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1.
Artigo em Inglês | MEDLINE | ID: mdl-32134107

RESUMO

OBJECTIVE: Gout is the most common inflammatory arthritis and the worldwide incidence is increasing. By revealing the metabolic alterations in serum and urine of gout patients, the first aim of our study was to discover novel molecular biomarkers allowing for early diagnosis. We also aimed to investigate the underlying pathogenic pathways. METHODS: Serum and urine samples from gout patients (n = 30) and age-matched healthy controls (n = 30) were analysed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to screen the differential metabolites and construct a diagnostic model. Next, the model was verified and optimized in the second validation cohort (n = 100). The pathways were illustrated to understand the underlying pathogenesis of gout. RESULTS: In general, serum metabolomics demonstrated a clearer distinction than urine metabolomics. In the discovery cohort, 40 differential serum metabolites were identified that could distinguish gout patients from healthy controls. Among them, eight serum metabolites were verified in the validation cohort. Through regression analysis, the final model consisted of three serum metabolites-pyroglutamic acid, 2-methylbutyryl carnitine and Phe-Phe-that presented optimal diagnostic power. The three proposed metabolites produced an area under the curve of 0.956 (95% CI 0.911, 1.000). Additionally, the proposed metabolic pathways were primarily involved in purine metabolism, branched-chain amino acids (BCAAs) metabolism, the tricarboxylic acid cycle, synthesis and degradation of ketone bodies, bile secretion and arachidonic acid metabolism. CONCLUSION: The metabolomics signatures could serve as an efficient tool for early diagnosis and provide novel insights into the pathogenesis of gout.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32193773

RESUMO

The article aimed to detect the early cardiac dysfunction in patients with systemic lupus erythematosus (SLE) and predict the relationships between the strain parameters and the disease activities. Three-dimensional speckle-tracking echocardiography was performed to measure left ventricular (LV) structures and global strains on 63 subjects (41 SLE patients with preserved EF and 22 healthy controls). The SLE disease activity was assessed using the SLE Disease Activity Index (SLEDAI), and all the SLE patients were further divided into two subgroups according to disease severity. SLEDAI scores 0-8 were defined as group A, 9-20 were defined as group B. Results indicated that all components of left ventricle global strain [global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS)] were significantly reduced in SLE patients. GLS, GRS, GCS had positive correlation with LVEF respectively (r = 0.619, 0.845, 0.91, absolute value, all P < 0.05). The E/e', LVEDVI, LVESVI, LVM, LVMI were increased in all SLE patients (all P < 0.05). In subgroups, GLS and GRS were decreased in group B. Multiple linear regressions analysis indicate that the SLEDAI score was a predictive factor for damage of GLS and GRS. These results indicate that myocardial damage and LV remodeling still occur in SLE patients even with normal EF. The severe disease activity followed with worsening myocardial injury. SLE disease activity might be a potential driver of LV damages.

3.
Analyst ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32124870

RESUMO

A methodology is presented for the determination of four pyrethroid (PYR) preservatives in wooden food contact materials (FCMs) using direct analysis in real time (DART) coupled with quadrupole-Orbitrap high-resolution mass spectrometry (Q-Orbitrap HRMS). The sampling mode and critical parameters of the DART-Q-Orbitrap HRMS protocol were systematically investigated. Good linearity was achieved for the four analytes with correlation coefficients all greater than 0.99. The limits of detection (LODs) and limits of quantitation (LOQs) of the method were in the range of 0.04-0.20 mg kg-1 and 0.10-0.50 mg kg-1, respectively. The mean recoveries ranged from 72.1% to 82.7% with relative standard deviations (RSDs) from 5.2% to 11.8% at three spiked levels. The developed method was proved to be suitable for rapid screening of PYRs in complex wooden FCM samples to ensure product safety and consumer health.

