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1.
Cell Cycle ; : 1-17, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064977

RESUMO

The roles of lncRNA TSLNC8 and its synergetic effects with osimertinib remain unknown in lung cancer. qRT-PCR or western blotting was performed to determine the expression levels of TSLNC8, EGFR and STAT3. Colony formation and MTT assays were used to evaluate cell proliferation. Transwell and wound healing assays were performed to assess migration and invasion abilities. Flow cytometry with Annexin V/PI staining was used to detect changes in cell apoptosis. Nude mice subcutaneous tumor model was constructed and used for validating the effects of TSLNC8 and osimertinib in vivo. Expression of TSLNC8 was down-regulated in clinical lung cancer tissues and cell lines. TSLNC8 overexpression or osimertinib administration led to promotion of apoptosis and inhibition of cell proliferation, migration and invasion, as well as deactivation of the EGFR-STAT3 pathway, whereas TSLNC8 knockdown had opposite effects. Moreover, the above effects of osimertinib were remarkably enhanced by TSLNC8 overexpression and inhibited by TSLNC8 knockdown, respectively. Meanwhile, the effects of TSLNC8 overexpression were reversed by STAT3 activation or EGFR overexpression. In the animal model, combination of TSLNC8 overexpression and osimertinib administration resulted in efficient suppression of tumor growth. In this study, we revealed a TSLNC8-EGFR-STAT3 signaling axis in lung cancer, and TSLNC8 overexpression significantly enhanced the anti-tumor effects of osimertinib via inhibiting EGFR-STAT3 signaling.

2.
Biomed Pharmacother ; 132: 110852, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33065390

RESUMO

As a common ocular complication and microangiopathy of type 2 diabetic mellitus, diabetic retinopathy (DR) can lead to vision loss or even blindness in diabetic patients. At present, the treatment methods of DR mainly include laser and anti-VEGF therapies. Nevertheless, the higher cost and obvious side effects seriously disturb the normal life of DR patients. Promisingly, traditional Chinese medicine (TCM) has been demonstrated to be effective in treating DR by tonifying Qi and nourishing Yin, as well clearing heat and breeding body fluids, thus activating blood and removing blood stasis. Therefore, we screened the literatures on TCM treatment of DR through the web of science, ScienceDirect, PubMed, Google scholar and CNKI online databases. The representative prescriptions, herbs and extracts, and identified compounds for treatment of DR were further summarized and analyzed. Moreover, the detailed mechanisms and involved network pathways of herbs-compounds-targets were visualized by Cytoscape software. Meanwhile, we discussed the existing limitations and deficiencies of TCM on treatment of DR and gave corresponding measures. In conclusion, TCM could significantly ameliorate DR via anti-inflammation, anti-oxidative stress, anti-angiogenesis and anti-apoptosis.

3.
J Pharm Sci ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33049258

RESUMO

Ursolic acid (UA) is a common pentacyclic triterpene phytochemical with various pharmacological activities. However, UA is classified as a class IV drug in BCS system and its development as an oral drug is limited. Pulmonary delivery is an effective way to improve the bioavailability of drugs with low absorption. In this study, the differences in pharmacokinetic behaviors of UA after pulmonary and oral administration was explored in rats. Compared with oral administration, the plasma concentration of UA increased rapidly after pulmonary administration, and the bioavailability increased about 80 times. UA instantly accumulated in the lungs after pulmonary administration, and the pulmonary AUC0-t/dose increased by 114 times compared to oral dosing. Incubation experiments showed that the metabolism of UA in rat lung microsomes was significantly reduced compared with that in liver microsomes, in which the clearance rate of phase I and phase II metabolism was reduced by 14.7 times and 1.4 times respectively. These results indicated that pulmonary administration could improve the bioavailability of UA and reduce its metabolism. This study not only provides a preferable route of administration for the application of UA but also offers new insights for the development of phytochemical drug candidates with poor pharmacokinetic properties.

