic translation initiation factor 4E-binding protein 1), and p-p70S6K (p70 ribosomal S6 kinase). Results: DHA increased LC3-II and the number of fluorescent GFP-LC3 puncta in HUVECs. Silencing ATG5 by siRNA interference attenuated DHA-induced LC3-II elevation. DHA enhanced ROS production, but pretreatment with antioxidant N-acety-l-cysteine (NAC) failed to reduce DHA-induced autophagy in HUVECs. Pretreatment with PD98059, SP600125 and SB203580, the inhibitors of ERK, JNK, and p38 MAPK, did not reverse autophagy in DHA-treated HUVECs. DHA significantly reduced phosphorylation of Akt, mTOR, p70S6K, 4E-BP1 in HUVECs. Rapamycin, an mTOR antagonist, compromised DHA-induced autophagy. Conclusion: DHA induces autophagy in HUVECs by inhibition of the Akt/mTOR pathway.

13.
Clin Sci (Lond) ; 133(21): 2171-2187, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31696218

RESUMO

Several diseases have been linked to particulate matter (PM) exposure. Outdoor activities, such as road running or jogging, are popular aerobic exercises due to few participatory limitations. Osteoarthritis (OA) is a progressive degenerative joint disease, usually observed at age 40, and not noticed before pain or diagnosis. Although exercise has health benefits, it is unclear whether outdoor jogging in higher PM (standard reference material 1649b, SRM 1649b) concentration environments could affect OA development or severity. Hence, a PM exposure monosodium iodoacetate (MIA)-induced OA animal jogged model was established for investigation. Results showed that high doses of PM (5 mg) significantly increased pro-inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, and IL-6, and M1 macrophages in the lung region, also obtained in systemic IL-6 and TNF-α expressions in this MIA-OA rat model. Moreover, levels of osteocalcin, cartilage oligomeric matrix protein (COMP), and N-telopeptides of type I collagen were especially influenced in MIA+PM groups. Morphological and structural changes of the knee joint were detected by micro-computed tomography images (micro-CT) and immunohistochemistry. MIA + PM rats exhibited severe bone density decrease, cartilage wear, and structure damages, accompanied by lower levels of physical activity, than the sham group and groups receiving MIA or PM alone. The findings suggest that the severity of OA could be promoted by PM exposure with a PM concentration effect via systemic inflammatory mechanisms. To the best of our knowledge, this is the first study to provide direct effects of PM exposure on OA severity.

14.
Medicine (Baltimore) ; 98(47): e18035, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764822

RESUMO

Chronic obstructive pulmonary disease (COPD) patients are at a higher risk of development of lung cancer. Frequent exacerbations of COPD trigger the disease course to chronic inflammation which likely plays a role in the pathogenesis of lung cancer. Previous studies showed influenza virus infection is one of important causes for exacerbations of COPD. Therefore, the aim of this study was to know whether influenza vaccination could reduce the incidence of lung cancer in patients with COPD.This cohort study enrolled patients (≥55 years old) with a recorded diagnosis of COPD between January 1, 2000 and December 31, 2012 by using the Taiwan Health Insurance Database. A propensity score was calculated to reduce vaccine therapy selection bias. Cox proportional hazard regressions were used to investigate the association between the influenza vaccination and lung cancer incidence after adjusting for known confounding factors. Besides, we categorized the patients into 4 groups according to vaccination status (unvaccinated, total number of vaccinations: 1, 2-3, ≥4) to evaluate the dose-dependent effect on reducing lung cancer occurrence of lung cancer in COPD patients.Our study comprised of 28,752 eligible individuals from the COPD cohort database. Among them, 51% (14,630) received influenza vaccination; the rest (49%) of the COPD patients did not receive influenza vaccination. We observed that COPD patients receiving influenza vaccination had a lower risk of lung cancer (adjusted HR = 0.40, 95% CI (0.35-0.45), P < .001). We also founded comparable protective effect in both sexes and all age groups (55-64, 65-74, ≥75) regardless of influenza seasonality. Furthermore, dose-dependent protective effect could be seen after stratifying patients according to the total number vaccinations, the adjusted HRs for lung cancer risk were 0.48 (0.40-0.54) and 0.24 (0.20-0.29) for patients who received 2 to 3 and ≥4 vaccinations during the follow-up period.This population-based cohort study demonstrated that annual influenza vaccination administration could reduce incidence of lung cancer in COPD patients.