4.
Int J Rheum Dis ; 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32107856

RESUMO

AIM: Genetic factors are believed to be implicated in the pathogenesis of relapsing polychondritis (RP). However, the molecular genetic determinants remain to be elucidated. This study aimed to detect the susceptibility genes of RP with whole-exome sequencing (WES) in a Chinese family and deepen our understanding of the pathogenesis of RP thereafter. METHOD: A 32-year-old Chinese female proband with RP and her family including her mother with RP were enrolled in the study. The genomic DNA of 6 human subjects was extracted from peripheral blood and then gene allele mutations were identified using WES. Candidate variants with low frequency (<0.1%) in the general population and predicted deleterious effects on gene function were identified. Sanger sequencing was applied subsequently to confirm the analyzed gene variants in 12 human blood samples. RESULTS: Nine single nucleotide polymorphism variants from different genes were identified to associate with RP by WES and further confirmed by Sanger sequencing, including Ring finger protein 207 (RNF207), collagen type XXII alpha 1 chain (COL22A1) rs200464636, glycosylphosphatidylinositol anchor attachment 1 (GPAA1) rs201424010, recQ like helicase 4 (RECQL4) rs757703895, folliculin (FLCN) NM_144606: c.G838A: p.E280K, DNA ligase 3 (LIG3) rs761808558, NM_207396: c.T425C:p.I142T, myosin heavy chain 15 (MYH15) NM_014981: c.G4462A: p.A1488T, purkinje cell protein 2 (PCP2) rs144974437 and coiled-coil domain containing 61 (CCDC61) rs777816675. CONCLUSIONS: This study suggests that coinheritance of multigene mutation may contribute to RP predisposition. The candidate genes mutated which we discovered are potential targets for in-depth functional studies.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31944535

RESUMO

The incidence of melanoma is rising globally including China. Comparing to Caucasians, the incidence of non-cutaneous melanomas is significantly higher in Chinese. Herein, we performed genomic profiling of 89 Chinese surgically resected primary melanomas, including acral (n = 54), cutaneous (n = 22), and mucosal (n = 13), by hybrid capture-based next-generation sequencing. We show that mucosal melanomas tended to harbor more pathogenic mutations than other types of melanoma, though the biological significance of this finding remains uncertain. Chromosomal arm-level alterations including 6q, 9p, and 10p/q loss were highly recurrent in all subtypes, but mucosal melanoma was significantly associated with increased genomic instability. Importantly, 7p gain significantly correlated with unfavorable clinical outcomes in non-cutaneous melanomas, representing an intriguing prognostic biomarker of those subtypes. Furthermore, focal amplification of 4q12 (KIT, KDR, and PDGFRα) and RAD51 deletion were more abundant in mucosal melanoma, while NOTCH2 amplification was enriched in acral melanoma. Additionally, cutaneous melanomas had higher mutation load than acral melanomas, while mucosal melanomas did not differ from other subtypes in mutation burden. Together, our data revealed important features of acral and mucosal melanomas in Chinese including distinctive driver mutation pattern and increased genomic instability. These findings highlight the possibilities of combination therapies in the clinical management of melanoma.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31985411

RESUMO

Breast cancer is one of the most frequently diagnosed solid cancers. Mammography is the most commonly used screening technology for detecting breast cancer. Traditional machine learning methods of mammographic image classification or segmentation using manual features require a great quantity of manual segmentation annotation data to train the model and test the results. But manual labeling is expensive, time-consuming, and laborious, and greatly increases the cost of system construction. To reduce this cost and the workload of radiologists, an end-to-end full-image mammogram classification method based on deep neural networks was proposed for classifier building, which can be constructed without bounding boxes or mask ground truth label of training data. The only label required in this method is the classification of mammographic images, which can be relatively easy to collect from diagnostic reports. Because breast lesions usually take up a fraction of the total area visualized in the mammographic image, we propose different pooling structures for convolutional neural networks(CNNs) instead of the common pooling methods, which divide the image into regions and select the few with high probability of malignancy as the representation of the whole mammographic image. The proposed pooling structures can be applied on most CNN-based models, which may greatly improve the models' performance on mammographic image data with the same input. Experimental results on the publicly available INbreast dataset and CBIS dataset indicate that the proposed pooling structures perform satisfactorily on mammographic image data compared with previous state-of-the-art mammographic image classifiers and detection algorithm using segmentation annotations.

