[Research advances of mesenchymal stem cell in allergic rhinitis].

Allergic rhinitis is a chronic nasal mucosal inflammation characterized by upper airway hyperresponsiveness, involving a variety of immune cells and inflammatory mediators. Drugs, immunotherapy, and surgical operation are the principal treatments at present. The study found that mesenchymal stem cells have the ability of immune regulation and have a promising clinical application in the treatment of allergic rhinitis. In this review, the action mechanism of mesenchymal stem cells, the immunomodulatory effect of mesenchymal stem cells on the key cells of allergic rhinitis, and the challenges of clinical application are reviewed, to provide new directions for the treatment of allergic rhinitis.

[CGRP inhibits proliferation, activation and cytokine secretion of group 2 innate lymphoid cells (ILC2) in peripheral blood from patients with allergic rhinitis].

Objective To investigate the effect of calcitonin gene-related peptide (CGRP) on the regulation of group 2 innate lymphoid cells (ILC2) in the peripheral blood of patients with allergic rhinitis (AR). Methods Peripheral blood mononuclear cells (PBMCs) were extracted from normal healthy individuals and AR patients, then stimulated with CGRP, interleukin 33 (IL-33) and CGRP combined with IL-33 for 3 days, with blank stimulus as control. The percentage of ILC2 in the four groups was measured by flow cytometry. After being sorted, ILC2 was given to CGRP, IL-33 and CGRP combined with IL-33 stimulation for 3 days, with blank stimulus as control. The percentage of IL-5 and IL-13 positive cells in ILC2 was detected by flow cytometry, and the levels of IL-5 and IL-13 in ILC2 supernatant were measured by ELISA. Results The percentage of ILC2 in the peripheral blood of AR patients was significantly higher than that of the control group. The levels of IL-5+ILC2 and IL-13+ILC2 were significantly increased by IL-33 single stimulation after culturing PBMCs. After adding IL-33 combined with CGRP stimulation, the levels of IL-5+ILC2 and IL-13+ILC2 in PBMCs were significantly reduced; after CGRP single stimulation, the levels of IL-5+ILC2 and IL-13+ILC2 in PBMCs were further decreased. After ILC2 was sorted and cultured, the levels of IL-5+ILC2 and IL-13+ILC2 showed significant increase after IL-33 single stimulation. The levels of IL-5+ILC2 and IL-13+ILC2 were decreased by IL-33 and CGRP co-stimulation, and they were further reduced after CGRP single stimulation. Compared to IL-33 single stimulation, IL-5 and IL-13 levels dropped significantly due to the IL-33 and CGRP co-stimulation. The levels of IL-5 and IL-13 were further reduced by CGRP single stimulation. Conclusion CGRP inhibits the proliferation and activation of peripheral blood ILC2 in AR and exert anti-inflammatory effects in AR.

A novel UPLC-ESI-MS assay for fifteen portal estrogens and metabolites detection and application in hepatic fibrosis.

Estrogens and their metabolites (EMs) are involved in chronic liver disease and gut microbiota regulates estrogen metabolism, whereas the role of enterogenous EMs in liver disease is still elusive. Because of the extremely low level of EMs in portal serum and the EMs contain multiple pairs of isomers, an accurate determination of portal serum EMs is urgently needed. This study established a quantitative detection method for portal serum EMs and applied to non-alcoholic fatty liver disease (NAFLD) related hepatic fibrosis mice model. The serum was derived with a novel derivatization reagent 4-acetyl aminobenzene sulfonyl chloride, and a UPLC-ESI-MS system was used for quantification of 15 EMs in 120 min. Compared with normal group, the concentrations of E1, E2 in model group were significantly decreased by 4-8 times, all the C2 and C4 substitution products (2-OHE1, 2-OHE2, 2-MeOE1, 4-OHE1, 4-MeOE1, 4-OHE2, 4-MeOE2, 2-MeOE2) were significantly decreased by 2-22 times. However, the C16 and C17 substitution products (E3, 16-epiE3, 17-epiE3, 16-ketoE2) levels were increased by 3-5 times (P < 0.01). This study elucidated the changes of enterogenous EMs which entered the liver via portal vein in NAFLD - related hepatic fibrosis and provided methodological platform for other related studies on estrogen metabolism.

