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1.
Neural Regen Res ; 17(5): 1125-1130, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34558541

RESUMO

Both interposition nerve grafts and masseter nerve transfers have been successfully used for facial reanimation after irreversible injuries to the cranial portion of the facial nerve. However, no comparative study of these two procedures has yet been reported. In this two-site, two-arm, retrospective case review study, 32 patients were included. Of these, 17 patients (eight men and nine women, mean age 42.1 years) underwent interposition nerve graft after tumor extirpation or trauma between 2003 and 2006 in the Ear Institute, School of Medicine, Shanghai Jiao Tong University, China, and 15 patients (six men and nine women, mean age 40.6 years) underwent masseter-to-facial nerve transfer after tumor extirpation or trauma between November 2010 and February 2016 in Shanghai Ninth People's Hospital, China. More patients achieved House-Brackmann III recovery after masseter nerve repair than interposition nerve graft repair (15/15 vs. 12/17). The mean oral commissure excursion ratio was also higher in patients who underwent masseter nerve transfer than in patients subjected to an interposition nerve graft. These findings suggest that masseter nerve transfer results in strong oral commissure excursion, avoiding obvious synkinesis, while an interposition nerve graft provides better resting symmetry. This study was approved by the Institutional Ethics Committee, Shanghai Ninth People's Hospital, China (approval No. SH9H-2019-T332-1) on December 12, 2019.

2.
J Sport Rehabil ; : 1-6, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34784583

RESUMO

CONTEXT: Many methods used to evaluate knee proprioception have shortcomings that limit their use in clinical settings. Based on an inexpensive 3D camera, a new portable device was recently used to evaluate the joint position sense (JPS) of the knee joint. However, the test-retest reliability of the new method remains unclear. This study aimed to evaluate the test-retest reliability of the new device and a long-arm goniometer for assessing knee JPS, and to compare the variability of the 2 methods. DESIGN: Prospective observational study of the test-retest reliability of knee JPS measurements. METHODS: Twenty-one healthy adults were tested in 2 sessions with a 1-week interval. Three target knee flexion angles (30°, 45°, and 60°) were reproduced in each session. Target and reproduced angles were measured with both methods. Intraclass correlation coefficients, standard error of the measurement, and Bland-Altman plots were used to quantify test-retest reliability. Paired t tests were used to compare knee JPS (absolute error of the target-reproduced angle) between the methods. RESULTS: The new device (good to excellent intraclass correlation coefficients .74-.80; standard error of the measurement 0.52°-0.61°) demonstrated better test-retest reliability than the goniometer (poor to fair intraclass correlation coefficients .23-.43; standard error of the measurement 0.89°-2.07°) and better test-retest agreement (respective mean differences for the 30°, 45°, and 60° knee angles: 0.11°, 0.13°, and 0.41° for the new system; 0.84°, 1.52°, and 1.18° for the goniometer). The measurements (absolute errors of the target-reproduced angles) with the goniometer were significantly greater than those with the new device (P < .05); the SDs of repeated measurements with the goniometer (1.50°-2.41°) were greater than with the new device (1.08°-1.38°). CONCLUSIONS: Given that the new device has good reliability and sufficient precision, it is the better alternative for evaluating knee JPS. Goniometers should be used with caution to assess knee JPS.

3.
J Sports Med Phys Fitness ; 61(10): 1333-1338, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34652086

RESUMO

BACKGROUND: The aim of the study is to compare a 16-week tai chi and Iyengar yoga program effects on muscle strength, static and dynamic balance, and balance confidence in elderly people. METHODS: A total of 48 participants (≥60 years old) without mobility-impairing neurological disease, dementia, cardiovascular disease/symptoms during moderate exercise, poorly controlled hypertension, or balance-impairing drug use. Participants were divided into a tai chi group, an Iyengar yoga group, and a control group (eight males and eight females per group), using a restricted randomization scheme generated by software. While the former two undertook 16-week exercise programs, the control group received general education. Maximum concentric strength was measured with an isokinetic dynamometer. The one-legged stand with eyes closed, "8 feet up and go," and Activities-specific Balance Confidence (ABC) scale were used to assess static balance, dynamic balance, and balance confidence in daily activities, respectively. RESULTS: Both programs improved all measures significantly with tai chi being more effective for increasing knee flexor strength (P=0.045) and extensor strength (P=0.032) and ABC score (P=0.034); Iyengar yoga was more effective for improving static balance (P=0.014) and dynamic balance (P=0.025; all P values here vs. the other program). CONCLUSIONS: Tai chi and Iyengar yoga can improve strength, balance, and balance confidence among older people. Both are suitable exercise choices for older adults.


