Abstract The aim of this study was to identify the risk factors for free flap failure after head and neck reconstructive surgery. The data of 881 consecutive patients who underwent free flap surgery ...at the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, between January 2013 and November 2016, were reviewed retrospectively. All surgeries were performed by a single head and neck surgical team. Patient demographic and surgical data that may have an influence on free flap outcomes were recorded. The χ2 test and multivariate logistic regression analysis were used to identify relevant risk factors. In total, 881 free tissue transfer surgeries were included in this study. Free flap failure occurred in 26 of 881 flaps (2.9%). A history of irradiation (odds ratio 0.205, 95% confidence interval 0.07–0.56; P = 0.002) was a statistically significant risk factor for free flap failure. Age, diabetes mellitus, history of previous neck surgery to the anastomosis side, donor site, choice of recipient vein, use of a coupler device, and postoperative anticoagulation were not associated with free flap outcomes. Thus, it is concluded that when performing head and neck reconstructive surgery, special attention should be paid to patients who have previously undergone irradiation.
Summary
Background
Serum vitamin D levels are associated with bone complications in patients with primary biliary cirrhosis (PBC). Increasing evidence suggests a nonskeletal role of vitamin D in ...various autoimmune and liver diseases.
Aim
To investigate the clinical relevance of vitamin D levels in PBC, especially their association with the therapeutic effects of ursodeoxycholic acid (UDCA).
Methods
Consecutive PBC patients were retrospectively reviewed. 25‐hydroxyvitamin D 25(OH)D levels were determined in frozen serum samples collected before initiation of UDCA treatment. Response to UDCA was evaluated by Paris‐I and Barcelona criteria. Logistic regressions were performed to identify the treatment response‐associated parameters.
Results
Among 98 patients, the mean serum 25(OH)D concentration was 17.9 ± 7.6 ng/mL. 25(OH)D levels decreased with increasing histological stage (P = 0.029) and were negatively correlated with bilirubin and alkaline phosphatase levels. After 1 year of UDCA therapy, 31 patients failed to achieve complete response according to Paris‐I criteria. The baseline 25(OH)D level was significantly lower in nonresponders (14.8 ± 6.4 vs. 19.3 ± 7.6 ng/mL, P = 0.005). Vitamin D deficiency at baseline was associated with an increased risk of incomplete response independent of advanced stages (OR = 3.93, 95% CI = 1.02–15.19, P = 0.047). Similar results were obtained when biochemical response was evaluated by Barcelona criteria. Furthermore, 25(OH)D levels were lower in patients who subsequently suffered death or liver transplantation (12.1 ± 4.6 vs. 18.4 ± 7.6 ng/mL, P = 0.023).
Conclusions
25(OH)D level is associated with biochemical and histological features in PBC. Pre‐treatment vitamin D status is independently related to subsequent response to UDCA. Our results suggest that vitamin D status may have important clinical significance in PBC.
Agyrotropic electron distributions are frequently taken as an indicator of electron diffusion regions of magnetic reconnection. However, they have also been found at electron‐scale boundaries of the ...non‐reconnecting magnetopause and are generated by the electron finite gyroradius effect. Here, we present magnetospheric multiscale observations of agyrotropic electron distributions in the foreshock region. These distributions are generated by the electron finite gyroradius effect after magnetic curvature scattering at a thin electron‐scale boundary. Meanwhile, the signatures of magnetic reconnection are absent at this boundary. The test‐particle simulation is adopted to verify the generation of the agyrotropic electron distributions by assuming one‐dimensional magnetic geometry. These observations suggest that agyrotropic electron distributions can be more widely formed at electron‐scale boundaries in space plasma environment.
Plain Language Summary
The agyrotropic electron distributions, which could be unstable to generate high frequency electrostatic waves, reveal valuable information of electron dynamics at electron scales. However, due to electron's small mass, the related observational study becomes only possible with the high‐resolution magnetospheric multiscale data. In this study, we show that the agyrotropic electron distributions can be also formed in the foreshock transients such as inside an hot flow anomaly, suggesting that agyrotropic electron distributions are ubiquitous in space plasma.
Key Points
We present the first magnetospheric multiscale observations of agyrotropic electron distributions in the foreshock transients
Accompanied with the agytropic electron distributions, clear signatures of magnetic reconnection are absent
The agytropic electron distributions are formed by the electron finite gyroradius effect at electron‐scale boundaries
In this study, we investigate detailed electron dynamics in strong guide‐field reconnection (the normalized guide field is ∼1.5). This reconnection event is observed by the Magnetospheric Multiscale ...(MMS) spacecraft at the center of a flux rope in the magnetotail. With the presence of a large parallel electric field (E‖) in the electron current sheet, electrons are accelerated when streaming into this E‖ region from one direction, and decelerated from the other direction. Some decelerated electrons can reduce the parallel speed to ∼0 to form relatively isotropic electron distributions at one side of the electron current sheet, as the estimated acceleration potential satisfies the relation eΦ‖ ≥ kTe,‖, where Te,‖ is the electron temperature parallel to the magnetic field. Therefore, a large E‖ is generated to balance the parallel electron pressure gradient across the electron current sheet, since electrons at the other side of the current sheet are still anisotropic. Based on these observations, we further show that the electron beta is an important parameter in guide‐field reconnection, providing a new perspective to solve the large parallel electric field puzzle in guide‐field reconnection.