Neuromedin U Induces Activation of Peripheral Group 2 Innate Lymphoid Cells through the ERK Pathway in Allergic Rhinitis Patients.

INTRODUCTION: In allergic diseases, group 2 innate lymphoid cells (ILC2s) play critical roles. Neuromedin U (NMU), a highly conserved multifunctional neuropeptide, is secreted by cholinergic neurons and involved in asthma pathogenesis by amplifying lung inflammation driven by ILC2s. However, the precise effects of NMU on ILC2s in allergic rhinitis (AR) and related diseases remain unclear. METHODS: A total of 15 patients with persistent AR and 8 healthy controls (HCs) were enrolled in the study. Visual analog scale (VAS) scores are used to assess the severity of clinical symptoms in AR patients. The percentages of ILC2s in peripheral blood mononuclear cells (PBMCs) were enumerated using flow cytometry. The soluble or intracellular cytokines (IL-5 and IL-13) in PBMCs or sorted ILC2s were assessed in response to various stimuli with IL-33, NMU, IL-33 combined with extracellular signal-related kinase (ERK) inhibitor or NMU combined with ERK inhibitor in the presence of IL-2. RESULTS: We confirmed the proportion of circulating ILC2s was significantly higher in AR patients than in HCs. ILC2s levels were found to be positively related to VAS scores. We also discovered that the release of IL-5 and IL-13 in AR patients' PBMCs stimulated by NMU (p < 0.0001 and p < 0.0001, respectively) or IL-33 (p = 0.002; p = 0.044, respectively) was significantly higher than in HCs. In AR patients, NMU stimulated PBMCs or ILC2s to generate greater inflammatory factors IL-5 and IL-13 compared to IL-33. Furthermore, we observed that NMU-promoted ILC2s activation and proliferation functions were restricted when the ERK pathway was inhibited. CONCLUSION: NMU effectively activated ILC2s in AR patients to produce Th2-type cytokines, and this activation can be prevented by ERK pathway inhibitors. Our findings shed new light on the neuro-immune mechanism of AR and offer new insights into its prevention and treatment.

Livin promotes Th2-type immune response in airway allergic diseases.

OBJECTIVES: To investigate the effects of livin on the Th2 immune response in airway allergic diseases (AAD) and explore the interaction among livin, GATA3, IL-4 in peripheral blood CD4+ T cells of AAD patients. METHODS: WT mice and livin KO mice were developed for model of AAD. Th2 cell levels in the lung tissues and spleen were assessed by flow cytometry. Also, it was assessed in the culture after exposing to livin inhibitor (Lp-15); the protein and mRNA levels of livin, GATA3 and IL-4 in peripheral blood CD4+ T cells isolated from patients with or without AAD were measured by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. Finally, Co-immunoprecipitation (Co-IP) was employed to identify the interaction between livin and GATA3. RESULTS: Compared with WT mouse, Th2 cell frequency in lung tissues and spleen was significantly decreased in livin KO mouse; after adding Lp-15, the differentiation from Naive CD4+T cells in spleen to Th2 cells was blocked; the protein and mRNA levels of livin, GATA3 and IL-4 in AAD group were higher than that in control group. The levels of livin were positively correlated with IL-4, and GATA3 was also positively correlated with IL-4 and livin. GATA3 was detected in the protein complex co-precipitated with livin antibody, and livin was also detected in the protein complex co-precipitated by GATA3 antibody. CONCLUSION: Livin increases the expression of IL-4 and facilitates naive CD4+ T cells to differentiate into Th2 cells, which triggers airway allergy.

Clinical Efficacy of Single Vidian Neurectomy in Chronic Rhinosinusitis with Nasal Polyps and Allergic Rhinitis.