Assuntos
Tai Ji , Ioga , Idoso , Feminino , Humanos , Joelho , Masculino , Pessoa de Meia-Idade , Força Muscular , Equilíbrio Postural
4.
J Appl Gerontol ; : 7334648211050376, 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34689638

RESUMO

Physical environmental cues can provide important support to people with dementia (PwD). Compared to interventions involving construction, some cues can be achieved more easily, with less expense, and with fewer disruptions to PwD's daily lives. This review aims to examine existing empirical evidence about the impacts of cues on PwD's behaviors. We adopted the PRISMA scoping review approach and identified 32 articles. The results show visual cues have been frequently studied. The signage facilitates PwD's wayfinding. Concealed doors (e.g., concealing doorknobs) effectively prevent exit attempts. PwD also eat better with tableware of higher-contrasting colors or good lighting conditions. Clearer toilet signage results in better continence. Applying cues properly contributes to improving PwD's well-being and decreasing the burden for caregivers. However, knowledge gaps still exist in the impacts of other sensory cues (e.g., tactile, olfactory, and auditory), which require further research.

5.
Arch Sex Behav ; 50(8): 3433-3445, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34704160

RESUMO

Although the majority of the Chinese general public remains unaccepting of same-sex sexual behaviors, results from multiple waves of the Chinese General Social Survey have shown a substantial change in the public tolerance for same-sex sexual behaviors between 2010 and 2017. Using logistic regression models and decomposition analysis, the current study revealed that while changes in the changes in the demographic predictors (e.g., cohort succession and improved education) contributed to some of the attitudinal change, changes in the predictor coefficients explained most of the attitudinal change. Specifically, the Internet historically played a critical role in shaping pro-LGBTQ consciousness in China, but its effect has diminished over time. Socioeconomic factors such as education and household registration status (i.e., urban versus rural origin) have gained statistical significance and effect size in their prediction of public tolerance. Policy and advocacy implications of the findings are also discussed.

6.
Sensors (Basel) ; 21(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34450966

RESUMO

To control the spread of coronavirus disease 2019 (COVID-19), it is effective to perform a fast screening of the respiratory rate of the subject at the gate before entering a space to assess the potential risks. In this paper, we examine the potential of a novel yet cost-effective solution, called thermopile-based respiratory gating, to contactlessly screen a subject by measuring their respiratory rate in the scenario with an entrance gate. Based on a customized thermopile array system, we investigate different image and signal processing methods that measure respiratory rate from low-resolution thermal videos, where an automatic region-of-interest selection-based approach obtains a mean absolute error (MAE) of 0.8 breaths per minute. We show the feasibility of thermopile-based respiratory gating and quantify its limitations and boundary conditions in a benchmark (e.g., appearance of face mask, measurement distance and screening time). The technical validation provided by this study is helpful for designing and implementing a respiratory gating solution toward the prevention of the spread of COVID-19 during the pandemic.