4.
Acta Pharmacol Sin ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028985

RESUMO

Metabolic reprogramming is associated with NLRP3 inflammasome activation in activated macrophages, contributing to inflammatory responses. Tanshinone IIA (Tan-IIA) is a major constituent from Salvia miltiorrhiza Bunge, which exhibits anti-inflammatory activity. In this study, we investigated the effects of Tan-IIA on inflammation in macrophages in focus on its regulation of metabolism and redox state. In lipopolysaccharides (LPS)-stimulated mouse bone marrow-derived macrophages (BMDMs), Tan-IIA (10 µM) significantly decreased succinate-boosted IL-1ß and IL-6 production, accompanied by upregulation of IL-1RA and IL-10 release via inhibiting succinate dehydrogenase (SDH). Tan-IIA concentration dependently inhibited SDH activity with an estimated IC50 of 4.47 µM in LPS-activated BMDMs. Tan-IIA decreased succinate accumulation, suppressed mitochondrial reactive oxygen species production, thus preventing hypoxia-inducible factor-1α (HIF-1α) induction. Consequently, Tan-IIA reduced glycolysis and protected the activity of Sirtuin2 (Sirt2), an NAD+-dependent protein deacetylase, by raising the ratio of NAD+/NADH in activated macrophages. The acetylation of α-tubulin was required for the assembly of NLRP3 inflammasome; Tan-IIA increased the binding of Sirt2 to α-tubulin, and thus reduced the acetylation of α-tubulin, thus impairing this process. Sirt2 knockdown or application of Sirt2 inhibitor AGK-2 (10 µM) neutralized the effects of Tan-IIA, suggesting that Tan-IIA inactivated NLRP3 inflammasome in a manner dependent on Sirt2 regulation. The anti-inflammatory effects of Tan-IIA were observed in mice subjected to LPS challenge: pre-administration of Tan-IIA (20 mg/kg, ip) significantly attenuated LPS-induced acute inflammatory responses, characterized by elevated IL-1ß but reduced IL-10 levels in serum. The peritoneal macrophages isolated from the mice displayed similar metabolic regulation. In conclusion, Tan-IIA reduces HIF-1α induction via SDH inactivation, and preserves Sirt2 activity via downregulation of glycolysis, contributing to suppression of NLRP3 inflammasome activation. This study provides a new insight into the anti-inflammatory action of Tan-IIA from the respect of metabolic and redox regulation.

5.
J Immunol ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32998984

RESUMO

BP180 (also termed type XVII collagen) is a hemidesmosomal protein and plays a critical role in cell-cell matrix adhesion in the skin; however, its other biological functions are largely unclear. In this study, we generated a BP180 functional-deficient mouse strain by deleting its extracellular domain of humanized NC16A (termed ΔNC16A mice). We found that BP180 is expressed by bone marrow mesenchymal stem cells (BM-MSC), and its functional deficiency leads to myeloid hyperplasia. Altered granulopoiesis in ΔNC16A mice is through bone marrow stromal cells evidenced by bone marrow transplantation. Furthermore, the level of G-CSF in bone marrow and circulation were significantly increased in ΔNC16A mice as compared with wild-type mice. The increased G-CSF was accompanied by an increased activation of the NF-κB signaling pathway in bone marrow and BM-MSC of ΔNC16A mice. Blockade of G-CSF restored normal granulopoiesis in ΔNC16A mice. Inhibition of NF-κB signaling pathway significantly reduces the release of G-CSF from ΔNC16A BM-MSC in vitro and the level of serum G-CSF in ΔNC16A mice. To our knowledge, these findings provide the first direct evidence that BP180 plays an important role in granulopoiesis through regulating NF-κB signaling pathway in BM-MSC.