OBJECTIVE: To investigate the clinical efficacy of single Vidian neurectomy (sVN) in the treatment of chronic rhinosinusitis with nasal polyps and allergic rhinitis (CRSwNP &AR). STUDY DESIGN: Descriptive study.   Place and Duration of Study: Otolaryngology-Head &Neck Surgery, Shanxi Medical University Second Affiliated Hospital, Taiyuan, China, February 2016 to February 2019. METHODOLOGY: Patients meeting the diagnostic criteria for AR and CRSwNP confirmed after assessment by an ENT physician; moderately severe and persistent AR, aged ≥18 years to ≤70 years; and testing positive for sIgE and were regularly treated with medications for three months or more before surgery with unsatisfactory symptom control. Exclusion criteria were patients with acute exacerbations of sinusitis or fungal sinusitis combined with nasal polyps, intolerant to aspirin, acute infection or sinus tumours; contraindications to general anaesthetic surgery or oral corticosteroids; and those who have received allergen immunotherapy, corticosteroids and antihistamines within one year. The relevant epidemiological data were collected, including IgE level, VAS, RQLQ, and the Lund-Kennedy scores, to assess patients' clinical symptoms and quality of life before and after surgery. RESULTS: Fifty-five patients were followed up for two years after surgery, and statistical analysis was performed using SPSS version 25.0. It was found that VAS scores, RQLQ scores, and Lund-Kennedy scores of the patients who underwent sVN were significantly lower at six months (all p <0.01), one year (all p <0.01, and two years all p <0.01) after surgery compared with those before surgery. CONCLUSION: sVN has better efficacy in patients with CRSwNP&AR, has the potential to reduce its recurrence rate, and seems to be a safe and effective treatment. KEY WORDS: Chronic rhinosinusitis with nasal polyps, Allergic rhinitis, Eosinophilic chronic rhinosinusitis with nasal polyps, Single Vidian neurectomy, Clinical efficacy.

Insights Into the Research Status of Neuromedin U: A Bibliometric and Visual Analysis From 1987 to 2021.

Neuromedin U (NMU) is a regulatory peptide that is widely distributed throughout the body and performs a variety of physiological functions through its corresponding receptors. In recent years, NMU has become the focus of attention in various fields of research as its diverse and essential functions have gradually been elucidated. However, there have been no bibliometrics studies on the development trend and knowledge structure of NMU research. Therefore, in this study, we used VOSviewer software to statistically analyze scientific data from articles related to NMU to track the developmental footprint of this research field, including relevant countries, institutions, authors, and keywords. We retrieved a total of 338 papers related to NMU, written by 1,661 authors from 438 organizations of 41 countries that were published in 332 journals. The first study on NMU was reported by a group in Japan in 1985. Subsequently, nine articles on NMU were published from 1987 to 2006. A small leap in this field could be detected in 2009, with 30 articles published worldwide. Among the various countries in which this research has been performed, Japan and the United States have made the most outstanding contributions. Miyazato M, Kangawa K, and Mori K from the Department of Biochemistry, National Retrain and Cardiovascular Center Research Institute in Japan were the most productive authors who have the highest number of citations. Keyword analysis showed six clusters: central-nervous-system, homeostasis, energy metabolism, cancer, immune inflammation, and food intake. The three most highly cited articles were associated with inflammation. Overall, this study demonstrates the research trends and future directions of NMU, providing an objective description of the contributions in this field along with reference value for future research.

Lowering hepatic venous pressure agent carvedilol versus variceal banding ligation for clinical outcomes of cirrhotic portal hypertension.

