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1.
Liver Int ; 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33389804

RESUMO

BACKGROUND & AIMS: Liver fibrosis score (LFS) has been used for predicting the cardiovascular outcomes (CVOs) in diverse populations. However, the association of LFS with CVOs in patients with previous myocardial infarction (MI) remains undetermined. We aimed to examine the prognostic value of LFS in patients with prior MI in a prospective cohort. METHODS: A total of 3718 patients with previous MI were consecutively enrolled from March 2009 to January 2019. Five LFSs including the fibrosis-4 (FIB-4) score, non-alcohol fatty liver disease fibrosis score (NFS), Forns score, HUI score and BARD score were used. The CVOs covered major adverse cardiac event (MACEs), cardiovascular mortality and all-cause mortality. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: During a mean follow-up of 47.4 ± 24.8 months, 431 (11.6%) MACEs occurred. Kaplan-Meier analysis demonstrated that higher LFSs resulted in a significantly higher probability of CVOs. Compared to the lowest score group, multivariable-adjusted HRs (95% CIs) of the highest group of FIB-4, NFS, Forns score, HUI score and BARD score were 1.75 (1.32-2.33), 2.37 (1.70-3.33), 2.44 (1.61-3.73), 1.58 (1.16-2.14) and 1.27 (1.03-1.57) respectively. These LFSs were also independent predictors of cardiovascular mortality and all-cause mortality. Similar results were observed across subgroups analysis. The addition of LFSs to a prediction model significantly increased the C-statistic for CVOs. CONCLUSIONS: The present study firstly demonstrated that LFS could be used as a risk stratification tool for predicting CVOs in patients with previous MI, which should be evaluated further.

2.
Biosensors (Basel) ; 11(1)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33430067

RESUMO

Fumonisin B1 (FB1), a mycotoxin classified as group 2B hazard, is of high importance due to its abundance and occurrence in varied crops. Conventional methods for detection are sensitive and selective; however, they also convey disadvantages such as long assay times, expensive equipment and instrumentation, complex procedures, sample pretreatment and unfeasibility for on-site analysis. Therefore, there is a need for quick, simple and affordable quantification methods. On that note, aptamers (ssDNA) are a good alternative for designing specific and sensitive biosensing techniques. In this work, the assessment of the performance of two aptamers (40 and 96 nt) on the colorimetric quantification of FB1 was determined by conducting an aptamer-target incubation step, followed by the addition of gold nanoparticles (AuNPs) and NaCl. Although MgCl2 and Tris-HCl were, respectively, essential for aptamer 96 and 40 nt, the latter was not specific for FB1. Alternatively, the formation of Aptamer (96 nt)-FB1-AuNP conjugates in MgCl2 exhibited stabilization to NaCl-induced aggregation at increasing FB1 concentrations. The application of asymmetric flow field-flow fractionation (AF4) allowed their size separation and characterization by a multidetection system (UV-VIS, MALS and DLS online), with a reduction in the limit of detection from 0.002 µg/mL to 56 fg/mL.

3.
Stroke Vasc Neurol ; 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431513

RESUMO

Ischaemic stroke is a leading cause of long-term disability in the world, with limited effective treatments. Increasing evidence demonstrates that exosomes are involved in ischaemic pathology and exhibit restorative therapeutic effects by mediating cell-cell communication. The potential of exosome therapy for ischaemic stroke has been actively investigated in the past decade. In this review, we mainly discuss the current knowledge of therapeutic applications of exosomes from different cell types, different exosomal administration routes, and current advances of exosome tracking and targeting in ischaemic stroke. We also briefly summarised the pathology of ischaemic stroke, exosome biogenesis, exosome profile changes after stroke as well as registered clinical trials of exosome-based therapy.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33452034

