107 research outputs found

    Establishment and evaluation of a predictive model for length of hospital stay after total knee arthroplasty: A single-center retrospective study in China

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    BackgroundTotal knee arthroplasty (TKA) is the ultimate option for end-stage osteoarthritis, and the demand of this procedure are increasing every year. The length of hospital stay (LOS) greatly affects the overall cost of joint arthroplasty. The purpose of this study was to develop and validate a predictive model using perioperative data to estimate the risk of prolonged LOS in patients undergoing TKA.MethodsData for 694 patients after TKA collected retrospectively in our department were analyzed by logistic regression models. Multi-variable logistic regression modeling with forward stepwise elimination was used to determine reduced parameters and establish a prediction model. The discrimination efficacy, calibration efficacy, and clinical utility of the prediction model were evaluated.ResultsEight independent predictors were identified: non-medical insurance payment, Charlson Comorbidity Index (CCI) ≥ 3, body mass index (BMI) > 25.2, surgery on Monday, age > 67.5, postoperative complications, blood transfusion, and operation time > 120.5 min had a higher probability of hospitalization for ≥6 days. The model had good discrimination [area under the curve (AUC), 0.802 95% CI, 0.754–0.850]] and good calibration (p = 0.929). A decision curve analysis proved that the nomogram was clinically effective.ConclusionThis study identified risk factors for prolonged hospital stay in patients after TKA. It is important to recognize all the factors that affect hospital LOS to try to maximize the use of medical resources, optimize hospital LOS and ultimately optimize the care of our patients

    BMI1 fine-tunes gene repression and activation to safeguard undifferentiated spermatogonia fate

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    Introduction: Spermatogenesis is sustained by the homeostasis of self-renewal and differentiation of undifferentiated spermatogonia throughout life, which is regulated by transcriptional and posttranscriptional mechanisms. B cell-specific Moloney murine leukemia virus integration site 1 (BMI1), one of spermatogonial stem cell markers, is a member of Polycomb repressive complex 1 (PRC1) and important to spermatogenesis. However, the mechanistic underpinnings of how BMI1 regulates spermatogonia fate remain elusive.Methods: We knocked down BMI1 by siRNA to investigate the role of BMI1 in undifferentiated spermatogonia. Differentially expressed genes were identified by RNA-seq and used for KEGG pathway analysis. We performed ChIP-seq analysis in wild type and BMI1 knockdown cells to explore the underlying molecular mechanisms exerted by BMI1. BMI1-associated alterations in repressive histone modifications were detected via Western blotting and ChIP-seq. Furthermore, we performed mass spectrometry and Co-immunoprecipitation assays to investigate BMI1 co-factors. Finally, we demonstrated the genomic regions occupied by both BMI1 and its co-factor.Results: BMI1 is required for undifferentiated spermatogonia maintenance by both repressing and activating target genes. BMI1 preserves PI3K-Akt signaling pathway for spermatogonia proliferation. Decrease of BMI1 affects the deposition of repressive histone modifications H2AK119ub1 and H3K27me3. BMI also positively regulates H3K27ac deposited genes which are associated with proliferation. Moreover, we demonstrate that BMI1 interacts with Sal-like 4 (SALL4), the transcription factor critical for spermatogonia function, to co-regulate gene expression.Discussion: Overall, our study reveals that BMI1 safeguards undifferentiated spermatogonia fate through multi-functional roles in regulating gene expression programs of undifferentiated spermatogonia

    RPS23RG1 modulates tau phosphorylation and axon outgrowth through regulating p35 proteasomal degradation