7.
Echocardiography ; 37(1): 104-113, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31981242

RESUMO

OBJECTIVES: To identify the risk factors causing misdiagnosis by echocardiography and missed diagnosis of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). MATERIALS AND METHODS: Echocardiographic results of 16 patients with ALCAPA confirmed by surgery in Union Hospital, Wuhan, were analyzed retrospectively. The influencing factors leading to echocardiographic misdiagnosis were analyzed from the aspects of confusing image characteristics, special pathological anatomy of the left coronary artery (LCA), and operators' working years. RESULTS: Echocardiography diagnosed 11 cases with an accuracy rate of 68.8%. Five cases were misdiagnosed, three cases as endocardial fibroelastosis, one case as mitral prolapse with severe insufficiency, and one case as coronary-pulmonary artery fistula. Display rate of the specific echocardiographic features for confirmed group and misdiagnosed group was statistically significantly different(P = .014). But the working years of the operator for confirmed group and misdiagnosed group were not statistically significantly different(P = .267). Some special pathological anatomy and pathophysiological features could be also the cause of misdiagnosis. CONCLUSIONS: Echocardiography is the first diagnostic choice of the ALCAPA in China. It is essential for the operator to have the knowledge, diagnostic awareness, and proficiency in manipulation in the accurate interpretation of echocardiography results.

8.
Medicine (Baltimore) ; 99(2): e18550, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914031

RESUMO

BACKGROUND: Adjuvant endocrine therapy is a vital portion of postoperative comprehensive treatment for breast cancer patients. In recent years, studies have shown that endocrine therapy has a certain impact on the serum lipids of breast cancer patients, and the changes of lipid profiles may bring a series of problems. However, very few studies focus on this issue to date. The results of these studies are inconsistent, and the influence of different adjuvant endocrine modalities on lipid profiles still remains controversial. In order to better explore this issue, we conduct this network meta-analysis. METHOD: The protocol followed preferred reporting items for systematic reviews and meta-analyses protocols. Three main databases (PubMed, Embase, and the Cochrane Library) will be searched systematically for eligible randomized controlled trials without language restriction. In addition, a manual search of the references of relevant published studies will also be considered. Two reviewers will conduct studies selection, data extraction, and risk of bias assessment independently. The primary outcome is the variation of biochemical parameters - the serum lipid profiles (cholesterol, triglyceride, high-density lipoprotein, low low-density lipoprotein). RESULTS: The results will provide useful information about the side effects of different adjuvant endocrine drugs on lipid profiles in postoperative breast cancer patients (estrogen receptor-positive and/or progesterone receptor-positive). CONCLUSION: The findings of this study will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42019129850.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Lipídeos/sangue , Anastrozol/farmacologia , Anastrozol/uso terapêutico , Androstadienos/farmacologia , Androstadienos/uso terapêutico , Inibidores da Aromatase/farmacologia , Inibidores da Aromatase/uso terapêutico , Quimioterapia Adjuvante , Humanos , Letrozol/farmacologia , Letrozol/uso terapêutico , Meta-Análise em Rede , Projetos de Pesquisa , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Toremifeno/farmacologia , Toremifeno/uso terapêutico
9.
J Neurol Sci ; 408: 116562, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31722256

RESUMO

The m.3243A > G mutation in the mitochondrial tRNALeu (UUR) gene is associated with a variety of phenotypic heterogeneity. The clinical spectrum and phenotypic-genotypic correlations in the Chinese patients are poorly understood. In the present study, we reported the clinical and genetic characterization, as well as haplogroups of seven Han Chinese families carrying the m.3243A > G mutation. Of the 39 matrilineal individuals, five suffered from mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), two had life-threatening mitochondrial myopathy (LTMM), and one patient had neuropathy, ataxia, and retinitis pigmentosa (NARP)-like syndrome. The LTMM and NARP like syndromes enriched the phenotypic profile of the m.3243A > G mutation. The heteroplasmy of the m.3243A > G mutation ranged from 16% to 59% in MELAS, 29% to 79% in LTMM, and 57% in a NARP-like syndrome patient. The levels ranged from 0% to 14% in patients that manifested with pure diabetes and pure hearing loss, and 0% to 5% in 13 normal family members. However, we particularly noticed heteroplasmy in four asymptomatic individuals in one LTMM family carried the heteroplasmy mutation ranged from 22% to 78%, implying that there were other modifying factors in this family. The modulation of the phenotype of mtDNA mutations requires further investigation.