Plain Language Summary
Magnetic reconnection is a universal process that rapidly converts energy from the magnetic field to plasma. The energy conversion at kinetic scales is of particular interest to researchers, as it is directly related to reconnection process in the central diffusion region. In general, the reconnecting magnetic fields do not have to be antiparallel, and an additional magnetic component known as the guide field (Bg) can appear in the direction perpendicular to the reconnecting plane. Recently, observations from Magnetospheric Multiscale (MMS) mission show a large electric field parallel to the local magnetic field, which is several times larger than the reconnection electric field, can appear in guide‐field reconnection, and impact electrons significantly. However, the generation of this large parallel electric field in strong guide‐field reconnection is still not fully understood. In this study, we suggest that the electron beta (ratio of the electron thermal pressure to the magnetic pressure) is an important parameter in guide‐field reconnection. Only within some proper electron beta range, a parallel pressure gradient across the electron current sheet can form to balance the large parallel electric field.
Key Points
We present detailed electron dynamics in guide‐field reconnection at the center of a flux rope
With eΦ‖ ≥ kTe,‖, the observed electron behaviors can be well explained
We suggest that electron beta is an important parameter for the generation of a large parallel electric field in guide‐field reconnection
Summary
Nucleotide‐binding, oligomerization domain (NOD)‐like receptor family, pyrin domain containing 3 (NLRP3) gene polymorphism was reported to be associated with susceptibility, disease activity ...or anti‐tumour necrosis factor (TNF) treatment response in rheumatoid arthritis (RA). However, the roles of NLRP3 inflammasome in the development of RA have not yet been elucidated fully. The present study aimed to study the role of NLRP3 inflammasome in RA. NLRP3 inflammasome activation in synovial tissues from RA and osteoarthritis (OA) patients were assessed by Western blot. Active caspase‐1 in synovia was stained by a FAM‐FLICA caspase‐1 probe. Mice with collagen‐induced arthritis (CIA) were treated with MCC950, a selective NLRP3 inhibitor, or vehicle for 2 weeks. The clinical score of arthritis, synovial inflammation and cartilage erosion were assessed. Proinflammatory cytokines were measured by enzyme‐linked immunosorbent assay (ELISA). The results showed that NLRP3 inflammasome was highly activated in both synovia from RA patients and CIA mice. Activation of NLRP3 inflammasome occurred mainly in the infiltrating monocyte/macrophages in synovia, but not in fibroblast‐like synoviocytes. Treatment with MCC950 resulted in significantly less severe joints inflammation and bone destruction. NLRP3 inflammasome activation in the synovia was inhibited significantly by MCC950 with reduced production of interleukin (IL)‐1β. The inhibition of NLRP3 inflammasome activation by MCC950 was confirmed further in a human monocytic cell line, THP‐1. In conclusion, NLRP3 inflammasome is involved in the pathogenesis of RA. Targeting NLRP3 inflammasome with a small molecule inhibitor might be a novel therapeutic strategy for RA.
NLRP3 inflammasome is involved in the pathogenesis of RA by promoting IL‐1β maturation and secretion. Targeting NLRP3 inflammasome with small molecule inhibitor might be a novel therapeutic strategy for RA.
Abstract
DrugBank (www.drugbank.ca) is a web-enabled database containing comprehensive molecular information about drugs, their mechanisms, their interactions and their targets. First described in ...2006, DrugBank has continued to evolve over the past 12 years in response to marked improvements to web standards and changing needs for drug research and development. This year's update, DrugBank 5.0, represents the most significant upgrade to the database in more than 10 years. In many cases, existing data content has grown by 100% or more over the last update. For instance, the total number of investigational drugs in the database has grown by almost 300%, the number of drug-drug interactions has grown by nearly 600% and the number of SNP-associated drug effects has grown more than 3000%. Significant improvements have been made to the quantity, quality and consistency of drug indications, drug binding data as well as drug-drug and drug-food interactions. A great deal of brand new data have also been added to DrugBank 5.0. This includes information on the influence of hundreds of drugs on metabolite levels (pharmacometabolomics), gene expression levels (pharmacotranscriptomics) and protein expression levels (pharmacoprotoemics). New data have also been added on the status of hundreds of new drug clinical trials and existing drug repurposing trials. Many other important improvements in the content, interface and performance of the DrugBank website have been made and these should greatly enhance its ease of use, utility and potential applications in many areas of pharmacological research, pharmaceutical science and drug education.
Bladder Cancer in the Genomic Era Guo, Charles C; Czerniak, Bogdan
Archives of pathology & laboratory medicine (1976),
06/2019, Letnik:
143, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Bladder cancer is a heterogeneous disease that exhibits a wide spectrum of clinical and pathologic features. The classification of bladder cancer has been traditionally based on morphologic ...assessment with the aid of immunohistochemistry. However, recent genomic studies have revealed that distinct alterations of DNA and RNA in bladder cancer may underlie its diverse clinicopathologic features, leading to a novel molecular classification of this common human cancer.
To update recent developments in genomic characterization of bladder cancer, which may shed insights on the molecular mechanisms underlying the origin of bladder cancer, dual-track oncogenic pathways, intrinsic molecular subtyping, and development of histologic variants.
Peer-reviewed literature retrieved from PubMed search and authors' own research.
Bladder cancer is likely to arise from different uroprogenitor cells through papillary/luminal and nonpapillary/basal tracks. The intrinsic molecular subtypes of bladder cancer referred to as
and
exhibit distinct expression signatures, clinicopathologic features, and sensitivities to standard chemotherapy. Genomic characterization of bladder cancer provides new insights to understanding the biological nature of this complex disease, which may lead to more effective treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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