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1.
J Orthop Surg Res ; 16(1): 293, 2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-33952274

RESUMEN

BACKGROUND: Peritendinous adhesion is among the common complications after tendon injury. Numerous studies have been carried out to prevent its formation, including modifications of surgical procedures, postoperative cares, application of medicines, etc. This study dynamically monitored fluctuations of inflammation, state of oxidative stress, and histopathologic changes around injured tendon to provide theoretical basis for further exploration in mechanisms of peritendinous adhesion formation. METHODS: Eighteen mature Sprague-Dawley male rats were randomly allocated into 6 equal groups. Compared with control and sham group, every rat's right hind Achilles tendon in experimental groups was cut and repaired by the modified Kessler technique. Besides control and sham group, samples of tendon margin and serum were collected at different time points after the surgery. Content of TNF-α, IL-1ß, and TGF-ß were assayed in harvested serum. Reactive oxygen species (ROS) were detected, expression levels of related genes (IL-1ß, IL-6, SOD1, SOD2, COL1, HIF1A) were quantified by qPCR, and various histopathological evaluations were performed. RESULTS: Indicators (TNF-α, IL-1ß, TGF-ß1, ROS) were noticed to have a similar trend of significant rising 24 h after the surgery except TGF-ß which was rising 72 h later. So were the expression trends of IL-1ß, IL-6, SOD1, SOD2, and COL1. HIF1A, inversely correlated with SOD2, showed the progressive relief of regional tissue hypoxia. Histological evaluation showed the same tendency that fibrosis and inflammation were getting serious 48 h later after the surgery. CONCLUSIONS: Inflammation, oxidative stress in injured tendon resulted from acute trauma, would be getting intense in 24 h. Peritendinous adhesion emerges and aggravates after 48 h. Thus, prompt efficient measures are advised to be taken after the injury as soon as possible.

2.
Front Immunol ; 12: 647588, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33936066

RESUMEN

Background: Previous research have implicated critical roles of systemic inflammation in the development of Multiple Sclerosis (MS). But the causal relationship between interleukins (ILs) and MS has not been fully elucidated. Objective: In this study, we applied Mendelian randomization (MR) approaches to address the causal associations between genetically determined circulating levels of ILs and the risk of MS. Methods: Genetic instruments for circulating IL-1 receptor antagonist (IL-1Ra), IL-2 receptor α subunit (IL-2Rα), IL-6, IL-16, IL-17, and IL-18 were obtained from recently published genome-wide association studies (GWAS). Summary-level data for MS were obtained from the International Multiple Sclerosis Genetics Consortium. MR analyses were performed using the R software (version 3.6.1, The R Foundation) and the TwoSampleMR package. Results: Genetic predisposition to higher circulating levels of IL-2Rα were significantly associated with MS risk. The odds ratio (OR) was 1.22 (95% confidence interval [CI], 1.12-1.32; p < 0.001) per one standard deviation increase in circulating IL-2Rα levels. There was a suggestive association of circulating IL-1Ra with MS risk (OR, 0.94; 95% CI, 0.88-0.99; p = 0.027). The other ILs were not associated with the outcome. Conclusion: Our results indicated that circulating IL-2Rα was causally associated with risk of MS.

3.
Arch Virol ; 2021 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-33871695

RESUMEN

To investigate the association between immune-cell-related cytokines and the development of chronic hepatitis B (CHB), patients with chronic hepatitis B virus (HBV) infection in the immunotolerant (IT) phase (n = 30) or hepatitis B envelope antigen (HBeAg)-positive CHB (n = 250) were enrolled in this study. Serological indicators and plasma cytokine levels were measured at the time of enrollment. The results showed that there were significant differences in the median age of the patients (27 vs. 31 years), alanine aminotransferase levels (ALT, 29.85 vs. 234.70 U/L), alanine aminotransferase levels (AST, 23.40 vs. 114.90 U/L), HBsAg levels (4.79 vs. 3.88 log10 IU/ml), HBeAg levels (1606.36 vs. 862.47 S/CO), and the HBV DNA load (8.17 vs. 6.71 log10 IU/ml) between the IT and CHB groups (all P < 0.01). The median values of Fms-like tyrosine kinase 3 ligand (FLT3-L), interferon-gamma (IFN-γ), interleukin- 17A (IL-17A), and transforming growth factor beta (TGF-ß1) were significantly higher in the IT group than in the CHB group (FLT3-L, 41.62 vs. 27.47 pg/ml; IFN-γ, 42.48 vs. 33.18 pg/ml; IL-17A, 15.66 vs. 8.90 pg/ml; TGF-ß1, 4921.50 vs. 2234 pg/ml; all P < 0.01). The median IFN-α2, TGF-ß3 and IL-10 levels in the IT group were significantly lower than those in the CHB group (IFN-α2, 15.24 vs. 35.78 pg/ml, P = 0.000; TGF-ß3, 131.69 vs. 162.61 pg/ml, P = 0.025; IL-10, 5.02 vs. 7.9 pg/ml, P = 0.012). Multivariate logistic regression analysis indicated that TGF-ß 1 (OR = 0.999, 95% CI 0.999-1.000, P < 0.001) and TGF-ß2 levels (OR = 1.008, 95%CI 1.004-1.012, P < 0.001) were modestly but significantly associated with the incidence of CHB. The results suggest that TGF-ß level might be an independent factor related to the occurrence of CHB.