6.
J Am Heart Assoc ; 9(19): e017789, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33006292

RESUMO

Background Atrial fibrillation (AF) driver mechanisms are obscured to clinical multielectrode mapping approaches that provide partial, surface-only visualization of unstable 3-dimensional atrial conduction. We hypothesized that transient modulation of refractoriness by pharmacologic challenge during multielectrode mapping improves visualization of hidden paths of reentrant AF drivers for targeted ablation. Methods and Results Pharmacologic challenge with adenosine was tested in ex vivo human hearts with a history of AF and cardiac diseases by multielectrode and high-resolution subsurface near-infrared optical mapping, integrated with 3-dimensional structural imaging and heart-specific computational simulations. Adenosine challenge was also studied on acutely terminated AF drivers in 10 patients with persistent AF. Ex vivo, adenosine stabilized reentrant driver paths within arrhythmogenic fibrotic hubs and improved visualization of reentrant paths, previously seen as focal or unstable breakthrough activation pattern, for targeted AF ablation. Computational simulations suggested that shortening of atrial refractoriness by adenosine may (1) improve driver stability by annihilating spatially unstable functional blocks and tightening reentrant circuits around fibrotic substrates, thus unmasking the common reentrant path; and (2) destabilize already stable reentrant drivers along fibrotic substrates by accelerating competing fibrillatory wavelets or secondary drivers. In patients with persistent AF, adenosine challenge unmasked hidden common reentry paths (9/15 AF drivers, 41±26% to 68±25% visualization), but worsened visualization of previously visible reentry paths (6/15, 74±14% to 34±12%). AF driver ablation led to acute termination of AF. Conclusions Our ex vivo to in vivo human translational study suggests that transiently altering atrial refractoriness can stabilize reentrant paths and unmask arrhythmogenic hubs to guide targeted AF driver ablation treatment.

7.
Phytomedicine ; 79: 153353, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-33007731

RESUMO

BACKGROUND: Increasing evidence has shown that microglia-induced neuroinflammation is involved in the pathogenesis of ischemic stroke. Stepharine, one of the alkaloids extracted from Stephania japonica (Thunb.) Miers, exhibited strong inhibitory effect on microglial overactivation. However, it is not known whether it has the potential to prevent ischemic stroke. METHODS: The neuroprotective and anti-neuroinflammatory effects of stepharine were investigated in vivo and in vitro, using a rat model of middle cerebral artery occlusion (MCAO) and lipopolysaccharide (LPS)-stimulated BV-2 cells, respectively. RESULTS: In vivo, stepharine (500 µg/kg) suppressed neurological deficits scores, brain water content and cerebral infarct volume induced by MCAO. Moreover, stepharine (500 µg/kg) inhibited NeuN+ cells loss and Iba-1+ cells increase in the MCAO ischemic cortex. In vitro, stepharine (10, 30 µM) substantially inhibited nitric oxide release as well as the mRNA and protein expression of pro-inflammatory mediators [inducible nitric oxide synthase, interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1ß] in LPS-activated BV-2 cells. LPS-induced increase of TLR4 expression, IκBα phosphorylation, and NF-κB p65 nuclear translocation was inhibited by stepharine (10, 30 µM). Molecular docking analysis showed that stepharine directly interacted with TLR4. SPR assay further confirmed that stepharine could bind to the TLR4/MD2 complex. Meanwhile, stepharine exhibited neuroprotective effects on SH-SY5Y cells cultured with LPS-treated conditioned medium. CONCLUSION: Our study demonstrated for the first time that stepharine improved the outcomes in MCAO rats, reduced neuronal loss, and suppressed microglial overactivation via the inhibition of TLR4/NF-κB pathway. These results suggest that stepharine might be a potential therapeutic agent for the treatment of ischemic stroke.

8.
J Phys Chem A ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33045834

RESUMO

Traditionally, chemistry problems are solved by means of a deductive approach. The question to be addressed is typically related to the value of a property that is either measured experimentally, computed using quantum-chemistry software, or (more recently) predicted using a machine-learned model. In this paper, we demonstrate that an inductive approach can be adopted using End-to-End (E2E) machine learning. This approach is illustrated for tackling the following chemistry problems: (i) determine the fully coordinated (FC) and undercoordinated (UC) atoms in a molecule with one missing atom, (ii) identify the type of atom that is missing in such an incomplete molecule, and (iii) predict the direction of a reaction between two molecules according to an existing dataset. The E2E approach leads to accuracies higher than 99%, 98%, and 93% for these three problems, respectively. Finally, in order to achieve such accuracies, a descriptor for the molecules, called bag of clusters, is introduced and compared with a series previously proposed descriptors, highlighting a series of advantages.

