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1.
Clin Exp Rheumatol ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33822701

RESUMO

OBJECTIVES: No approved pharmacotherapies are available for patients with interstitial pneumonia with autoimmune features (IPAF). In the present work, we aimed to evaluate the efficacy and safety of pirfenidone for the treatment of IPAF. METHODS: A retrospective cohort study consisting of patients who met diagnostic criteria for IPAF was performed after a multidisciplinary review, and the patients receiving pirfenidone were compared with those in the non-pirfenidone group. The baseline data and diagnostic characteristics of patients were assessed. Pulmonary function and prednisone dose were analysed by a mix-effects model. RESULTS: A total of 184 patients, who met the diagnostic criteria of IPAF, were divided into two groups: pirfenidone group (n=81) and non-pirfenidone group (n=103). Patients in the pirfenidone group had a lower forced vital capacity (FVC%, p<0.001) and a lower diffusion capacity for carbon monoxide (DLCO%, p=0.003). The pirfenidone group exhibited a greater increase of FVC% at 6 (p=0.003), 12 (p=0.013), and 24 (p=0.003) months. After adjustment for sex, age, UIP pattern, baseline FVC% and DLCO%, patients in the pirfenidone group continued to show a greater improvement in FVC% (χ2(1)=4.59, p=0.032). Subgroup analysis identified superior therapeutic effects of pirfenidone in patients with dosage >600 mg/day (p=0.010) and medication course >12 months (p=0.007). Besides, the pirfenidone group had a lower prednisone dose than the non-pirfenidone group after 12 months of treatment (p=0.002). Moreover, 17 patients (19.32%) experienced side effects after taking pirfenidone, including one case of anaphylactic shock. CONCLUSIONS: Pirfenidone (600-1,800 mg/day) might help improve FVC, with an acceptable safety and tolerability profile in IPAF patients.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33834866

RESUMO

Extracellular matrix (ECM) exerts a list of biological functions, contributing to almost 30% of the osteogenic process. Periostin is a secreted protein that can alter ECM remodeling in response to vascular injury. However, the functional role of periostin in vascular calcification has yet to be fully described. Ex vivo, recombinant periostin accelerated thoracic aortas calcification, increased the expression of glycolysis key enzymes, and disturbed the normal oxidative phosphorylation (OXPHOS), which could be alleviated by the peroxisome proliferation-activated receptor γ (PPARγ) agonist pioglitazone. In vascular smooth muscle cells (VSMCs), recombinant periostin promoted VSMC-osteoblastic phenotype transition and calcium deposition, and suppressed PPARγ expression. Mechanistically, recombinant periostin caused over-activation of glycolysis and mitochondrial dysfunction in VSMCs, as assessed by extracellular acidification rate (ECAR), oxygen consumption rate, and mitochondrial respiratory chain complexes activities. Targeted glycolysis inhibitors reduced mitochondrial calcium overload, apoptosis, and periostin-induced VSMCs calcification. PPARγ agonists preserved glycolysis and OXPHOS in the stimulated microenvironment, and reversed periostin-promoted VSMC calcification. Furthermore, plasma periostin, lactate, and matrix Gla protein levels were measured in 274 patients who underwent computed tomography to determine coronary artery calcium score (Agatston score). Plasma periostin and lactate levels were both linked to an Agatston score of more than zero in patients with coronary artery calcification. There is also a positive correlation between plasma periostin and lactate levels. This study suggests that downregulation of PPARγ is involved in the mechanism by which periostin accelerates arterial calcification, partly through excessive glycolysis activation and unbalanced mitochondrial homeostasis.