RESUMO

Rieske non-heme iron oxygenases (ROs) catalyze the oxidation of a wide variety of substrates and play important roles in aromatic compound degradation along with polycyclic aromatic hydrocarbons degradation. Those Rieske dioxygenases that usually act on hydrophobic substrates have been extensively studied and structurally characterized. Here we report the crystal structure of a novel Rieske monooxygenase NagGH, the oxygenase component of a salicylate 5-monooxygenase from Ralstonia sp. strain U2 that catalyzes the hydroxylation of a hydrophilic substrate salicylate (2-hydroxybenzoate), forming gentisate (2, 5-dihydroxybenzoate). The large subunit NagG and small subunit NagH, share the same fold as that for their counterparts of Rieske dioxygenases and assemble the same α3ß3 hexamer though they share low (even none for NagH) sequence identities with those dioxygenase counterparts. A potential substrate binding pocket was observed in the vicinity of non-heme iron site. It featured a positively-charged residue Arg323 that was surrounded by hydrophobic residues. The shift of non-heme iron atom caused by residue Leu228 disrupted the usual substrate pocket observed in other ROs. Residue Asn218 at the usual substrate pocket observed in other ROs was exactly involved in substrate binding and oxidation, yet residues Gln316 and Ser367 away from that usual substrate pocket of other ROs played a more important role in substrate oxidation than Asn218. The unique binding pocket and unusual substrate-protein hydrophilic interaction provided new insight into Rieske monooxygenases.IMPORTANCE Rieske oxygenases are involved in the degradation of various aromatic compounds. Those dioxygenases, usually carry out hydroxylation of hydrophobic aromatic compounds and supply substrates with hydroxyl groups for extradiol/intradiol dioxygenases to cleave ring, have been extensively studied. Salicylate 5-hydroxylase NagGH is a novel Rieske monooxygenase with high similarity with Rieske dioxygenases, also shares reductase and ferredoxin with a Rieske dioxygenase naphthalene 1,2-dioxygenase (NagAcAd) in Ralstonia sp. strain U2. The structure of NagGH, the oxygenase component of salicylate 5-monooxygenase, gives a representative of those monooxygenases and will help us understand the mechanism of their substrate binding and product regioselectivity.

5.
BMJ Open ; 11(1): e037340, 2021 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-33455923

RESUMO

OBJECTIVE: The aim of the study was to investigate the impacts of triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) dyslipidaemia on prognosis in coronary artery disease (CAD) patients with different glucose metabolism status. DESIGN: An observational cohort study. SETTING/PARTICIPANTS: A total of 3057 patients with stable CAD were consecutively enrolled and divided into three groups according to different glucose metabolism status. Atherogenic dyslipidaemia (AD) was defined as TG ≥1.7 mmol/L and HDL-C <1.0 mmol/L for men or <1.3 mmol/L for women. The patients were further classified into six subgroups by status of AD. All subjects were followed up for the cardiovascular events (CVEs). PRIMARY OUTCOME MEASURES: The primary endpoints were cardiovascular mortality, non-fatal myocardial infarction and non-fatal stroke. RESULTS: During a median follow-up of 6.1 years, 308 (10.1%) CVEs occurred. No significant difference in the occurrence of CVEs was observed between normal glucose regulation (NGR) and pre-diabetes (pre-DM) groups (HR: 1.25, 95% CI 0.89 to 1.76) while DM group presented 1.45-fold higher risk of CVEs (HR: 1.45, 95% CI 1.02 to 2.05). When the participants were categorised according to combined status of two parameters, the cardiovascular risk was significantly elevated in pre-DM or DM plus AD group compared with the NGR plus non-AD group (HR: 1.76, 95% CI 1.10 to 2.80 and HR: 1.87, 95% CI 1.17 to 2.98). CONCLUSIONS: The present study suggested that the presence of AD might affect the prognosis in patients with DM or pre-DM and stable CAD.

