Efficacy of dexmedetomidine versus midazolam when combined with butorphanol for sedation and analgesia during burn dressing changes: A randomized clinical trial.

Objective: The aim of this study was to compare dexmedetomidine-butorphanol (DB) and midazolam-butorphanol (MB) combinations for sedation, and analgesia in burn patients undergoing dressing changes. Methods: A total of 56 ASA I-II burn patients were included in this single-center randomized clinical trial. The ages of these patients were between 20 and 60 years. TBSA ranged from 10% to 50%. They were randomized to group DB and group MB during dressing change. In the DB group, each patient received a bolus dose of dexmedetomidine (0.5 µg kg-1) and intermittent boluses of butorphanol (20 µg kg-1). In the MB group, each patient received a bolus dose of midazolam (0.05 mg kg-1) and intermittent boluses of butorphanol (20 µg kg-1). The primary outcomes were sedation scores and pain scores. The second outcomes were vital signs, side effects, and butorphanol consumption. Results: The sedation scores of these two groups did not differ significantly (p > 0.05), and the pain scores of these groups were not significantly different (p > 0.05). More patients had hypotension in the DB group than in the MB group (6 versus 0, p = 0.01), but the number of patients who had respiratory depression was higher in the MB group compared with the DB group (4 versus 0, p = 0.038). Butorphanol consumption in the MB group was higher than in the DB group (p = 0.025). Conclusion: Dexmedetomidine is comparable to midazolam when combined with butorphanol in burn patients during dressing change. Compared with midazolam, it has the advantage of opioid-sparing effect. Clinical Trial Registration: [http://www.chictr.org.cn/showproj.aspx&proj=130622], identifier [ChiCTR2100049325].

Network Pharmacology and Molecular Docking Study of Yupingfeng Powder in the Treatment of Allergic Diseases.

Objective: To explore the potential mechanisms of Yupingfeng Powder (YPFP) in the treatment of allergic diseases by using network pharmacology and molecular docking technology. Methods: The active components and targets of YPFP were screened by the TCMSP database. The targets associated with atopic dermatitis, asthma, allergic rhinitis, and food allergy were obtained from GeneCards and OMIM databases, respectively. The intersection of the above disease-related targets was identified as allergy-related targets. Then, allergy-related targets and YPFP-related targets were crossed to obtain the potential targets of YPFP for allergy treatment. A protein-protein-interaction (PPI) network and a drug-target-disease topology network were constructed to screen hub targets and key ingredients. Next, GO and KEGG pathway enrichment analyses were performed separately on the potential targets and hub targets to identify the biological processes and signaling pathways involved. Finally, molecular docking was conducted to verify the binding affinity between key ingredients and hub targets. Results: In this study, 45 active ingredients were identified from YPFP, and 48 allergy-related targets were predicted by network pharmacology. IL6, TNF, IL1B, PTGS2, CXCL8, JUN, CCL2, IL10, IFNG, and IL4 were screened as hub targets by the PPI network. However, quercetin, kaempferol, wogonin, formononetin, and 7-O-methylisomucronulatol were identified as key ingredients by the drug-target-disease topological network. GO and KEGG pathway enrichment analysis indicated that the therapeutic effect of YPFP on allergy involved multiple biological processes and signaling pathways, including positive regulation of fever generation, positive regulation of neuroinflammatory response, vascular endothelial growth factor production, negative regulation of cytokine production involved in immune response, positive regulation of mononuclear cell migration, type 2 immune response, and negative regulation of lipid storage. Molecular docking verified that all the key ingredients had good binding affinity with hub targets. Conclusion: This study revealed the key ingredients, hub targets, and potential mechanisms of YPFP antiallergy, and these data can provide some theoretical basis for subsequent allergy treatment and drug development.

A Critical Role of the IL-1ß-IL-1R Signaling Pathway in Skin Inflammation and Psoriasis Pathogenesis.