9.
Biomed Res Int ; 2020: 3516128, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029504

RESUMO

Ulcerative colitis is one of the IBD which cause a chronic intestinal inflammation and dysfunctional of the mucosal barrier. For now, the incident of UC was steadily increased all over the world. It has become a novel independent risk factor of several severe diseases especially colon-rectal cancer. However, the etiology of UC was still obscure. Previous studies show that high-fat diet contributed to the pathogenesis of immune system dysregulation, and farnesoid X receptor (FXR) was also implicated in the pathogenesis of various inflammatory symptoms. Yet, their inner roles in the pathogenesis of UC have not been mentioned. In this study, we aim to investigate the role of FXR in UC. High-fat diet (HFD) promotes the progression of DSS-induced UC, shows an increasing secretion of bile acid in serum, and leads to a downregulation of FXR target genes (FXRα, Shp, and lbabp). Adding FXR agonist FexD rescues the phenotype induced by high-fat diet, whereas TGFBRI inhibitor SB431542 abrogates the restoration by FexD in DSS-induced UC mice. To further verify the relationship between the FXR and TGFB signaling pathway, we made a UC-HFD model in the Caco2 cell line. Results shows the same conclusion that FXR mitigate UC inflammation through a TGFB-dependent pathway. These results expand the role of FXR in ulcerative colitis and suggest that FXR activation may be considered a therapeutic strategy for UC.

10.
Med Hypotheses ; 145: 110332, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33039950

RESUMO

At the end of 2019, a new kind of pneumonia which was proven to be supported by novel coronaviruses named SARS-CoV-2 emerges and it seems to be more complicate in its clinical course and management. Related researches have demonstrated that SARS-CoV-2 serves roles in respiratory, intestinal and neuronal diseases. Given the growing cases of COVID-19, analyzing the relevance between COVID-19 and fragile patients who suffer from bone destruction is entirely indispensable. Accordingly, the recapitulatory commentary is necessary to advance our knowledge on COVID-19 and orthopedics. In this article, we particularly clarify the possible relationship between the newly COVID-19 infection and bone lesions from the standpoints of dysimmunity and inflammatory storm.

11.
Burns ; 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32900549

RESUMO

BACKGROUND: Survival after burn injury has steadily improved in recent decades. The models for assessing the severity of burn injury and predicting burn-associated mortality have been used for over 20 years. The predictive accuracy of these models should be reconsidered now. METHOD: In this retrospective study on all burn patients (n = 9625) admitted to the Burn Department, Southwest Hospital between 2008 and 2017, we compared the predictive performance of the four burn-severity models (Abbreviated Burn Severity Index, Ryan score, revised Baux score and Belgian Outcome of Burn Injury) by area under the receiver operating curve (AUC) and Hosmer-Lemeshow test. We developed a new model with the data from 2008 to 2012 (5006 patients) by logistic regression, data from 2013 to 2017 (4619 patients) were used for validation. RESULT: The overall mortality rate of the burn patients was 1.14%. The four previously validated burn models showed good discrimination power of death risk (AUC > 0.890) but poor fitness to the observed mortality rate (p < 0.001). Risk factors associated with mortality included sex, age, total burn area, full thickness burn area, and inhalation injury. The new logistic model was devised with high sensitivity and specificity (0.913 and 0.806, respectively) and an AUC of 0.940. The new model also had good fitness to the observed mortality of burn patients (p = 0.588). CONCLUSION: The four widely used burn models have poor accuracy in predicting burn-associated mortality, and an accurate new model was developed based on simple and objective clinical characteristics of burn patients at admission.

12.
J Pharm Sci ; 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32976901

RESUMO

Artemisinin (ART) drugs showed declining plasma concentrations after repeated oral dosing, known as time-dependent pharmacokinetics (PK). ART and dihydroartemisinin (DHA) were adopted as representatives to evaluate the roles of first-pass effects and systemic metabolism in time-dependent PK by comparison of oral versus intravenous administration and 1 dose versus 5 consecutive doses PK in rats and dogs, respectively. The hepatic extraction ratio (ERh) and the intestinal elimination changes were further investigated in rats to distinguish the roles of hepatic first-pass effect or intestinal first-pass effect. The induction capacities of ARTs to cytochrome P450 (CYP450) in rats and human cells were evaluated as well. For ART, only the oral groups showed time-dependent PK. A fairly high ERh that obtained for ART was not sensitive to multiple oral doses. An increased elimination and CYP450 expression have also been found in the intestine. For DHA, though a significant CYP450 induction was observed, neither time-dependent PK nor changes in the first-pass effects was found. In conclusion, time-dependent PK of ART was mainly caused by the increased intestinal first-pass effect rather than hepatic first-pass effect or systemic metabolism. DHA was not involved in auto-induction elimination, thus showing no time-dependent PK.

