Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Objective To establish a bidirectional fluid-structure interaction model of the venaflow acting on the lower limb for investigating its pressure and depressure modes,and analyzing the velocity distribution of venous flow in the lower limb and therapeutic efficacy,thereby providing guidance for the resonable setting of working parameters of the Veneflow.Methods The right lower limb of a 24-year-old healthy man was taken as the object.The outer contour was obtained with a 3D scanner,and the inner diameters,wall thicknesses and resting blood flow velocities of the great saphenous vein,small saphenous vein and posterior tibial vein were measured with color Doppler ultrasonography.A 3D solid model of the lower limb was built with SolidWorks,and a bidirectional fluid-structure interaction model of the venaflow acting on the lower limb was constructed with Ansys Workbench.Results The velocity distributions of venous flow in the lower limb in the pressure and depressure modes of the venaflow were obtained.Conclusion Through the analysis with the bidirectional fluid-structure interaction model of the venaflow acting on the lower limb,the pressure and depressure modes of the venaflow are optimized,which can enhance the therapeutic efficacy and improve the safety.

Objective To explore the association,consistency and complications prognostic value of thromboelastography and conventional coagulation tests in detecting coagulation function of antiplatelet after endovascular treatments in patients with acute ischemic stroke.Methods A retrospective cohort survey of 240 patients,admitted to our hospital from September 2012 to December 2017,was performed.All acute ischemic stroke patients accepted coagulation function monitoring 5 d after aspirin and clopidogrel and endovascular treatments by thromboelastography (R time,K time,α angle,maximum amplitude [MA]) and routine coagulation tests (prothrombin time [PT],activated partial thromboplastin time [APTT],fibrinogen [FIB],international normalized ratio [INR],blood platelet count).The association,consistency,and sensitivity,specificity,positive predictive value,negative predictive value of complications prognostic value of thromboelastography and conventional coagulation tests were analyzed.Results (1) R time and APTT,K time and APTT,α angle and FIB,and α angle and PLT were positively correlated;K time and FIB,R time and PLT,and α angle and APTT were negatively correlated.(2) R time and APTT (κ=0.266,P=0.000),K time and APTT (κ=0.134,P=0.024),and α angle and FIB (κ=0.162,P=0.007) had agreement in identifying hypercoagulability;R time and APTT (κ=0.211,P=0.001),K time and APTT (κ=0.198,P=0.002),and blood platelet count and K (κ=0.388,P=0.000),and α angle and PLT (κ=0.099,P=0.041) had agreement in identifying hypocoagulability.(3) The sensitivity of thromboelastography and routine coagulation tests in identifying early neurological deterioration was 17.65％ and 58.82％,and the sensitivity in identifying symptomatic hemorrhages by thromboelastography and routine coagulation tests was 73.68％ and 47.39％.Conclusions Some parameters has correlations in peroperative period,and has agreement in identifying hypercoagulability and hypocoagulability.Accordingly,routine coagulation tests might be superior in evaluating early neurological deterioration,and thromboelastography might be superior in evaluating symptomatic hemorrhages in patients with acute ischemic stroke.