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1.
Am J Hum Genet ; 105(4): 706-718, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31564435

RESUMO

Hemoglobin A1c (HbA1c) is widely used to diagnose diabetes and assess glycemic control in individuals with diabetes. However, nonglycemic determinants, including genetic variation, may influence how accurately HbA1c reflects underlying glycemia. Analyzing the NHLBI Trans-Omics for Precision Medicine (TOPMed) sequence data in 10,338 individuals from five studies and four ancestries (6,158 Europeans, 3,123 African-Americans, 650 Hispanics, and 407 East Asians), we confirmed five regions associated with HbA1c (GCK in Europeans and African-Americans, HK1 in Europeans and Hispanics, FN3K and/or FN3KRP in Europeans, and G6PD in African-Americans and Hispanics) and we identified an African-ancestry-specific low-frequency variant (rs1039215 in HBG2 and HBE1, minor allele frequency (MAF) = 0.03). The most associated G6PD variant (rs1050828-T, p.Val98Met, MAF = 12% in African-Americans, MAF = 2% in Hispanics) lowered HbA1c (-0.88% in hemizygous males, -0.34% in heterozygous females) and explained 23% of HbA1c variance in African-Americans and 4% in Hispanics. Additionally, we identified a rare distinct G6PD coding variant (rs76723693, p.Leu353Pro, MAF = 0.5%; -0.98% in hemizygous males, -0.46% in heterozygous females) and detected significant association with HbA1c when aggregating rare missense variants in G6PD. We observed similar magnitude and direction of effects for rs1039215 (HBG2) and rs76723693 (G6PD) in the two largest TOPMed African American cohorts, and we replicated the rs76723693 association in the UK Biobank African-ancestry participants. These variants in G6PD and HBG2 were monomorphic in the European and Asian samples. African or Hispanic ancestry individuals carrying G6PD variants may be underdiagnosed for diabetes when screened with HbA1c. Thus, assessment of these variants should be considered for incorporation into precision medicine approaches for diabetes diagnosis.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31608558

RESUMO

This study aimed to conduct a comprehensive analysis of clinical studies on acupuncture treatment for breast cancer-related lymphedema (BCRL), so as to explore the efficacy and safety of acupuncture treatment and provide evidence for the clinical decision-making. Public databases, mainly including China Academic Journals Full-text Database, Database of Chinese Sci-Tech Journal, Wanfang, PubMed, Embase and the Cochrane Library, from the establishment of databases to December 2018 were searched for randomized controlled trials (RCT) of acupuncture for BCRL. Clinical RCT on the treatment of BCRL with acupuncture combined with drugs or functional exercise were enrolled for the analysis. Bias risk and quality were assessed by two investigators according to the Cochrane Handbook 5.1.0 standard, and the Revman 5.3 software was used for meta-analysis. A total of 13 studies were enrolled, comprising 747 patients (377 in the treatment group and 370 in the control group). The results of meta-analysis showed that acupuncture intervention could improve the total effective rate for the treatment of BCRL (odds ratio = 4.62; 95% confidence interval 2.61-8.17). Recent studies suggest that acupuncture therapy can alleviate the upper limb swelling and improve the subjective pain and discomfort in patients with BCRL, regardless of the control intervention used. However, the number of high-quality RCT is low. Moreover, most of the studies adopted inconsistent efficacy indicators. Hence, additional blinded, large-sample, randomized, well-controlled studies with objective and uniform efficacy indicators are needed, especially in China, to confirm the findings.