13.
Bioresour Technol ; 318: 124069, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32916460

RESUMO

The 2-keto-L-gulonic acid (2-KLG) is the direct precursor for industrial vitamin C production. The main biosynthetic method for 2-KLG production is the classical two-step fermentation route. However, disadvantages of this method are emerging, including high consumption of energy, difficulties in strain screening, complex operation, and poor stability. In this study, five recombinant Escherichia coli strains overexpressing different sorbose/sorbosone dehydrogenases were constructed and used for 2-KLG production. By optimizing catalytic conditions and further expressing pyrroloquinoline quinone in the recombinant strain, the titer of 2-KLG reached 72.4 g/L, with a conversion ratio from L-sorbose of 71.2% in a 5-L bioreactor. To achieve direct biosynthesis of 2-KLG from D-sorbitol, a co-culture system consisting of Gluconobacter oxydans and recombinant E. coli was designed. With this co-culture system, 16.8 g/L of 2-KLG was harvested, with a conversion ratio from D-sorbitol of 33.6%. The approaches developed here provide alternative routes for the efficient biosynthesis of 2-KLG.

14.
Arch Gerontol Geriatr ; 92: 104255, 2020 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-32966944

RESUMO

BACKGROUND: Older people present to the emergency department (ED) with distinct patterns and emergency care needs. This study aimed to use comprehensive geriatric assessment (CGA) surveying the patterns of ED visits among older patients and determine frailty associated with the risk of revisits/readmission. METHODS: This prospective study screened 2270 patients aged ≥75 years in the ED from August 2018 to February 2019. All patients underwent CGA. A 3-months follow-up was conducted to observe the hospital courses of admission and revisit/readmission. RESULTS: A total of 270 older patients were enrolled. The independent predictors of admission at initial ED visit were the risk of nutritional deficit and instrumental activities of daily living (IADL). In the admission group, the independent predictors of revisit/readmission were a fall in the past year and mobility difficulties. In the discharge group, the independent predictors of revisit/readmission were frailty and insomnia. Regardless if older patients were either admitted or discharged at the initial ED visit, the independent predictor of revisit/readmission for older patients was frailty. CONCLUSION: Our study showed that frailty was the only independent predictor for revisit/readmission after ED discharge during the 3-month follow up. For ED physicians, malnutrition and IADL were independent predictors in recognizing whether the older patient should be admitted to the hospital. For discharged older ED patients, frailty was the independent predictor for the integration of community services for older patients to decrease the rate of revisit/readmission in 3 months.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32921129

RESUMO

Background - Atrial fibrillation (AF) can be maintained by localized intramural reentrant drivers. However, AF driver detection by clinical surface-only multi-electrode mapping (MEM) has relied on subjective interpretation of activation maps. We hypothesized that application of Machine Learning (ML) to electrogram frequency spectra may accurately automate driver detection by MEM and add some objectivity to the interpretation of MEM findings. Methods - Temporally and spatially stable single AF drivers were mapped simultaneously in explanted human atria (n=11) by subsurface near-infrared optical mapping (NIOM) (0.3mm2 resolution) and 64-electrode MEM (Higher-Density (HD) or Lower-Density (LD) with 3mm2 and 9mm2 resolution, respectively). Unipolar MEM and NIOM recordings were processed by Fourier Transform analysis into 28407 total Fourier spectra. Thirty-five features for ML were extracted from each Fourier spectrum. Results - Targeted driver ablation and NIOM activation maps efficiently defined the center and periphery of AF driver preferential tracks and provided validated classifications for driver vs non-driver electrodes in MEM arrays. Compared to analysis of single electrogram frequency features, averaging the features for each surrounding 8 electrodes neighborhood, significantly improved classification of AF driver electrograms. The classification metrics increased when less strict annotation including driver periphery electrodes were added to driver center annotation. Notably, f1-score for the binary classification of HD catheter dataset were significantly higher than that of LD catheter (0.81 ± 0.02 vs 0.66 ± 0.04, p<0.05). The trained algorithm correctly highlighted 86% of driver regions with HD but only 80% with LD MEM arrays (81% for LD+HD arrays together). Conclusions - The ML model pre-trained on Fourier spectrum features allows efficient classification of electrograms recordings as AF driver or non-driver compared to the NIOM gold-standard. Future application of NIOM-validated ML approach may improve the accuracy of AF driver detection for targeted ablation treatment in patients.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32975928