5.
Nucleic Acids Res ; 2021 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-33905513

RESUMEN

Technological advances in rare DNA mutations detection have revolutionized the diagnosis and monitoring of tumors, but they are still limited by the lack of supersensitive and high-coverage procedures for identifying low-abundance mutations. Here, we describe a single-tube, multiplex PCR-based system, A-Star, that involves a hyperthermophilic Argonaute from Pyrococcus furiosus (PfAgo) for highly efficient detection of rare mutations beneficial from its compatibility with DNA polymerase. This novel technique uses a specific guide design strategy to allow PfAgo selective cleavage with single-nucleotide resolution at 94°C, thus mostly eliminating wild-type DNA in the denaturation step and efficiently amplifying rare mutant DNA during the PCR process. The integrated single-tube system achieved great efficiency for enriching rare mutations compared with a divided system separating the cleavage and amplification. Thus, A-Star enables easy detection and quantification of 0.01% rare mutations with ≥5500-fold increase in efficiency. The feasibility of A-Star was also demonstrated for detecting oncogenic mutations in solid tumor tissues and blood samples. Remarkably, A-Star achieved simultaneous detection of multiple oncogenes through a simple single-tube reaction by orthogonal guide-directed specific cleavage. This study demonstrates a supersensitive and rapid nucleic acid detection system with promising potential for both research and therapeutic applications.

6.
Acta Pharmacol Sin ; 2021 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-33850274

RESUMEN

Systemic sclerosis (SSc) is a life-threatening chronic connective tissue disease with the characteristics of skin fibrosis, vascular injury, and inflammatory infiltrations. Though inhibition of phosphodiesterase 4 (PDE4) has been turned out to be an effective strategy in suppressing inflammation through promoting the accumulation of intracellular cyclic adenosine monophosphate (cAMP), little is known about the functional modes of inhibiting PDE4 by apremilast on the process of SSc. The present research aimed to investigate the therapeutic effects and underlying mechanism of apremilast on SSc. Herein, we found that apremilast could markedly ameliorate the pathological manifestations of SSc, including skin dermal thickness, deposition of collagens, and increased expression of α-SMA. Further study demonstrated that apremilast suppressed the recruitment and activation of macrophages and T cells, along with the secretion of inflammatory cytokines, which accounted for the effects of apremilast on modulating the pro-fibrotic processes. Interestingly, apremilast could dose-dependently inhibit the activation of M1 and T cells in vitro through promoting the phosphorylation of CREB. In summary, our research suggested that inhibiting PDE4 by apremilast might provide a novel therapeutic option for clinical treatment of SSc patients.

7.
Appl Opt ; 60(10): 2912-2918, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33798173

RESUMEN

Muscle ischemia injury is the essence of compartment syndrome (CS). Photoacoustic (PA) imaging can monitor hemoglobin concentration changes in ischemic tissue by determining the state of light-absorbing molecules. This study investigated whether PA imaging can provide accurate CS monitoring. Rats received compression on the lower hind limb for 3 h to induce ischemia injury, followed by PA imaging of desired muscles for 24 h. PA intensities of the injured group were significantly lower than that in the control group. Histology findings correlated well with the PA findings. The results demonstrated that PA imaging could be a noninvasive and timely tool for clinically monitoring CS.

