Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 699
Filtrar
1.
Front Public Health ; 9: 638704, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33732678

RESUMO

Background: The population is aging much faster in China than other low- and middle-income countries. With the accelerated aging of the population, incidence and disease burden of age-related diseases have also continued to increase. Exploring the burden of age-related diseases is crucial for early disease prevention, assessing the extent of population aging, and achieving the goal of healthy aging. Methods: We used the dataset from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), and selected data on incidence, prevalence, and disease burden in China, in 1997, 2007, and 2017. We classified age-related diseases, which were defined as diseases in which the incidence rate increased quadratically with age in the adult population. Additionally, we described the changes in age-related diseases during the study period by different GBD categories. It also measured changes in the age-related disease burden in our study period, including disability-adjusted life years (DALY), years of life lost (YLL), and years lived with disability (YLD). Finally, we compared the differences in the age-related disease burdens for men and women. Results: Among the 293 diseases listed in the GBD study, 69 in 2017, 78 in 1997 and 72 in 2007 were identified as age-related diseases. More than half of the age-related diseases belonged to non-communicable diseases (NCDs) in our study period. The rate of age-standardized age-related disease burden decreased between 1997 and 2017. DALYs decreased by 24.89% for non-age-related diseases and by 50.15% in age-related diseases from 1997 to 2017. The age-related disease burden of men was higher than that of women; we found a decreasing trend, with -46.23% in men and -54.90% in women. Conclusions: Comparing characteristics of the aging population in China and the world, we found that China does not have the typical disease characteristics of aging society. Currently, China faces the dual threat of NCDs and communicable diseases, and NCDs account for the vast majority of the age-related disease burden. Our health systems should focus on disease prevention and early detection among the entire population, instead of treatment. Further studies should focus on reducing the duration and severity of morbidity in later life.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33704645

RESUMO

In this study, biochar was generated from chicken manure by using a tube furnace under different temperatures (300, 500, and 700 °C), and the treatments were noted as J300, J500, and J700, respectively. In comparison, another type of biochar was prepared under 500 °C with a muffle furnace, and the treatment was noted as JM500. Biochar in treatment group J500 was subsequently modified with HNO3 and NaOH, and the treatments were noted as J500-HNO3 and J500-NaOH, respectively. The sorption efficiencies of naphthalene by the above six types of biochar were evaluated. Characteristic results showed that the surface pores of the biochar were improved with the increase of temperature, and biochar under the treatments J300, J500, J700, and JM500 experienced a high speed of adsorption within 1 h after the naphthalene adsorption started. The adsorption capacity of naphthalene increased with the increase of the initial concentration of naphthalene. Treatment J700 exhibited the largest adsorption capacity since its biochar surface pore structure was more fully developed with a crystal structure formed, and its specific surface area was increased by about 20 times compared to the original chicken manure. After biochar modification using HNO3 and NaOH, the infrared spectrum changed, and the adsorption active sites were increased. The biochar modification by HNO3 had a high naphthalene adsorption efficiency compared to NaOH. The order of adsorption capacity was as follows: J500 ≈ JM500 < J300 < J500-NaOH < J500-HNO3 < J700.

3.
PLoS One ; 16(2): e0247641, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33635924

RESUMO

Angiogenesis plays an essential role in many pathological processes such as tumor growth, wound healing, and keloid development. Low oxygen level is the main driving stimulus for angiogenesis. In an animal tissue, the oxygen level is mainly determined by three effects-the oxygen delivery through blood flow in a refined vessel network, the oxygen diffusion from blood to tissue, and the oxygen consumption in cells. Evaluation of the oxygen field is usually the bottleneck in large scale modeling and simulation of angiogenesis and related physiological processes. In this work, a fast numerical method is developed for the simulation of oxygen supply in tissue with a large-scale complex vessel network. This method employs an implicit finite-difference scheme to compute the oxygen field. By virtue of an oxygen source distribution technique from vessel center lines to mesh points and a corresponding post-processing technique that eliminate the local numerical error induced by source distribution, square mesh with relatively large mesh sizes can be applied while sufficient numerical accuracy is maintained. The new method has computational complexity which is slightly higher than linear with respect to the number of mesh points and has a convergence order which is slightly lower than second order with respect to the mesh size. With this new method, accurate evaluation of the oxygen field in a fully vascularized tissue on the scale of centimeter becomes possible.