RESUMO

Nickel-rich layered oxides, as the most promising commercial cathode material for high-energy density lithium-ion batteries, experience significant surface structural instabilities that lead to severe capacity deterioration and poor thermal stability. To address these issues, radially aligned grains and surface LixNiyWzO-like heterostructures are designed and obtained with a simple tungsten modification strategy in the LiNi0.91Co0.045Mn0.045O2 cathode. The formation of radially aligned grains, manipulated by the WO3 modifier during synthesis, provides a fast Li+ diffusion channel during the charge/discharge process. Moreover, the tungsten tends to enter into the lattice of the primary particle surface, and the armor-type tungsten-rich heterostructure protects the bulk material from microcracks, structural transformations, and surface side reactions. First-principles calculations indicate that oxygen is more stable in the surface tungsten-rich heterostructure than elsewhere, thus triggering an improved surface structural stability. Consequently, the 2 wt % WO3-modified LiNi0.91Co0.045Mn0.045O2 (NCM@2W) material shows outstanding prolonged cycling performance (capacity retention of 80.85% after 500 cycles) and excellent rate performance (5 C, 188.4 mA h g-1). In addition, its layered-to-rock salt phase transition temperature is increased by 80 °C compared with that of the pristine cathode. This work provides a novel surface modification approach and an in-depth understanding of the overall performance enhancement of nickel-rich layered cathodes.

17.
Zhongguo Gu Shang ; 33(8): 788-92, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32875774

RESUMO

Joint contracture is one of the common musculoskeletal disorders. It has seriously disturbed patients' activities of daily living in various aspects. The pathogenesis of it is eager to explore to distinct degree. Nowadays the thickeness and fibrosis of joint capsular is redarded as the major reason to joint contracture. It is reported that excessive fibroblasts and myofibroblasts activity, collagen hyperplasia, and extracellular matrix (ECM) deposition in these fibrotic condtions lead to the contracture. In addition, upregulators of myofibroblast and collagen synthesis, transforming growth factor-beta 1 (TGF-ß1), and connective tissue growth factor (CTGF) were shown to be increased. Altered levels of cytokines were also thought to play a role in this process as elevated levelsof tumor necrosis factor-α(TNF-α), matrix metalloproteinases(MMPs) and abnormal distribution tissue inhibitors of MMPs(TIMPs) were demonstrated in contracted capsules. At present, the methods for clinical treatment of joint contracture mainly include two major categories:stretching therapy, physical factor therapy, exercise therapy, botulinum toxin injection and other non-surgical treatments, arthroscopic lysis, open lysis, and other surgical treatments. Surgical treatment is performed when non-surgical treatment is difficult to achieve further improvement. It has a good effect on mild to moderate joint contracture, but it is difficult to completely restore joint activity for serious joint contracture. Although clinical treatment methods are diverse, the clinical effects are staggered and the effectiveness of their treatment is controversial. Joint contracture is an important challenge faced by orthopedics and rehabilitation physicians, therapists and patients. The review summarized the pathogenesisand treatment of joint contracture and provided a theoretical basis for clinical diagnosis and treatment.


Assuntos
Atividades Cotidianas , Contratura , Fibroblastos , Fibrose , Humanos , Cápsula Articular , Fator de Crescimento Transformador beta1
18.
Sci Rep ; 10(1): 14478, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32879354