6.
Theranostics ; 11(3): 1232-1248, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391532

RESUMO

Rationale: Glial scars present a major obstacle for neuronal regeneration after stroke. Thus, approaches to promote their degradation and inhibit their formation are beneficial for stroke recovery. The interaction of microglia and astrocytes is known to be involved in glial scar formation after stroke; however, how microglia affect glial scar formation remains unclear. Methods: Mice were treated daily with M2 microglial small extracellular vesicles through tail intravenous injections from day 1 to day 7 after middle cerebral artery occlusion. Glial scar, infarct volume, neurological score were detected after ischemia. microRNA and related protein were examined in peri-infarct areas of the brain following ischemia. Results: M2 microglial small extracellular vesicles reduced glial scar formation and promoted recovery after stroke and were enriched in miR-124. Furthermore, M2 microglial small extracellular vesicle treatment decreased the expression of the astrocyte proliferation gene signal transducer and activator of transcription 3, one of the targets of miR-124, and glial fibrillary acidic protein and inhibited astrocyte proliferation both in vitro and in vivo. It also decreased Notch 1 expression and increased Sox2 expression in astrocytes, which suggested that astrocytes had transformed into neuronal progenitor cells. Finally, miR-124 knockdown in M2 microglial small extracellular vesicles blocked their effects on glial scars and stroke recovery. Conclusions: Our results showed, for the first time, that microglia regulate glial scar formation via small extracellular vesicles, indicating that M2 microglial small extracellular vesicles could represent a new therapeutic approach for stroke.

7.
Mol Cell Endocrinol ; 522: 111138, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33352225

RESUMO

The apoptosis of foam cells leads to instability of atherosclerotic plaques. This study was designed to explore the protective role of CTRP9 in foam cell apoptosis. In our experiment, CTRP9 alleviated foam cell apoptosis. Meanwhile, CTRP9 upregulated the expression of proteins important for cholesterol efflux, such as LXRα, CYP27A1, ABCG1 and ABCA1, and improved cholesterol efflux in foam cells. Moreover, CTRP9 inhibited Wnt3a and ß-catenin expression and ß-catenin nuclear translocation in foam cells. In addition, adenovirus overexpression of Wnt3a abolished the effect of CTRP9 on macrophage apoptosis. Mechanistically, the AMPK inhibitor abolished the effect of CTRP9 on foam cell apoptosis, and downregulation of AdipoR1 by siRNA abrogated the activation of AMPK and the effect of CTRP9 on foam cell apoptosis. We concluded that CTRP9 achieved these protective effects on foam cells through the AdipoR1/AMPK pathway.

8.
J Affect Disord ; 278: 311-319, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32979562

RESUMO

BACKGROUND: The microbiome-gut-brain axis, especially the microbial tryptophan biosynthesis and metabolism pathway (MiTBamp), is closely connected to bipolar disorder with current major depressive episode (BPD). METHODS: We performed shotgun metagenomics sequencing (SMS) of faecal samples from 25 BPD patients and 28 healthy controls (HCs). Except for the microbiota taxa and MiTBamp analyses, we also built a classification model using the Random Forests (RF) and Boruta algorithm to find the microbial biomarkers for BPD. RESULTS: Compared to HCs, the phylum Bacteroidetes abundance was significantly reduced, whereas that of the Actinobacteria and Firmicutes were significantly increased in BPD patients. We also identified 38 species increased and 6 species decreased significantly in the BPD group. In the MiTBamp, we identified that two Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K00658 and K00837) were significantly lower in the BPD, and five KOs (K01696, K00382, K00626, K01667, and K03781) were significantly higher in the BPD group. We also identified significant genera and species which were closely related to these KOs. Finally, RF classification based on gut microbiota at the genus level can achieve an area under the receiver operating characteristic curve of 0.997. LIMITATIONS: The features of cross-sectional design, limited sample size, the heterogeneity of bipolar disorders, and a lack of serum/plasma tryptophan concentration measurements. CONCLUSIONS: The present findings enable a better understanding of changes in gastrointestinal microbiome and MiTBamp in BPD. Alterations of microbes may have potential as biomarkers for distinguishing the BPD patients form HCs.