Assuntos
COVID-19 , Humanos , Pandemias , Taxa Respiratória , SARS-CoV-2 , Processamento de Sinais Assistido por Computador
7.
J Am Chem Soc ; 143(30): 11370-11381, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34291952

RESUMO

Phase separation of DNA is involved in chromatin packing for the regulation of gene transcription. Visualization and manipulation of DNA phase separation in living cells present great challenges. Herein, we present a Ru(II) complex (Ru1) with high DNA binding affinity and DNA "light-switch" behavior that can induce and monitor DNA phase separation both in vitro and in living cells. Molecular dynamics simulations indicate that the two phen-PPh3 ligands with positively charged lipophilic triphenylphosphine substituents and flexible long alkyl chains in Ru1 play essential roles in the formation of multivalent binding forces between DNA molecules to induce DNA phase separation. Importantly, the unique environmental sensitive emission property of Ru1 enables direct visualization of the dynamic process of DNA phase separation in living cells by two-photon phosphorescent lifetime imaging. Moreover, Ru1 can change the gene expression pattern by modulating chromatin accessibility as demonstrated by integrating RNA-sequencing and transposase-accessible chromatin with high-throughput sequencing. In all, we present here the first small-molecule-based tracer and modulator of DNA phase separation in living cells and elucidate its impact on the chromatin state and transcriptome.

8.
Huan Jing Ke Xue ; 42(7): 3442-3450, 2021 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-34212671

RESUMO

Based on Landsat satellite remote sensing images, this study interprets land use changes in the Yangtze River Delta (YRD) region from 2000 to 2018. Combined with changes in nitrogen fertilizer application, the changes in ammonia emissions from farmland ecosystem due changes in land use and nitrogen fertilizer application were further investigated. The results show that along with the rapid urbanization process, the area of cultivated land in the YRD region has gradually decreased from 276269 km2 (49% of total land area) in 2000 to 244001 km2 (44%) in 2018. The effects of changes in land use and nitrogen fertilizer application on ammonia emissions from farmland ecosystems mainly include emissions from soil background and nitrogen fertilizer application. From 2000 to 2018, ammonia emissions due to the application of nitrogen fertilizer decreased from 690 kt·a-1 to 541 kt·a-1 (relative decrease by 22%), while the ammonia emissions from the soil background reduced from 32 kt·a-1 to 29 kt·a-1 (decrease by 9%). During the past 20 years, urbanization in the YRD region has accelerated, and the area of cultivated land and the total amount of nitrogen fertilizer application have significantly reduced, thus resulting in reductions in ammonia emissions from the farmland ecosystem.


Assuntos
Amônia , Ecossistema , Agricultura , Amônia/análise , China , Fertilizantes/análise , Nitrogênio/análise , Rios , Solo
9.
Quant Imaging Med Surg ; 11(7): 3059-3069, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34249635

RESUMO

Background: Detecting discomfort in infants is an important topic for their well-being and development. In this paper, we present an automatic and continuous video-based system for monitoring and detecting discomfort in infants. Methods: The proposed system employs a novel and efficient 3D convolutional neural network (CNN), which achieves an end-to-end solution without the conventional face detection and tracking steps. In the scheme of this study, we thoroughly investigate the video characteristics (e.g., intensity images and motion images) and CNN architectures (e.g., 2D and 3D) for infant discomfort detection. The realized improvements of the 3D-CNN are based on capturing both the motion and the facial expression information of the infants. Results: The performance of the system is assessed using videos recorded from 24 hospitalized infants by visualizing receiver operating characteristic (ROC) curves and measuring the values of area under the ROC curve (AUC). Additional performance metrics (labeling accuracy) are also calculated. Experimental results show that the proposed system achieves an AUC of 0.99, while the overall labeling accuracy is 0.98. Conclusions: These results confirms the robustness by using the 3D-CNN for infant discomfort monitoring and capturing both motion and facial expressions simultaneously.

10.
Se Pu ; 39(2): 125-129, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-34227344

RESUMO

The large surface area, adjustable pore structure, good thermal and chemical stabilities, and abundant π-electron systems make triazine-based porous organic polymers (TPOPs) as promising porous materials for gas storage, catalysis, energy conversion and adsorption. Recently, TPOPs have aroused ever-increasing interest and are considered as one of the research highlights in solid phase microextraction (SPME) and other sample pretreatment techniques. This minireview summarizes the recent advancements in the synthesis of TPOPs and their applications in SPME. The application prospects of the TPOPs in SPME and other sample pretreatment techniques are also presented.