8.
Postgrad Med ; 2021 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-33866924

RESUMEN

OBJECTIVE: Small-vessel occlusions are the most common causes of mild strokes and, in China, account for approximately 27.3% of ischemic stroke cases. However, the factors associated with short- and long-term outcomes appear contradictory. Thus, we assessed the factors related to outcomes 3 years after small-vessel occlusion among patients aged 18 to 55 years. METHODS: Between 2007 and 2014, we recruited patients who experienced small-vessel occlusion (according to Trial of Org 10172 in Acute Stroke Treatment [TOAST] classification) aged 18 to 55 years and conducted a hospital-based follow-up study. The assessed outcomes were mortality, recurrence, and dependency within 3 years after the initial stroke. The outcome determinants were assessed using a multivariate logistic regression analysis. RESULTS: A total of 276 patients (men, 76.09%) with small-vessel occlusions were enrolled in this study. In addition, 85.1% of the patients had strokes between the ages of 45 and 55 years. The risk of recurrence within 3 years was higher for patients who had moderate strokes than for those who had mild events (relative risk [RR], 3.09; 95% confidence interval [CI], 1.14-8.34; P <0.05). Further, the risk of dependency within 3 years was 2.61 times higher in obese patients than in non-obese patients (RR, 2.61; 95% CI, 1.00-6.79; P <0.05). The risks of recurrence and dependency within 3 years increased by 17% and 18%, respectively, for each 1-unit increase in fasting plasma glucose levels (RR, 1.17; 95% CI, 1.05-1.30 and RR, 1.18; 95% CI, 1.06-1.32, respectively; both P <0.05). CONCLUSION: Our findings suggest that small-vessel occlusions cause the heaviest disease burden in patients aged 45 to 55 years. To reduce stroke recurrence, young and middle-aged patients with small-vessel occlusions should control their fasting plasma glucose levels and manage their weight.

9.
Arthritis Res Ther ; 23(1): 102, 2021 04 07.
Artículo en Inglés | MEDLINE | ID: mdl-33827676

RESUMEN

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized systemic, immune-mediated, and fibro-inflammatory disease. Hypocomplementemia was found in part of IgG4-RD patients especially in the setting of active disease. OBJECTIVES: This study aimed to clarify the clinical features, treatment efficacy, and outcome in IgG4-RD patients with hypocomplementemia. METHODS: 312 IgG4-RD patients were recruited in our prospective cohort conducted in Peking Union Medical College Hospital. Patients were divided into hypocomplementemia group and normal complement group according to serum C3 and C4 levels measured at baseline before treatment. Low serum C3 levels (< 0.73 g/L) and/or C4 levels (< 0.10 g/L) were defined as hypocomplementemia. Demographic data, clinical characteristics, laboratory parameters, treatment, and outcome of two groups were analyzed and compared. RESULTS: Hypocomplementemia was identified in 65 (20.8%) cases of untreated IgG4-RD patients at baseline. The average age of hypocomplementemia group was 55.85 ± 10.89 years, with male predominance (72.3%). Compared with normal complement group, patients with hypocomplementemia were likely to have more involved organs, higher IgG4-RD responder index (IgG4-RD RI), and higher laboratory parameters such as counts of eosinophils, inflammatory markers, immunoglobulin G (IgG), IgG1, IgG3, IgG4, and IgE. In addition, lymph nodes, lacrimal gland, submandibular gland, parotid gland, paranasal sinus, bile ducts, and prostate gland were more commonly affected (p < 0.05). Serum C3 and C4 showed a significant positively correlation with each other. Both C3 and C4 were negatively correlated with the number of involved organs, IgG, IgG3, IgG4, and IgG4-RD RI, as well as positively correlated with IgA and hypersensitive C reactive protein (hsCRP). 64 (98.5%) patients responded quickly to initial therapy at a 3-month follow-up. Fifteen (23.1%) patients relapsed during follow-up with mean recurrence time of 14.2 ± 13.8 months. Compared with normal complement group, there was no significant difference of relapse rate in two groups (P = 0.401). CONCLUSIONS: Clinical characteristics of IgG4-related disease with hypocomplementemia differ from normal complement group. Serum C3 and C4 at baseline before treatment could be biological markers for disease activity. IgG4-RD with hypocomplementemia responded well to treatment and had no significant difference of relapse rate in IgG4-RD with normal complement.