4.
J Cell Mol Med ; 25(6): 2900-2908, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33506637

RESUMO

Lung cancer is the leading cause of cancer-related death worldwide, and non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer diagnoses. As an ancient therapy, moxibustion has been used to treat cancer-related symptoms in clinical practice. However, its antitumour effect on NSCLC remains largely unexplored. In the present study, a Lewis lung cancer (LLC) xenograft tumour model was established, and grain-sized moxibustion (gMoxi) was performed at the acupoint of Zusanli (ST36). Flow cytometry and RNA sequencing (RNA-Seq) were used to access the immune cell phenotype, cytotoxicity and gene expression. PK136, propranolol and epinephrine were used for natural killer (NK) cell depletion, ß-adrenoceptor blockade and activation, respectively. Results showed that gMoxi significantly inhibited LLC tumour growth. Moreover, gMoxi significantly increased the proportion, infiltration and activation of NK cells, whereas it did not affect CD4+ and CD8+ T cells. NK cell depletion reversed gMoxi-mediated tumour regression. LLC tumour RNA-Seq indicated that these effects might be related to the inhibition of adrenergic signalling. Surely, ß-blocker propranolol clearly inhibited LLC tumour growth and promoted NK cells, and gMoxi no longer increased tumour regression and promoted NK cells after propranolol treatment. Epinephrine could inhibit NK cell activity, and gMoxi significantly inhibited tumour growth and promoted NK cells after epinephrine treatment. These results demonstrated that gMoxi could promote NK cell antitumour immunity by inhibiting adrenergic signalling, suggesting that gMoxi could be used as a promising therapeutic regimen for the treatment of NSCLC, and it had a great potential in NK cell-based cancer immunotherapy.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33480337

RESUMO

BACKGROUND: Atherosclerosis (AS) is an important pathological basis for the occurrence of coronary atherosclerotic disease (CAD), stroke and other adverse cardiovascular events. AS is an inflammatory disease, and macrophages are the main inflammatory cells in AS lesions, playing a leading role in the formation of atherosclerotic plaques and the development and regression of AS. Various pro-inflammatory and anti-inflammatory factors act on macrophages to regulate AS. Pro-inflammatory factors recruit monocytes to accumulate in the inflammatory site and promote the transformation of monocytes to macrophages. A large number of aggregated macrophages secrete various inflammatory mediators to promote AS. Pro-inflammatory factors can induce the polarization of M1-type macrophages to start and maintain inflammation, promote the accumulation of lipids in macrophages, and accelerate the formation of foam cells; Anti-inflammatory factors can not only induce M2-type macrophages polarization, promote tissue remodeling and repair, and reduce the occurrence of AS, but also promote the metabolism of fatty acid oxidation and oxidative phosphorylation of macrophages, regulate lipid metabolism, stabilize plaques, and induce the transformation of helper T cells type 1/2 (Th1/Th2) to Th2 cells, thus reducing inflammation. CONCLUSION: This review summarizes the effect and underlying regulatory mechanism of macrophages in the development of AS, which can provide new ideas for the diagnosis and treatment of AS targeting macrophages.

6.
Chem Biol Drug Des ; 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33470049

RESUMO

Sustained androgen receptor (AR) signaling and apoptosis evasion are among the main hurdles of castration-resistant prostate cancer (CRPC) treatment. We designed and synthesized isothiocyanate (ITC)-containing hybrid AR antagonist (ITC-ARi) and rationally combined ITC-ARi with GSH synthesis inhibitor buthionine sulfoximine (BSO) to efficiently downregulate AR/AR splice variant and induce ferroptosis in CRPC cells. The representative ITC-ARi 13 is an AR ligand that contains an N-acetyl cysteine-masked ITC moiety and gradually releases parental unconjugated ITC 12b in aqueous solution. The in vitro anti-PCa activities of 13, such as growth inhibition and AR downregulation, are significantly enhanced when combined with BSO. The drug combination caused notable lipid peroxidation and the cell viability was effectively rescued by iron chelator, antioxidants or the inhibitor of heme oxygenase-1, supporting the induction of ferroptosis. 13 and BSO cooperatively downregulate AR and induce ferroptosis likely through increasing the accessibility of 13/12b to cellular targets, escalating free intracellular ferrous iron and attenuating GSH-centered cellular defense and adaptation. Further studies on the combination of ITC-ARi and GSH synthesis inhibitor could result in a new modality against CRPC.