3.
Acta Biomater ; 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31629895

RESUMO

Infection is a main cause of implant failure. Early implant-related infections often occur in the first 4 weeks post-operation. Inhibiting bacterial adhesion and biofilm formation at the early stage and promoting subsequent implant osseointegration are important for implant success. Our previous studies demonstrated that dimethylaminododecyl methacrylate (DMADDM) provided dental materials with antibacterial effects. In the present study, DMADDM and hydroxyapatite (HA) are loaded on to the titanium (Ti) surface via poly dopamine (PDA) self-polymerization. This local DMADDM-delivery Ti is referred as Ti-PHD. Here we report the two-staged capability of Ti-PHD: (1) in the first stage, releasing DMADDM during the high-infection-risk initial period post-implantation for 4 weeks; (2) then in the second stage, enhancing osteogenesis and promoting osseointegration. Ti-PHD has a porous surface with higher average roughness and greater hydrophilicity than pure Ti. Its biocompatibility is verified in vitro and in vivo. During the first 4 weeks of release, both DMADDM remaining on Ti surface and DMADDM released into the soaking medium greatly reduced the adherence and growth of pathogens. This is further confirmed by the prevention of bone destruction in a rat osteomyelitis model. After releasing DMADDM for 4 weeks, Ti-PHD promotes osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) and new bone formation around the implants in vivo. This article represents the first report on the two-staged, time-dependent antibacterial and osteogenesis effects of Ti-PHD, demonstrating its potential for clinical applications to inhibit implant-associated infections. STATEMENT OF SIGNIFICANCE: The present study develops a two-staged time-dependent system for local dimethylaminododecyl methacrylate (DMADDM) delivery via Ti implant (referred to as Ti-PHD). DMADDM and hydroxyapatite (HA) are loaded on to the Ti surface with poly dopamine (PDA). Ti-PHD can release DMADDM during the high-risk period of infection in the first stage, and then promote osseointegration and new bone formation in the second stage. This bioactive and therapeutic Ti is promising to inhibit infections and enhance implant success.

4.
Magn Reson Imaging ; 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31484043

RESUMO

PURPOSE: To investigate the utility of diffusion kurtosis imaging (DKI) MRI for evaluation of renal fibrosis in rats with unilateral ureteral obstruction (UUO). METHODS: Twenty-five rats had UUO, and ten rats were subjected to sham operation as control. DKI was performed on a 3.0 T MRI scanner on days 1, 3, 5, and 7 after ligation. All rats then underwent 18F-FDG dynamic PET to evaluate unilateral renal function, followed by histological analysis to examine α-smooth muscle actin (α-SMA) expression. DKI metrics were assessed among the time points and between two sides, and compared with maximum standardized uptake value (SUVmax), serum levels of creatinine and urea, and fibrosis marker α-SMA. RESULTS: Mean kurtosis (MK) on day 7, axial kurtosis (Ka) on days 3 and 7, mean diffusivity (MD) on days 1, 3, 5, and 7, and fractional anisotropy (FA) on days 3, 5, and 7 of cortex and medulla between the UUO and contralateral sides were significantly different (all p < 0.05). Over the course of UUO progression, there were significant changes in Ka, MD and FA of medulla (all p < 0.05). FA of medulla was positively correlated with SUVmax (r = 0.641, p < 0.001), and MD of cortex was negatively correlated with urea (r = -0.534, p = 0.001). MD of cortex was negatively correlated with α-SMA on UUO sides (r = -0.710, p < 0.001). CONCLUSIONS: DKI shows the potential for noninvasive assessment of renal fibrosis and unilateral renal function induced by UUO.

5.
World J Pediatr ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31487005

RESUMO

BACKGROUND: Interferon alpha (IFN-α) is a preferred therapy for antiviral treatment of children with chronic hepatitis B (CHB) aged > 1 year currently. Peginterferon alpha-2a (Peg-IFN α-2a) is a recommended international guideline for treatment of CHB children, which is limited to children aged > 3 years. But the exact efficacy and safety of IFN-α and Peg-IFN α-2a for treating CHB are not sufficient. METHODS: Clinical manifestations, baseline characteristics, related laboratory tests and adverse events were retrospectively analyzed in children with CHB, who visited Children's Hospital of Fudan University and were treated with IFN α-2b or Peg-IFN α-2a monotherapy and followed up from January 2003 to October 2018. RESULTS: A total of 36 immune-active patients without advanced fibrosis were enrolled to be treated with IFN α-2b (group A, n = 18) or Peg-IFN α-2a (group B, n = 18). IFN α-2b or Peg-IFN α-2a was administered for a median of 48 weeks subcutaneously by body surface area (BSA) category at a dose of 3 MU/m2 or 104 µg/m2, respectively. HBV e antigen (HBeAg) seroconversion rates at 48 weeks post-treatment were higher in group A than group B (92.9% vs. 87.5%), so as the rates of HBsAg clearance (22.2% vs. 11.1%), and hepatitis B virus (HBV)-DNA < 1000 IU/mL (88.9% vs. 83.3%). Only mild flu-like symptoms and transient neutropenia appeared in some children at the early stage of treatment. No severe abnormal results was observed in other laboratory assessments. CONCLUSION: The antiviral monotherapy of 48-week IFN α-2b or Peg-IFN α-2a in children with CHB is well tolerated and effective, which is associated with higher rates of HBeAg seroconversion and HBsAg clearance than in adults and previously pediatric patients.

