BACKGROUND: Hepatic inflammatory cell accumulation and the subsequent systematic inflammation drive acute-on-chronic liver failure (ACLF) development. Previous studies showed that the vagus nerve exerts anti-inflammatory activity in many inflammatory diseases. Here, we aimed to identify the key molecule mediating the inflammatory process in ACLF and reveal the neuroimmune communication arising from the vagus nerve and immunological disorders of ACLF. METHODS: Proteomic analysis was performed and validated in ACLF model mice or patients, and intervention animal experiments were conducted using neutralizing antibodies. PNU-282987 (acetylcholine receptor agonist) and vagotomy were applied for perturbing vagus nerve activity. Single-cell RNA sequencing (scRNA-seq), flow cytometry, immunohistochemical and immunofluorescence staining, and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) technology were used for in vivo or in vitro mechanistic studies. RESULTS: The unbiased proteomics identified C-X-C motif chemokine ligand 9 (CXCL9) as the greatest differential protein in the livers of mice with ACLF and its relation to the systematic inflammation and mortality were confirmed in patients with ACLF. Interventions on CXCL9 and its receptor C-X-C chemokine receptor 3 (CXCR3) improved liver injury and decreased mortality of ACLF mice, which were related to the suppressing of hepatic immune cells' accumulation and activation. Vagus nerve stimulation attenuated while vagotomy aggravated the expression of CXCL9 and the severity of ACLF. Blocking CXCL9 and CXCR3 ameliorated liver inflammation and increased ACLF-associated mortality in ACLF mice with vagotomy. scRNA-seq revealed that hepatic macrophages served as the major source of CXCL9 in ACLF and were validated by immunofluorescence staining and flow cytometry analysis. Notably, the expression of CXCL9 in macrophages was modulated by vagus nerve-mediated cholinergic signaling. CONCLUSIONS Our novel findings highlighted that the neuroimmune communication of the vagus nerve-macrophage-CXCL9 axis contributed to ACLF development. These results provided evidence for neuromodulation as a promising approach for preventing and treating ACLF.
Animals ; Mice ; Chemokine CXCL9/metabolism* ; Vagus Nerve/physiology* ; Acute-On-Chronic Liver Failure/metabolism* ; Humans ; Male ; Mice, Inbred C57BL ; Proteomics ; Flow Cytometry ; Receptors, CXCR3/metabolism*

Objective:To verify the clinical efficacy and safety of Qufeng Tongxuan method in treating low- and moderate-volume intracerebral hemorrhage at acute stage.Methods:A prospective, multicenter, randomized, double-blind, placebo-controlled study was performed; patients with low- and moderate-volume intracerebral hemorrhage at the basal ganglia and/or thalamus accepted treatment in 16 hospitals from September 2019 to April 2022 were enrolled. These patients were divided into experimental and control groups with a block randomized method by SAS software. Patients in control group were given conventional western medicine treatment; those in experimental group accepted Qufeng Tongxuan method (sequential therapy of Shexiang Huayu Xingnao granules and Zhilong Huoxue Tongyu granules) besides conventional western medicine treatment. NIHSS was used to assess neurological function before treatment and on 7 th, 14 th, 30 th, and 90 th d of treatment. Prognoses of these patients were assessed by modified Rankin scale (mRS) before treatment and on 180 th d of treatment. Brain CT was performed before treatment and on 7 th and 14 th d of treatment to calculate the hematoma volume. Before treatment and on 14 th d of treatment, changes of coagulation function, liver and kidney functions of the 2 groups were compared. Adverse reactions during treatment in the 2 groups were recorded. Results:No significant differences in NIHSS scores were noted between the 2 groups before treatment, on 7 th, 14 th, and 30 th d of treatment ( P>0.05); NIHSS scores in experimental group on 90 th d of treatment were signficantly lower than those in control group ( P<0.05); NIHSS scores in experimental group decreased gradually before treatment and on 7 th, 14 th, 30 th and 90 th d of treatment, with statistical significances ( P<0.05). No significant differences in mRS scores were noted between the 2 groups before treatment ( P>0.05); mRS scores in experimental group on 180 th d of treatment were signfciantly lower than those in control group ( P<0.05). No significant difference in hematoma volume was noted between the 2 groups before treatment and on 7 th and 14 th d of treatment ( P>0.05); both groups had gradually decreased hematoma volumes before treatment and on 7 th and 14 th d of treatment, respectively, with significant differences ( P<0.05); the volume difference of hematoma between 14 th d of treatment and before treatment in experimental group (6.42[4.10, 11.73]) was significantly higher than that in control group (4.00[1.25, 10.58], P<0.05). No significant differences in liver and kidney function indexes or coagulation function indexes were noted between the 2 groups before treatment and on 14 th d of treatment ( P>0.05). Adverse reaction incidence was 9.52% ( n=12) in experimental group and 10.34% ( n=12) in control group, without statistical difference ( P>0.05). Conclusion:Under premise of conventional western medicine treatment, Qufeng Tongxuan method can promote hematoma absorption and improve neurological deficit symptoms in low- and moderate-volume intracerebral hemorrhage at acute stage, without obvious adverse reactions.

OBJECTIVE To explore the clinical efficacy of adenoidectomy in treating pediatric secretory otitis media,sinusitis and snoring. METHODS A retrospective study was conducted to analyze the clinical features,therapeutic methods and prognosis of 68 children in hospital who underwent adenoidectomy to treat secretory otitis media,sinusitis or snoring. RESULTS The conditions of the 68 children were marked improved after the removal of hypertrophic adenoids. The total clinical effectiveness rate was 100 % and the cure rate was 86.8 %. CONCLUSION Hypertrophic adenoids is a fundamental cause of pediatric secretory otitis media,sinusitis and snoring. The removal of hypertrophic adenoids is a safe and effective method for treating pediatric secretory otitis media,sinusitis and snoring.