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    Tau蛋白病(Tauopathies)是由过度磷酸化的tau蛋白聚集形成神经纤维缠结为特征的一类神经退行性疾病,包括阿尔茨海默病(Alzheimer’s disease, AD)、进行性核上性麻痹(Progressive superanuclear palsy, PSP)、额颞叶痴呆(Frontotemporal dementia, FTD)等。随着全球社会结构的老龄化,tau蛋白病患者比率迅速增加,给个人和社会带来巨大的经济及精神负担。厦门大学神经科学研究所张云武教授团队最新发现RPS23RG1(RR1)的胞内羧基端区域能够与Cdk5激酶的激活蛋白p35的氨基端相互作用,介导p35的膜定位并影响其泛素化降解,从而调控在tau蛋白异常磷酸化过程中发挥重要作用的Cdk5激酶的活性。团队研究表明RPS23RG1通过其胞内羧基端与p35相互作用,介导p35膜结合和降解,从而抑制Cdk5活性,平衡tau磷酸化水平,促进轴突生长。此外,RPS23RG1的跨膜区与腺苷酸环化酶AC相互作用,抑制GSK3-β活性,同样控制tau过度磷酸化。提示RPS23RG1是改善tau过度磷酸化水平及治疗tau蛋白病的潜在靶点。 厦门大学医学院神经科学研究所博士后赵东栋为该研究第一作者,张云武教授为通讯作者。【Abstract】Tauopathies are a group of neurodegenerative diseases characterized by hyperphosphorylation of the microtubule-binding protein, tau, and typically feature axon impairment and synaptic dysfunction. Cyclin-dependent kinase5 (Cdk5) is a major tau kinase and its activity requires p35 or p25 regulatory subunits. P35 is subjected to rapid proteasomal degradation in its membrane-bound form and is cleaved by calpain under stress to a stable p25 form, leading to aberrant Cdk5 activation and tau hyperphosphorylation. The type Ib transmembrane protein RPS23RG1 has been implicated in Alzheimer’s disease (AD). However, physiological and pathological roles for RPS23RG1 in AD and other tauopathies are largely unclear. Herein, we observed retarded axon outgrowth, elevated p35 and p25 protein levels, and increased tau phosphorylation at major Cdk5 phosphorylation sites in Rps23rg1 knockout (KO) mice. Both downregulation of p35 and the Cdk5 inhibitor roscovitine attenuated tau hyperphosphorylation and axon outgrowth impairment in Rps23rg1 KO neurons. Interestingly, interactions between the RPS23RG1 carboxyl-terminus and p35 amino-terminus promoted p35 membrane distribution and proteasomal degradation. Moreover, P301L tau transgenic (Tg) mice showed increased tau hyperphosphorylation with reduced RPS23RG1 levels and impaired axon outgrowth. Overexpression of RPS23RG1 markedly attenuated tau hyperphosphorylation and axon outgrowth defects in P301L tau Tg neurons. Our results demonstrate the involvement of RPS23RG1 in tauopathy disorders, and implicate a role for RPS23RG1 in inhibiting tau hyperphosphorylation through homeostatic p35 degradation and suppression of Cdk5 activation. Reduced RPS23RG1 levels in tauopathy trigger aberrant Cdk5-p35 activation, consequent tau hyperphosphorylation, and axon outgrowth impairment, suggesting that RPS23RG1 may be a potential therapeutic target in tauopathy disorders.This work was supported by grants from National Key Research and Development Program of China (2016YFC1305903 and 2018YFC2000400 to Y-wZ), National Natural Science Foundation of China (81771377, U1705285, 91332112, and 81225008 to Y-wZ), Fundamental Research Funds for the Central Universities (20720180049 to Y-wZ), the Fujian Provincial Health Commission-Education Department Joint Tackling Plan (WKJ2016-2-18 to F-rL), and Postdoctoral Science Foundation of China (2020M671948 to DZ)

    Spatial and temporal variation in soil bulk density and saturated hydraulic conductivity and its influencing factors along a 500 km transect

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    Soil bulk density (BD) and saturated hydraulic conductivity (Ks) are two critical soil physical parameters that affect soil water holding capacity, infiltration, carbon stocks, and many land and surface processes. Although variations in spatial and temporal BD and Ks are widely recognized and known to differ at different scales, little large-scale data is available. This study explores changes in spatial and temporal BD and Ks along a 500 km transect on the Chinese Loess Plateau (CLP). On seven different occasions, we took BD and Ks measurements in undisturbed soil samples within the surface (0-10 cm) and subsurface (10-20 cm) soil layers from August 2015 to October 2018 along this long transect. This transect covers two climate zones (subhumid and semiarid) and mainly includes five land-use types. BD and log10-transformed Ks (LogKs) exhibited weak and moderate spatial variations during different sampling periods along the long transect, respectively. The highest LogKs values of the two soil layers were observed in summer. Only BD (LogKs) in the surface soil layer of semiarid zone was significantly higher (lower). Grassland had slightly lower BD and higher Ks compared to the other land-use types. Climate had no significant effect on BD and Ks variability. Land-use type and season separately had a significant impact on BD and Ks variability, while sampling time significantly influenced both BD and Ks variability. Ks was negatively correlated with soil water content in spring, summer and autumn. In this long transect, spatial and temporal variations in BD and Ks are determined by land-use types, seasonal changes, sampling time and soil water condition. Understanding temporal BD and Ks variations and their dominant factors will help in the selection of soil physical parameters to optimize hydrological models more accurately at a regional scale

