The consumption of a high-fat diet(HFD)has been linked to osteoporosis and an increased risk of fragility fractures.However,the specific mechanisms of HFD-induced osteoporosis are not fully understood.Our study shows that exposure to an HFD induces premature senescence in bone marrow mesenchymal stem cells(BMSCs),diminishing their proliferation and osteogenic capability,and thereby contributes to osteoporosis.Transcriptomic and chromatin accessibility analyses revealed the decreased chromatin accessibility of vitamin D receptor(VDR)-binding sequences and decreased VDR signaling in BMSCs from HFD-fed mice,suggesting that VDR is a key regulator of BMSC senescence.Notably,the administration of a VDR activator to HFD-fed mice rescued BMSC senescence and significantly improved osteogenesis,bone mass,and other bone parameters.Mechanistically,VDR activation reduced BMSC senescence by decreasing intracellular reactive oxygen species(ROS)levels and preserving mitochondrial function.Our findings not only elucidate the mechanisms by which an HFD induces BMSC senescence and associated osteoporosis but also offer new insights into treating HFD-induced osteoporosis by targeting the VDR-superoxide dismutase 2(SOD2)-ROS axis.

The consumption of a high-fat diet(HFD)has been linked to osteoporosis and an increased risk of fragility fractures.However,the specific mechanisms of HFD-induced osteoporosis are not fully understood.Our study shows that exposure to an HFD induces premature senescence in bone marrow mesenchymal stem cells(BMSCs),diminishing their proliferation and osteogenic capability,and thereby contributes to osteoporosis.Transcriptomic and chromatin accessibility analyses revealed the decreased chromatin accessibility of vitamin D receptor(VDR)-binding sequences and decreased VDR signaling in BMSCs from HFD-fed mice,suggesting that VDR is a key regulator of BMSC senescence.Notably,the administration of a VDR activator to HFD-fed mice rescued BMSC senescence and significantly improved osteogenesis,bone mass,and other bone parameters.Mechanistically,VDR activation reduced BMSC senescence by decreasing intracellular reactive oxygen species(ROS)levels and preserving mitochondrial function.Our findings not only elucidate the mechanisms by which an HFD induces BMSC senescence and associated osteoporosis but also offer new insights into treating HFD-induced osteoporosis by targeting the VDR-superoxide dismutase 2(SOD2)-ROS axis.

Endodontic microsurgery is a vital treatment modality for teeth with persistent periradicular pathoses that have not responded to nonsurgical retreatment. The principle is to determine the reason for failure, completely eliminate the infection and promote periapical healing. Within recent years, endodontic microsurgery has evolved to become standardized and presents with a high success rate. However, its outcome is still influenced by many factors, including anatomy, periodontal condition, crown-to-root ratio, occlusion, the type of periradicular lesion, and prosthesis. Moreover, endodontists always concentrate on “the apex”, paying little attention to the general preoperative evaluation, accurate diagnosis, and comprehensive treatment plan. This article reviews the latest literature on these issues and the clinical experience of our research group and discusses the correlation between endodontic microsurgery and other oral disciplines, including periodontology, prosthodontics, oral implantology, oral and maxillofacial surgery and orthodontics. The oral interdisciplinary assessment should be made with comprehensive consideration of the root canal system, periradicular lesion, adjacent anatomical relationships, periodontal condition, occlusion, and esthetic rehabilitation. Based on these findings, the continuity of treatment will be optimized, and the best treatment plan will be proposed to provide clinical strategies for the diagnosis and treatment of complex periradicular diseases.

Objective:To evaluate correlation between left ventricular mechanical contraction synchrony and left ventricular systolic function by gated myocardial perfusion imaging(GMPI) using Cadmium-Zine-Telluride (CZT) SPECT.Methods:Three hundred and forty three consecutive patients( 232 males, 111 females, age (60.08±12.88) years) who underwent CZT SPECT GMPI in Shanxi Cardiovascular Hospital between January and August 2019 were retrospectively analyzed. The Emory cardiac toolbox was used to process the imaging data, and the left ventricular systolic synchrony parameters and systolic function parameters were acquired, including peak phase(PP), phase standard deviation (PSD), phase histogram bandwidth(PHB), histogram skewness(HS), histogram kurtosis(HK), and end-diastolic volume( EDV), end-systolic volume (ESV), left ventrieular ejection fraction (LVEF). All patients were divided into 4 groups: the normal group (147 cases), ischemic cardiomyopathy group (114 cases), nonischemic cardiomyopathy without left bundle branch block (LBBB) group(50 cases)and nonischemic cardiomyopathy with LBBB group(32 cases). The relationship between systolic synchrony parameters and systolic function parameters were analyzed with Pearson correlation analysis.Results:Statistic results for all patients showed that PSD and PHB were well correlated with LVEF( r values: -0.790, -0.799, both P<0.01), but PP was poorly correlated with LVEF( r=-0.194, P<0.01); HS, HK were positively correlated with LVEF( r values: 0.767, 0.676, both P<0.01); PSD, PHB were positively correlated with ESV( r values: 0.778, 0.795, both P<0.01) and EDV ( r values: 0.722, 0.732, both P<0.01); but PP was poorly correlated with ESV( r=0.145, P<0.01) and not correlated with EDV ( r=0.095, P>0.01). HS, HK were negatively correlated with EDV and ESV ( r values: -0.700 to -0.580, all P<0.01). PSD and PHB showed negatively correlation with LVEF ( r values: -0.834 to -0.492, all P<0.01), while HS, HK showed positive correlation with LVEF ( r values: 0.243-0.792, all P<0.01) in normal group, the ischemic cardiomyopathy group, the nonischemic cardiomyopathy without LBBB group and the nonischemic cardiomyopathy with LBBB group. Conclusions:The left ventricular systolic synchrony parameters provided by CZT SPECT GMPI correlate well with the left ventricular systolic function parameters, and the worse systolic function, the worse systolic synchrony. Both ischemic cardiomyopathy and non-ischemic cardiomyopathy can affect left ventricular mechanical contraction synchrony, and the effect on contraction synchrony in non-ischemic cardiomyopathy patients with LBBB is greater.

Objective To study the effect of pirfenidone (PFD) on the transformation of rat corneal stromal cells into fibroblasts in vitro and further explore the anti-fibrotic effect of PFD. Methods The corneal stromal cells from SD rat was isolated and cultured ,and was determined by vimentin stain. The experiment was divided into control group(DMEM+10%FBS),TGF-β1 group(2 ng/mL TGF-β1+DMEM+10%FBS)and PFD group(1 mg/mL PFD+ 2 ng/mL TGF-β1+DMEM+ 10%FBS). Cell proliferation was detected by CCK-8 assay. Collagen Ⅰ,Collagen Ⅲ,Keratocan and CD99 expression were detected by Western blot. Results Compared with control group and TGF-β1 group,the cell proliferation were significantly decreased in PFD group(P<0.05). Western blot showed that PFD can up-regulated Collagen Ⅰand Keratocan but down-regulated Collagen ⅢCD90 expression(P < 0.05). The ratio of Collagen Ⅲ/Collagen Ⅰ in PFD group was lowest in all groups(P < 0.05). Conclusion PFD can resistant fibration in corneal stromal cells may through the inhibition of TGF-β ,which affect the collagen synthesis and Keratocan,CD90 expression.