6.
Medicine (Baltimore) ; 98(32): e16683, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393369

RESUMO

Interferon-alpha (IFN-α) is currently the preferred antiviral treatment for children with chronic hepatitis B (CHB) aged >1-year-old. However, the evidence regarding the exact efficacy and safety in the real world is not sufficient. This study aimed to investigate the efficacy of IFN-α therapy in children with CHB and to provide a theoretical basis for practically identifying ideal antiviral therapies for CHB children.Clinical manifestations, baseline characteristics, related laboratory tests, and adverse events were retrospectively analyzed in children with CHB who visited the Children's Hospital of Fudan University, were treated with IFN-α and were followed up from January 2003 to October 2018.A total of 18 immune-active patients without advanced fibrosis were enrolled, and their average age at the start of treatment was 4.45 ±â€Š2.75 years old. IFN α-2b was administered subcutaneously by body surface area (BSA) category, based on 3 MU/m, for a median 48 weeks. Before treatment, the alanine aminotransferase (ALT) range was 81 to 409 U/L (median 158 U/L). The median hepatitis B virus (HBV)-DNA load was 9.89 × 10 IU/mL, and the HBV-DNA load varied from 3.10 × 10 to 4.56 × 10 IU/mL. The ALT levels of 17 children became normal at an average of 12 weeks during treatment, and those of 1 child became normal at 6 weeks after IFN-α withdrawal. Sixteen (88.9%, 16/18) children became HBV-DNA negative (<10 IU/mL) at an average of 24 weeks during treatment, while 1 became negative at 96 weeks after IFN-α withdrawal and 1 remained HBV-DNA positive. HBV e antigen (HBeAg) seroconversion occurred in 13 of 14 (92.9%, 13/14) HBeAg-positive patients at an average of 12 weeks during treatment. HBV s antigen (HBsAg) loss or seroconversion occurred in 4 (22.2%, 4/18) patients at an average of 21 weeks during treatment. Only mild flu-like symptoms and transient neutropenia appeared in some children at the early treatment stage. No severe abnormal results were observed in other laboratory parameters.The antiviral monotherapy of 48 weeks of IFN-α was well tolerated and good responded, which was associated with higher rates of HBeAg seroconversion and HBsAg clearance in the children in this study than in previously reported adults and pediatric patients.


Assuntos
Antivirais/administração & dosagem , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Adolescente , Antivirais/farmacologia , Criança , Pré-Escolar , China , Estudos de Coortes , Feminino , Seguimentos , Humanos , Injeções Subcutâneas , Interferon-alfa/farmacologia , Masculino , Soroconversão/efeitos dos fármacos , Carga Viral/efeitos dos fármacos
7.
Braz J Med Biol Res ; 52(8): e8309, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31411246

RESUMO

This study aimed to detect the expression of the long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) and evaluate its correlation with disease risk, stenosis degree, inflammation, as well as overall survival (OS) in coronary artery disease (CAD) patients. A total of 230 patients who underwent diagnostic coronary angiography were consecutively recruited and assigned to CAD group (n=125) or control group (n=105) according to presence or absence of CAD. Gensini score was calculated to assess the severity of coronary artery damage. Plasma samples were collected and the expression ANRIL was detected in all participants. High-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), and cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, IL-8, IL-10, and IL-17 in CAD patients were measured and OS was calculated. The relative expression of ANRIL was higher in CAD patients compared to controls (P<0.001). Receiver operating characteristic disclosed that ANRIL could distinguish CAD patients from controls with an area under the curve of 0.789 (95%CI: 0.731-0.847). Spearman's rank correlation test revealed that expression of ANRIL was positively correlated with Gensini score (P=0.001), levels of hs-CRP (P=0.001), ESR (P=0.038), TNF-α (P=0.004), and IL-6 (P<0.001), while negatively correlated with IL-10 level (P=0.008) in CAD patients. Kaplan-Meier curve revealed that high expression of ANRIL was associated with shorter OS (P=0.013). In conclusion, circulating ANRIL presented a good diagnostic value for CAD, and its high expression was associated with increased stenosis degree, raised inflammation, and poor OS in CAD patients.