RESUMO

Frailty is common among older people and results in adverse health outcomes. We investigated whether exposure to PM2.5 is associated with frailty. This cross-sectional study involved 20,606 community-dwelling participants aged ≥ 65 years, residing in New Taipei City, Taiwan. Analytic data included phenotypic frailty, disease burden by Charlson Comorbidity Index (CCI), urban or rural residence, and household income. PM2.5 exposure was calculated from air quality monitoring records, with low exposure defined as the lowest quartile of the study population. 1,080 frail participants (5.2%) were older, predominantly female, had more comorbidities, lived rurally, and had low PM2.5 exposure (all p < 0.001). In multinomial logistic regression analyses, the likelihood of high PM2.5 exposure was higher in prefrail (OR 1.4, 95% CI 1.3-1.5) and frail adults (OR 1.5, 95% CI 1.2-1.9) than in robust individuals, with stronger associations in those who were male (frail: OR 2.1, 95% CI 1.5-3.1; prefrail: OR 2.2, 95% CI 1.9-2.6), ≥ 75 years old (frail: OR 1.8, 95% CI 1.3-2.4; prefrail: OR 1.5, 95% CI 1.3-1.8), non-smokers (frail: OR 1.6, 95% CI 1.3-2.0; prefrail: OR 1.4, 95% CI 1.2-1.5), had CCI ≥ 2 (frail: OR 5.1, 95% CI 2.1-12.6; prefrail: OR 2.1, 95% CI 1.2-3.8), and with low household income (frail: OR 4.0, 95% CI 2.8-5.8; prefrail: OR 2.7, 95% CI 2.2-3.3). This study revealed a significant association between PM2.5 exposure and frailty, with a stronger effect in vulnerable groups.

19.
IEEE Trans Med Imaging ; PP2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32915731

RESUMO

Diabetic Retinopathy (DR) grading is challenging due to the presence of intra-class variations, small lesions and imbalanced data distributions. The key for solving fine-grained DR grading is to find more discriminative features corresponding to subtle visual differences, such as microaneurysms, hemorrhages and soft exudates. However, small lesions are quite difficult to identify using traditional convolutional neural networks (CNNs), and an imbalanced DR data distribution will cause the model to pay too much attention to DR grades with more samples, greatly affecting the final grading performance. In this paper, we focus on developing an attention module to address these issues. Specifically, for imbalanced DR data distributions, we propose a novel Category Attention Block (CAB), which explores more discriminative region-wise features for each DR grade and treats each category equally. In order to capture more detailed small lesion information, we also propose the Global Attention Block (GAB), which can exploit detailed and class-agnostic global attention feature maps for fundus images. By aggregating the attention blocks with a backbone network, the CABNet is constructed for DR grading. The attention blocks can be applied to a wide range of backbone networks and trained efficiently in an end-to-end manner. Comprehensive experiments are conducted on three publicly available datasets, showing that CABNet produces significant performance improvements for existing state-of-the-art deep architectures with few additional parameters and achieves the state-of-the-art results for DR grading. Code and models will be available at https://github.com/he2016012996/CABnet.

20.
Life Sci ; 261: 118354, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32866517

RESUMO

AIMS: Recent studies have shown that the hyperactive Notch pathway is involved in cirrhosis and hepatocellular carcinoma (HCC) development by regulating differentiation of hepatic oval cells (HOCs) into cancer cells. The aim of this study was to investigate whether matrine can alleviate liver injury and promote HOC differentiation into hepatocytes by suppression of Notch pathway. MAIN METHODS: We evaluated the expression of Notch-1, Jagged-1, and Hes-1 in HCC tissue by immunohistochemistry. Stem cell characteristics of HOCs were evaluated by CCK-8, cell cycle, and apoptosis. The expression of Notch pathway, HOC markers and albumin (ALB) was detected by immunohistochemistry, QRT-PCR and western blotting. The effects of matrine in protecting liver in vivo were investigated in a rat Solt-Farber precancerous model. KEY FINDINGS: We found an abnormal activated Notch pathway in HCC tissue, and the hyperactive Notch pathway was strongly associated with poor liver function in patients with cirrhosis with HCC. Using siNotch-1 to inhibit Notch pathway confirmed that Notch pathway could maintain stem cell characteristics of HOCs. Matrine inhibited stem cell characteristics of HOCs, the expression of Notch pathway and HOC markers but upregulated ALB. Matrine in combined with siNotch-1 RNA decreased the more potently inhibited HOC markers and Notch pathway. In rat Solt-Farber precancerous model, prophylactic application of matrine alleviated liver injury, downregulated Notch pathway and HOC markers, and upregulated ALB in a dose-dependent manner. SIGNIFICANCE: Matrine could promote the differentiation of HOCs into hepatocytes by inhibiting the Notch signalling pathway and alleviate liver injury.

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