7.
J Stroke Cerebrovasc Dis ; 30(3): 105587, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33450606

RESUMO

OBJECTIVES: Inflammation is associated with the occurrence and prognosis of ischemic stroke. The aim of this study was to evaluate the association between inflammatory biomarkers and the short-term clinical outcomes of acute ischemic stroke (AIS) patients after intravenous thrombolysis (IVT). MATERIALS AND METHODS: A total of 208 AIS patients treated with IVT were enrolled in this retrospective study. Blood tests of inflammatory biomarkers, including the leukocyte count, neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio and high-sensitivity C-reactive protein level, were conducted within 24 h after IVT. The primary outcome was decent functional recovery (DFR) [modified Rankin Scale score (mRS) of 0-2] at 3 months. The secondary outcomes included symptomatic intracranial hemorrhage and 3-month mortality. A multivariate analysis was performed to evaluate the associations between inflammatory biomarkers and 3-month clinical outcomes. RESULTS: At 3 months follow-up, 113 (62.2%) patients achieved DFR. As compared to patients with DFR, patients without DFR had higher leukocyte counts (8.5 ± 2.4 × 109/L versus 6.9 ± 1.7 × 109/L, P=0.000), neutrophil counts (6.1 ± 2.3 × 109/L versus 4.6±1.7 × 109/L, P=0.000) and neutrophil-to-lymphocyte ratio (4.6 ± 2.4 versus 3.3 ± 1.9, P=0.000). After adjusting for the stroke subtype, severity of stroke, and medical history, the leukocyte count and neutrophil count remained significantly correlated with non-DFR (adjusted odds ratio [OR] 1.488; 95% confidence interval [CI], 1.247-1.776; P=0.000 and adjusted OR 1.522; 95% CI, 1.269-1.826; P=0.000, respectively). CONCLUSIONS: This study demonstrates that increased levels of inflammatory biomarkers are independently associated with poor outcomes at 3 months in AIS patients treated with IVT.


Assuntos
Proteína C-Reativa/análise , Fibrinolíticos/administração & dosagem , Mediadores da Inflamação/sangue , Terapia Trombolítica , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Avaliação da Deficiência , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Infusões Intravenosas , /diagnóstico , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
8.
Hum Brain Mapp ; 42(1): 192-203, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33030795

RESUMO

Subjective cognitive decline (SCD) is a high-risk yet less understood status before developing Alzheimer's disease (AD). This work included 76 SCD individuals with two (baseline and 7 years later) neuropsychological evaluations and a baseline T1-weighted structural MRI. A machine learning-based model was trained based on 198 baseline neuroimaging (morphometric) features and a battery of 25 clinical measurements to discriminate 24 progressive SCDs who converted to mild cognitive impairment (MCI) at follow-up from 52 stable SCDs. The SCD progression was satisfactorily predicted with the combined features. A history of stroke, a low education level, a low baseline MoCA score, a shrunk left amygdala, and enlarged white matter at the banks of the right superior temporal sulcus were found to favor the progression. This is to date the largest retrospective study of SCD-to-MCI conversion with the longest follow-up, suggesting predictable far-future cognitive decline for the risky populations with baseline measures only. These findings provide valuable knowledge to the future neuropathological studies of AD in its prodromal phase.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33340608