    Characterizing spatial-temporal patterns and abrupt changes in deep soil moisture across an intensively managed watershed

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    Soil moisture content (SMC) is highly variable in space and time due to the combined effects of natural processes and human influences. This study was conducted to explore the temporal-spatial patterns of deep SMC and detect possible abrupt changes in SMC in deep soil layers across an intensively managed watershed. We monitored SMC to a depth of 500 cm from 2016 to 2017 at the Gutun watershed (N = 89) on the Chinese Loess Plateau and determined related soil and vegetation properties. The mean SMC on the slopes at different depths were lower than in the gullies at the intensively managed areas affected by the "Grain for Green" project and the "Gully Land Consolidation" project. With increasing soil depth, slope SMCs gradually increased to 14%, while gully SMCs reached 40%. The spatial structures and patterns of mean SMCs within the 0-500 cm profile were similar but differed among different sub-layers. The detected fast changing layers (FCLs) of SMC (mean thickness = 76 cm) often occurred on the slopes of the watershed, while the relatively stable layers of SMC (mean thickness = 257 cm) were often located in the gullies. In deep soil layers (below 300 cm), we detected deep-FCLs at eight sites (mean thickness = 60 cm) which were all located on the slopes and under the same species (Robinia pseudoacacia L.). The mean SMCs within each of the eight deep-FCLs demonstrated a decreasing trend with time, which may be caused by the distribution of fresh roots. Human management had a profound impact on the spatial and temporal patterns of SMC in deep soil profiles at the watershed scale. This information should be considered by hydrologists and policy makers when developing eco-hydrology models and best management practices at multiple scales in a watershed

    Microstructural Characteristics and Mechanical Properties of Water Cooling Bobbin-Tool Friction Stir Welded 6063-T6 Aluminum Alloy

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    In this study, a novel welding method called water cooling bobbin-tool friction stir welding (WBT-FSW) was developed. 4 mm-thick 6063-T6 aluminum alloy sheets were successfully jointed by WBT-FSW. Comparative studies on macro/microstructural characteristics and mechanical properties of the WBT-FSW and conventional bobbin-tool friction stir welding (BT-FSW) joints were carried out. The results indicated that the water mist cooling can significantly decrease the welding temperature and improve both the weld formation and the mechanical properties of the joint. The tensile strength of the WBT-FSW joint was 11.4% higher than that of BT-FSW joint

    Exploring Scale-Specific Controls on Soil Water Content across a 500-Kilometer Transect Using Multivariate Empirical Mode Decomposition

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    Soil water content (SWC) varies both spatially and temporally and is highly controlled by various factors operating at different intensities and scales. In this study, we investigated the scale-specific controls of SWC along a 500-km transect using multivariate empirical mode decomposition (MEMD) at 42 sites. Soil water content and six environmental factors were divided into different intrinsic mode functions (IMFs) and residuals to represent different scales. Different values of IMFs for SWC and environmental factors were obtained throughout the whole profile and within five soil layers (0–1, 1–2, 2–3, 3–4, and 4–5 m). The largest scales (i.e., the scales that explain largest portion of variances) of SWC and environmental factors depended on the soil layer from which SWC was involved in MEMD analysis, and they were 272, 126, 134, 126, 117, and 121 km for soil layers from 0 to 1, 1 to 2, 2 to 3, 3 to 4, 4 to 5, and 0 to 5 m, respectively. The residuals accounted for a majority (33–78.1%) of the variance of the original data. At large scales (>250 km), precipitation and temperature were the controlling factors on SWC, whereas at moderate scales (65 km), elevation and sand were the factors determining SWC. In contrast, at all scales, clay content affected SWC distribution. The scale-specific prediction of SWC on the basis of IMFs and residuals contained more information on environmental factors than the results obtained at the measurement scale. Overall, SWC prediction from IMFs and their residuals were superior to those based on the original data. Using information obtained from MEMD could improve our understanding of the scale-specific characteristics of soil water and environmental factors across a long transect scale
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