3.
Environ Int ; 153: 106538, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33839551

RESUMO

BACKGROUND: Exposure to multiple metals is recognized as a common and real scenario in daily life. However, limited prospective studies have assessed associations between multiple metals exposure and hypertension. METHODS: In total, 2625 adults in a local area on the Yangtze River were investigated at baseline from 2014 to 2015 and followed up in 2019. We measured baseline urine levels of 22 metals and used multivariate logistic analysis and Bayesian kernel machine regression (BKMR) to explore associations between multiple metals exposure and the risk of hypertension. RESULTS: A total of 385 individuals (29.6%) were diagnosed with hypertension. Five metals (cadmium, copper, magnesium, molybdenum and zinc) were positively associated with hypertension in single-metal models. Cadmium and zinc remained significantly positive associations after adjusting for these five metals, with the odds ratio (OR) in the highest quartiles of 1.49 (95% CI: 1.01, 2.21; p-trend = 0.05) and 1.60 (95% CI: 1.08, 2.38; p-trend = 0.02), respectively. BKMR analysis showed a significant joint effect of multiple metals on hypertension when the concentrations of five metals were at or above their 55th percentile compared with their median values. A potential interaction between cadmium and zinc in increasing the risk of hypertension was observed with the ORint of 1.41 (95%CI: 1.05, 1.89). CONCLUSIONS: We identified the joint effect of multiple metals on hypertension and observed a significant interaction between cadmium and zinc. Further cohort studies are needed to clarify the health effects of multiple metals exposure in a larger population.

4.
Int J Med Sci ; 18(9): 1999-2007, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33850470

RESUMO

Precartilaginous stem cells (PCSCs) are able to initiate chondrocyte and bone development. The present study aimed to investigate the role of miR-143 and the underlying mechanisms involved in PCSC proliferation. In a rat growth plate injury model, tissue from the injury site was collected and the expression of miR-143 and its potential targets was determined. PCSCs were isolated from the rabbits' distal epiphyseal growth plate. Cell viability, DNA synthesis, and apoptosis were determined with MTT, BrdU, and flow cytometric analysis, respectively. Real time PCR and western blot were performed to detect the mRNA and protein expression of the indicated genes. Indian hedgehog (IHH) was identified as a target gene for miR-143 with luciferase reporter assay. Decreased expression of miR-143 and increased expression of IHH gene were observed in the growth plate after injury. miR-143 mimics decreased cell viability and DNA synthesis and promoted apoptosis of PCSCs. Conversely, siRNA-mediated inhibition of miR-143 led to increased growth and suppressed apoptosis of PCSCs. Transfection of miR-143 decreased luciferase activity of wild-type IHH but had no effect when the 3'-UTR of IHH was mutated. Furthermore, the effect of miR-143 overexpression was neutralized by overexpression of IHH. Our study showed that miR-143 is involved in growth plate behavior and regulates PCSC growth by targeting IHH, suggesting that miR-143 may serve as a novel target for PCSC-related diseases.

5.
Micromachines (Basel) ; 12(3)2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33803645

RESUMO

The tiny magnetic steel pair (TMSP), composed by two tiny magnetic steel blocks (TMSBs), is critical for some precision instruments. Incorrect matching of TMSP may result in insufficient instrument performance. Herein, the matching method of TMSP based on the Kuhn-Munkres algorithm is proposed. Further, an automatic TMSP matching device is developed. Especially, an ingenious clamp for multiple constraints of TMSB is presented and a visual/magnetism/force hybrid control strategy is realized for the safe and efficient manipulation of TMSBs in a magnetic environment. Moreover, with the TMSBs of a pendulum accelerometer, the matching experiments are conducted to validate the comprehensive performance. The result of the numerical experiment shows that the Kuhn-Munkres algorithm-based method is stable and efficient. The results of measurement and TMSP matching experiments show that the device has good repeatability (<1 mT) and practicability. The proposed matching method has great application prospect in various matching and microassembly of TMSPs.

6.
Pharmacol Res ; 167: 105571, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33753244

RESUMO

Emerging evidence supports an essential role of trace amine-associated receptor 1 (TAAR1) in neuropsychiatric disorders such as depression and schizophrenia. Stressful events are critical contributors to various neuropsychiatric disorders. This study examined the role of TAAR1 in mediating the negative outcomes of stressful events. In mice that experienced chronic social defeat stress but not acute stress, a significant reduction in the TAAR1 mRNA level was found in the medial prefrontal cortex (mPFC), a brain region that is known to be vulnerable to stress experience. Conditional TAAR1 knockout in the mPFC mimicked the cognitive deficits induced by chronic stress. In addition, chronic treatment with the selective TAAR1 partial agonist RO5263397 ameliorated chronic stress-induced changes in cognitive function, dendritic arborization, and the synapse number of pyramidal neurons in the mPFC but did not affect chronic stress-induced anxiety-like behaviors. Biochemically, chronic stress reduced the ratio of vesicular transporters of glutamate-1 (VGluT1) / vesicular GABA transporter (VGAT) in the mPFC,most prominently in the prelimbic cortex, and RO5263397 restored the excitatory-inhibitory (E/I) imbalance. Together, the results of this study reveal an essential role of TAAR1 in mediating chronic stress-induced cognitive impairments and suggest that TAAR1 agonists may be uniquely useful to treat MDD-related cognitive impairments.