11.
Biomed Opt Express ; 12(5): 2813-2824, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34168904

RESUMO

Camera-based pulse-oximetry enables contactless estimation of peripheral oxygen saturation (SpO2). Because of the lack of readily available and affordable single-optics multi-spectral cameras, custom-made multi-camera setups with different optical filters are currently mostly used. The introduced parallax by these cameras could however jeopardise the SpO2 algorithm assumptions, especially during subject movement. In this paper we investigate the effect of parallax quantitatively by creating a large dataset consisting of 150 videos with three different parallax settings and with realistic and challenging motion scenarios. We estimate oxygen saturation values with a previously used global frame registration method and with a newly proposed adaptive local registration method to further reduce the parallax-induced image misalignment. We found that the amount of parallax has an important effect on the accuracy of the SpO2 measurement during movement and that the proposed local image registration reduces the error by more than a factor of 2 for the most common motion scenarios during screening. Extrapolation of the results suggests that the error during the most challenging motion scenario can be reduced to approximately 2 percent when using a parallax-free single-optics camera. This study provides important insights on the possible applications and use cases of remote pulse-oximetry with current affordable and readily available cameras.

12.
Gait Posture ; 88: 231-237, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34119778

RESUMO

BACKGROUND: Knee injuries often occur during or shortly after marathon running, and are linked to altered knee kinematics. RESEARCH QUESTION: The kinematics of healthy knees during pre- and post-marathon running have not been examined with high-speed fluoroscopy. This study aimed to evaluate the effects of marathon running on knee kinematics during walking and running by using a combined high-speed fluoroscopy and MRI technique. METHODS: Ten healthy runners underwent knee MRI within 24 h before marathon running to construct three-dimensional (3D) knee models. Knee kinematics during treadmill walking and running were evaluated using high-speed fluoroscopy (200hz) within 24 h before and as soon as possible (within 5 h) after marathon running. All pre- and post-marathon measurements were compared. RESULTS: (1) For post-marathon walking, posterior femoral translation increased 1.4 mm at initial contact (p = 0.015); proximal-distal distance of tibia and femur decreased 0.7 mm and 0.8 mm at initial contact and after contact, respectively (p = 0.039, p = 0.046); and valgus femur rotation increased 1.2° after contact (p = 0.027). (2) For post-marathon running, proximal-distal distance decreased 0.7 mm and 1.0 mm at initial contact and after contact (p = 0.011, p = 0.003) respectively; knee flexion decreased 4.3° before contact (p = 0.007); knee flexion increased 1.8° and 2.6° at initial contact and after contact, respectively (p = 0.038, p = 0.011); external femoral rotation increased 1.2° and 1.8° at initial contact and after contact, respectively (p = 0.012, p = 0.037). Valgus femoral rotation after contact increased 2.3° (p = 0.001). SIGNIFICANCE: Post-marathon changes in valgus and external femoral rotation, knee flexion, posterior femoral translation, and proximal-distal distance may increase the risk of knee injury. This study provides information to better understand the response of the knee to marathon running.


Assuntos
Articulação do Joelho , Corrida de Maratona , Fenômenos Biomecânicos , Fêmur , Fluoroscopia , Humanos , Imageamento Tridimensional , Amplitude de Movimento Articular , Tíbia
13.
J Magn Reson Imaging ; 54(5): 1585-1593, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34031930