10.
Infect Genet Evol ; 78: 104125, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31770595

RESUMO

Both Clonorchis sinensis and Metorchis orientalis are the fish-borne zoonotic trematodes, and have a wide distribution of southeastern Asia, especially in China. Due to the similar morphology, life cycle, and parasitic positions are difficult to differentiate between both metacercariae. In the present study, the complete rDNA sequences of five C. sinensis and five M. orientalis were obtained and compared for the first time. And the IGS rDNA sequences were tested as a genetic marker. The results showed complete rDNA lengths of C. sinensis were range from 8049 bp to 8391 bp, including 1991 bp, 1116 bp, 3854 bp, and 1088-1430 bp belonging to 18S, ITS, 28S and IGS, respectively. And the complete rDNA lengths of M. orientalis were range from 7881 bp to 9355 bp, including 1991 bp, 1077 bp, 3856 bp, and 957-2431 bp belonging to 18S, ITS, 28S and IGS, respectively. Comparative analyses reveal length difference main in IGS, which has higher intraspecific and interspecific variations than other ribosomal regions. Forty four repeat (forward and inverted) sequences were found in the complete rDNAs of C. sinensis and M. orientalis. The phylogenetic analyses showed that the sequences of ITS1, ITS2, 18S and 28S could be used as different level genetic markers. In IGS phylogenetic tree, Opisthorchiidae, Paramphistomidae, Dicrocoeliidae, and Schistosomatidae formed monophyletic groups, and the same length sequences were clustered together in the same species. These findings of the present study provide the new molecular data for studying the complete rDNA of C. sinensis and M. orientalis, and indicate IGS sequences may used as a novel genetic marker for studying intraspecific variation in trematodes.

11.
Melanoma Res ; 30(1): 85-101, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31095042

RESUMO

We evaluated the expression of programmed cell death protein-1 (PD-1), programmed cell death ligand 1 (PD-L1), and NY-ESO-1 antigen; the infiltration of CD3+ T cells; and the microsatellite instability (MSI) phenotype, as well as the relationship of each factor to survival in malignant melanoma patients. Malignant melanoma samples from 89 patients were stained by immunohistochemistry to evaluate PD-1, PD-L1, CD3+ tumor-infiltrating lymphocytes (TILs), NY-ESO-1, and MSI. PD-1 and PD-L1 were expressed in 19.1 and 32.6% of the 89 samples, respectively. There was a significant correlation between PD-1 and PD-L1 expression (r = 0.207, P = 0.046). High infiltration of CD3+ T cells was observed in 41.6% of the samples, and increased cell infiltration was associated with increased PD-1 expression (P = 0.001). NY-ESO-1 antigen was detected in 13.5% of all samples, and the expression of NY-ESO-1 was positively correlated with the expression of PD-1 (P < 0.001). In our research, MSI was detected in 18 samples (20.2%). Survival analysis showed that a high infiltration of CD3+ T cells was related to longer progression-free survival (PFS) [24.0 months, 95% confidence interval (CI): 7.4-40.6 vs. 11.0 months, 95% CI: 7.1-12.9, P = 0.031], similarly, the median overall survival (OS) of the CD3+ T cell high-infiltration patients was also longer (53.0 vs. 38.0 months), but with no statistical significance (P = 0.200). The results for the immune markers mentioned above provide a theoretical basis for the prognosis and immunotherapy selection of malignant melanoma patients.

13.
Int J Pharm ; 575: 118951, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31843550

RESUMO

In this study, FK506-loaded poly(lactide-co-glycolide) nanoparticles (PLGA-FK506-NPs) were developed using an O/W emulsion solvent evaporation method. The PLGA-FK506-NPs were observed to be monodispersed and spherical by transmission and scanning electron microscopy. The mean size and zeta potential measured by dynamic light scattering were 110 ± 1.3 nm and -20.56 ± 3.65 mV, respectively. The FK506 entrapment and loading efficiency were 94.46 ± 1.88% and 5.38 ± 0.24%, respectively. Moreover, a pharmacokinetics study revealed that the PLGA-FK506-NPs behaved significantly different than free FK506 by exhibiting a higher area under curve (1.69-fold), higher mean residence time (1.29-fold), slower clearance and longer elimination half-life. Notably, the concentrations of FK506 in the spleen and mesenteric lymph nodes of the PLGA-FK506-NP group were 3.1-fold and 2.9-fold higher than those of the free FK506 group. Furthermore, the immunosuppressive efficacy was evaluated in a rat heterotopic heart transplantation model, and the results showed that PLGA-FK506-NP treatment could successfully alleviate acute rejection and prolong allograft survival compared with the free FK506 treatment (mean survival time, 17.1 ± 2.0 versus 13.3 ± 1.7 days). In conclusion, PLGA-FK506-NPs are a promising formulation for spleen and lymph node delivery and have potential use in the treatment of cardiac allograft acute rejection.