7.
BMC Med Imaging ; 21(1): 54, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33743615

RESUMO

BACKGROUND: Distinguishing parotid pleomorphic adenoma (PPA) from parotid adenolymphoma (PA) is important for precision treatment, but there is a lack of readily available diagnostic methods. In this study, we aimed to explore the diagnostic value of radiomic signatures based on magnetic resonance imaging (MRI) for PPA and PA. METHODS: The clinical characteristic and imaging data were retrospectively collected from 252 cases (126 cases in the training cohort and 76 patients in the validation cohort) in this study. Radiomic features were extracted from MRI scans, including T1-weighted imaging (T1WI) sequences and T2-weighted imaging (T2WI) sequences. The radiomic features from three sequences (T1WI, T2WI and T1WI combined with T2WI) were selected using univariate analysis, LASSO correlation and Spearman correlation. Then, we built six quantitative radiomic models using the selected features through two machine learning methods (multivariable logistic regression, MLR, and support vector machine, SVM). The performances of the six radiomic models were assessed and the diagnostic efficacies of the ideal T1-2WI radiomic model and the clinical model were compared. RESULTS: The T1-2WI radiomic model using MLR showed optimal discriminatory ability (accuracy = 0.87 and 0.86, F-1 score = 0.88 and 0.86, sensitivity = 0.90 and 0.88, specificity = 0.82 and 0.80, positive predictive value = 0.86 and 0.84, negative predictive value = 0.86 and 0.84 in the training and validation cohorts, respectively) and its calibration was observed to be good (p > 0.05). The area under the curve (AUC) of the T1-2WI radiomic model was significantly better than that of the clinical model for both the training (0.95 vs. 0.67, p < 0.001) and validation (0.90 vs. 0.68, p = 0.001) cohorts. CONCLUSIONS: The T1-2WI radiomic model in our study is complementary to the current knowledge of differential diagnosis for PPA and PA.

8.
Langmuir ; 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33760619

RESUMO

Sweeping deposited particles is absolutely essential in order to maintain the excellent functionality of superhydrophobic surfaces. Many methods have been proposed to sweep microparticles deposited on tips of micro/nanostructures. However, how to sweep nanoparticles trapped in cavities of superhydrophobic surfaces has remained an outstanding issue. Here, we show that harnessing the reversible wetting transition provides a feasible way to sweep such nanoparticles. Using molecular dynamics simulations, we demonstrate that the electrically induced CB-W wetting transition makes liquid intrude into a groove and wet a trapped hydrophilic nanoparticle; however, once the electric field is removed, a spontaneous W-CB dewetting transition happens, and the extruded liquid transports the hydrophilic nanoparticle to the groove top, successfully picking up the trapped hydrophilic nanoparticle. We further find that the adhesion between the nanoparticle and groove bottom wall hinders the successful pickup, and picking up such a nanoparticle requires a stronger particle hydrophilicity. With the introduction of amphiphilic Janus particles into a liquid, we exhibit that the electrically induced reversible wetting transition can also successfully pick up a trapped hydrophobic nanoparticle. By means of calculations of the potential of mean force (PMF), we reveal pathways of both the CB-W wetting transition and the W-CB dewetting transition and hence answer why and how a hydrophilic or a hydrophobic nanoparticle is picked up successfully.