Assuntos
Doença da Artéria Coronariana/diagnóstico , RNA Longo não Codificante/genética , Idoso , Sedimentação Sanguínea , Proteína C-Reativa/análise , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/genética , Estenose Coronária/complicações , Citocinas/sangue , Feminino , Humanos , Inflamação/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Análise de Sobrevida
8.
CNS Neurosci Ther ; 25(9): 899-910, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31334608

RESUMO

As an endogenous neuroprotectant agent, adenosine is extensively distributed and is particularly abundant in the central nervous system (CNS). Under physiological conditions, the concentration of adenosine is low intra- and extracellularly, but increases significantly in response to stress. The majority of adenosine functions are receptor-mediated, and primarily include the A1, A2A, A2B, and A3 receptors (A1R, A2AR, A2BR, and A3R). Adenosine is currently widely used in the treatment of diseases of the CNS and the cardiovascular systems, and the mechanisms are related to the disease types, disease locations, and the adenosine receptors distribution in the CNS. For example, the main infarction sites of cerebral ischemia are cortex and striatum, which have high levels of A1 and A2A receptors. Cerebral ischemia is manifested with A1R decrease and A2AR increase, as well as reduction in the A1R-mediated inhibitory processes and enhancement of the A2AR-mediated excitatory process. Adenosine receptor dysfunction is also involved in the pathology of Alzheimer's disease (AD), depression, and epilepsy. Thus, the adenosine receptor balance theory is important for brain disease treatment. The concentration of adenosine can be increased by endogenous or exogenous pathways due to its short half-life and high inactivation properties. Therefore, we will discuss the function of adenosine and its receptors, adenosine formation, and metabolism, and its role for the treatment of CNS diseases (such as cerebral ischemia, AD, depression, Parkinson's disease, epilepsy, and sleep disorders). This article will provide a scientific basis for the development of novel adenosine derivatives through adenosine structure modification, which will lead to experimental applications.

9.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 36(3): 460-467, 2019 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-31232550

RESUMO

In order to quantitatively evaluate the performance of dry electrode for fabric surface bioelectricity, a set of active measuring devices that can simulate electrocardiosignal has been developed on the basis of passive system by our group. Five Ag/AgCl fabric dry electrodes were selected to test and evaluate the devices. The results show that the deviation ratios of peak time interval of the five electrodes are all less than 1%. The maximum voltage amplitude decay rate is 7.2%, and the noise amplitudes are lower than 0.004 mV. The variable coefficient of peak time offset is less than 8%. The variable coefficient of voltage amplitude is less than 2%. The variable coefficient of noise amplitude is less than 10%. Research shows the devices has good repeatability and stability in measuring the simulated electrocardiosignal. The active measuring devices proposed in this paper can provide a new method for performance evaluation and standard formulation of surface bioelectricity dry electrode.


Assuntos
Eletrodos , Têxteis , Dispositivos Eletrônicos Vestíveis
10.
Nature ; 570(7762): 514-518, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31217584