RESUMO

BACKGROUND: Stimulator of interferon genes (STING) activation favors effective innate immune responses against viral infections. Its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unknown. OBJECTIVE: Our aim was to explore the expression, regulation, and function of STING in CRSwNP. METHODS: STING expression in sinonasal mucosal samples was analyzed by means of quantitative RT-PCR, immunohistochemistry, flow cytometry, and Western blotting. Regulation and function of STING expression were explored by using cultured primary human nasal epithelial cells (HNECs) and cells of the line BEAS-2B in vitro. RESULTS: STING expression was reduced in eosinophilic nasal polyps compared with that in noneosinophilic nasal polyps and control tissues. STING was predominantly expressed by epithelial cells in nasal tissue and was downregulated by IL-4 and IL-13 in a signal transducer and activator of transcription 6 (STAT6)-dependent manner. HNECs derived from eosinophilic polyps displayed compromised STING-dependent type I interferon production but heightened IL-13-induced STAT6 activation and CCL26 production as compared with HNECs from noneosinophilic polyps and control tissues, which were rescued by exogenous STING overexpression. Knocking down or overexpressing STING decreased or enhanced expression of suppressor of cytokine signaling 1 (SOCS1) in BEAS-2B cells, respectively, independent of the canonic STING pathway elements TBK1 and IRF3. Knocking down SOCS1 abolished the inhibitory effect of STING on IL-13 signaling in BEAS-2B cells. STING expression was positively correlated with SOCS1 expression but negatively correlated with CCL26 expression in nasal epithelial cells from patients with CRSwNP. CONCLUSIONS: Reduced STING expression caused by the type 2 milieu not only impairs STING-dependent type I interferon production but also amplifies IL-13 signaling by decreasing SOCS1 expression in nasal epithelial cells in eosinophilic CRSwNP.

10.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(12): 1063-1068, 2020 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-33325358

RESUMO

Objective To investigate the role and mechanism of aldo-keto reductase 1 member B1 (AKR1B1) in regulating microglial cell polarization and thereby regulating the activity of retinal ganglion cells (RGCs). Methods Lipopolysaccharide (LPS) was used to induce BV-2 polarization in microglia cells. AKR1B1 siRNA and inhibitor ponalrestat/Statil were used to treat BV-2 cells, and the effect of AKR1B1 on cell polarization was identified through morphology and inflammatory cytokine expression detection, including tumor necrosis factor α(TNF-α), interleukin 1ß(IL-1ß), cyclooxygenase 2(COX2), and inducible nitric oxide synthase(iNOS). Primary RGCs were cultured with the indicated BV-2 conditional medium. The activity of RGCs was detected by brain-specific homeobox protein 3a (Brn-3a) immunofluorescence staining, and apoptosis was observed by TUNEL staining. The expression of phosphorylated IKK and p65 in the nucleus were detected by Western blotting. Results LPS induced M1-type polarization of BV-2 cells, while its conditioned medium induced decreased RGC activity and increased apoptosis. Inhibition of AKR1B1 blocked M1 type polarization of BV-2 cells and restored RGC activity. Inhibition of AKR1B1 can block LPS-induced IKK phosphorylation and NF-κBp65 nuclear localization. Conclusion AKR1B1 can induce microglial activation by activating NF-κB pathway, which in turn inhibit the activity and promote apoptosis of RGCs.


Assuntos
Microglia , Aldo-Ceto Redutases , Animais , Linhagem Celular , Inflamação , Lipopolissacarídeos , Camundongos , Microglia/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Células Ganglionares da Retina/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo
11.
Appl Opt ; 59(35): 11053-11058, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33361931

RESUMO

Graphene as a new two-dimensional material can be utilized to design tunable optical devices owing to its exceptional physical properties, such as high mobility and tunable conductivity. In this paper, we present the design and analysis of a tunable broadband terahertz absorber based on periodic graphene ring arrays. Due to plasmon hybridization modes excited in the graphene ring, the proposed structure achieves a broad absorption bandwidth with more than 90% absorption in the frequency range of 0.88-2.10 THz under normal incidence, and its relative absorption bandwidth is about 81.88%. Meanwhile, it exhibits polarization-insensitive behavior and maintains high absorption over 80% when the incident angle is up to 45° for both TE and TM polarizations. Additionally, the peak absorption rate of the absorber can be tuned from 21% to nearly 100% by increasing the graphene's chemical potential from 0 to 0.9 eV. Such a design can have some potential applications in various terahertz devices, such as modulators, detectors, and spatial filters.