RESUMO

BACKGROUND: Quantitative susceptibility mapping (QSM) has been used to study the magnetic susceptibility properties of collagen fibers in articular cartilage; however, it is unclear whether QSM is sensitive to changes due to degradation caused by long-distance running. It is clinically important to understand the link between long-distance running and microstructural changes in knee cartilage. PURPOSE: To investigate the ability of QSM to assess microstructural changes within cartilage after repetitive loading. STUDY TYPE: Prospective. POPULATION: Thirteen recreational, male long-distance runners. FIELD STRENGTH/SEQUENCE: Three-dimensional gradient recalled echo acquired at 3 T. ASSESSMENT: Magnetic resonance imaging (MRI) and 3D kinematics (translations and rotations during treadmill walking and running) of the knee joint were collected before and after marathon running. The compartments for analysis included the patella, trochlea, and subregions of femoral and tibial cartilage. Changes in regional susceptibility and cartilage thickness were calculated after marathon running. A susceptibility profile was obtained by fitting susceptibility as a function of the normalized depth of cartilage from the superficial to deep layers. STATISTICAL TESTS: Paired t-test or Wilcoxon signed-rank test, 95% confidence interval (CI) of the depth-wise susceptibility profile, Pearson correlation or Spearman correlation. RESULTS: There was a statistically significant increase in susceptibility value in the weight-bearing region of central medial femoral cartilage (cMF-c) after marathon running (pre-marathon: -0.0219 ± 0.0151 ppm, post-marathon: -0.0070 ± 0.0213 ppm, P < 0.05), while the cartilage thickness did not show significant changes in any regions (P-value range: 0.068-0.963). Significant susceptibility elevations occurred in the middle and deep layers of cMF-c (95% CIs did not overlap). A trend toward a positive correlation was found between the changes in susceptibility value in cMF-c and proximal-distal translation of the knee joint during walking (r = 0.55, P = 0.101) and running (r = 0.57, P = 0.089). DATA CONCLUSION: Localized magnetic susceptibility alterations were observed within knee cartilage in the weight-bearing area after repetitive loading without any morphologic changes. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.


Assuntos
Cartilagem Articular , Corrida , Cartilagem Articular/diagnóstico por imagem , Humanos , Articulação do Joelho/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Corrida de Maratona , Estudos Prospectivos
14.
Oncogene ; 40(22): 3885-3898, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33972683

RESUMO

N6-methyladenosine (m6A) is the most abundant internal mRNA modification in eukaryotes and plays an important role in tumorigenesis. However, the underlying mechanism remains largely unclear. Here, we established a cell model of rapamycin-induced autophagy to screen m6A-modifying enzymes. We found that m6A demethylase fat mass and obesity-associated protein (FTO) plays a key role in regulating autophagy and tumorigenesis by targeting the gene encoding eukaryotic translation initiation factor gamma 1 (eIF4G1) in oral squamous cell carcinoma (OSCC). Knocked down of FTO expression in OSCC cell lines, resulting in downregulation of eIF4G1 along with enhanced autophagic flux and inhibition of tumorigenesis. Rapamycin inhibited FTO activity, and directly targeted eIF4G1 transcripts and mediated their expression in an m6A-dependent manner. Dual-luciferase reporter and mutagenesis assays confirmed that YTH N6-methyladenosine RNA-binding protein 2 (YTHDF2) targets eIF4G1. Conclusively, after FTO silencing, YTHDF2 captured eIF4G1 transcripts containing m6A, resulting in mRNA degradation and decreased expression of eIF4G1 protein, thereby promoting autophagy and reducing tumor occurrence. Therefore, rapamycin may regulate m6A levels, determining the autophagic flux of OSCC, thereby affecting the biological characteristics of cancer cells. This insight expands our understanding of the crosstalk between autophagy and RNA methylation in tumorigenesis, which is essential for therapeutic strategy development for OSCC.

15.
Front Oncol ; 11: 656628, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33937067

RESUMO

MiR-21-5p is one of the most common oncogenic miRNAs that is upregulated in many solid cancers by inhibiting its target genes at the posttranscriptional level. However, the upstream regulatory mechanisms of miR-21-5p are still not well documented in cancers. Here, we identify a super-enhancer associated with the MIR21 gene (MIR21-SE) by analyzing the MIR21 genomic regulatory landscape in head and neck squamous cell carcinoma (HNSCC). We show that the MIR21-SE regulates miR-21-5p expression in different HNSCC cell lines and disruption of MIR21-SE inhibits miR-21-5p expression. We also identified that a key transcription factor, FOSL1 directly controls miR-21-5p expression by interacting with the MIR21-SE in HNSCC. Moreover, functional studies indicate that restoration of miR-21-5p partially abrogates FOSL1 depletion-mediated inhibition of cell proliferation and invasion. Clinical studies confirmed that miR-21-5p expression is positively correlated with FOSL1 expression. These findings suggest that FOSL1-SE drives miR-21-5p expression to promote malignant progression of HNSCC.