9.
Coron Artery Dis ; 32(1): 78-83, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32804783

RESUMO

BACKGROUND: Lipoprotein(a) [Lp(a)] has been emerged as a risk factor for coronary artery disease (CAD), but there is currently insufficient data on the relationship between Lp(a) and premature CAD (PCAD). Thus, this study aimed to examine the association between Lp(a) and PCAD in a Chinese cohort. METHODS: Data on 2433 individuals (male <55 years old and female <65 years old) who underwent coronary angiography from March 2016 to February 2019 were included in this study and were divided into the PCAD group (n = 1751) and non-CAD group (n = 682) according to the angiography results. Their clinical and laboratory parameters were collected, and plasma Lp(a) level was measured by immunoturbidimetry. The severity of CAD was evaluated using Gensini score (GS) and divided into three subgroups. The relationship between plasma Lp(a) levels and the presence and severity of PCAD was analyzed. RESULTS: The level of plasma Lp(a) in the PCAD group was significantly higher than that in the non-CAD group (P < 0.001). The plasma Lp(a) concentration in the highest GS group was significantly higher than that in the lowest GS group (P < 0.001). Multivariate linear regression analysis showed that elevated plasma Lp(a) levels were correlated with higher GS (b = 0.41, P < 0.001). Multivariate logistic regression showed that elevated plasma Lp(a) levels were independently associated with PCAD (odds ratio = 2.91, P < 0.001). Moreover, elevated plasma Lp(a) levels correlated with higher GS (b = 0.41, P < 0.001). CONCLUSION: In this study, Lp(a) concentration was associated with the presence and severity of PCAD, suggesting that Lp(a) may be a marker or target for patients with PCAD.

10.
Eur J Radiol ; 134: 109404, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33276248

RESUMO

PURPOSE: To perform a meta-analysis evaluating the diagnostic accuracy of the Liver Imaging Reporting and Data System (LI-RADS) category ≥ 3 (LI-RADS 3-5v) for detecting hepatocellular carcinoma (HCC). METHOD: A systematic PubMed, Embase, and Web of Science electronic database search was performed for original diagnostic studies published through July 31, 2018. Statistical analysis included data pooling, forest plot construction, heterogeneity testing, meta-regression, and subgroup analyses. RESULTS: Eighteen studies (v2011, v2014 and v2017) involving 3386 patients were included in the meta-analysis. The pooled sensitivity and specificity of LI-RADS ≥ 3 for diagnosing HCC were 0.86 (95 % confidence interval (CI): 0.78-0.91) and 0.85 (95 % CI: 0.78-0.90), respectively. The area under the curve (AUC) was 0.92 (95 % CI: 0.89-0.94). Meta-regression analysis showed that the publication year, blinding to the reference standard and the number of readers were significant factors affecting heterogeneity. In subgroup analyses, magnetic resonance imaging (MRI) demonstrated higher sensitivity (0.82 vs. 0.73) and comparable specificity (0.79 vs. 0.78) than computed tomography (CT). For HCCs ≤30 mm, LI-RADS showed lower sensitivity of 0.72 and specificity of 0.80 compared with HCC of all sizes. LR-5 showed higher sensitivity and specificity than LR-3 (sensitivity: 0.67 vs. 0.07, P = 0.02; specificity: 0.93 vs. 0.75, p < 0.001) and higher sensitivity than LR-4 (sensitivity: 0.67 vs. 0.29, P = 0.02; specificity: 0.93 vs. 0.80, p = 0.75). LR ≥ 5 had higher specificity at the cost of decreased sensitivity than LR ≥ 3 (specificity: 0.94 vs. 0.68, p < 0.001; sensitivity: 0.66 vs. 0.74, P = 0.70) and LR ≥ 4 (specificity: 0.94 vs. 0.84, p < 0.001; sensitivity: 0.66 vs. 0.74, P = 0.77). CONCLUSIONS: LI-RADS ≥ 3 shows high diagnostic accuracy for HCCs, with a pooled sensitivity of 0.86 and specificity of 0.85. The specificity is higher for LR-5 and LR ≥ 5. However, further prospective studies on LI-RADS ≥ 3 are needed to elucidate its value for diagnosing small HCCs (≤20 mm).