14.
Mikrochim Acta ; 186(12): 860, 2019 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-31786663

RESUMO

An aptasensor is described for the electrochemical determination of bisphenol A (BPA). Gold-coated multiwalled carbon nanotubes (Au/MWCNTs) and a single-stranded DNA-dye complex are used as a double signal-amplification system. The BPA-binding aptamer was assembled on a disposable electrode modified with Au/MWCNTs. Methylene blue (MB) was then intercalated into the immobilized aptamer with an approximately molecular ratio of 4 to form a complex. Upon interaction with BPA, the immobilized aptamer underwent a conformational change. This causes the intercalated MB to be released from the complex into solution. As a result, the electrochemical signal of the intercalated MB, typically measured using square wave voltammetry at a potential of -0.20 V (vs. Ag/AgCl (saturated KCl)) decreases. The fabrication of the aptasensor was characterized by the scanning electron microscopy, atomic force microscopy, and electrochemical techniques. Under optimal experimental conditions, the current drops linearly with the logarithm of BPA concentrations over the range from 10 fM to 1 nM, and the limit of detection is 8 fM. The assay was applied to the determination of BPA in plastic drinking bottles, tap water, and milk. Graphical AbstractSchematic illustration of fabricating the aptasensor for bisphenol A (BPA) based on double signal amplification via gold-coated multiwalled carbon nanotubes (Au/MWCNT) and an aptamer-dye complex. PET: poly(ethylene terephthalate).

15.
BMC Geriatr ; 19(1): 352, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842780

RESUMO

BACKGROUND: Statins play an important role in the care of patients with cardiovascular disease and have a good safety record in clinical practice. Hepatotoxicity is a barrier that limits the ability of primary care physicians to prescribe statins for patients with elevated liver transaminase values and/or underlying liver disease. However, limited population-based data are available on the use of statin therapy and on the hepatotoxicity of statins in very elderly patients. This prospective study evaluated the liver enzyme elevation during statin therapy in very elderly patients (≥80 years old). METHODS: Patients with hypercholesterolemia (LDL-C levels ≥3.4 and < 5.7 mmol/L), atherosclerosis, coronary heart disease (CHD), or a CHD-risk equivalent were enrolled and received once-daily statin treatment. Multivariate logistic regression models were used to study the impact of age, gender, hepatitis B infection, fatty liver disease, biliary calculus, other chronic diseases, drug kinds, alcohol abuse, statin variety, and statin dose variables. RESULTS: A total of 515 consecutive patients ranging from 80 to 98 years old were included in the analysis. These patients were treated with simvastatin, fluvastatin, pravastatin, rosuvastatin, or atorvastatin. Twenty-four patients (4.7, 95% CI 2.7-6.6) showed an increase in their hepatic aminotransferase levels. No significant difference of hepatic aminotransferase elevation rates was observed in different statin treatment groups. The incidence of mild, moderate, and severe elevation of aminotransferase levels was 62.5% (15/24), 29.2% (7/24), and 8.3% (2/24), respectively. None of the patients developed hepatic failure. Nine patients with moderate or severe aminotransferase elevations discontinued therapy. The time of onset of hepatic aminotransferase elevation ranged from 2 weeks to 6 months after statin treatment. The onset of hepatic aminotransferase elevation was within 1 month for 70.8% of patients. The patients took 2 weeks to 3 months to recover their liver function after statin therapy cessation. Multivariate analysis identified chronic hepatitis B infection and alcohol consumption as independent factors associated with the hepatic response to statins: OR, 12.83; 95% CI (4.36-37.759) and OR, 2.736; 95% CI (1.373-5.454), respectively. CONCLUSION: The prevalence of elevated transaminases was higher than published data in very elderly patients. Overall, statin treatment is safe for patients ≥80 years old.