16.
J Crohns Colitis ; 15(11): 1852-1863, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-33884415

RESUMO

BACKGROUND AND AIMS: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. Here, we evaluate the efficacy and safety of tofacitinib re-treatment following treatment interruption in patients with ulcerative colitis. METHODS: Here, patients with clinical response to tofacitinib 10 mg b.d. induction therapy were randomised to receive placebo in OCTAVE Sustain. Those experiencing treatment failure after Week 8 of OCTAVE Sustain entered OCTAVE Open and re-initiated tofacitinib 10 mg b.d. [re-treatment subpopulation]; efficacy and safety data are presented up to Month 36 of OCTAVE Open. RESULTS: Median time to treatment failure following interruption was 169 (95% confidence interval [CI], 94.0-179.0) and 123 [95% CI, 91.0-168.0] days for induction remitters, and induction responders but non-remitters, respectively. Following re-treatment with tofacitinib, rates (non-responder imputation after a patient discontinued; latest observation carried forward imputation after a patient advanced to a subsequent study [NRI-LOCF]) of clinical response, remission, and endoscopic improvement were 74.0%, 39.0%, and 55.0% at Month 2, and 48.5%, 37.4%, and 42.4% at Month 36, respectively. Among induction remitters and induction responders but non-remitters, clinical response rates at Month 36 were 60.6% and 42.4% [NRI-LOCF], respectively. Efficacy was recaptured regardless of prior tumour necrosis factor inhibitor failure status. The safety profile of tofacitinib 10 mg b.d. re-treatment was consistent with the overall cohort and demonstrated no new safety risks associated with exposure of ≤36 months. CONCLUSIONS: Median time to treatment failure was numerically higher in induction remitters versus induction responders but non-remitters. Following treatment interruption, efficacy was safely and successfully recaptured with tofacitinib 10 mg b.d. re-treatment in a substantial proportion of patients [ClinicalTrials.gov:NCT01458574;NCT01470612].

17.
Sensors (Basel) ; 21(5)2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33800716

RESUMO

Contact-free sensors offer important advantages compared to traditional wearables. Radio-frequency sensors (e.g., radars) offer the means to monitor cardiorespiratory activity of people without compromising their privacy, however, only limited information can be obtained via movement, traditionally related to heart or breathing rate. We investigated whether five complex hemodynamics scenarios (resting, apnea simulation, Valsalva maneuver, tilt up and tilt down on a tilt table) can be classified directly from publicly available contact and radar input signals in an end-to-end deep learning approach. A series of robust k-fold cross-validation evaluation experiments were conducted in which neural network architectures and hyperparameters were optimized, and different data input modalities (contact, radar and fusion) and data types (time and frequency domain) were investigated. We achieved reasonably high accuracies of 88% for contact, 83% for radar and 88% for fusion of modalities. These results are valuable in showing large potential of radar sensing even for more complex scenarios going beyond just heart and breathing rate. Such contact-free sensing can be valuable for fast privacy-preserving hospital screenings and for cases where traditional werables are impossible to use.