11.
Insights Imaging ; 11(1): 131, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33296046

RESUMO

OBJECTIVES: While the Novel Coronavirus (COVID-19) pandemic looks to persist, institutions promote delaying procedures. Understanding trends and demands of interventional radiology (IR) procedures in the infected and COVID-free populations are needed in long-term planning. We detail IR procedure trends in the first 27 weeks of the pandemic and compare with the pre-pandemic era. METHODS: In this IRB approved retrospective electronic case review, all IR patients in our institution from 1 January to 9 July 2020, the same period in 2019 pre-pandemic and the Severe Acute Respiratory Syndrome (SARS-CoV) outbreak were included. IR procedures were classified using Interventional Radiology-Procedure Acuity Scale (IR-PAS) and category of IR procedures. Along with descriptive frequencies, the Mann-Whitney U test and Chi-square test of independence were performed. RESULTS: During the pandemic, 3655 IR procedures were performed compared to 3851 procedures pre-pandemic. No statistically significant difference in weekly IR caseloads across IR-PAS tiers between both periods (p = .088) and category of procedure (p = .054) were noted. General intervention procedures remained the largest proportion and musculoskeletal procedures the minority, in both periods. More general intervention radiology and oncology procedures were performed during the COVID-19 pandemic compared to the SARS-CoV outbreak. Thirty-four (0.93%) IR procedures were performed on 30 COVID-19 patients. There was no IR procedure-related COVID-19 cross-transmission. CONCLUSIONS: Demand for IR procedures among COVID-free patients remains high, and IR procedures involving COVID-19 represents a fraction of the IR caseload. A sustainable model in providing timely IR services to COVID-free patients needs to be considered.

12.
Korean J Radiol ; 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33289356

RESUMO

OBJECTIVE: To evaluate the radiological tumor response patterns and compare the response assessments based on immune-based therapeutics Response Evaluation Criteria in Solid Tumors (iRECIST) and RECIST 1.1 in metastatic clear-cell renal cell carcinoma (mccRCC) patients treated with programmed cell death-1 (PD-1) inhibitors. MATERIALS AND METHODS: All mccRCC patients treated with PD-1 inhibitors at Henan Cancer Hospital, China, between January 2018 and April 2019, were retrospectively studied. A total of 30 mccRCC patients (20 males and 10 females; mean age, 55.6 years; age range, 37-79 years) were analyzed. The target lesions were quantified on consecutive CT scans during therapy using iRECIST and RECIST 1.1. The tumor growth rate was calculated before and after therapy initiation. The response patterns were analyzed, and the differences in tumor response assessments of the two criteria were compared. The intra- and inter-observer variabilities of iRECIST and RECIST 1.1 were also analyzed. RESULTS: The objective response rate throughout therapy was 50% (95% confidence interval [CI]: 32.1-67.9) based on iRECIST and 30% (95% CI: 13.6-46.4) based on RECIST 1.1. The time-to-progression (TTP) based on iRECIST was longer than that based on RECIST 1.1 (median TTP: not reached vs. 170 days, p = 0.04). iRECIST and RECIST 1.1 were discordant in 8 cases, which were evaluated as immune-unconfirmed PD based on iRECIST and PD based on RECIST 1.1. Six patients (20%, 6/30) had pseudoprogression based on iRECIST, of which four demonstrated early pseudoprogression and two had delayed pseudoprogression. Significant differences in the tumor response assessments based on the two criteria were observed (p < 0.001). No patients demonstrated hyperprogression during the study period. CONCLUSION: Our study confirmed that the iRECIST criteria are more capable of capturing immune-related atypical responses during immunotherapy, whereas conventional RECIST 1.1 may underestimate the benefit of PD-1 inhibitors. Pseudoprogression is not rare in mccRCC patients during PD-1 inhibitor therapy, and it may last for more than the recommended maximum of 8 weeks, indicating a limitation of the current strategy for immune response monitoring.

13.
Thromb Haemost ; 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33339063

RESUMO

Lipoprotein(a) [Lp(a)] has been documented to be associated with atherothrombotic diseases. However, the prognostic impact of Lp(a) on long-term clinical outcomes among patients with previous myocardial infarction (MI) remains unclear. In this prospective cohort study, we consecutively enrolled 3864 post-MI patients to assess the cardiovascular events (CVEs), including MI, ischemic stroke, and cardiac mortality. Lp(a) levels were determined using an immunoturbidimetry assay and the participants were categorized according to Lp(a) quartiles. Cox proportional hazards model was used to calculate hazard ratios (HR) with 95% confidence intervals (CI). During a median follow-up of 4.1 years, 331 (8.6%) CVEs were identified. Lp(a) was significantly higher in the patients with CVEs [25.17 (11.13-47.83) vs. 18.18 (7.90-40.30) mg/dL, p=0.001]. The cumulative rates of CVEs and cardiac mortality were significantly higher in patients with high Lp(a) levels (both log-rank p<0.001). Multivariate Cox regression analysis showed a significant correlation between Lp (a) levels treated as a natural logarithm-transformed continuous variable and increased CVEs (adjusted HR:1.22, 95%CI:1.09-1.35, p=0.001) or cardiac mortality (HR:1.30, 95%CI:1.14-1.48, p<0.001). The addition of Lp(a) to a prognostic model revealed a significant improvement in C-statistic, net reclassification and integrated discrimination. In conclusion, elevated levels of Lp(a) were indeed associated with long-term worse outcomes in patients with prior MI, suggesting a novel hint that the measurement of Lp(a) might help to risk stratification and future management in those high-risk individuals.