RESUMO

Genome-wide association studies (GWAS) have laid the foundation for investigations into the biology of complex traits, drug development and clinical guidelines. However, the majority of discovery efforts are based on data from populations of European ancestry1-3. In light of the differential genetic architecture that is known to exist between populations, bias in representation can exacerbate existing disease and healthcare disparities. Critical variants may be missed if they have a low frequency or are completely absent in European populations, especially as the field shifts its attention towards rare variants, which are more likely to be population-specific4-10. Additionally, effect sizes and their derived risk prediction scores derived in one population may not accurately extrapolate to other populations11,12. Here we demonstrate the value of diverse, multi-ethnic participants in large-scale genomic studies. The Population Architecture using Genomics and Epidemiology (PAGE) study conducted a GWAS of 26 clinical and behavioural phenotypes in 49,839 non-European individuals. Using strategies tailored for analysis of multi-ethnic and admixed populations, we describe a framework for analysing diverse populations, identify 27 novel loci and 38 secondary signals at known loci, as well as replicate 1,444 GWAS catalogue associations across these traits. Our data show evidence of effect-size heterogeneity across ancestries for published GWAS associations, substantial benefits for fine-mapping using diverse cohorts and insights into clinical implications. In the United States-where minority populations have a disproportionately higher burden of chronic conditions13-the lack of representation of diverse populations in genetic research will result in inequitable access to precision medicine for those with the highest burden of disease. We strongly advocate for continued, large genome-wide efforts in diverse populations to maximize genetic discovery and reduce health disparities.

11.
Sci Rep ; 9(1): 6421, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015507

RESUMO

Abnormalities of thyroid function are common in patients with nephrotic syndrome (NS). However, a limited number of studies have reported on the association between clinicopathologic features and thyroid dysfunction in patients with NS. We retrospectively studied 317 patients who had been definitively diagnosed with NS. The NS patients with thyroid dysfunction showed higher urine protein, creatinine and lipid levels and lower albumin and hemoglobin than those with normal thyroid function, with no significant differences of pathological types. After dividing thyroid dysfunction groups into five subgroups, interestingly, membranous nephropathy was the most common pathologic type, both in normal thyroid group and in subclinical hypothyroidism group (40.4% and 46.7%, respectively), followed by minimal change disease (28.1% and 21.7%, respectively); while in the hypothyroid, low T3, and low T3T4 groups minimal change disease is now the leading type (48.8%, 33.3% and 38.6%, respectively). High levels of urinary protein, creatinine, cholesterol, and platelets were independent risk factors predicting thyroid dysfunction, while higher albumin and hemoglobin were protective factors. We demonstrated that the type of renal pathology was different among NS patients in different thyroid dysfunction subgroups. Interpretation of the interactions between thyroid and renal function is a challenge for clinicians involved in the treatment of patients with NS.

12.
Biosci Rep ; 39(4)2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-30923227

RESUMO

Cannabinoid receptor 2 (CB2R) has been reported to play an important role in the regulation of pathogenesis and progression of myocardial infarction (MI). Here we tried to investigate its potential mechanisms. The ratio of infarct size in heart issue was detected by TTC staining, and cardiac functions were calculated according to echocardiographic evaluation. Cell viability in cardiomyocytes was investigated by Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) release assays. Western blot was used to detect autophagy-related proteins including Beclin-1, LC3, p62, adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-mammalian target of rapamycin rabbit (mTOR)-p70 ribosomal protein S6 kinase (p70S6K) signaling-related proteins including AMPK, mTOR, p70S6K, and their phosphorylation formation. Rapamycin was used for the induction of autophagy. Cleaved caspase-3 and Bax were detected for analyzing apoptosis. TEM was used for the detection of autophagosomes. We found that CB2R deletion (CB2R KO) largely deteriorated the severity of MI and the cardiac function as well as cell viability of cardiomyocytes. Knocking out CB2R decreased the level of autophagy in heart issues from MI mice as well as cardiomyocytes under oxygen-glucose deprivation (OGD). Furthermore, CB2R dysfunction significantly attenuated the cardiac protective effects of rapamycin both in vivo and in vitro Finally, we found that CB2R-mediated autophagy was induced by AMPK-mTOR-p70S6K signaling pathway. Our current study demonstrated for the first time that CB2R deletion led to a detrimental effect of MI through the dysfunction of AMPK-mTOR-p70S6K signaling pathway, which might provide a novel insight in the treatment of MI.