12.
PLoS One ; 15(11): e0242747, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33232375

RESUMO

BACKGROUND: J wave syndromes (JWS), including Brugada (BrS) and early repolarization syndromes (ERS), are associated with increased risk for life-threatening ventricular arrhythmias. Pharmacologic approaches to therapy are currently very limited. Here, we evaluate the effects of the natural flavone acacetin. METHODS: The effects of acacetin on action potential (AP) morphology and transient outward current (Ito) were first studied in isolated canine RV epicardial myocytes using whole-cell patch clamp techniques. Acacetin's effects on transmembrane APs, unipolar electrograms and transmural ECGs were then studied in isolated coronary-perfused canine RV and LV wedge preparations as well as in whole-heart, Langendorff-perfused preparations from which we recorded a 12 lead ECG and unipolar electrograms. Using floating glass microelectrodes we also recorded transmembrane APs from the RVOT of the whole-heart model. The Ito agonist NS5806, sodium channel blocker ajmaline, calcium channel blocker verapamil or hypothermia (32°C) were used to pharmacologically mimic the genetic defects and conditions associated with JWS, thus eliciting prominent J waves and provoking VT/VF. RESULTS: Acacetin (5-10 µM) reduced Ito density, AP notch and J wave area and totally suppressed the electrocardiographic and arrhythmic manifestation of both BrS and ERS, regardless of the experimental model used. In wedge and whole-heart models of JWS, increasing Ito with NS5806, decreasing INa or ICa (with ajmaline or verapamil) or hypothermia all resulted in accentuation of epicardial AP notch and ECG J waves, resulting in characteristic BrS and ERS phenotypes. Phase 2-reentrant extrasystoles originating from the RVOT triggered VT/VF. The J waves in leads V1 and V2 were never associated with a delay of RVOT activation and always coincided with the appearance of the AP notch recorded from RVOT epicardium. All repolarization defects giving rise to VT/VF in the BrS and ERS models were reversed by acacetin, resulting in total suppression of VT/VF. CONCLUSIONS: We present experimental models of BrS and ERS capable of recapitulating all of the ECG and arrhythmic manifestations of the JWS. Our findings provide definitive support for the repolarization but not the depolarization hypothesis proposed to underlie BrS and point to acacetin as a promising new pharmacologic treatment for JWS.

13.
Transl Oncol ; 14(1): 100907, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33217646

RESUMO

Early diagnosis has been proved to improve survival rate of lung cancer patients. The availability of blood-based screening could increase early lung cancer patient uptake. Our present study attempted to discover Chinese patients' plasma metabolites as diagnostic biomarkers for lung cancer. In this work, we use a pioneering interdisciplinary mechanism, which is firstly applied to lung cancer, to detect early lung cancer diagnostic biomarkers by combining metabolomics and machine learning methods. We collected total 110 lung cancer patients and 43 healthy individuals in our study. Levels of 61 plasma metabolites were from targeted metabolomic study using LC-MS/MS. A specific combination of six metabolic biomarkers note-worthily enabling the discrimination between stage I lung cancer patients and healthy individuals (AUC = 0.989, Sensitivity = 98.1%, Specificity = 100.0%). And the top 5 relative importance metabolic biomarkers developed by FCBF algorithm also could be potential screening biomarkers for early detection of lung cancer. Naïve Bayes is recommended as an exploitable tool for early lung tumor prediction. This research will provide strong support for the feasibility of blood-based screening, and bring a more accurate, quick and integrated application tool for early lung cancer diagnostic. The proposed interdisciplinary method could be adapted to other cancer beyond lung cancer.

14.
Front Oncol ; 10: 1639, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194569

RESUMO

Background: Both stereotactic body radiotherapy (SBRT) and radiofrequency ablation (RFA) are effective local treatments for hepatocellular carcinoma (HCC), but whether RFA is superior to SBRT is still controversial. Therefore, we performed a meta-analysis to compare the treatment outcomes of SBRT with RFA as curable or bridge intention. Methods: We searched online databases for studies that compared treatment outcomes for SBRT and RFA. Eligibility criteria included evaluation of local control, overall survival (OS), transplant rate, and post-transplant pathological necrosis. Results: As no randomized clinical trials met the criteria, 10 retrospective studies with a total of 2,732 patients were included. Two studies were in favor of SBRT in local control, two studies preferred RFA in OS, and others reported comparable outcomes for both. SBRT demonstrated significantly higher 1- and 3-year local control than RFA [odds ratio (OR) 0.42, 95% CI 0.24-0.74, P = 0.003; and OR 0.54, 95% CI 0.37-0.80, P = 0.002, respectively]. However, SBRT reported significantly shorter 1- and 2-year OS (OR 1.52, 95% CI 1.21-1.90, P = 0.0003; and OR 1.66, 95% CI 1.38-2.01, P < 0.00001, respectively). As bridge treatment, no significant difference was shown in transplant rate and post-transplant pathological necrosis rate (OR 0.57, 95% CI 0.32-1.03, P = 0.060; and OR 0.49, 95% CI 0.13-1.82, P = 0.290, respectively). Conclusions: This study demonstrates SBRT is able to complete a better local control for HCC than RFA, though the OS is inferior to RFA because of tumor burden or liver profiles of the enrolled studies. Well-designed, randomized, multicenter trials will be required to further investigate the conclusion.

