Clinical Effect Analysis of Fire-needle Acupuncture at Neiyingxiang Treating Persistent Allergic Rhinitis.

OBJECTIVES: We conducted the first trial to evaluate the effect that fire-needle acupuncture at Neiyingxiang (ExHN 9) in patients with moderate to severe persistent AR. METHODS: This was a randomized, single-center, sham, and placebo-controlled rial. Patients were kept blinded to their group assignment. All participants were equally assigned to the fire-needle acupuncture (FA) treatment group, sham fire-needle acupuncture (SFA) group, or loratadine group. The trial was designed with an acupuncture intervention once a week for 4 weeks and follow-up 4 weeks. The Total Nasal Symptom Scores (TNSS), Total Non-Nasal Symptom Scores (TNNSS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Allergic Rhinitis Control Test (ARCT), and total nasal resistance of 150 Pa were evaluated as outcome measures. RESULTS: A total of 180 participants were enrolled, and 175 participants completed the trials. At 2 and 4 weeks, the TNSS, TNNSS, and RQLQ scores of the FA and loratadine groups were significantly lower than those of the SFA group. At 8 weeks, the scores of loratadine group increased compared with the FA group (Cohen's d >0.80, p < 0.01). The ACRT score of the FA treatment group rose gradually. After treatment, the total nasal resistance of the FA group was significantly decreased and was lower than that of the other two groups (Cohen's d >0.80, p < 0.01). CONCLUSION: Fire-needle acupuncture at Neiyingxiang (ExHN 9) is effective for improving nasal allergy symptoms and quality of life in patients with moderate and severe persistent AR, and the duration of its effects is long. LEVEL OF EVIDENCE: 2 Laryngoscope, 2024.

Fire needle acupuncture at Neiyingxiang (EX-HN 9) in the treatment of moderate and severe refractory perennial allergic rhinitis: A case report.

RATIONALE: In recent decades, the incidence of perennial allergic rhinitis (PAR) has been increasing annually. However, some patients could not achieve adequate symptomatic relief with routine pharmacological treatment. Consequently, there exists an urgent clinical imperative for the development of safe and efficacious treatments with sustained therapeutic impact to ameliorate the symptomatic burden and enhance the quality of life. PATIENT CONCERNS: The patient was a 35-year-old woman. She had suffered moderate and severe refractory PAR for decades and failed to sustain symptom mitigation from regular treatment. DIAGNOSES: Perennial allergic rhinitis. INTERVENTIONS: The patient underwent a 4-week course of fire needle acupuncture at Neiyingxiang, administered weekly, during which all allopathic medication was discontinued. OUTCOMES: The total nasal symptoms score, total non nasal symptoms score, rhinoconjunctivitis quality of life questionnaire, and the total nasal resistance of the patient were decreased after treatment and achieved symptomatic relief. Follow-up conducted 3 months post-treatment revealed enduring symptom relief, with only sporadic nasal congestion elicited by cold stimulus. LESSONS: This case proves that, fire needle acupuncture at Neiyingxiang may be beneficial in treating moderate and severe refractory PAR patient and have a lasting effect.

Catalpol Regulates Oligodendrocyte Regeneration and Remyelination by Activating the GEF-Cdc42/Rac1 Signaling Pathway in EAE Mice.