9.
Clin Transl Gastroenterol ; 12(3): e00321, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33704100

RESUMO

INTRODUCTION: Strong evidence indicates that multiple genetic and environmental risk factors play a role in the pathogenesis of nonalcoholic steatohepatitis (NASH). We aimed to develop and validate a novel nomogram, incorporating both genetic and clinical factors, for predicting NASH. METHODS: A total of 1,070 Asian individuals with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) from 2 countries (China and South Korea) were recruited. The histological spectrum of NAFLD was classified according to the NASH clinical research network scoring system. The nomogram was developed in the Chinese training set (n = 402), and then, it was validated in both the Chinese internal validation set (n = 136) and the external Korean validation cohort (n = 532), respectively. RESULTS: Sex, metabolic syndrome, insulin resistance, serum aspartate aminotransferase levels, and PNPLA3 (rs738409) and HSD17B13 (rs72613567) genetic variants were strongly associated with NASH. Based on their regression coefficients, we developed a nomogram with good discriminatory ability (area under the receiver operating characteristic curve: 0.81, 95% confidence interval [CI] 0.77-0.85) and good calibration (Hosmer-Lemeshow test, P = 0.794) for identifying NASH. In the 2 validation cohorts, the nomogram showed high area under the receiver operating characteristic curves (internal validation set: 0.80, 95% CI 0.72-0.88; external validation cohort: 0.76, 95% CI 0.72-0.80) and good calibration. DISCUSSION: Our newly developed and externally validated nomogram, incorporating both genetic and clinical risk factors, may be conveniently used to predict NASH. Further validation studies in other ethnic groups are warranted to confirm its diagnostic utility to identify NASH, among patients with biopsy-proven NAFLD.

10.
Orthop Surg ; 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33709625

RESUMO

OBJECTIVE: To explore the kinematic biomechanical changes and symmetry in the left and right sides of the facet joints of lumbar spine segments under different functional loads. METHODS: Participants (n = 10) performing standing flexion and extension movements were scanned using computed tomography (CT) and dual fluoroscopy imagine system. Instantaneous images of the L3 -S1 vertebrae were captured, and by matching a three-dimensional CT model with contours from dual fluoroscopy images, in vivo facet joint movements were reproduced and analyzed. Translations and rotations of lumbar vertebral (L3 and L4 ) facet joints of data were compared for different loads (0, 5, 10 kg). The participants performed flexion and extension movements in different weight-bearing states, the translations and angles changes were calculated respectively. RESULTS: From standing to extension, there were no statistical differences in rotation angles for the facet joint processes of different vertebral segment levels under different weight loads (P > 0.05). Mediolateral axis and cranio-caudal translations under different weight loads were not statistically different for vertebral segment levels (P > 0.05). Anteroposterior translations for L3 (1.4 ± 0.1 mm) were greater than those for L4 (1.0 ± 0.1 mm) under the different load conditions (P = 0.04). Bilaterally, mediolateral, anteroposterior, and cranio-caudal translations of the facet joints under different weights (0, 10 kg) for each segment level (L3 and L4 ) were symmetric (P > 0.05). From flexion to standing, there were no statistical differences in rotation angles for different weights (0, 5, 10 kg) for each level (L3 and L4 ) (P > 0.05). There were no statistical differences between mediolateral, anteroposterior, and cranio-caudal translations at each segment level (L3 and L4 ) under different loads (P > 0.05). Under the condition of no weight (0 kg), L3 mediolateral translations on the left side (1.7 ± 1.6 mm) were significantly greater (P = 0.03) than those on the right side (1.6 ± 1.6 mm). Left side (1.0 ± 0.7 mm) L4 mediolateral translations were significantly smaller (P = 0.03) than those on the right side (1.1 ± 0.7 mm). There were no statistical differences between different weights for either anteroposterior and cranio-caudal translations (P > 0.05). There were no statistical differences for mediolateral, anteroposterior, and cranio-caudal translations for 10 kg (P > 0.05). CONCLUSION: Lumbar spine facet joint kinematics did not change significantly with increased loads. Anteroposterior translations for L3 were greater than those for L4 of the vertebral segments are related to the coronal facet joint surface. Changes in facet surface symmetry indicates that the biomechanical pattern between facet joints may change.