Assuntos
Vacinas contra Influenza/uso terapêutico , Influenza Humana/complicações , Influenza Humana/prevenção & controle , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/prevenção & controle , Doença Pulmonar Obstrutiva Crônica/complicações , Idoso , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Esquemas de Imunização , Incidência , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade
15.
Clin Breast Cancer ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31669267

RESUMO

INTRODUCTION: We evaluated the current status of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) detection in invasive breast carcinoma (IBC) in various laboratories across China. MATERIALS AND METHODS: The Breast Pathology Study Group of the Chinese Society of Pathologists collected HR and HER2 data from 12,467 IBC cases from 19 representative clinical centers in China. The data from every center were compared with the pooled data from the other centers. RESULTS: The assessment of HR status showed that the overall positive estrogen receptor (ER) and progesterone receptor (PR) rates were 71.7% and 63.7% (range, 60.9%-87.9% and 43.9%-84.8%), respectively. The ER results in 3 centers and the PR results in 6 centers were outside the 99.5% confidence interval and were considered to be outliers (P < .0005). Of the 12,467 cases, 62.4% were ER+/PR+, 9.3% were ER+/PR-, 1.3% were ER-/PR+, and 27.0% were ER-/PR-. The assessment of HER2 status showed that the overall positive rate of HER2 (with a definition of immunohistochemistry [IHC] 3+ or IHC2+/ in situ hybridization-positive) was 24.7% (range, 13.7%-35.7%) in each center. Three centers were outside the 99.5% confidence interval and were considered to be outliers (P < .0005). The proportion of HER2 IHC3+ was 21.1%. The positive rates of HER2 gene amplification in IHC 0/1+, 2+, 3+ cases were 2.0%, 17.6%, and 85.9%, respectively. CONCLUSIONS: As the largest study of HR and HER2 status in Chinese patients with IBC, the data from the present study have indicated that the overall rates of HR and HER2 were comparable to those reported in previous studies. However, the rates varied among the laboratories. Individual centers had not met the target values, and they need to improve the detection.

16.
BMC Pediatr ; 19(1): 422, 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31707984

RESUMO

BACKGROUND: Splenogonadal fusion (SGF) is a rare congenital malformation that occurs during embryonic development. SGF typically presents as a left-sided scrotal swelling, left inguinal hernia, scrotal mass, or cryptorchidism. Therefore, it is easily misdiagnosed, and unnecessary orchiectomy may occur. This study aimed to report a rare case of SGF. CASE PRESENTATION: A 5-month-old male child presented with a history of obvious left scrotal swelling for 1 month, which progressively worsened 10 h before the hospital visit. The ultrasound examination exhibited a solid mass in the left scrotum, with echo quite similar to that in the testicle and went up into the abdominal cavity through an identical echogenic band structure. After surgical resection, the pathological examination confirmed that the submitted tissue was spleen tissue with extensive bleeding. CONCLUSION: Ultrasound can provide important information regarding the diagnosis of SGF. The possibility of SGF should be considered for further differential diagnosis in the case of similar patients.

17.
J Comput Phys ; 383: 72-93, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31595091

RESUMO

We develop a robust and efficient iterative method for hyper-elastodynamics based on a novel continuum formulation recently developed in [1]. The numerical scheme is constructed based on the variational multiscale formulation and the generalized-α method. Within the nonlinear solution procedure, a block factorization is performed for the consistent tangent matrix to decouple the kinematics from the balance laws. Within the linear solution procedure, another block factorization is performed to decouple the mass balance equation from the linear momentum balance equations. A nested block preconditioning technique is proposed to combine the Schur complement reduction approach with the fully coupled approach. This preconditioning technique, together with the Krylov subspace method, constitutes a novel iterative method for solving hyper-elastodynamics. We demonstrate the efficacy of the proposed preconditioning technique by comparing with the SIMPLE preconditioner and the one-level domain decomposition preconditioner. Two representative examples are studied: the compression of an isotropic hyperelastic cube and the tensile test of a fully-incompressible anisotropic hyperelastic arterial wall model. The robustness with respect to material properties and the parallel performance of the preconditioner are examined.