10.
Artículo en Inglés | MEDLINE | ID: mdl-33930105

RESUMEN

OBJECTIVE: To investigate the role of Programmed cell death protein 1 (PD-1) and its two ligands PD-L1 and PD-L2 in the pathogenesis of IgG4-RD. METHODS: Patients with IgG4-RD (n = 43) as well as healthy controls (n = 34) were recruited. Expression levels of PD-1, PD-L1 and PD-L2 in plasma, submandibular gland and T cell subsets were determined by ELISA, immunohistochemistry and flow cytometry. Naive T cells were stimulated with or without PD-L1/PD-L2 or anti-PD-L1/anti-PD-L2 for 7 days and the proportion of CD4+CD25+Treg cells was detected by flow cytometry. RESULTS: The expression of PD-1, PD-L1 and PD-L2 in the plasma, submandibular gland and on the surface of Treg cells were increased in IgG4-RD patients. Plasma sPD-1 was positively correlated with serum IgG, IgG1, IgG3, IgG4, IgG4-RD RI and numbers of organs involved, and negatively correlated with serum IgM, IgA, C3 and C4. Plasma sPD-L2 was positively correlated with serum IgG1, plasma sPD-L1 was positively correlated with sPD-L2 and negatively correlated with C3. Stimulation of PD-L1 but not PD-L2 promoted the differentiation of naive T cells from IgG4-RD patients into CD4+CD25+Treg cells. CONCLUSION: Plasma concentration of sPD-1, sPD-L1 and sPD-L2 were significantly increased in patients with IgG4-RD, and the expression of PD-1 and PD-L2 on Treg cells were upregulated. PD-1/PD-L1 can promote the differentiation of naive T cells into Treg cells and thus participate in the pathogenesis of IgG4-RD.

12.
Burns ; 2021 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-33707088

RESUMEN

PURPOSE: This study examines the differences in parent-perceived and patient-reported quality of life (QoL) among young adult burn patients three years after injury and the factors affecting these differences. METHOD: The sample comprised 35 burn patients from the Formosa Fun Coast Water Park dust explosion and their parents. The study was conducted from June 2016 to August 2018. We used self-report questionnaires to collect socio-demographic data, the adapted Chinese version of the Burn Specific Health Scale-Brief, and the Impact of Events Scale for Burn. RESULTS: The analysis indicated that simple abilities recovered the fastest, while body image recovered the slowest. The variation trends of these factors were similar but parents' scores were lower than patients' scores. Parents' post-traumatic stress disorder (PTSD) scores were higher than that of patients, but were not statistically significant. Parents' gender and PTSD levels and patients' burn area affected differences in parent-perceived QoL among patients. PTSD levels were significantly higher among mothers. CONCLUSIONS: For parents, PTSD is a common response to their children experiencing burn injuries. Parents' observations of warning signs enable early medical intervention. Establishing a family-centered care plan, providing psychological support for both parents and patients, and forming a continuous care system with efficient communication can support patients' return to society.

13.
Int Urol Nephrol ; 2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33710531

RESUMEN

BACKGROUND: Accurate estimating glomerular filtration rate (GFR) is crucial both in clinical practice and epidemiological survey. We incorporated semi-supervised learning technology to improve GFR estimation performance. METHODS: AASK [African American Study of Kidney Disease and Hypertension], CRIC [Chronic Renal Insufficiency Cohort] and DCCT [Diabetes Control and Complications Trial] studies were pooled together for model development, whereas MDRD [Modification of Diet in Renal Disease] and CRISP [Consortium for Radiological Imaging Studies of Polycystic Kidney Disease] studies for model external validation. A total of seven variables (Serum creatinine, Age, Sex, Black race, Diabetes status, Hypertension and Body Mass Index) were included as independent variables, while the outcome variable GFR was measured as the urinary clearance of 125I-iothalamate. The revised CKD-EPI [Chronic Kidney Disease Epidemiology Collaboration] creatinine equations was selected as benchmark for performance comparisons. Head-to-head performance comparisons from four-variable to seven-variable combination were conducted between revised CKD-EPI equations and semi-supervised models. RESULTS: In each independent variables combination, the semi-supervised models consistently achieved superior results in all three performance indicators compared with corresponding revised CKD-EPI equations in the external validation data set. Furthermore, compared with revised four-variable CKD-EPI equation, the seven-variable semi-supervised model performed less biased (mean of difference: 0.03 [- 0.28, 0.34] vs 1.53 [1.28, 1.85], P < 0.001), more precise (interquartile range of difference: 7.94 [7.37, 8.50] vs 8.28 [7.76, 8.83], P = 0.1) and accurate (P30: 88.9% [87.4%, 90.2%] vs 86.0% [84.4%, 87.4%], P < 0.001. CONCLUSIONS: The superior performance of the semi-supervised models during head-to-head comparisons supported the hypothesis that semi-supervised learning technology could improve GFR estimation performance.