11.
Langmuir ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33529533

RESUMO

In transfer printing, the loaded droplet on the probe has a significant influence on the dispensing resolution. A suitable loading approach for a high-viscous liquid is highly required. Herein, a novel electrostatic loading method is presented, in which the main aim is to control precisely the formation and breaking of a cone-shaped liquid bridge. An experimental device is developed. The influence of electrical and geometric parameters on the feature size of the liquid bridge is investigated in detail. In the formation of the liquid bridge, the increase of voltage or the decrease of the air gap can enhance the electric field intensity, thus reducing the formation period and increasing the initial cone tip diameter of the liquid cone. After the liquid bridge is formed, both the circuit current implying the liquid wetted area on the probe surface and the lifting velocity of the probe are utilized to further regulate the volume of the loaded droplet. Loaded droplets ranging from 60 to 600 pL are obtained via the method with a standard deviation of 4 to 30 pL. Moreover, a dot array is transferred with different loaded droplets. The minimum diameter of the printed dots is about 140 µm with a variation less than 5%. The advantages include the reduced risk of contamination, the droplet-size independent of the size of the probe, and the low cost of the device.

12.
Clin Appl Thromb Hemost ; 27: 1076029621989813, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33523719

RESUMO

Brain-derived neurotrophic factor (BDNF) plays a functional role in vascular endothelium homeostasis and the alleviation of atherosclerosis. Matrix gla protein (MGP) and Nε-(1-carboxymethyl)-l-lysine (CML) are both confirmed to be VC predictors. This study investigated the association between BDNF, MGP, CML and coronary artery calcification (CAC). Plasma BDNF, MGP, and CML levels were measured in 274 patients who underwent computed tomography to determine the CAC score (Agatston score). It was found that patients with CAC exhibited lower BDNF and MGP and higher CML levels than those without CAC. Plasma BDNF levels in patients with diabetes or hypertension were lower compared with the control groups. In logistic regression analysis, age, hypertension, BDNF, and MGP were independent predictors of CAC. Plasma BDNF and MGP levels were both correlated with the Agatston score even after adjustment for age, total cholesterol level, triglycerides, low-density lipoprotein level, creatinine clearance rate, and the presence of hypertension and diabetes mellitus. In 167 patients with CAC, circulating BDNF level was inversely associated with CML level and positively related to MGP level. In the receiver operating characteristic analysis for CAC, the areas under the curves for BDNF, MGP, and CML were 0.757, 0.777 and 0.653, respectively. In summary, plasma BDNF levels are associated with the Agatston score, and BDNF further predicts the occurrence of CAC.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Doença da Artéria Coronariana/sangue , Calcificação Vascular/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteínas de Ligação ao Cálcio/sangue , Estudos de Casos e Controles , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Estudos Transversais , Proteínas da Matriz Extracelular/sangue , Feminino , Humanos , Lisina/análogos & derivados , Lisina/sangue , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Calcificação Vascular/diagnóstico por imagem
13.
J Phys Chem B ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33412855

RESUMO

We use the pulse current thermoplastic forming technique based on joule heating to rejuvenate the atomic structure of a La62Al14Ag2.34Ni10.83Co10.83 bulk metallic glass (BMG). The pulse-formed sample exhibits more pronounced ß-relaxation than the as-cast one due to the increased free volume. Instead, the sub-Tg annealing clearly weakens the ß-relaxation and also makes it more isolated from the α-relaxation, showing contributions from free volume and preferred structure. However, both treatments exhibit little influence on the following α-relaxation and high temperature crystallization kinetics. Our results open an effective way to rejuvenate the structure of BMGs and provide an in-depth understanding of the relationship between structural relaxations and crystallization kinetics of BMGs.

14.
Cell Res ; 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514914

RESUMO

Cathepsin D (cathD) is traditionally regarded as a lysosomal protease that degrades substrates in acidic compartments. Here we report cathD plays an unconventional role as a cofilin phosphatase orchestrating actin remodeling. In neutral pH environments, the cathD precursor directly dephosphorylates and activates the actin-severing protein cofilin independent of its proteolytic activity, whereas mature cathD degrades cofilin in acidic pH conditions. During development, cathD complements the canonical cofilin phosphatase slingshot and regulates the morphogenesis of actin-based structures. Moreover, suppression of cathD phosphatase activity leads to defective actin organization and cytokinesis failure. Our findings identify cathD as a dual-function molecule, whose functional switch is regulated by environmental pH and its maturation state, and reveal a novel regulatory role of cathD in actin-based cellular processes.