The main obstacle to remyelination in demyelinating diseases, such as multiple sclerosis, is the inability of oligodendrocyte precursor cells (OPCs) to differentiate into mature oligodendrocytes (OLs) in the demyelinating region. Consequently, promoting OL differentiation and myelin remodeling is a key goal in the search for treatments. Rho GTPases play diverse and important roles throughout the development of neuronal axons and the formation of the myelin sheath. The current study aimed to investigate the direct protective effects of catalpol on demyelination damage induced by myelin oligodendrocyte glycoprotein (MOG) immunization and to explore whether the GEF-Cdc42/Rac1 signaling pathway contributes to the regeneration effect induced by catalpol. In the MOG-induced experimental autoimmune encephalomyelitis (EAE) mouse model of demyelination, we observed that catalpol significantly promoted OL development by enhancing the expression of glutathione S-transferase pi (GST-pi) in the affected brain. By Luxol fast blue staining and myelin basic protein (MBP) expression assessment, catalpol was found to increase MBP expression and promote myelin repair. Furthermore, catalpol promoted OL differentiation associated with the upregulation of Cdc42/Rac1 expression and activation in vivo. In addition, PAK1/MRCKα, proteins downstream of Cdc42/Rac1, was positively regulated by catalpol. We also found that catalpol alleviated clinical neurological dysfunction, inhibited inflammatory infiltration, increased the proportion of Treg cells, and suppressed demyelination. Overall, our study is the first to reveal that catalpol can promote OL generation and myelination and contributes to the crucial regulatory process of GEF-Cdc42/Rac1 signaling expression and activation. Therefore, catalpol is a promising drug candidate for the potential treatment of demyelinating diseases.

Association of Pain with Plasma C5a in Patients with Neuromyelitis Optica Spectrum Disorders During Remission.

Objective: To investigate the association of pain with plasma C5a levels and other related inflammatory cytokines in neuromyelitis optica spectrum disorders (NMOSD) patients during remission. Participants and Methods: NMOSD patients (n = 87) and healthy controls (HC; n = 44) were consecutively recruited between January 2017 and April 2018. Plasma complement 5 (C5), C5a, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1ß levels were detected. Visual Analogue Scale (VAS), ID pain scale, 24-item Hamilton Depression Scale (HAMD), Multiple Sclerosis Impact Scale (MSIS-29), and Kurtzke Expanded Disability Status Scale (EDSS) were used to evaluate the degree and types of pain, the existence of depression and anxiety, and the life quality and disability status of patients. Binary logistic regression equation was used to assess the association of pain with plasma C5a levels. Results: Among the 87 NMOSD patients, 40 complained of pain that in 67.5% (27/40) of cases had a neuropathic component (ID pain ≥2). Plasma C5a, IL-6, TNF-α, and IL-1ß levels were significantly elevated in NMOSD patients than in HC. Plasma C5 levels were negatively correlated with the time from sampling to the last relapse or disease onset. NMOSD patients with pain had higher plasma C5a levels, and they suffered from a higher disability, more anxiety, and worse life quality compared to those patients without pain. In NMOSD patients with pain, there were not significant differences between plasma levels of C5, C5a, IL-6, TNF-α, or IL-1ß, regardless of neuropathic pain or not. Binary logistic regression showed that the OR of plasma C5a level was 1.002, with gender and EDSS score were identified as independent factors associated with pain in NMOSD. Conclusion: NMOSD patients during remission had elevated C5a and related inflammatory cytokines levels in peripheral blood. Elevated C5a may have a unique role in the pathogenesis of pain in NMOSD patients.

Neuroprotective Effects of Fingolimod Supplement on the Retina and Optic Nerve in the Mouse Model of Experimental Autoimmune Encephalomyelitis.

Favorable effects exerted by long-term administration of fingolimod therapy in multiple sclerosis (MS) patients have been reported, but sporadic side effects, such as reversible macular edema, also have been recorded. The present study aimed to determine whether fingolimod therapy is beneficial to the visual system in experimental autoimmune encephalomyelitis (EAE) mice. A decrease in demyelination and axon loss in the optic nerve as well as cellular infiltration, especially the recruited macrophages, was observed in EAE with fingolimod treatment. Fingolimod administration diminished hypergliosis of macroglia, including astrocytes and Müller cells in the retina and optic nerve in EAE. Microglia were hyperactivated in the retina and optic nerve in the EAE mice compared to controls, which could be alleviated by fingolimod treatment. Moreover, apoptosis of retinal ganglion cells (RGC) and oligodendrocytes in the optic nerve was significantly reduced with fingolimod treatment compared to that in the untreated EAE mice. These results suggested that fingolimod exerts neuroprotective and anti-inflammatory effects on the retina and optic nerve in a mouse model of EAE. Considering the paradox of favorable and side effects of fingolimod on visual system, we speculate that side effects including macular oedema caused by fingolimod during MS treatment is tendency to be vasogenic rather than hypergliosis in optic nerve and retina which warrants further neuroophthalmological investigation.

