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@#Objective To investigate the expression of α7 nicotinic acetylcholine receptor (α7 nAChR) in thymocytes of patients with myasthenia gravis (MG) and its effect on cytokine secretion and T cell proliferation. Methods Patients with MG who underwent expanded thoracoscopic thymectomy in the Comprehensive Diagnosis and Treatment Center of the Henan Provincial People’s Hospital from June 2021 to June 2022 were selected and allocated to a MG group. Patients who underwent partial thymectomy to expose the surgical field during the cardiac disease surgery from June 2021 to September 2022 in the Department of Adult Cardiac Surgery of Fuwai Huazhong Cardiovascular Hospital were selected as the control group. Thymic single cell suspensions were prepared from MG and control groups, and the expression of α7 nAChR in thymocytes of the two groups was detected by real-time polymerase chain reaction and Western blotting. Then CD3/CD28 monoclonal antibody coupled with magnetic beads was used to induce T cell activation, and the levels of cytokines interferon-gamma (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-6, IL-10, IL-17, and IL-21 in thymocytes of the two groups were detected by enzyme-linked immunosorbent assay (ELISA). The activated T cells of the MG group were divided into a blank control group, an α7 nAChR antagonist group, and an α7 nAChR agonist group according to different treatment methods. After 72 hours of culture, IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-17, and IL-21 expression levels in the culture supernatant were measured by ELISA. Afterwards, CD4-PE and CD8-APC antibodies were added, and the proliferation of T cell subsets was detected by flow cytometry. Results A total of 10 MG patients were collected, including 3 males and 7 females with an average age of 19.25±6.28 years; and 15 control patients were collected, including 6 males and 9 females with an average age of 26.18±6.77 years. Compared with the control group, the mRNA and protein levels of α7 nAChR in the thymocytes of MG group were decreased, and the expression levels of IFN-γ, TNF-α, IL-4, IL-6 and IL-21 in the supernatant were increased (P<0.05), but there was no statistical difference in the expression of IL-10 and IL-17 (P>0.05). The cell-culture experiment showed that compared with the blank control group, the levels of IFN-γ, TNF-α, IL-6 and IL-21 secreted by T cells in the α7 nAChR antagonist group were increased (P<0.05), while they were decreased in the α7 nAChR agonist group (P<0.05). There was no statistical difference in the secretion levels of IL-4, IL-10 or IL-17 among the three groups (P>0.05). CD4+ T and CD8+ T cells in the α7 nAChR agonist group were significantly less than those in the blank control group and α7 nAChR antagonist group (P<0.001), while they were significantly more in the α7 nAChR antagonist group than those in the blank control group (P<0.001). Conclusion The expression of α7 nAChR in thymocytes of MG patients is decreased, and α7 nAChR may be involved in the inflammatory response in thymocytes and thus in thymic function.
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@#Objective To exploring the effectiveness of perioperative application of new surgical clinical classification and staging for myasthenia gravis (MG) in reducing the incidence of postoperative myasthenic crisis (MC). Methods The clinical data of patients with generalized MG admitted to the Comprehensive Treatment Center for Myasthenia Gravis of Henan Provincial People’s Hospital from January 2018 to June 2022 were retrospectively analyzed, who were scored with myasthenia gravis-activities of daily living (MG-ADL) score and quantification of the myasthenia gravis (QMG) score at the first visit, 1 day before surgery, and 3 days after surgery. The patients were divided into a group A (typeⅡ) and a group B (typeⅢ+Ⅳ+Ⅴ) by the new surgical clinical classification and staging of MG according to the disease progression process, and all patients underwent expanded thoracoscopic thymus (tumor) resection after medication and other interventions to control symptoms in remission or stability. The incidence of MC and the efficiency rate after surgery were analyzed. The normal distribution method and percentile method were used to calculate the unilateral 95% reference range of the QMG score and MG-ADL score. Results Finally 126 patients were enrolled, including 62 males and 64 females, aged 13-71 years, with an average age of 46.00±13.00 years. There were 95 patients in the group A and 31 patients in the group B, and the differences of the preoperative baseline data between the two groups were not statistically significant (P>0.05). The incidence of postoperative MC was 1.05% (1/95) in the group A and 3.23%(1/31) in the group B (P>0.05). The effective one-sided 95% reference range of the QMG score and MG-ADL score 1 day before surgery was 0-7.75 and 0-5.00, and there was no postoperative death in both groups. Conclusion The new surgical clinical classification and staging of MG can guide the timing of surgery, which can benefit patients undergoing surgery for MG and greatly reduce the incidence of postoperative MC.