15.
Sci Adv ; 6(50)2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33298434

RESUMO

Organelle transport requires dynamic cytoskeleton remodeling, but whether cytoskeletal dynamics are, in turn, regulated by organelles remains elusive. Here, we demonstrate that late endosomes, a type of prelysosomal organelles, facilitate actin-cytoskeleton remodeling via cytosolic translocation of immature protease cathepsin D (cathD) during microglia migration. After cytosolic translocation, late endosome-derived cathD juxtaposes actin filaments at the leading edge of lamellipodia. Suppressing cathD expression or blocking its cytosolic translocation impairs the maintenance but not the initiation of lamellipodial extension. Moreover, immature cathD balances the activity of the actin-severing protein cofilin to maintain globular-actin (G-actin) monomer pool for local actin recycling. Our study identifies cathD as a key lysosomal molecule that unconventionally contributes to actin cytoskeleton remodeling via cytosolic translocation during adenosine triphosphate-evoked microglia migration.

16.
Nat Commun ; 11(1): 6045, 2020 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-33247136

RESUMO

Touch can positively influence cognition and emotion, but the underlying mechanisms remain unclear. Here, we report that tactile experience enrichment improves memory and alleviates anxiety by remodeling neurons along the dorsoventral axis of the dentate gyrus (DG) in adult mice. Tactile enrichment induces differential activation and structural modification of neurons in the dorsal and ventral DG, and increases the presynaptic input from the lateral entorhinal cortex (LEC), which is reciprocally connected with the primary somatosensory cortex (S1), to tactile experience-activated DG neurons. Chemogenetic activation of tactile experience-tagged dorsal and ventral DG neurons enhances memory and reduces anxiety respectively, whereas inactivation of these neurons or S1-innervated LEC neurons abolishes the beneficial effects of tactile enrichment. Moreover, adulthood tactile enrichment attenuates early-life stress-induced memory deficits and anxiety-related behavior. Our findings demonstrate that enriched tactile experience retunes the pathway from S1 to DG and enhances DG neuronal plasticity to modulate cognition and emotion.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33250371

RESUMO

BACKGROUND AND AIMS: Some previous studies reported serum autoantibody positivity in patients with nonalcoholic fatty liver disease (NAFLD). The clinical significance of these findings remains uncertain. We aimed to investigate the association between the presence of serum autoantibodies and liver disease severity in NAFLD. METHODS AND RESULTS: A total of 388 consecutive patients with biopsy-proven NAFLD were included in the study. Various serum autoantibodies (including also anti-nuclear antibodies [ANA]) were detected by indirect immunofluorescent or immunoblotting assays. Overall, 84 (21.6%) patients with biopsy-confirmed NAFLD had positivity for at least one of the measured serum autoantibodies. ANA positivity was present in 50 (12.9%) patients, whereas anti-U1RNP or pANCA antibodies were detectable in 9 (2.3%) and 6 (1.5%) patients, respectively. Multivariate logistic regression analysis showed that ANA positivity (adjusted-odds ratio: 4.51, 95%CI: 1.77-11.5; P = 0.002) or positivity of any serum autoantibodies (adjusted-odds ratio: 3.14, 95%CI: 1.30-7.62; P = 0.01) were independently associated with advanced liver fibrosis (stages F3-F4). In serum autoantibody/ANA-positive patients, the proportion of those with advanced fibrosis was also greater among carriers of PNPLA3 rs738409 GG or CG than among those carrying PNPLA3 rs738409 CC genotype. CONCLUSIONS: Serum autoantibody positivity was independently associated with advanced liver fibrosis in patients with biopsy-proven NAFLD. The presence of serum autoantibodies in patients with advanced fibrosis occurred more frequently amongst those carrying PNPLA3 rs738409 GG or CG genotypes.

