Bimin Kang ameliorates the minimal persistent inflammation in allergic rhinitis by reducing BCL11B expression and regulating ILC2 plasticity.

ETHNOPHARMACOLOGICAL RELEVANCE: Minimal persistent inflammation (MPI) is a major contributor to the recurrence of allergic rhinitis (AR). The traditional Chinese herbal medicine known as Bimin Kang Mixture (BMK) have been used in clinics for decades to treat AR, which can relieve AR symptoms, reduce inflammatory response and improve immune function. However, its mechanism in controlling MPI is still unclear. AIM OF THE STUDY: This study aims to assess the therapeutic effect of BMK on MPI, and elaborate the mechanism involved in BMK intervention in BCL11B regulation of type 2 innate lymphoid cell (ILC2) plasticity in the treatment of MPI. MATERIAL AND METHODS: The effect of BMK (9.1 ml/kg) and Loratadine (15.15 mg/kg) on MPI was evaluated based on symptoms, pathological staining, and ELISA assays. RT-qPCR and flow cytometry were also employed to assess the expression of BCL11B, IL-12/IL-12Rß2, and IL-18/IL-18Rα signaling pathways associated with ILC2 plasticity in the airway tissues of MPI mice following BMK intervention. RESULTS: BMK restored the airway epithelial barrier, and markedly reduced inflammatory cells (eosinophils, neutrophils) infiltration (P < 0.01) and goblet cells hyperplasia (P < 0.05). BCL11B expression positively correlated with the ILC2 proportion in the lungs and nasal mucosa of AR and MPI mice (P < 0.01). BMK downregulated BCL11B expression (P < 0.05) and reduced the proportion of ILC2, ILC3 and ILC3-like ILC2 subsets (P < 0.05). Moreover, BMK promoted the conversion of ILC2 into an ILC1-like phenotype through IL-12/IL-12Rß2 and IL-18/IL-18Rα signaling pathways in MPI mice. CONCLUSION: By downregulating BCL11B expression, BMK regulates ILC2 plasticity and decreases the proportion of ILC2, ILC3, and ILC3-like ILC2 subsets, promoting the conversion of ILC2 to ILC1, thus restoring balance of ILC subsets in airway tissues and control MPI.

Transcutaneous Electrical Acupoint Stimulation Combined with Moderate Sedation of Remimazolam Tosilate in Gastrointestinal Endoscopy: A Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

INTRODUCTION: Further clinical validation is required to determine whether transcutaneous electrical acupoint stimulation (TEAS) can replace opioids and be used in combination with remimazolam for sedation during gastrointestinal endoscopy. METHODS: A total of 108 outpatients who underwent diagnostic gastrointestinal endoscopy were randomly divided into three groups: fentanyl plus remimazolam group (group C), TEAS plus remimazolam group (group E), and placebo-TEAS plus remimazolam group (group P). The assessments of patient satisfaction, physician satisfaction, and pain scale score during the examination constituted the primary endpoints of the study. The secondary endpoints were the time of recovery, recovery of normal behavioral function and discharge, incidence of adverse reactions, and dose of remimazolam. RESULTS: Compared with group C, group E had a greater median score for patient satisfaction at follow-up and a slightly lower median score for physician satisfaction. The pain score of group E was slightly greater than that of group C, but the difference was not significant. However, in group C, the incidence of hypoxemia, the rate of nausea and the severity of vertigo were greater, and the number of patients discharged and resuming normal behavioral function was greater than those in the other two groups. The dose of remimazolam in group C and group E was less than that in group P. CONCLUSIONS: TEAS combined with moderate sedation of remimazolam can provide an ideal sedative effect, which preferably suppresses discomfort caused by gastrointestinal endoscopy and has fewer sedation-related complications. TRIAL REGISTRATION: ID: NCT05485064; First registration (29/07/2022); Last registration (02/11/2022) (Clinical Trials.gov).

Molecular Mechanisms Underlying the Effects of Bimin Kang Mixture on Allergic Rhinitis: Network Pharmacology and RNA Sequencing Analysis.