18.
Bioorg Med Chem Lett ; 29(23): 126666, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31629631

RESUMO

A series of novel 4-phenoxyquinoline derivatives containing 3-oxo-3,4-dihydro-quinoxaline moiety were synthesized and evaluated for their antiproliferative activity against five human cancer cell lines (A549, H460, HT-29, MKN-45 and U87MG) in vitro. Most of the tested compounds exhibited more potent inhibitory activities than the positive control foretinib. Compound 1b, 1s and 1t were further examined for their inhibitory activity against c-Met kinase. The most promising compound 1s (with c-Met IC50 value of 1.42 nM) showed remarkable cytotoxicity against A549, H460, HT-29, MKN45 and U87MG cell lines with IC50 values of 0.39 µM, 0.18 µM, 0.38 µM, 0.81 µM, respectively. Their preliminary structure-activity relationships (SARs) study indicated that the replacement of the aromatic ring with the cyclohexane improved their antiproliferative activity.

19.
Arch Pharm (Weinheim) ; 352(11): e1900129, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31478565

RESUMO

To gain further knowledge of the structure-activity relationship and druggability of novel oxazolidinone-based UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) inhibitors as Gram-negative antibacterial agents, compounds containing the hydrophobic tails with different lengths and terminal substitutions were synthesized and their antibacterial activities against standard and clinically isolated Gram-negative strains were evaluated. We summarized their structure-activity relationships and found that oxazolidinone-based compounds exhibited a narrower antibacterial spectrum compared with threonine-based compounds. Furthermore, we parallelly compared the metabolic stabilities of the compounds with the classic threonine scaffold and the novel oxazolidinone scaffold in liver microsomes. The results indicated that the druggability of the oxazolidinone scaffold may be inferior to the classic threonine scaffold in the design of LpxC inhibitors.

20.
BMJ Open ; 9(9): e029974, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481562

RESUMO

OBJECTIVE: To investigate anticoagulant adherence and its associated factors, including demographics, clinical variables, atrial fibrillation (AF) severity, knowledge, satisfaction with services, perceived barriers, perceived benefits, symptom severity and self-efficacy in patients with AF. DESIGN: This is a cross-sectional study. PARTICIPANTS AND SETTING: A convenient sample of patients with AF were recruited from cardiology clinics of two teaching hospitals in Taiwan. MEASURES: Data were collected using the study questionnaires, including the AF-related symptom subscale of the AF Severity Scale, the Knowledge of Warfarin Anticoagulation Treatment Scale, the Satisfaction Scale about Service and Warfarin Treatment, the perceived benefits subscale of the Beliefs about Anticoagulation Survey, the Concerns about Anticoagulation Therapy Scale, The Self-efficacy for Appropriate Medication Use Scale and the short-form Adherence to Refills and Medications Scale. RESULTS: A total of 151 patients with AF participated in the study; 53 treated with warfarin and 98 treated with novel oral anticoagulants (NOACs). The difference in adherence to warfarin (mean=8.6; SD=1.6) and NOACs (mean=8.9; SD=2.0) was statistically insignificant. Multiple linear regression analysis showed that perceived barriers (ß=0.18, p=0.017) and self-efficacy (ß=-0.48, p<0.001) were significant predictors of anticoagulation adherence. For every 1-unit increase in the perceived barriers, there will be a 0.18-unit increase in the adherence to anticoagulation therapy. For every 1-unit increase in the self-efficacy, there will be a 0.48-unit decrease in the adherence to anticoagulation therapy. Perceived barriers and self-efficacy collectively explained 34.0% of the variance in adherence to anticoagulation therapy (F(2,149)=38.11, p<0.001). CONCLUSION: We found no better adherence to NOACs compared with warfarin. Patients with greater self-efficacy and perceived fewer barriers showed better adherence to anticoagulation therapy.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA