Objective:To investigate the effects of Ziyin Liangxue formula combined with prednisone on immune function and the ST2/IL-33 pathway in mice with immune thrombocytopenia.Methods:In 40 BALB/c mice,32 were constructed as immune thrombocytopenia mouse models by antiplatelet serum injection.After successful modeling,the mice were randomly divided into model group,Ziyin Liangxue formula group(0.2 ml/10 g),prednisone group(0.2 ml/10 g),and Ziyin Liangxue formula+prednisone group(0.2 ml/10 g),8 mice in each group,and the other 8 mice were set as control group.The drugs were administered by gavage at the dose,and the model group and control group were given equal amounts of saline by gavage once a day for 2 weeks of continuous intervention.Blood samples and spleen tissues were collected,the peripheral platelet count was measured by automatic hematology analyzer,the pathological changes in spleen tissue was observed by HE staining,the levels of serum transforming growth factor(TGF)-β,interleukin(IL)-17,and peripheral blood thrombopoietin(TPO)were detected by enzyme-linked immunosorbent assay(ELISA),the expression of IL-33,sST2,and ST2 in spleen tissue was detected by Western blot,and the cell counts of peripheral blood Th17 and Treg were detected by flow cytometry.Results:Compared with the control group,the number of platelets,the level of TPO,TGF-β,and Treg cells were significantly decreased(P＜().05),while the level of IL-17,Thl7 cells,and the expression of IL-33,sST2,and ST2 protein were significantly increased in the model group(P＜0.01).Compared with the model group,the number of platelets,the level of TPO,TGF-β,and Treg cells were significantly increased(P＜0.05),while the level of IL-17,Th17 cells,and the expression of IL-33,sST2,and ST2 protein were significantly decreased in the Ziyin Liangxue formula+prednisone group(P＜0.01).Conclusion:Ziyin Liangxue formula+prednisone can effectively regulate Th17/Treg balance,thus effectively improve immune thrombocytopenia,and the mechanism may be related to the regulation of ST2/IL-33 signaling pathway.

Objective To observe the clinical efficacy and safety of budesonide inhalation aerosol combined with non-invasive positive pressure ventilation(NIPPV)in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD)combined with typeⅡ respiratory failure.Methods According to cohort method,patients with AECOPD and type Ⅱ respiratory failure were divided into treatment group and control group.The control group was given NIPPV(4 h/once,tid),while treatment group was given budesonide inhalation aerosol(344 μg/once,bid)on basis of control group.All patients were treated for 4 weeks.The clinical curative effect,disease severity,respiratory,pulmonary function indexes[peak expiratory flow(PEF),forced expiratory volume in one second(FEV1),vital capacity(VC)],serum inflammatory factors[interleukin(IL)-17,IL-6,soluble intercellular adhesion molecule(sICAM)-1]were compared,and evaluated the safety.Results There were 38 cases in control group and 42 cases in treatment group.After treatment,total response rates in treatment group and control group were 92.86％(39 cases/42 cases)and 76.32％(29 cases/38 cases),and the difference was significant(P＜0.05).After treatment,scores of COPD assessment test(CAT)in treatment group and control group were(9.61±1.86)and(15.23±2.45)points;scores of modified british medical research council respiratory questionnaire(mMRC)were(1.74±0.31)and(2.43±0.35)points;PEF were(374.63±30.42)and(345.82±26.34)L·min-1;FEV,were(1.59±0.40)and(1.30±0.33)L;VC were(2.64±0.64)and(2.07±0.56)L;levels of serum IL-17 were(67.03±8.21)and(80.79±10.49)μg·L-1;IL-6 levels were(14.86±3.75)and(20.42±4.39)ng·L-1;sICAM-1 levels were(118.63±17.72)and(156.42±24.38)ng·mL-1,and the differences were statistically significant(all P＜0.05).In treatment group,adverse drug reactions were mainly on palpitation,dizziness and dry mouth,while which were mainly on dizziness,dry mouth and nausea in control group.There was no significant difference in total incidence of adverse drug reactions between treatment group and control group[9.52％(4 cases/42 cases)vs 7.89％(3 cases/38 cases),P＞0.05].Conclusion Budesonide inhalation aerosol combined with NNIPPV can effectively control disease severity,relieve dyspnea,improve pulmonary function and alleviate inflammatory response in patients with AECOPD and type Ⅱ respiratory failure,which has good safety.

