OBJECTIVE To explore the effect and potential mechanism of 717 Jiedu decoction in ameliorating local tissue injury induced by Gloydius brevicaudus venom via regulating macrophage phenotype transformation.METHODS Rat blank-serum and drug-containing serum were prepared by intragastric administration of normal saline， tail-vein injection of anti- G. brevicaudus venom serum （0.6 mL per rat）， and intragastric administration of 717 Jiedu decoction at doses of 0.495， 0.99 and 1.98 g/kg （calculated as crude drug）. M0-type macrophages derived from human leukemia monocytic THP-1 cells induced and differentiated by PMA were divided into normal control group， model group， positive control group， and low-， medium- and high-concentration 717 Jiedu decoction drug-containing serum groups. Except for the normal control group， all other groups were treated with 10 μg/mL G. brevicaudus venom working solution and 10% blank or drug-containing serum. After the cultivation period， the cellular ultrastructural changes in each group were observed； the proportions of M1- and M2-type macrophages， as well as the mRNA and protein expression of macrophage phenotype transformation and hypoxia-inducible factor-1α （HIF-1α） were detected.RESULTS Compared with the normal control group， cells in the model group presented ultrastructural injuries including mitochondrial swelling， cristae rupture and cytoplasmic vacuolization. The proportion of M1-type macrophages and the mRNA and protein expression levels of related phenotype transformation markers [inducible nitric oxide synthase， tumor necrosis factor-α， interleukin-6 （IL-6）， IL-1β] and HIF-1α were significantly increased （ P ＜0.05），whereas the proportion of M2-type macrophages and the mRNA and protein expression levels of related phenotype transformation markers （arginase-1， IL-10， mannose receptor C type 1 and chitinase-3-like protein 1） were significantly decreased （ P ＜0.05）. Compared with the model group， cellular ultrastructural injuries were obviously alleviated， and the above-mentioned indexes were significantly reversed in the high-concentration 717 Jiedu decoction drug-containing serum group （ P ＜0.05）.CONCLUSIONS717 Jiedu decoction can exert anti-inflammatory and tissue-repairing effects by regulating the balance of M1-， M2-type macrophages phenotype transformation and repairing cellular ultrastructural damage. Its mechanism may be related to inhibiting the excessive activation of the HIF-1α pathway.

G protein-coupled receptor kinase 2 (GRK2) participates in the phosphorylation and desensitization of G protein-coupled receptor (GPCR), impacting various biological processes such as inflammation and cell proliferation. Dysregulated expression and activity of GRK2 have been reported in multiple cells in rheumatoid arthritis (RA). However, whether and how GRK2 regulates synovial hyperplasia and fibroblast-like synoviocytes (FLSs) proliferation is poorly understood. In this study, we investigated the regulation of GRK2 and its biological function in RA. We found that GRK2 transmembrane activity was increased in FLSs of RA patients and collagen-induced arthritis (CIA) rats. Additionally, we noted a positive correlation between high GRK2 expression on the cell membrane and serological markers associated with RA and CIA. Immunoprecipitation-mass spectrometry and pull-down analyses revealed tumor necrosis factor receptor-associated factor 2 (TRAF2) as a novel substrate of GRK2. Furthermore, surface plasmon resonance (SPR) and molecular docking assays determined that the C-terminus of GRK2 binds to the C-terminus of TRAF2 at the Gln340 residue. GRK2 knockdown and the GRK2 inhibitor CP-25 attenuated synovial hyperplasia and FLS proliferation in CIA both in vitro and in vivo by decreasing GRK2 membrane expression and activity. Mechanistically, increased GRK2 transmembrane activity contributed to the recruitment of TRAF2 on the cell membrane, promoting GRK2-TRAF2 interactions that facilitate the recruitment of the E3 ubiquitin ligase TRIM47 to TRAF2. This enhanced TRAF2 Lys63 polyubiquitylation and induced nuclear factor (NF)-κB activation, leading to synovial hyperplasia and abnormal proliferation of FLSs. Our study provides a mechanistic and preclinical rationale for further evaluation of GRK2 as a therapeutic target for RA.

Congenital insensitivity to pain with anhidrosis (CIPA)is a rare disease which mainly affects infants, children and adolescents. As an autosomal recessive disorder, CIPA is also known as familial autonomic dysfunction type 2. The diagnosis of CIPA mainly relies on clinical observation and genetic testing. Currently there is a lack of effective treatment, and it is mainly treated by cooling, anti-inflammatory and strengthened guardianization. This article has reviewed the literature and summarized the research on CIPA and progress made in its diagnosis and treatment, with an aim to improve the understanding of this disorder.

Inflammatory skin diseases(ISD)are characterized by persistent inflammatory cell infiltration and lingering and intractable skin lesions.At present,corticosteroids are the main drugs used in the treatment of ISD.However,due to the characteristics of recurrent and intractable ISD,long-term use of these hormone drugs may cause serious side effects in patients.In recent years,increasingly more studies are confirming that bee venom has significant anti-inflammatory,anti-apoptosis,anti-fibrosis,antibacterial,and other effects and could effectively treat ISD.In this paper,the main active components and anti-inflammatory mechanisms of bee venom are reviewed.The latest attempts to use bee venom for acne,atopic dermatitis,psoriasis,urticaria,and systemic lupus erythematosus are discussed,providing a reference for basic research and the clinical treatment of ISD.

Objective To explore the effect of cytoglobin (CYGB) low expression on the proliferation of glioma cells and its mechanism.Methods Glioma samples were chosen from patients accepted glioma resection in our hospital from June 2012 to December 2015;primary glioma cells extracted from these samples were cultured and performed purity identification.The nominated cells were divided into transfection of 24 h group,transfection of 48 h group,transfection of 72 h group,and negative control group;cells,excepted from negative control group,were transfected by CYGB shRNA for 24,48 and 72 h,respectively,to inhibit the CYGB expression.CCK-8 assay was used to observe the proliferation of glioma cells after different transfection times (0,1,2,3,4 and 5 d after cell culture).The expressions of CYGB,phosphatidylinositol 3 kinase (PI3K),total alanine aminotransferase (Akt) and phosphorylated (p)-Akt were detected by Western blotting,and the levels of interleukin (IL)-6,IL-10,tumor necrosis factor (TNF)-α,transforming growth factor (TGF)-β and vascular endothelial growth factor (VEGF) were examined by ELISA.Results (1) The proliferation of glioma cells was enhanced at different times after CYGB shRNA transfection,and the optical density showed significant differences at different times after CYGB shRNA transfection (P＜0.05);as compared with those in the negative control group,the cell proliferative capacity and optical density in the transfection of 24 h group,transfection of 48 h group and transfection of 72 h group were significantly increased (P＜0.05).As compared with those in the negative control group,the CYGB protein expression was significantly d ecreased and PI3K and p-Akt protein expressions were significantly increased in the transfection of 24 h group,transfection of 48 h group and transfection of 72 h group,accordingly (P＜0.05),while no significant difference was noted in the total Akt protein expression (P＞0.05).The levels of IL6,IL10,TNF-α,TGF-β,and VEGF were successively increased in the transfection of 24 h group,transfection of 48 h group and transfection of 72 h group as compared with those in the negative control group (P＜0.05).Spearman correlation analysis showed that the expression of CYGB in the glioma was negatively correlated with PI3K and p-Akt expressions,and IL-6,IL-10,TNF-α,TGF-β,and VEGF levels (P＜0.05).Conclusion The effect of cytoglobin on proliferation of glioma cells may be related to the signal pathway of PI3K-Akt.