15.
Front Oncol ; 10: 585292, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194732

RESUMO

Cancer patients who initially benefit from Erlotinib, a drug targeting EGFR path, eventually develop resistance to the drug. The underlying mechanism is largely unknown. This study investigated the role of ARL4C in Erlotinib resistance development of NSCLC. qRT-PCR and Western blotting were performed to analyze the expression of mRNA and protein of ARL4C in two NSCLC cell lines (HCC827 and PC-9). Several assays (MTS, colony formation, transwell migration, luciferase reporter, and chromatin-immunoprecipitation) were used to explore the role of ARL4C in biofunctional changes of Erlotinib-resistant cells and their associations with Jak2/Stat 5/ß-catenin signaling. Results demonstrated that (1) long-term use of Erlotinib resulted in downregulation of ARL4C; (2) overexpression of ARL4C could regain the sensitivity to Erlotinib in the drug-resistant HCC827/ER cells, while downregulation of ARL4C increased HCC827, and PC-9 cells' resistance to the drug; (3) Erlotinib-induced downregulation of ARL4C resulted in phosphorylation of Jak2/Stat5 and upregulation of ß-catenin and their related molecules Axin2, CD44, Ccnd1, Lgr-5, and MMP7, which promoted the malignant behaviors of Erlotinib-resistant cells; (4) chromatin immunoprecipitation and luciferase reporter assay revealed that Stat5 could bind to ß-catenin promoter to upregulate molecules to maintain the malignant behaviors, which might count for how Erlotinib-resistant cell survived while EGFR path was blocked; (5) the expression of ARL4C was not associated with known EGFR gene mutations in both Erlotinib-resistant cells and NSCLC tissues. Our data suggest that Erlotinib resistance of NSCLCs is associated with downregulation of ARL4C via affecting Jak/Stat/ß-catenin signaling. ARL4C could serve as a biomarker to predict the effectiveness of TKI targeting therapy and a potential therapeutic target for overcoming Erlotinib resistance in NSCLC.

16.
Proc Natl Acad Sci U S A ; 117(48): 30639-30648, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33203678

RESUMO

IL-17-producing Th17 cells are implicated in the pathogenesis of rheumatoid arthritis (RA) and TNF-α, a proinflammatory cytokine in the rheumatoid joint, facilitates Th17 differentiation. Anti-TNF therapy ameliorates disease in many patients with rheumatoid arthritis (RA). However, a significant proportion of patients do not respond to this therapy. The impact of anti-TNF therapy on Th17 responses in RA is not well understood. We conducted high-throughput gene expression analysis of Th17-enriched CCR6+CXCR3-CD45RA- CD4+ T (CCR6+ T) cells isolated from anti-TNF-treated RA patients classified as responders or nonresponders to therapy. CCR6+ T cells from responders and nonresponders had distinct gene expression profiles. Proinflammatory signaling was elevated in the CCR6+ T cells of nonresponders, and pathogenic Th17 signature genes were up-regulated in these cells. Gene set enrichment analysis on these signature genes identified transcription factor USF2 as their upstream regulator, which was also increased in nonresponders. Importantly, short hairpin RNA targeting USF2 in pathogenic Th17 cells led to reduced expression of proinflammatory cytokines IL-17A, IFN-γ, IL-22, and granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as transcription factor T-bet. Together, our results revealed inadequate suppression of Th17 responses by anti-TNF in nonresponders, and direct targeting of the USF2-signaling pathway may be a potential therapeutic approach in the anti-TNF refractory RA.