Background: Allergic rhinitis (AR) is a highly prevalent chronic inflammatory disease of the respiratory tract. Previous studies have demonstrated that Bimin Kang Mixture (BMK) is effective in alleviating AR symptoms and reducing the secretion of inflammatory factors and mucin; however, the precise mechanisms underlying these effects remain unclear. Methods: We built target networks for each medication component using a network pharmacology technique and used RNA-seq transcriptome analysis to screen differentially expressed genes (DEGs) for AR patients and control groups. The overlapping targets in the two groups were assessed using PPI networks, GO, and KEGG enrichment analyses. The binding ability of essential components to dock with hub target genes was investigated using molecular docking. Finally, we demonstrate how BMK can treat AR by regulating the NF-κB signaling pathway through animal experiments. Results: Effective targets from network pharmacology were combined with DEGs from RNA-seq, with 20 intersections as key target genes. The construction of the PPI network finally identified 5 hub target genes, and all hub target genes were in the NF-κB signaling pathway. Molecular docking suggests that citric acid, deoxyandrographolide, quercetin, luteolin, and kaempferol are structurally stable and can spontaneously attach to IL-1ß, CXCL2, CXCL8, CCL20, and PTGS2 receptors. Animal experiments have shown that BMK inhibits NF-κB transcription factor activation, reduces the expression of proinflammatory cytokines and chemokines IL-1ß, CXCL2, IL-8, and COX-2, and exerts anti-inflammatory and anti-allergic effects. Conclusion: BMK by regulating the NF-κB signaling pathway improves inflammatory cell infiltration, regulates mucosal immune balance, and reduces airway hypersensitivity. These findings provide theoretical support for the clinical efficacy of BMK for AR treatment.

[Study on the Element Composition of Ancient Fossils and Meteorites].

The ancient fossils are formed by the ancient animals and plants after a long geological period and geological processes. They have witnessed the history of the earth and recorded the information of the evolution of the earth's ecological environment; Meteorites traveling in the solar system for a long time with the abrasion of nuclear reactions and atmosphere of the universe, have formed a unique shape and texture. They recorded the original information about the formation and evolution of out space. The analysis of the ancient fossils composition is the scientific basis for the study of the origin and evolution of the earth; the meteorites as rock sample from outer space are gifts from nature. They are extremely valuable and rare; the analysis of the composition of meteorites can provide a better foundation for the development of the foreign planet exploration and the development of the celestial chemistry. In this paper, the method of sample dissolution was selected and optimized. The final choice of nitric acid, hydrofluoric acid and perchloric acid as the mixed reagent, a microwave digestion method was used in treatment of ancient fossil samples; The aqua regia, nitric acid, hydrofluoric acid and perchloric acid as the mixed reagent, both microwave digestion method and wet digestion method were used in treatment of meteorite samples. Inductively coupled plasma atomic emission spectrometry (ICP-AES) was used to determine three different ancient fossil samples and three meteorite samples. And the content of same elements was compared. Analysis results show that the ancient fossils and meteorites contain Pb, Hg, Ge, Fe, Ni, Cu, Co, Mn and other heavy metal elements as well as part of the rare earth element. The standard addition recovery of the method was between 98.2%~106%, and the relative standard deviation was less than 2.12%. The method had high sensitivity, accuracy and precision.

CD73+ adipose-derived mesenchymal stem cells possess higher potential to differentiate into cardiomyocytes in vitro.

Adipose-derived mesenchymal stem cells (ADMSCs) are an attractive adult-derived stem cell population for cardiovascular repair. ADMSCs are heterogeneous cell populations with pluripotent capacity to differentiate into different types of cells. In the present study, we investigated the biological characteristics and differentiation potential of CD73-positive (CD73(+)) and CD73-negative (CD73(-)) ADMSCs. Our results show that in terms of morphological shape, CD73(+)-ADMSCs are mainly small-sized cells, whereas CD73(-)-ADMSCs are big-sized cells; both subpopulations can equally differentiate into adipocytes and osteoblasts in vitro. However, the CD73(+)-ADMSCs possess a higher potential to differentiate into cardiomyocytes than the CD73(-)-ADMSCs. The expression of the cardiac-specific genes, cTnT, Gata4, and Nkx2.5, is much higher in the CD73(+)-ADMSCs than in the CD73(-)-ADMSCs. Furthermore, Nanog expression at both the mRNA and protein levels is significantly higher in CD73(+)-ADMSCs than in CD73(-)-ADMSCs, suggesting that CD73(+)-ADMSCs are an undifferentiated subpopulation that can differentiate into cardiomyocytes in vitro more efficiently. Therefore, this study facilitates a better understanding of the differentiation of the ADMSCs subgroups and attempts to identify if CD73 is a useful marker for sorting and purifying the subpopulation of ADMSCs with a higher capacity for differentiation into cardiomyocytes.