OBJECTIVE: Carvedilol is nonselective beta-blocker with a mild anti-alpha-1-adrenergic effect. Several studies proposed improved hemodynamic effects of carvedilol compared with propanolol. Our study was to perform a systematic review and meta-analysis of randomized control trials comparing carvedilol with variceal banding ligation (VBL). METHODS: Studies were searched on online databases MEDLINE, EMBASE(Ovid), the Cochrane Library, Chinese Wanfang Database, and China National Knowledge Infrastructure between January 2000 and May 2018. Incidence of bleeding and mortality were main outcome measures. Subgroup analysis and sensitivity analysis were conducted to ensure the robustness of pooled estimates. RESULTS: Ten randomized control trials including 1,269 cirrhotic patients were chosen. Compared with VBL, carvedilol showed similar preventive efficacy of risk ratios (RRs) in variceal bleeding, and bleeding-related mortality over different follow-up periods from 6 months to 24 months. Also, significant differences between carvedilol and VBL in overall mortality and other causes of mortality were failed to be found. Carvedilol achieved a lower incidence of portal hypertension gastropathy in both 6 months (RR=0.49, 95% CI: 0.38-0.64, P<0.00001) and 12 months (RR=0.35, 95% CI: 0.26-0.47, P<0.00001). Two trials compared combination of carvedilol and VBL with VBL alone; however, the results failed to find an improved preventive efficacy of bleeding (RR=0.71, 95% CI: 0.15-3.30, P=0.67). CONCLUSION: Carvedilol is equivalent to invasive VBL for variceal bleeding prevention. It can be well tolerated and may be of benefit to portal hypertension gastropathy. However, available data during 24 months follow-up did not support a potential advantage of carvedilol for prognosis as a lowering hepatic venous pressure agent.

Efficacy and Safety of Endoscopic Intralesional Triamcinolone Injection for Benign Esophageal Strictures.

OBJECTIVES: To evaluate the efficacy and safety of endoscopic intralesional triamcinolone injection (ITI) for benign esophageal strictures combined with endoscopic dilation (ED). METHODS: Online databases including MEDLINE, EMBASE, the Cochrane Library, and Web of Science were comprehensively searched for prospective randomized control trials (RCTs) between 1966 and March 2018. A meta-analysis was conducted according to the methods recommended by the Cochrane Collaboration. RESULTS: Six RCTs consisting of 176 patients were selected. Meta-analysis results showed that additional ITI had a significant advantage in terms of stricture rate and required ED sessions. Surgery-related and non-surgery-related strictures showed similar results. Additional ITI was not associated with significantly increased risk of complications. CONCLUSIONS: Our meta-analysis showed that additional ITI therapy was supposed to be effective and safe for benign esophageal strictures as it reduced the stricture rate and required ED sessions. However, more RCTs are necessary to support these findings.

[Investigation on the role of TIM4 in the pathogenesis of allergic rhinitis in mice].

OBJECTIVE: To investigate the role of TIM4 (T cell immunoglobulin and mucin domain molecule 4) in the pathogenesis of allergic rhinitis (AR) in mice, and to identify a novel therapeutic target for the treatment of AR. METHODS: Twenty-one male BALB/C mice of clean grade were divided into three groups randomly (n = 7 per group) including control, AR and anti-TIM4 antibody treatment groups. In order to induce upper airway allergic inflammation, the mice from AR and anti-TIM4 antibody treatment groups were sensitized by intraperitoneal injection followed by intranasal challenge with ovalbumin. Before the ovalbumin challenge, a group of mice was treated with anti-TIM4 antibody. To assess the AR model, behavioral observation with immunological assessments and HE staining of nasal tissues were performed. The TIM4 expression in nasal tissues in different groups of mice were assessed by immunofluorescence and RT-PCR.SPSS18.0 software was used to analyze the data. RESULTS: The AR model in mice was successfully established as shown by behavioral observation and immunological evaluation. RT-PCR assays showed the relative expression of TIM4 mRNA in nasal mucosa of AR, control and anti-TIM4 antibody treatment mice was 16.29 ± 3.80, 0.51 ± 0.60, 1.64 ± 0.98, respectively. There was statistically significant differences mong three group (F = 46.56, P < 0.05). The expression of TIM4 in AR group was significantly higher than those in control group (t = 8.650, P < 0.05) and anti-TIM4 group (t = 8.027, P < 0.05). The expression of TIM4 was significantly reduced in the anti-TIM4 antibody group, as well as control group (t = -0.623, P > 0.05). More expression of TIM4 was detected in local nasal tissues of AR mice, mainly located below the pseudostratified ciliated columnar epithelium. CONCLUSIONS: TIM4 plays a crucial role in the pathogenesis of AR. Effective inhibition of TIM4 expression can partially reverse the pathological changes of AR.