13.
J Ethnopharmacol ; 241: 111801, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-30878546

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola crenulata, a traditional Tibetan medicine, has shown promise in the treatment of hypobaric hypoxia (HH)-induced brain injury. However, the underlying mechanisms remain unclear. This study investigated the protective effects of R. crenulata aqueous extract (RCAE) on HH-induced brain injury in rats. MATERIALS AND METHODS: An animal model of high-altitude hypoxic brain injury was established in SD rats using an animal decompression chamber for 24 h. Serum and hippocampus levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG), and lactate dehydrogenase (LDH) were then determined using commercial biochemical kits. Neuron morphology and vitality were also evaluated using H&E and Nissl staining, and TUNEL staining was used to examine apoptosis. Gene and protein expression of HIF-1α, microRNA 210, ISCU1/2, COX10, Apaf-1, cleaved Caspase-3, Caspase-3, Bax, Bcl-2, and Cyto-c were determined by western blot, immunohistochemical and qRT-PCR analysis. RESULTS: RCAE administration attenuated HH-induced brain injury as evidenced by decreased levels of MDA, LDH, and GSSG, increased GSH and SOD, improvements in hippocampus histopathological changes, increased cell vitality and ATP level, and reduced apoptotic cell numbers. RCAE treatment also enhanced HIF-1α, ISCU1/2, COX10, and Bcl-2 protein expression, while dramatically inhibiting expression of Apaf-1, Bax, Cyto-c, and cleaved Caspase-3. Treatment also increased gene levels of HIF-1α, microRNA 210, ISCU1/2, and COX10, and decreased Caspase-3 gene production. CONCLUSIONS: RCAE attenuated HH-induced brain injury by regulating apoptosis and mitochondrial energy metabolism via the HIF-1α/microRNA 210/ISCU1/2 (COX10) signaling pathway.

14.
Mol Med Rep ; 19(4): 2758-2766, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30720143

RESUMO

This study was conducted to establish a stable hypobaric hypoxia brain injury model. SD rats were randomly separated into control and model groups, and placed outside or inside of a hypobaric chamber, respectively. Subsequent to 24 h anoxic exposure, plasma superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG) and lactate dehydrogenase (LDH) were measured using commercial biochemical kits. Hematoxylin­eosin (H&E), Nissl's and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to observe the morphology of neurons in the hippocampus. The protein expression levels of apoptotic protease activating factor­1 (Apaf­1), hypoxia inducible factor­1α (HIF­1α), caspase­3, cleaved caspase­3, Bcl­2­associated X protein (Bax) and cytochrome c (cyto­c) were detected using western blot and immunohistochemistry analyses. Hypoxic substantially induced morphological lesions in the hippocampus concomitant with the physical behavioral performance deficit. Furthermore, hypoxia markedly exacerbated the levels of MDA, LDH and GSSG, and restrained GSH (P<0.01) and SOD (P<0.05) levels compared with the control group. In addition, hypoxia significantly induced the protein expression of Apaf­1, HIF­1α, caspase­3, cleaved caspase­3, Bax and Cyto­c (P<0.01) compared with the control group. Finally, a lower number and volume of Nissl bodies were verified in the hypoxic group. TUNEL results demonstrated a greater number of apoptotic cells in the hypoxic group. The present study demonstrates a model of rat hypoxic brain injuries induced by a hypobaric chamber at 9,000 m for 24 h. Furthermore, the redox enzyme, HIF­1α and mitochondrial apoptosis­associated protein, along with H&E and Nissl's staining, may be applied to evaluate the degree of injury.


Assuntos
Altitude , Lesões Encefálicas/etiologia , Lesões Encefálicas/metabolismo , Hipóxia/complicações , Animais , Comportamento Animal , Biomarcadores , Lesões Encefálicas/patologia , Modelos Animais de Doenças , Expressão Gênica , Hipóxia/genética , Hipóxia/metabolismo , Imuno-Histoquímica , Masculino , Mitocôndrias/genética , Mitocôndrias/metabolismo , Estresse Oxidativo , Células Piramidais/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
15.
Huan Jing Ke Xue ; 40(1): 200-210, 2019 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-30628276