18.
Cell Signal ; 78: 109843, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33253911

RESUMO

NLRP3 inflammasome-mediated vascular EC pyroptosis is a key event in the pathogenesis of atherosclerosis. Dysregulation of glucose metabolism is involved in EC dysfunction. Although BDNF plays a protective role in vascular endothelium physiological activity, the mechanisms underlying this activity are not yet clear. In this study, we investigated the role of BDNF in NLRP3 inflammasome-mediated EC pyroptosis and its associated reprogramming of glucose metabolism. HUVECs were treated with human rBDNF under ox-LDL stimulation. rBDNF alleviated ox-LDL-induced NLRP3 inflammasome formation and HUVEC pyroptosis, as evaluated by NLRP3, caspase1-p10, interleukin-18, and interleukin-1ß protein levels, co-localization of NLRP3 and apoptosis-associated speck-like protein, and lactate dehydrogenase release. These effects were prevented by tropomyosin receptor kinase B inhibition and KLF2 silencing. The hyper-activation of glycolysis induced by ox-LDL-induced was mitigated by rBDNF via KLF2 as assessed by glucose uptake, lactate production, and extracellular acidification rate. In addition, the BDNF/KLF2 pathway preserved the mitochondrial membrane potential, intracellular reactive oxygen species generation, electron transport chain processing, oxygen consumption rate, and adenosine triphosphate production. Furthermore, KLF2 interacted with HK1 and HK1 overexpression evoked NLRP3 inflammasome formation. At the clinical level, plasma BDNF and lactate levels were measured in 274 patients who underwent computed tomography and coronary angiography for CAD diagnosis. Patients with CAD had lower BDNF and increased lactate levels than those without CAD. In 94 patients with CAD, circulating BDNF levels were inversely associated with lactate levels. In the receiver operating characteristic analysis of CAD, the areas under the curves for 1/BDNF, lactate, and 1/BDNF+lactate were 0.707, 0.702, and 0.753 respectively. These results indicate that BDNF and lactate are linked in atherosclerotic patients, and BDNF inhibits ox-LDL induced NLRP3 inflammasome formation and pyroptosis in HUVECs via KLF2/HK1-mediated glucose metabolism modulation and mitochondrial homeostasis preservation.

19.
Front Surg ; 7: 594027, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33195394

RESUMO

Background: Supracondylar humerus fracture is the most common elbow fracture in children, which often requires closed reduction and percutaneous pinning (CRPP) procedure for full recovery. In addition to the traditional sterile technique with full prep and draping, the semi-sterile technique without sterile gowns and drapes has been suggested to be a viable alternative for CRPP. Methods: Here, we performed a retrospective study over a 3-year period to comprehensively evaluate the outcomes of the semi-sterile and the sterile techniques for CRPP in supracondylar humerus fractured patients. Demographic data, fracture type, nerve injury status and the type of preparation technique (semi-sterile vs. sterile) were recorded. Time of preparation and operation, costs and elbow recovery status were compared. Outcomes of the two techniques were compared with bivariate analysis. Results: In a total of 137 patients, we found that the semi-sterile technique could significantly reduce the total operation room usage time (80 ± 13 min vs. 94 ± 12 min, 15% reduction, P < 0.001) and costs of CRPP. Specifically, anesthesia and medical waste costs were reduced by 139 RMB (1,736 ± 128 vs. 1,875 ± 197, 7.4% reduction, P < 0.001) and 103.0 RMB (14.6 vs. 117.9) per operation, respectively. At the meantime, the infection rate and recovery efficiency (89 ± 10 vs. 91 ± 9 of the Mayo Elbow Performance Score, P = 0.352) were almost unchanged as compared to the sterile technique group. Conclusions: Our study suggests that the semi-sterile technique can be used as a cost-effective alternative for CRPP in supracondylar humerus fracture and even other bone-related non-surgical approaches. Level of Evidence: The present study is a retrospective cohort study with a level III of evidence.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33058063

RESUMO

The heavy metals, which derived from accumulated coal gangue, are important source of environmental pollution. In this study, coal gangue dumps, collected in Shaanxi Province, China, were used to evaluate the potential ecological risks and release characteristics of heavy metals, including the chemical forms, release characteristics, and potential ecological risks by using the methods of Tessier's sequential extractions, leaching experiments, gray GM (1, 1) forecasting mode, and potential ecological risk index. The results indicated that gangue samples contained high levels of metals, especially of Pb, which was the 20-31 times of the background value, whereas the sum of exchangeable and carbonate fractions in Co and Cu was a large proportion (4-11%) of the total. Potential ecological risks were at strong level regardless of the type of the coal gangue because of Mo and Pb and the comprehensive ecological risk index of 351.51-412.27. Weathering promotes the release of heavy metals in the gangue. Furthermore, the contents of Cu and Pb in leaching solution and their release times in weathered gangue were significantly higher than those of the fresh one. This research provides a scientific basis for the prevention and control of heavy metal pollution in coal-containing areas.

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