14.
Fitoterapia ; 151: 104886, 2021 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-33757847

RESUMEN

Two undescribed sesamin-type sesquilignans ptehoosines A (1) and B (2), together with 4 known lignans (3-6), were isolated from Pterocephalus hookeri (C.B. Clarke) Höeck which was widely used as traditional Tibetan medicine for treatment of rheumatoid arthritis. Their structures were determined by HR-ESI-MS, NMR analysis and CD experiment. The in vitro antiangiogenic effect of all isolated compounds against human umbilical vein endothelial cells (HUVECs) were evaluated by CCK-8 assay. Among them, compound 1 exhibited significant proliferative inhibition on HUVECs with IC50 value of 32.82 ± 0.99 µM. Further in vitro study indicated 1 could arrest cell cycle at G0/G1 phase and reduce the migration of HUVECs. In vivo experiment exhibited 1 could inhibit tail vessels plexus in zebrafish. The above finding suggested that 1 was a promising lead compound against RA by inhibiting of angiogenesis.

15.
Anal Bioanal Chem ; 413(12): 3193-3199, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33755768

RESUMEN

CD147 is involved in various physiological processes and plays important roles for tumor metastasis. Glycosylation of the protein determines numerous functions of CD147. Up to now, hardly any sensor has been developed for detecting glycosylation of CD147 in live cells. There is a pressing requirement of development of a selective and continuous biosensor for cell imaging. The emergence of gene-encoded fluorescence resonance energy transfer (FRET) sensor provides a new way to develop the sensors to analysts. We designed and constructed novel gene-encoded FRET proteins sensing glycosylation of CD147 by measuring FRET ratio of two intermolecular motifs. With the decrease of CD147 glycosylation level in cells, the FRET ratio increased significantly. The specificity of the sensor targeting to CD147 was also determined by siRNA interference experiment. Finally, continuous living cell image of deglycosylation process of CD147 using the newly developed sensor has been performed successfully. The work not only provides useful tools for analyzing glycosylation of CD147 in living cells, but also implicates alternative strategy for detecting other glycosylated proteins.

16.
Elife ; 102021 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-33724184

RESUMEN

Despite the rising prevalence of methadone treatment in pregnant women with opioid use disorder, the effects of methadone on neurobehavioral development remain unclear. We developed a translational mouse model of prenatal methadone exposure (PME) that resembles the typical pattern of opioid use by pregnant women who first use oxycodone then switch to methadone maintenance pharmacotherapy, and subsequently become pregnant while maintained on methadone. We investigated the effects of PME on physical development, sensorimotor behavior, and motor neuron properties using a multidisciplinary approach of physical, biochemical, and behavioral assessments along with brain slice electrophysiology and in vivo magnetic resonance imaging. Methadone accumulated in the placenta and fetal brain, but methadone levels in offspring dropped rapidly at birth which was associated with symptoms and behaviors consistent with neonatal opioid withdrawal. PME produced substantial impairments in offspring physical growth, activity in an open field, and sensorimotor milestone acquisition. Furthermore, these behavioral alterations were associated with reduced neuronal density in the motor cortex and a disruption in motor neuron intrinsic properties and local circuit connectivity. The present study adds to the limited body of work examining PME by providing a comprehensive, translationally relevant characterization of how PME disrupts offspring physical and neurobehavioral development.

17.
Science ; 371(6536): 1359-1364, 2021 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-33766883

RESUMEN

The stabilization of black-phase formamidinium lead iodide (α-FAPbI3) perovskite under various environmental conditions is considered necessary for solar cells. However, challenges remain regarding the temperature sensitivity of α-FAPbI3 and the requirements for strict humidity control in its processing. Here we report the synthesis of stable α-FAPbI3, regardless of humidity and temperature, based on a vertically aligned lead iodide thin film grown from an ionic liquid, methylamine formate. The vertically grown structure has numerous nanometer-scale ion channels that facilitate the permeation of formamidinium iodide into the lead iodide thin films for fast and robust transformation to α-FAPbI3 A solar cell with a power-conversion efficiency of 24.1% was achieved. The unencapsulated cells retain 80 and 90% of their initial efficiencies for 500 hours at 85°C and continuous light stress, respectively.

