الملخص
ObjectiveTo investigate the mechanism of Xuefu Zhuyu capsules against atherosclerosis via regulating polarization of macrophages based on Notch1/jagged canonical Notch ligand 1（Jagged1）/Hes family BHLH transcription factor 1（Hes1） signaling pathway. MethodThe mouse models with atherosclerosis were prepared by feeding the mice with an ApoE-/- high-fat diet for four weeks， and they were randomly divided into the model group， Xuefu Zhuyu capsule group， and atorvastatin group. C57BL/6 mice were fed as a normal group. The Xuefu Zhuyu capsule group was intragastrically given Xuefu Zhuyu capsules （0.728 g·kg-1·d-1）， and the atorvastatin group was intragastrically given atorvastatin tablet （6.07 mg·kg-1·d-1）. The normal group and the model group were given equal volume of the deionized water by intragastric administration， and the intervention lasted for 12 weeks. Aortic plaque morphology was observed by hematoxylin-eosin （HE） staining， and aortic plaque area and lipid deposition were observed by oil red O staining. The positive expression levels of CD86 and CD206 in aortic tissue were detected by immunohistochemistry， and serum levels of tumor necrosis factor （TNF）-α， interleukin（IL）-1β， transforming growth factor （TGF）-β1， and IL-10 were detected by enzyme-linked immunosorbent assay （ELISA）. The relative mRNA expressions of inducible nitric oxide synthase （iNOS）， arginase-1 （Arg-1）， Notch1， Jagged1， and Hes1 in aortic tissue were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The relative protein expression of iNOS， Arg-1， Notch1， Jagged1， and Hes1 in aortic tissue was detected by Western blot. ResultCompared with the normal group， the model group had significant aortic plaque and lipid deposition， and the expression levels of pro-inflammatory cytokines TNF-α and IL-1β were increased （P<0.01）. The expression level of anti-inflammatory cytokine TGF-β1 showed a downward trend， but the difference was not statistically significant. The mRNA and protein expressions of iNOS were increased （P<0.01）. The protein expression of Arg-1 was decreased （P<0.01）， and the mRNA expression of related pathway molecule Jagged1， as well as the protein expressions of Notch1， Jagged1， and Hes1 were increased in the model group （P<0.05， P<0.01）. Compared with those in the model group， the plaque area and lipid deposition had a decreasing trend in the Xuefu Zhuyu capsule group， and the expressions of TNF-α and IL-1β showed a downward trend. The expression of TGF-β1 was increased （P<0.05）， and the expression of macrophage marker CD86 was decreased. The mRNA and protein expressions of iNOS were decreased （P<0.01）. The mRNA and protein expressions of Arg-1 were increased （P<0.05， P<0.01）. Furthermore， the mRNA and protein expressions of Notch1， Jagged1， and Hes1 were decreased （P<0.01）. ConclusionXuefu Zhuyu capsules can reduce aortic plaque area and lipid deposition in mice with atherosclerosis， alleviate inflammation， inhibit M1 macrophages， and promote the expression of M2 macrophages， and the mechanism may be related to the regulation of Notch1/Jagged1/Hes1 signaling pathway.
الملخص
Objective:To describe a series of systemic sclerosis (SSc) patients with the combination of scleroderma renal crisis (SRC) and pulmonary arterial hypertension (PAH).Methods:The medical records of 472 SSc patients in Peking Union Medical College Hospital between January 2012 and October 2020 were reviewed and a retrospective analysis of the characteristics of patients with SRC and PAH among SSc patients was conducted.Results:Thirteen patients suffered from SRC and PAH in the SSc patients, 1 case was limited cutaneous SSc, and 12 cases were diffuse cutaneous SSc. Five patients had renal crisis before pulmonary arterial hypertension, 4 patients had pulmonary arterial hypertension before the occurrence of renal crisis, and the remaining 4 patients were found at the same time. Among them, 11 patients had Raynaud's phenomenon, 7 had gastrointestinal bleeding, 6 had pulmonary edema and 3 had telangiectasias. Twelve cases were positive for anti-nuclear antibodies and 4 cases were positive for anti-Scl-70 antibodies. N-terminal pro-brain natriuretic peptide (NT-proBNP)>1 400 ng/L in 11 patients. Two patients had thrombotic microangiopathy (TMA). Among the 13 patients, 3 patients died during hospitalization, 2 patients were lost to follow-up, and 2 patients died within 5 years of follow-up. Six patients survived, and 1 of the 4 patients with regular dialysis were discharged from dialysis.Conclusion:In patients with scleroderma, SRC can occur earlier, later than, or at the same time with SSc-PAH. Patients may have a higher incidence of gastrointestinal bleeding and higher level of NT-proBNP. PDE5i or ERAs may be beneficial.
الملخص
Adult-onset Still disease (AOSD) is a polygenic autoinflammatory disease with uncertain etiology.The clinical manifestations are complex,including high-spiking fever,rash,arthritis,arthralgia,lymphadenopathy,and leukocytosis.The pathogenesis of AOSD is still unclear,whereas it has been confirmed that many inflammatory cells and cytokines take part in the development of AOSD.The treatment of AOSD is mainly based on corticosteroids and immunosuppressive agents.Recently,with the research progress of autoinflammatory diseases and the emerging biological agents,we have new knowledge on the pathogenesis and therapeutic strategies of AOSD.This article reviews the current progress in pathogenesis and therapy of AOSD.