14.
J Biomed Nanotechnol ; 16(7): 1065-1081, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33308375

RESUMO

Cardiovascular disease (CVD) is one of the most serious health disorders with increasing prevalence and high morbidity and mortality. Although diagnosis and treatment of CVD have achieved huge breakthrough in recent years, it still needs additional enhancements, which result in the demand for new techniques. Artificial intelligence (AI) is an emerging science field that has been widely used to guide diseases diagnosis, evaluation and treatment. AI techniques are promising in CVD to explore novel pathogenic genes phenotype, guide optimal individualized therapeutic strategy, improve the management and quality of discharged patients, predict disease prognosis, and as adjuvant therapy tool. Thus, we summarize the latest application of AI techniques in clinical diagnosis, evaluation and treatment of CVD, aiming to provide novel beneficial evidence of AI and promote its application in CVD.


Assuntos
Inteligência Artificial , Doenças Cardiovasculares , Humanos
15.
ACS Sens ; 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33332104

RESUMO

Second-harmonic generation (SHG) integrated with diverse nonlinear optical activity characterization has high sensitivity to detect the symmetry of materials at an interface, but the study is in its infancy. Here, we employ SHG with linear dichroism (or SHG-LD) to study the chiroptical origin of silver (Ag) chiral nanoparticles (CNPs) deposited by glancing angle deposition (GLAD). It is found that Ag CNPs show the chiroptical activity ascribed to not only the structural chirality (i.e., atomically chiral lattices) but also one-fold anisotropy at an interface due to the substrate rotation during GLAD. Therefore, the SHG-LD shows great potential to provide valuable complementary information to study the chiroptical properties of chiral metamaterials.

16.
Chem Commun (Camb) ; 56(92): 14401-14403, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33141126

RESUMO

A novel ligand (6) for copper-catalyzed azide-alkyne cycloaddition (CuAAC) in bioconjugation has been developed. Both in vitro and in vivo experiments indicate that 6 is more efficient and less cytotoxic than the canonical CuAAC ligands. Besides, 6 is easily accessible and can be prepared at gram scale. Our study reveals that 6 might be an ideal CuAAC ligand for bioconjugations.

17.
J Hypertens ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33186323

RESUMO

OBJECTIVE: Previous studies have demonstrated that small dense LDL-cholesterol (sdLDL-C) is related to the pathogenesis of coronary artery disease (CAD). However, its prognostic role in hypertensive patients with CAD has been undetermined. The aim of the study was to investigate the association between sdLDL-C with disease severity, hypertensive status and clinical outcome in patients with CAD. METHODS: A total of 4594 patients with angiography-proven CAD were consecutively enrolled and categorized into subgroups according to blood pressure status. Serum sdLDL-C levels were measured by direct quantitative measurement using automated chemistry analyzers. The severity of coronary artery lesions were determined by Gensini score, Syntax score and the number of lesion vessels. The associations of sdLDL-C with disease severity, hypertensive status and cardiovascular events (CVEs) were evaluated. RESULTS: Patients with hypertension had higher sdLDL-C levels than ones without (P = 0.010). In hypertensive patients, sdLDL-C was positively associated with the severity of CAD (P < 0.05). In addition, hypertensive patients with poorly controlled hypertension had higher sdLDL-C levels than those with well controlled (P < 0.05). Moreover, 149 CVEs occurred in patients with poorly controlled hypertension and Cox regression analysis indicated that elevated sdLDL-C levels were independently associated with CVEs in hypertensive patients with poorly controlled hypertension (adjusted hazard ratio: 1.673, 95% confidence interval: 1.105-2.535, P = 0.015). CONCLUSION: The current data, for the first time, showed that serum sdLDL-C levels were correlated with hypertension control, disease severity and worse outcomes in hypertensive patients with CAD, suggesting that paying more attention on sdLDL-C in these patients were warranted.