18.
Medicine (Baltimore) ; 100(13): e25343, 2021 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-33787634

RESUMEN

ABSTRACT: This study was carried out to estimate the incidence and to determine socio-demographic risk factors for dementia among individuals residing in rural northern China.The current prospective, population-based study was conducted between 2011 and 2016. Follow-up interviews were conducted annually from 2014 to 2016. The study involved 1511 dementia-free individuals aged 60 years or above from rural China. Standard criteria were used to make diagnoses for dementia and Alzheimer disease (AD).At least one follow up survey was completed with 1181 study participants. At the 5-year follow-up, 127 individuals had developed dementia, 75 had developed AD, and 32 had developed vascular dementia (VaD). With a total of 5649.2 risk years for the sample, the estimated incidence rates per 1000 person-years were 22.48 (95% CI: 18.62, 26.35) for dementia and 13.28 (95% CI: 10.29, 16.26) for AD. Incidence rates for dementia and AD increased with age across the 10-year age groups. Poor education (illiteracy) was an independent risk factor for both AD and VaD. Being engaged in social activities was an independent protective factor for VaD.The incidence of dementia in rural China was found to be higher than previously reported. Incidence of dementia increased with age, and AD was the most frequent type of dementia. Poor education was associated with a higher risk of VaD and AD. Engagement in social activities was an independent protective factor for VaD.


Asunto(s)
Enfermedad de Alzheimer/epidemiología , Demencia Vascular/epidemiología , Población Rural/estadística & datos numéricos , Factores de Edad , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico , China/epidemiología , Demencia Vascular/diagnóstico , Escolaridad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Factores Protectores , Factores de Riesgo , Factores Sexuales , Participación Social
19.
Artículo en Inglés | MEDLINE | ID: mdl-33713851

RESUMEN

Transcriptional regulators (TRs) participate in essential processes in cancer pathogenesis and are critical therapeutic targets. Identification of drug response-related TRs from cell line-based compound screening data is often challenging due to low mRNA expression levels of TRs, protein modifications, and other confounders. In this study, we developed a regression-based pharmacogenomic and ChIP-seq data integration method (RePhine) to infer the impact of TRs on drug response through integrative analysis of pharmacogenomic and ChIP-seq data. RePhine was evaluated in simulation and pharmacogenomic data and was applied to pan-cancer datasets with the goal of biological discovery. In simulation data with added noise or confounders and in pharmacogenomic data RePhine demonstrated an improved performance in comparison with several commonly used methods such as correlation analysis and gene set enrichment analysis. Utilizing RePhine and Cancer Cell Line Encyclopedia data, we observed that RePhine-derived TR signatures could effectively cluster drugs with different mechanisms of action. RePhine predicted that loss of function of EZH2/PRC2 reduces cancer cell sensitivity toward the BRAF inhibitor PLX4720. Experimental validation confirmed that pharmacological EZH2 inhibition increases the resistance of cancer cells to PLX4720 treatment. Our results support that RePhine is a useful tool for inference of the TRs related to drug response and for potential therapeutic applications. The source code for RePhine is freely available at https://github.com/coexps/RePhine.

20.
J Cardiothorac Surg ; 16(1): 54, 2021 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-33766043

RESUMEN

BACKGROUND: Long-term placement of airway stents has a high probability of restenosis of the airway due to granulation tissue hyperplasia, and it is difficult to remove the stent. Our aim is to evaluate the success rate and complications of removal of tracheal tube metallic stents under fluoroscopic guidance, and to compare the difference between uncovered stent and covered stent. METHODS: We retrospectively reviewed 45 cases (31 males and 14 females; age, 12-71 years) of tracheal metallic stent removal performed at our center between January 2014 and December 2019. Covered stents were applied in 36 cases, and uncovered stents were applied in 9 cases. In the covered stent group, 15 patients presented with granulation tissue at both ends; 3 cases, with stent fracture; and 2, with stent intolerance due to severe airway foreign body sensation. In the uncovered stents group, all patients presented with granulation tissue formation; 2 patients, with stent fracture; and 1 patient, with stent intolerance. RESULTS: A total of 41 (91.1%) stents were successfully removed (34 [94.4%] in the covered stent group and 7 [77.8%] in the uncovered stent group). The average duration of stent placement was 3.2 ± 0.7 and 2.5 ± 1.2 months in the covered stent group and uncovered stent group, respectively. With regard to the complications, hemoptysis occurred in 4 cases (average blood volume lost, 100 ml), tracheal mucosa tear occurred in 5 cases, tracheal collapse requiring emergency airway stent placement occurred in 1 case, and tracheal rupture requiring emergency surgical suture occurred in 1 case. No procedure-related deaths occurred in either group. CONCLUSIONS: It is safe to remove the metal stent of the tracheal tube under the guidance of fluoroscopy, with low complications, and can avoid the long-term placement of the airway stent.

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