The IL-1 signaling pathway has been shown to play a critical role in the pathogenesis of chronic, autoinflammatory skin diseases such as psoriasis. However, the exact cellular and molecular mechanisms have not been fully understood. Here, we show that IL-1ß is significantly elevated in psoriatic lesional skin and imiquimod-treated mouse skin. In addition, IL-1R signaling appears to correlate with psoriasis disease progression and treatment response. IL-1 signaling in both dermal γδ T cells and other cells such as keratinocytes is essential to an IMQ-induced skin inflammation. IL-1ß induces dermal γδ T cell proliferation and IL-17 production in mice. In addition, IL-1ß stimulates keratinocytes to secrete chemokines that preferentially chemoattract peripheral CD27- CCR6+IL-17 capable of producing γδ T cells (γδT17). Further studies showed that endogenous IL-1ß secretion is regulated by skin commensals to maintain dermal γδT17 homeostasis in mice. Mouse skin associated with Corynebacterium species, bacteria enriched in human psoriatic lesional skin, has increased IL-1ß and dermal γδT17 cell expansion. Thus, the IL-1ß-IL-1R signaling pathway may contribute to skin inflammation and psoriasis pathogenesis via the direct regulation of dermal IL-17-producing cells and stimulation of keratinocytes for amplifying inflammatory cascade.

Yi-Qi-Ping-Chuan-Fang Reduces TSLP Elevation Caused by LPS + Poly(I:C) via Inhibiting TLR4/MYD88/NF-κB Signaling Pathway.

OBJECTIVE: To explore the correlation between Thymic Stromal Lymphopoietin (TSLP) and the Nuclear Factor- (NF-) κB signaling pathways in bronchial epithelial cells and to clarify whether the traditional Chinese medicine formula Yi-Qi-Ping-Chuan-Fang (YQPC) reduces inflammation by inhibiting TSLP/NF-κB signaling pathways. METHODS: Cells were stimulated with LPS + Poly(I:C) and treated with YQPC. The expressions of TSLP and NF-κB signaling pathways related proteins P65, IκK, IκBa, P-P65, P-IκK, P-IκBa were detected. The effects of NF-κB upstream molecules, Toll-like receptors 3 and 4, myeloid differentiation primary response gene 88 (Myd88), TIR-domain-containing adapter-inducing interferon-ß (TRIF), and downstream inflammatory cytokines, TNF-α, IL-1ß, IL-6, and IL-8, were assessed. RESULTS: The mRNA and protein expressions of TSLP were significantly increased after LPS + Poly(I:C) stimulation, the total protein IκBa and IκK decreased (P < 0.05), and the phosphorylated protein P-P65, P-IκK, and P-IκBα increased. After YQPC treatment, the expression of TSLP, P-P65, P-IκBa, and P-IκK was significantly inhibited (P < 0.05). The activation of TLR4 and MyD88 decreased, and release of IL-1ß, IL-6, IL-8, and TNF-α reduced (P < 0.05). CONCLUSION: In summary, the expression of TSLP is activated by the NF-κB signaling pathway. YQPC alleviated inflammation by inhibiting TSLP through regulating the NF-κB activation and translocation.

Innate γδT17 cells play a protective role in DSS-induced colitis via recruitment of Gr-1+CD11b+ myeloid suppressor cells.

Innate γδ T cells play critical roles in mucosal immunity such as regulating intestinal epithelial homeostasis. In addition, γδ T cells are significantly increased in the inflamed mucosa of patients with ulcerative colitis. However, γδ T cells are a heterogeneous population. IL-17-producing versus IFNγ-producing γδ T cells play differential roles in different disease settings. Therefore, dissecting the exact role of different subsets of γδ T cells in colitis is essential for understanding colitis immunopathogenesis. In the current study, we found that TCR δ-deficient mice had a more severe dextran sodium sulfate (DSS)-induced colitis that was reduced upon reconstitution of γδT17 cells but not IFNγ-producing γδ T cells. Immunophenotyping of the cellular infiltrate upon DSS-induced colitis showed a reduced infiltration of Gr-1+CD11b+ myeloid cells into the sites of inflammation in mice lacking γδT17 cells. Further experiments demonstrated that IL-17, IL-18, and chemokine CXCL5 were critical in Gr-1+CD11b+ myeloid cell recruitment. In vitro T cell suppressive assay indicated that this Gr-1+CD11b+ population was immunosuppressive. Depletion of Gr-1+CD11b+ myeloid cells resulted in an increase severity of DSS-induced colitis. Our study elucidates a new immune pathway involving γδT17-dependent recruitment of Gr-1+CD11b+ myeloid cells to the site of colitis inflammation important in the protection of colitis initiation and progression.