19.
Int J Biol Macromol ; 166: 166-178, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33172616

RESUMO

Chronic diabetic wound causes serious threat to human health due to its long inflammatory phase and the reduced vascularization. Herein, we develop a hydrogel system for the treatment of diabetic wound, which can short the inflammatory stage (through the use of ori) and promote the angiogenesis (through the addition of siRNA-29a gene). Based on the Schiff base bonds, the Gel/Alg@ori/HA-PEI@siRNA-29a hydrogel was prepared by mixing oxidized hydroxymethyl propyl cellulose (OHMPC), adipic dihydrazide-modified hyaluronic acid (HA-ADH), oridonin (ori) loaded alginate microspheres (Alg@ori) and siRNA-29a gene-loading hyaluronic acid-polyethyleneimine complex HA-PEI@siRNA-29a (HA-PEI@siRNA-29a) under physiological conditions, which had moderate mechanical strength, appropriate swelling property, impressive stability, and slow release ability of ori and siRNA-29a. Excellent biocompatibility of the prepared hydrogel was also confirmed by in vitro mouse fibroblasts L929 cells culture study. Moreover, in vivo experiments further demonstrated that the prepared Gel/Alg@ori/HA-PEI@siRNA-29a hydrogel not only significantly accelerated the diabetic wound healing, angiogenesis factors (α-SMA and CD31) production, but also inhibited pro-inflammatory factors (IL-6 and TNF-α). In summary, we believe that the prepared hydrogels exhibit great potential for the treatment of chronic diabetic wound.


Assuntos
Anti-Inflamatórios/administração & dosagem , Angiopatias Diabéticas/terapia , Técnicas de Transferência de Genes , Ácido Hialurônico/química , Hidrogéis/química , MicroRNAs/metabolismo , Nanopartículas/química , Alginatos/química , Animais , Anti-Inflamatórios/uso terapêutico , Linhagem Celular , Celulose/análogos & derivados , Angiopatias Diabéticas/tratamento farmacológico , Diterpenos do Tipo Caurano/administração & dosagem , Diterpenos do Tipo Caurano/uso terapêutico , Camundongos , MicroRNAs/genética , Neovascularização Fisiológica , Polietilenoimina/química , Terapêutica com RNAi/métodos , Ratos , Ratos Sprague-Dawley , Bases de Schiff/química
20.
Dig Dis Sci ; 66(8): 2732-2743, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-32816215

RESUMO

BACKGROUND: Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Creatine kinase (CK) levels and CK-related adverse events (AEs) in tofacitinib-treated patients with UC were evaluated. METHODS: Data were analyzed for three UC cohorts: Induction (phase 2 and 3 induction studies); Maintenance (phase 3 maintenance study); Overall [patients who received tofacitinib 5 or 10 mg twice daily (b.d.) in phase 2, phase 3, or open-label, long-term extension studies; data at November 2017]. Clinical trial data for tofacitinib-treated patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis are presented for contextualization. RESULTS: Week 8 mean change from baseline CK with tofacitinib 10 mg b.d. induction therapy was 91.1 U/L (95% CI, 48.1-134.1) versus 19.2 U/L (8.5-29.9) with placebo. Among patients completing induction with 10 mg b.d. and re-randomized to 52 weeks of maintenance therapy, mean increases from induction baseline to the end of maintenance were 35.9 (8.1-63.7), 90.3 (51.9-128.7), and 115.6 U/L (91.6-139.7), with placebo, 5 and 10 mg b.d., respectively. The incidence rate (unique patients with events per 100 patient-years) for AEs of CK elevation in the tofacitinib-treated UC Overall cohort was 6.6 versus 2.2, 6.5, and 3.7 for tofacitinib-treated patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis, respectively. No serious AEs of CK elevation or AEs of myopathy occurred in UC studies. CONCLUSIONS: In patients with UC, CK elevations with tofacitinib appeared reversible and not associated with clinically significant AEs. UC findings were consistent with tofacitinib use in other inflammatory diseases. TRIAL REGISTRATION: NCT00787202; NCT01465763; NCT01458951; NCT01458574; NCT01470612; NCT01262118; NCT01484561; NCT00147498; NCT00413660; NCT00550446; NCT00603512; NCT00687193; NCT01059864; NCT01164579; NCT00976599; NCT01359150; NCT02147587; NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055; NCT00413699; NCT00661661; NCT01710046; NCT00678210; NCT01276639; NCT01309737; NCT01241591; NCT01186744; NCT01163253; NCT01877668; NCT01882439; NCT01976364.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Creatina Quinase/sangue , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piperidinas/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Psoríase/tratamento farmacológico , Pirimidinas/administração & dosagem , Fatores de Risco
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