Influences of pregnancy on neuromyelitis optica spectrum disorders and multiple sclerosis.

OBJECTIVE: To assess the influences of pregnancy on disease progression of neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS). METHODS: A total of 148 NMOSD patients and 170 MS patients were reviewed retrospectively. The changes in mean annualized relapse rate (ARR) in NMOSD and MS during and after pregnancy were compared. The influences of different pregnancy outcomes on disease courses were also analyzed. RESULTS: Sixty-two relapses had occurred during pregnancy or within 1 year after delivery/abortion in NMOSD patients and 64 in MS patients. The proportion of pregnancy-related onset and relapse in NMOSD was not significantly higher than that in MS. The ARR during 0-3 months and 7-9 months postpartum/postabortal periods in NMOSD and during 0-3 months and 10-12 months postpartum/postabortal periods in MS increased significantly. The ARR in 7-9 months postpartum/postabortal period in NMOSD patients was significantly higher than that in MS patients. Different pregnancy outcomes affected the course of disease similarly in patients irrespective of NMOSD or MS. CONCLUSIONS: Both NMOSD and MS presented increased onset and relapses after delivery/abortion. Significant differences were observed in ARRs at different stages between them. Both delivery and abortion exerted detrimental effects on disease courses in NMOSD and MS.

Elevated Plasma Chemokines for Eosinophils in Neuromyelitis Optica Spectrum Disorders during Remission.

BACKGROUND: A prominent pathological feature of neuromyelitis optica spectrum disorders (NMOSD) is markedly greater eosinophilic infiltration than that seen in other demyelinating diseases, like multiple sclerosis (MS). Eosinophils express the chemokine receptor CCR3, which is activated by eotaxins (CCL11/eotaxin-1, CCL24/eotaxin-2, CCL26/eotaxin-3) and CCL13 [monocyte chemoattractant protein (MCP)-4]. Moreover, CCL13 is part of the chemokine set that activates CCR2. The present study aimed to evaluate plasma levels of eotaxins (CCL11, CCL24, and CCL26) and MCPs (CCL13, CCL2, CCL8, and CCL7) in patients with NMOSD during remission. METHODS: Healthy controls (HC; n = 30) and patients with MS (n = 47) and NMOSD (n = 58) in remission were consecutively enrolled in this study between January 2016 and August 2017. Plasma CCL11, CCL24, CCL26, CCL2, CCL8, CCL7, CCL13, tumor necrosis factor (TNF)-α, and interleukin (IL)-1ß levels were detected using the human cytokine multiplex assay. RESULTS: Plasma CCL13, CCL11, and CCL26 levels were all significantly higher in patients with NMOSD than in HC and patients with MS. No significant differences were found in the CCL13, CCL11, or CCL26 levels between patients with NMOSD receiving and not receiving immunosuppressive therapy. The plasma levels of TNF-α and IL-1ß, which stimulate the above chemokines, were higher in patients with NMOSD than in HC. There was no difference in CCL24 levels among the three groups. In most cases, the CCL7 levels were below the threshold value of the human cytokine multiplex assay, which is in line with other studies. Adjusted multiple regression analyses showed a positive association of CCL13 levels with the number of relapses after controlling gender, age, body mass index, and disease duration in patients with NMOSD. CONCLUSION: The study indicates that in NMOSD, the overproduction of cytokines such as IL-1ß and TNF-α during remission stimulates eosinophilic chemoattractants such as CCL13, CCL11, and CCL26, which in turn bind to their receptor (CCR3); this could lead to eosinophil hypersensitivity. These findings suggest that the elevated secretion of CCL13, CCL11, and CCL26 may be a critical step in eosinophil recruitment during NMOSD remission.