RESUMO

Multispectral satellite sensors have several limitations with respect to capturing the target's spectral information due to their band setting and number of bands. The hyperspectral reconstruction technique is an effective method to obtain hyperspectral information from multispectral data. In this study, we propose a hyperspectral reconstruction algorithm based on the sparse representation of water remote sensing reflectance. The proposed algorithm was validated for five ocean color sensors (Sentinel-2A MSI, MERIS, MODIS Aqua, GOCI, and ⅦRS) using in situ measured above-water remote sensing reflectance. The mean absolute percentage error (MAPE) and root mean square error (RMSE) of the reconstructed and measured spectra for five ocean color sensors were less than 10% and 0.005 sr-1, respectively. Compared with the spectra reconstruction algorithm based on multi-variable linear regression, the proposed algorithm can obtain the features of complex water remote sensing reflectance without using in situ-measured reflectance for algorithm tuning. In addition, the accuracy of the proposed algorithm is better than the spectra reconstruction algorithm based on multi-variable linear regression. Two spectra reconstruction algorithms were applied to five ocean color sensors to test the applicability of the remotely estimated water constituent concentration. The statistical results for the reconstructed spectral factors and in situ water constituent concentration suggest that the reconstructed reflectance derived by the proposed algorithm has a performance similar to that of in situ-measured hyperspectral reflectance. The reconstructed reflectance derived by the proposed algorithm performs better than the spectra reconstruction algorithm based on multi-variable linear regression. Finally, the proposed algorithm was applied to GOCI data to remotely estimate the chlorophyll-a and total suspended matter concentrations. The accuracy of the water constituent concentration estimated from reconstructed images is better than that using original multispectral images. For the estimation of the chlorophyll-a concentration, the MAPE improved from 80.6% to 51.5% and the RMSE improved from 12.175 µg·L-1 to 7.125 µg·L-1. For the estimation of total suspended matter, the MAPE improved from 19.1% to 18.8% and the RMSE improved from 29.048 mg·L-1 to 28.596 mg·L-1.

16.
Sensors (Basel) ; 19(2)2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30634717

RESUMO

Thrusters are the bottom actuators of the amphibious spherical robot, and play an important role in the motion control of these robots. To realize accurate motion control, a thrust model for a new water-jet thruster based on hydrodynamic analyses is proposed in this paper. First, the hydrodynamic characteristics of the new thruster were numerically analyzed using computational fluid dynamics (CFD) commercial software CFX. The moving reference frame (MRF) technique was utilized to simulate propeller rotation. In particular, the hydrodynamics of the thruster were studied not only in the axial flow but also in oblique flow. Then, the basic framework of the thrust model was built according to hydromechanics theory. Parameters in the basic framework were identified through the results of the hydrodynamic simulation. Finally, a series of relevant experiments were conducted to verify the accuracy of the thrust model. These proved that the thrust model-based simulation results agreed well with the experimental results. The maximum error between the experimental results and simulation results was only 7%, which indicates that the thrust model is precise enough to be utilized in the motion control of amphibious spherical robots.

17.
J Lipid Res ; 60(2): 421-429, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30552288

RESUMO

The effects of PUFAs on metabolic syndrome (MetS) remain to be characterized, particularly in Asians. We aimed to investigate the prospective associations of PUFAs with MetS and the role of acylcarnitines in these associations in Chinese individuals. Among 1,245 Chinese men and women aged 50-70 years who completed a 6 year follow-up, baseline erythrocyte FAs and plasma acylcarnitines were profiled using gas chromatography coupled with positive chemical ionization and liquid chromatography-tandem mass spectrometry, respectively. Total n-6 PUFAs and three 22-carbon n-6 PUFAs were significantly associated with lower MetS risk comparing extreme quartiles: relative risks (RRs) (95% CIs) were 0.75 (0.57, 0.97) for total n-6 PUFAs, 0.69 (0.56, 0.85) for 22:2n-6, 0.76 (0.59, 0.99) for 22:4n-6, and 0.74 (0.58, 0.94) for 22:5n-6, while 18:3n-3 and 18:3n-6 were positively associated with MetS risk. In a network analysis, a module mostly consisting of long-chain n-6 PUFAs and very-long-chain saturated FAs was inversely associated with incident MetS (RR per SD: 0.84; 95% CI: 0.76, 0.92), and this module was more strongly associated with lower MetS risk when a short- to medium-chain acylcarnitine (C5-C10) module score was lower (P interaction = 0.03). Our data suggested inverse associations of total n-6 and certain long-chain n-6 PUFAs with cardiometabolic disorders, and this association might be modified by certain acy-l-carnitines.