16.
Front Pharmacol ; 10: 1073, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31620002

RESUMO

The objective of this study was to identify the prevalence and risk factors of renal complications of spondyloarthritis (SpA) patients, and to assess increased risks compared to general people. We conducted a retrospective study enrolled with consecutive SpA patients from an inpatient department and age, sex-matched general population (GP). The renal disorders investigated in this study contained decreased estimated glomerular filtration rate (eGFR), hematuria, proteinuria and nephrolithiasis. A total of 350 admitted SpA patients with complete medical records and 323 age and sex-matched GP were enrolled. Most SpA patients were male (n = 283, 80.9%) and the mean age was 31.61 ± 10.73 years old. Among 350 SpA patients, 29 (8.8%) suffered from hematuria, six (1.8%) suffered from proteinuria, one (0.3%) had decreased eGFR, and 27 (13.0%) presented with nephrolithiasis. The relative risk (RR) of nephrolithiasis in SpA compared to the GP was 2.24 (95% CI, 1.00-4.98), and the RR of renal insufficiency was 2.04 (95% CI, 1.11-3.77). In a univariate analysis, nephrolithiasis was significantly associated with age, age of onset, smoking, extra-articular manifestation and a bamboo spine. Renal insufficiency was significantly associated with age, peripheral manifestation, serum albumin, C-reactive protein and erythrocyte sedimentation rate. In a multivariable analysis, only extra-articular manifestation (OR = 8.43, 95% CI, 1.65-43.06, p = 0.010) and bamboo spine (OR = 3.47, 95% CI, 1.01-12.06, p = 0.049) remained significantly associated with nephrolithiasis. However, no variable was recognized as an independent risk factor for renal insufficiency. Renal complications are more common in SpA patients, with more than two-fold increased risk compared with GP. Extra-articular manifestation and bamboo spine are independent risk factors of renal disease in SpA patients.

17.
J Rheumatol ; 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31523044

RESUMO

OBJECTIVE: We aimed to present a systematic evaluation of 47 non Major Histocompatibility Complex (MHC) Ankylosing Spondylitis (AS) susceptibility loci which have been initially discovered through Caucasian Genome-wide association studies (GWASs) in Han Chinese. METHODS: Totally 10,743 samples representing north and south Chinese in four datasets were obtained. After data quality control and imputation, meta-analysis results of 94,621 variants within 47 loci were extracted. Four ERAP1 single-nucleotide polymorphisms (SNPs) and HLA-B27 tag SNP rs13202464 were used for interaction analysis. Population-attributable risk percentages (PARPs) of AS-associated variants were compared. Functional annotation of AS-associated variants were conducted using HaploReg, RegulomeDB and rVarBase Database. RESULTS: We revealed 16 AS-associated variants with nominal evidence in Han Chinese, including rs10865331 (P=6.30×10-10), rs10050860 (P=4.09×10-5) and rs8070463 (P=1.03×10-4). Potential susceptible SNPs within these 47 loci were also identified, such as rs13024541 (2p15), rs17401719 (5q15) and rs62074054 (17q21). Epistatic ineractions between three ERAP1 SNPs (rs17401719, rs30187 and rs10050860) and HLA-B27 were confirmed. Among the 16 AS-associated variants, rs30187 showed weaker risk effect while rs10050860 and rs12504282 seemed to attribute more risk in Han Chinese than Caucasians. Further genomic annotation pinpointed 35 candidate functional SNPs, especially in 2p15, ERAP1 and NPEPPS-TBKBP1 region. CONCLUSION: Our results provided a detailed spectrum of all the reported non-MHC AS susceptibility loci in Han Chinese, which comprehensively exhibited the ethnic heterogeneity of AS susceptibility and highlighted that 2p15, ERAP1 and NPEPPS-TBKBP1 region may play a critical role in AS pathogenesis across diverse populations.