Interferon-γ (IFN-γ) has been used to control cancers in clinical treatment. However, an increasing number of reports have suggested that in some cases effectiveness declines after a long treatment period, the reason being unclear. We have reported previously that long-term IFN-γ treatment induces malignant transformation of healthy lactating bovine mammary epithelial cells (BMECs) in vitro. In this study, we investigated the mechanisms underlying the malignant proliferation of BMECs under IFN-γ treatment. The primary BMECs used in this study were stimulated by IFN-γ (10 ng/mL) for a long term to promote malignancy. We observed that IFN-γ could promote malignant cell proliferation, increase the expression of cyclin D1/cyclin-dependent kinase 4 (CDK4), decrease the expression of p21, and upregulate the expression of cellular-abelsongene (c-Abl) and histone deacetylase 2 (HDAC2). The HDAC2 inhibitor, valproate (VPA) and the c-Abl inhibitor, imatinib, lowered the expression level of cyclin D1/CDK4, and increased the expression level of p21, leading to an inhibitory effect on IFN-γ-induced malignant cell growth. When c-Abl was downregulated, the HDAC2 level was also decreased by promoted proteasome degradation. These data suggest that IFN-γ promotes the growth of malignant BMECs through the c-Abl/HDAC2 signaling pathway. Our findings suggest that long-term application of IFN-γ may be closely associated with the promotion of cell growth and even the carcinogenesis of breast cancer.
Animals ; Carcinogenesis/pathology* ; Cattle ; Cell Cycle Proteins/metabolism* ; Cell Proliferation/drug effects* ; Cell Transformation, Neoplastic/pathology* ; Cells, Cultured ; Epithelial Cells/pathology* ; Female ; Histone Deacetylase 2/metabolism* ; Imatinib Mesylate/pharmacology* ; Interferon-gamma/pharmacology* ; Mammary Glands, Animal/pathology* ; Mammary Neoplasms, Experimental/pathology* ; Proto-Oncogene Proteins c-abl/metabolism* ; Signal Transduction ; Valproic Acid/pharmacology*

Recent studies have shown that diet can affect the body's immunity. Roughage of dairy cows consists of a variety of plant materials which make different contributions to health. This study investigated the effect of different roughages on the immunity of dairy cows. Serum, peripheral blood mononuclear cells (PBMCs), and milk samples were collected from 20 multiparous mid-lactation cows fed mixed forage (MF)- or corn straw (CS)-based diets. Expression profile analysis was used to detect the differentially expressed genes (DEGs) from PBMCs. The results showed that milk protein in the MF group increased to 3.22 g/100 ml, while that of the CS group milk was 2.96 g/100 ml; by RNA sequencing, it was found that 1615 genes were differentially expressed between the CS group and the MF group among the 24 027 analyzed probes. Gene ontology (GO) and pathway analysis of DEGs suggested that these genes (especially genes coding cytokines, chemokine and its receptors) are involved in the immune response. Results were confirmed at the protein level via detecting the levels of interleukin-2 (IL-2), IL-6, IL-10, IL-12, leptin (LEP), interferon-γ (IFN-γ), transforming growth factor-β1 (TGF-β1), and tumor necrosis factor-α (TNF-α) in peripheral blood by enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay analysis. Our data supported the conclusions that the protein content in milk of the MF group was higher than that of the CS group, the CS-based diets induced more release of cytokines than the MF-based diets in dairy cows' PBMCs, and milk protein content may be affected by cytokines.
Animals ; Cattle/immunology* ; Cytokines/physiology* ; Diet ; Female ; Gene Ontology ; Leukocytes, Mononuclear/immunology* ; Milk/chemistry* ; Transforming Growth Factor beta/physiology* ; Zea mays