18.
Magn Reson Imaging ; 55: 52-59, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30240758

RESUMO

PURPOSE: To evaluate the utility of volumetric histogram analysis of monoexponential and non-Gaussian distribution DWI models for discriminating pancreatic ductal adenocarcinoma (PDAC) and neuroendocrine tumor (pNET). MATERIALS AND METHODS: A total of 340 patients were retrospectively reviewed. Finally, 62 patients with histopathological confirmed PDAC (n = 42) and pNET (n = 20) were enrolled in the study. All the patients accepted magnetic resonance imaging (MRI) at 3 T (including multi-b value DWI, 0-1000 s/mm2). Isotropic apparent diffusion coefficient (ADC), true molecular diffusion (Dt), perfusion-related diffusion (Dp), perfusion fraction (f), distributed diffusion coefficient (DDC) and alpha (α) were obtained from different DWI models. Then, mean value, median value, 10th and 90th percentiles were obtained from histogram analysis of each DWI parameter. RESULTS: Histogram metrics derived from ADC, Dp, f and DDC were significantly lower in PDAC than pNET group (P < 0.05). In contrast, histogram metrics derived from α were observed significantly higher in the PDAC than pNET group (P < 0.05). No significant difference was found in Dt (P ≥ 0.05) between PDAC and pNET patients. Among all parameters, f-median had the highest diagnostic performance (AUC 0.91, cutoff value 0.188, sensitivity 97.62%, specificity 80%). CONCLUSIONS: f-Median derived from IVIM DWI model may be potentially more valuable parameter than ADC, Dp, DDC and α for discriminating PDAC and pNET. Histogram analysis based on the entire tumor was an emerging and valuable tool.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Carcinoma Ductal Pancreático/diagnóstico por imagem , Tumores Neuroendócrinos/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Adulto , Idoso , Difusão , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética , Masculino , Microcirculação , Pessoa de Meia-Idade , Modelos Teóricos , Tumores Neuroendócrinos/diagnóstico , Distribuição Normal , Perfusão , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade
19.
Braz. j. med. biol. res ; 52(8): e8309, 2019. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-1011605

RESUMO

This study aimed to detect the expression of the long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) and evaluate its correlation with disease risk, stenosis degree, inflammation, as well as overall survival (OS) in coronary artery disease (CAD) patients. A total of 230 patients who underwent diagnostic coronary angiography were consecutively recruited and assigned to CAD group (n=125) or control group (n=105) according to presence or absence of CAD. Gensini score was calculated to assess the severity of coronary artery damage. Plasma samples were collected and the expression ANRIL was detected in all participants. High-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), and cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-8, IL-10, and IL-17 in CAD patients were measured and OS was calculated. The relative expression of ANRIL was higher in CAD patients compared to controls (P<0.001). Receiver operating characteristic disclosed that ANRIL could distinguish CAD patients from controls with an area under the curve of 0.789 (95%CI: 0.731-0.847). Spearman's rank correlation test revealed that expression of ANRIL was positively correlated with Gensini score (P=0.001), levels of hs-CRP (P=0.001), ESR (P=0.038), TNF-α (P=0.004), and IL-6 (P<0.001), while negatively correlated with IL-10 level (P=0.008) in CAD patients. Kaplan-Meier curve revealed that high expression of ANRIL was associated with shorter OS (P=0.013). In conclusion, circulating ANRIL presented a good diagnostic value for CAD, and its high expression was associated with increased stenosis degree, raised inflammation, and poor OS in CAD patients.

20.
Chem Commun (Camb) ; 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30506077

RESUMO

A radical cascade cyclization of 2-alkynylthioanisoles with α-oxocarboxylic acids with AgNO3 has been described. This reaction provides a novel route to directly access 3-acylbenzothiophenes from simple chemical feedstocks. In particular, the utility of the approach was demonstrated by its application to the synthesis of a polymerization inhibitor and a raloxifene precursor.

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