18.
Front Oncol ; 9: 710, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417875

RESUMO

Purpose: The expression and role of sperm protein antigen 17 (SPA17), which has been confirmed to be immunogenic, in breast cancer remain unclear. We examined the expression of SPA17 in breast cancer and assessed its effect on patient prognosis and its function in breast cancer development. Methods: SPA17 expression was evaluated by immunohistochemistry and Q-RT-PCR in 120 breast tissue samples. Correlation of SPA17 expression with the patients' clinicopathological parameters and overall survival was assessed. The function of SPA17 was also explored. Results: By reviewing Gene Expression Omnibus datasets, we found that SPA17 expression in ductal breast carcinoma in situ (log2[fold change] = 1.14, p-value = 0.004) and invasive ductal breast cancer (log2[fold change] = 1.03, p-value = 0.016) tissues was 2.20 and 2.05 times higher, respectively, than that in normal breast tissues. Our result also showed that 27% (27/100) of breast cancer samples expressed SPA17 but none of the normal breast (0/20) samples did. Lymph node metastasis (p < 0.001) and molecular subtyping (p = 0.002) were independent factors associated with SPA17 expression. Most importantly, SPA17 expression resulted in poor prognosis. In addition, cell function assay validated that SPA17 increased the migration (p < 0.001) and invasion (p = 0.007) of breast cancer cells, but not affected the proliferation of breast cancer cells. Conclusion: Our results demonstrated the vital role of SPA17 in the development and metastasis of breast cancer and that SPA17 may be a new therapeutic target in improving breast cancer prognosis.

19.
Bioprocess Biosyst Eng ; 42(12): 1983-1992, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31420725

RESUMO

N2O production from NH2OH oxidation involved in a heterotrophic nitrifier Alcaligenes faecalis strain NR was studied. 15N-labeling experiments showed that biological NH2OH consumption by strain NR played a dominant role in N2O production, although chemical reaction between NH2OH and O2 indeed existed. Hydroxylamine oxidoreductase (HAO) from strain NR was partially purified by (NH4)2SO4 fractionation and DEAE Cartridge chromatography. The maximum activity of HAO was 9.60 mU with a specific activity of 92.04 mU/(mg protein) when K3Fe(CN)6 was used as an electron acceptor. The addition of Ca2+ promoted the HAO activity, while the presence of Mn2+ inhibited the enzyme activity. The optimal temperature and pH for HAO activity were 30 °C and 8. Analysis of enzyme-catalyzed products demonstrated that NH2OH oxidation catalyzed by HAO from strain NR played significant role in the production of N2O.

20.
Arch Osteoporos ; 14(1): 85, 2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31367860

RESUMO

While adherence to osteoporosis treatment is low, patients' preference for osteoporosis treatment is unknown in Chinese patients. Chinese patients are willing to receive treatments with higher clinical efficacy and lower out-of-pocket cost. In addition, annual intravenous infusion and 6-month subcutaneous injection are preferred over weekly oral tablets. PURPOSE: This study was performed to elicit Chinese patients' preferences for osteoporosis medication treatment and to investigate the heterogeneities of the preferences in subgroups. METHODS: A discrete choice experiment comprising 15 choice sets with 4 important attributes was conducted in a Chinese population at risk of osteoporotic fracture. The four attributes were treatment efficacy in reducing the risk of fracture, out-of-pocket cost per year, adverse effects of treatment, and mode of administration. The patients were asked to choose between two hypothetical treatments; they could also choose no treatment. Mixed logit models were used, and any observed heterogeneity in the patients' preferences was further assessed in subgroup analyses. RESULTS: In total, 267 patients were analysed. On average, the patients preferred to receive treatment rather than no treatment. The patients preferred treatment with higher efficacy in preventing fracture and lower out-of-pocket cost. The least preferred adverse effect of medication was gastrointestinal disorders, followed by flu-like symptoms and finally skin reactions. The most preferred mode of administration was annual intravenous infusion, followed by 6-month subcutaneous injection, a weekly oral tablet, and daily nasal spray; daily oral tablets ranked as the least preferred mode of administration. The differences in the patients' preferences among all attributes were statistically significant (p < 0.05). Patients' age was found to contribute to the observed preference heterogeneity in most of the included attributes. CONCLUSIONS: This study revealed Chinese patients' preferences for osteoporosis treatments. Annual intravenous infusion and 6-month subcutaneous injection were significantly preferred over weekly oral tablets in this Chinese population.

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