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Objective To study the effect of S1P on HLF cell fibrosis and its mechanism. Methods (1) The expression of ECM in HLF cells was analyzed by using Western Blot after treatment by S1P(1 μmol/L), FTY720-P(5μmol/L),ponesimod(5μmol/L)and SEW2871(5μmol/L)24 h;(2)The HLF cells were pre-treated using selective S1PR antagonist W146(1 μmol/L),JTE-013(0.2 μmol/L),and TY-52156(1.25 μmol/L)1 h before incubation by S1P and S1PR agonists 24 h and then the expression of ECM was analyzed;(3)The HLF cells were pre-incubated using JTE-013(0.2μmol/L)and TY-52156(1.25μmol/L)for 1 h and then the expression of ECM was analyzedafter being treated by S1P and S1PR agonists 24 h. Results (1)S1P and selective S1P receptor agonist increased the expression of ECM to various extents;(2)The S1P1R antagonist W146 did not affectthe expression of ECM induced by S1P and S1PR agonists and S1P2R antagonist JTE-013 and S1P3R antagonist TY-52156 both decreased the expression of ECM induced by S1P and S1PR agonists;(3)The expression of ECM induced by S1P and S1PR agonists further decreased using both JTE-013 and TY-52156 but not using ponesimod. Conclusion S1P2R and S1P3R are activated under the influence of S1P so as to increase the synthesis of ECM and promote fibrosis gene expression in HLF cells.
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Objective To investigate the influence factors for immediate outcome after thymectomy for patients with myasthenia gravis (MG). Methods The clinical data of 108 patients with MG who received thymectomy in the Department of Thoracic Surgery, the Second Affiliated Hospital of Zhengzhou University from July 2009 to July 2012 were retrospectively investigated, including gender, age, duration of disease, clinical classification, pathological classification of thymus and anti-acetylcholine receptor antibodies (AChRab). The immediate outcome after thymectomy was also observed. Thirty-two cases of MG who had immediate outcome after thymectomy were enrolled into experimental group, while 76 cases who did not have immediate outcome after thymectomy were regarded as control group. Results The immediate outcome after thymectomy was associated with duration of disease (χ2=98.550, P<0.01), clinical classification (χ2=40.434, P<0.01), pathological classification of thymus (χ2=11.154, P=0.004) and AChRab (χ2=5.590, P=0.018). There were statistically significant differences between the two groups in the one-year (31.3% in the experimental group vs 14.5% in the control group, χ2=4.046, P=0.044), two-year (40.6% vs 21.1%, χ2=4.392, P=0.036) and three-year complete remission rates (46.9% vs 25.0%, χ2=4.995, P=0.025). Conclusion Duration of disease, clinical classification, pathological classification of thymus and AChRab could be influence factors for immediate outcome and complete remission for patients with MG after thymectomy.
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Objective To explore the expressions and clinical significance of epidermal growth factor receptor (EGFR),COOH-terminus tensin-like molecule (CTEN)and epithelial cadherin (E-cad)in non-small cell lung cancer (NSCLC).Methods The expressions of EGFR,CTEN and E-cad in 36 cases of normal lung tissue and 82 cases of NSCLC tissues were observed with immunohistochemical SP method and their correlation with NSCLC invasion,metastasis and prognosis was analyzed.Results The positive rate of EGFR,CTEN and E-cad was 58.5% (48/82),69.5% (57/82)and 28.1% (23/82)in 82 cases of lung cancer,while 13.9% (5/36),0.0% (0/36)and 100% (36/36)in normal tissues;the differences were all significant (P<0.05).EGFR,CTEN and E-cad expressions in NSCLC tissues were significantly correlated with tumor differentiation,TNM stage and lymph node metastasis (P<0 .0 5 ).The expressions of EGFR and CTEN were correlated with each other in NSCLC (r=0 .5 3 0 , P<0.001),while the expressions of EGFR and CTEN were correlated with that of E-cad (r=0.499,P<0.001;r=0.333,P=0.001 ).Multivariate Cox regression analysis showed that CTEN expression in NSCLC was an independent prognostic factor (P<0.05 ).Conclusion EGFR,CTEN and E-cad may play a role in the development,invasion and metastasis of NSCLC and have some significance in predicting the prognosis of NSCLC.