18.
Dalton Trans ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33201957

RESUMO

A new hybrid lead(ii) halide perovskite, (TzH)2PbCl4, ([TzH+] = 1,2,4-triazolium), adopts a (001)-oriented layered perovskite structure, which can be considered as derived from the n = 1 Ruddlesden-Popper (RP) type. Variable temperature single crystal X-ray diffraction reveals a structural phase transition in the region 125 K < T < 173 K between a high temperature, high symmetry polymorph, space group Cmcm, and a low temperature, low symmetry chiral polymorph, space group P212121, which has a tripled unit cell volume. UV-Vis spectra suggest a band gap of 3.30 eV for (TzH)2PbCl4. A second polymorph of the bromide analogue, (TzH)2PbBr4-II, is also reported, and structural relationships between all three variants are discussed.

19.
Injury ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33139034

RESUMO

Intramedullary nails are the common treatment options for femoral intertrochanteric fractures. However, aseptic loosening is considered to be one of the primary forms of failure that can be caused by the stress shielding between the bone and implants. The matching in mechanical properties of implant and bone is a key issue to prevent this failure. Polyetheretherketone (PEEK) and Function-graded (FG) materials are widely used in clinical because of their excellent mechanical properties. In this study, to investigate the biomechanical behaviors of intramedullary nails made of Ti-6Al-4V alloy, Stainless Steel (SS), PEEK and two FG materials, three-dimensional finite element models of intertrochanteric fracture femur with intramedullary nail were constructed with ABAQUS. The maximum von Mises stress on the femoral fracture surface fixed by PEEK intramedullary nail was the largest, followed by FG intramedullary nail, which help stimulate bone growth and subsequently reduce fracture healing time. Compared with traditional metal intramedullary nails, PEEK and FG implants might increase von Mises stress along the same path in the proximal femur. The results showed that PEEK and FG intramedullary nails obviously changed the stress distributions in the bone and reduced stress shielding. This finding indicated that PEEK and FG intramedullary nails have the potential to become alternatives to the conventional metal intramedullary nails.

20.
J Neuroinflammation ; 17(1): 329, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33153476

RESUMO

BACKGROUND: Neuroinflammation is the major pathogenesis of cerebral ischemia. Microglia are activated and polarized to either the pro-inflammatory M1 phenotype or anti-inflammatory M2 phenotype, which act as a critical mediator of neuroinflammation. Sestrin2 has pro-survival properties against ischemic brain injury. However, whether sestrin2 has an anti-inflammatory function by shifting microglia polarization and its underlying mechanism is unknown. METHODS: Adult male C57BL/6 mice (N = 108) underwent transient middle cerebral artery occlusion (tMCAO) and were treated with exogenous sestrin2. Neurological deficit scores and infarct volume were determined. Cell apoptosis was examined by TUNEL staining and Western blotting. The expression of inflammatory mediators, M1/M2-specific markers, and signaling pathways were detected by reverse transcription-polymerase chain reaction, immunostaining, and Western blotting. To explore the underlying mechanism, primary neurons were subjected to oxygen-glucose deprivation (OGD) and then treated with oxygenated condition medium of BV2 cells incubated with different doses of sestrin2. RESULTS: Sestrin2 attenuated the neurological deficits, infarction volume, and cell apoptosis after tMCAO compared to those in the control (p < 0.05). Sestrin2 had an anti-inflammatory effect and could suppress M1 microglia polarization and promote M2 microglia polarization. Condition medium from BV2 cells cultured with sestrin2 reduced neuronal apoptosis after OGD in vitro. Furthermore, we demonstrated that sestrin2 drives microglia to the M2 phenotype by inhibiting the mammalian target of rapamycin (mTOR) signaling pathway and restoring autophagic flux. CONCLUSIONS: Sestrin2 exhibited neuroprotection by shifting microglia polarization from the M1 to M2 phenotype in ischemic mouse brain, which may be due to suppression of the mTOR signaling pathway and the restoration of autophagic flux.

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