17.
Heart Rhythm ; 17(10): 1801, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33004123
18.
Artigo em Inglês | MEDLINE | ID: mdl-33049775

RESUMO

OBJECTIVES: The debate concerning the optimal choice of tricuspid position continues. We compared the long-term results of mechanical and biological prostheses in patients who underwent isolated or combined tricuspid valve replacement, at 2 major cardiac surgical centres in central China. METHODS: From January 1999 to December 2018, 338 patients underwent tricuspid valve replacement. Patients were divided into an isolated group or a combined group according to whether their surgery was combined with a left heart valve surgery. Mechanical tricuspid valve replacement was performed in 142 patients (isolated group: 41 vs combined group: 101), and 196 patients underwent bioprosthetic tricuspid valve replacement (isolated group: 145 vs combined group: 51). Operative results, long-term survival and tricuspid valve-related events were compared. RESULTS: Early mortality in the combined group was higher (n = 6, 4%) than that in the isolated group (n = 3, 2%), but no significant difference was observed between the mechanical and biological subgroups. In the isolated group, there was a higher event-free rate in the biological subgroup than in the mechanical subgroup (P = 0.042) and a similar result was also observed for patients without Ebstein's anomaly (P = 0.039). In the combined group, no significant difference was observed (P = 0.98). Survival rates were similar between the mechanical and biological subgroups in both the isolated (P = 0.54) and combined (P = 0.81) groups. Mechanical valves in isolated tricuspid valve replacement were more prone to valve thrombosis and bleeding. CONCLUSIONS: Every decision regarding tricuspid valve prostheses should be individualized, but biological prostheses may be an optimal choice for patients, especially for patients without Ebstein's anomaly, in isolated tricuspid valve replacement.

19.
Cell ; 183(4): 918-934.e49, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33113354

RESUMO

Learning valence-based responses to favorable and unfavorable options requires judgments of the relative value of the options, a process necessary for species survival. We found, using engineered mice, that circuit connectivity and function of the striosome compartment of the striatum are critical for this type of learning. Calcium imaging during valence-based learning exhibited a selective correlation between learning and striosomal but not matrix signals. This striosomal activity encoded discrimination learning and was correlated with task engagement, which, in turn, could be regulated by chemogenetic excitation and inhibition. Striosomal function during discrimination learning was disturbed with aging and severely so in a mouse model of Huntington's disease. Anatomical and functional connectivity of parvalbumin-positive, putative fast-spiking interneurons (FSIs) to striatal projection neurons was enhanced in striosomes compared with matrix in mice that learned. Computational modeling of these findings suggests that FSIs can modulate the striosomal signal-to-noise ratio, crucial for discrimination and learning.

20.
Eur J Ophthalmol ; : 1120672120965512, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33092409

RESUMO

AIM: To investigate the safety and feasibility of individualized transscleral cyclophotocoagulation (TSCPC) as the initial non-incisional surgical intervention for medically uncontrolled glaucoma after blunt trauma. METHODS: The therapy records were reviewed of medically uncontrolled traumatic glaucoma after blunt trauma treated with TSCPC in a single hospital between January 2014 and December 2018. Thirty-one patients (31 eyes) received individualized TSCPC after ultrasound biomicroscopy and gonioscopy examination to localize and quantify the injured quadrants of the anterior chamber angle. In addition to the number of IOP lowing drugs, visual acuity (VA), IOP, inflammation and hemorrhage in the anterior chamber were analyzed at 1 day, 3 weeks and 3 months after operation, respectively. Success was defined as the IOP was not more than 21 mmHg. RESULTS: Compared with the data of pre-operation, constituent ratio of VA had no significant difference at 3 weeks (χ2 = 0.56, p > 0.75). At 3 months the average IOP was 22.2 ± 6.8 mmHg, which was significantly lower than that of pre-operation (46.6 ± 5.6 mmHg) (t = 19.818, p < 0.001). No IOP lowing drug was needed in 12 eyes, and more than three kinds of drugs were still needed in five eyes. The average number of medications decreased to 1.2 ± 1.2 (χ2 = 93.496, p < 0.001). The complete success rate was 38.7% and the relative success rate (combined with no more than two kinds of drugs) was 83.9% at 3 months. CONCLUSIONS: Individualized TSCPC could be applied as an initial non-incisional surgical intervention to treat traumatic glaucoma refractory to the medicine therapy.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...