1.A preliminary study on the role of the E2 subunit of pyruvate dehydrogenase modified by xenobiotics in the pathogenesis of primary biliary cholangitis
Yaqian LIU ; Zongwen SHUAI ; Xianglian ZHOU ; Shanyu CHEN ; Mu LI
Chinese Journal of Rheumatology 2017;21(2):82-88
Objective To explore preliminarily the role of the E2 subunit of pymvate dehydrogenase (PDC-E2) modified by xenobiotics (e.g.2-octynic acid,2-OA) in the pathogenesis of primary biliary cirrhosis (PBC).Methods Patients of PBC (102 cases),primary sclerosing cholangitis (PSC,34 cases) and healthy controls (HC,50 cases) were selected.The anti-PDC-E2,anti-2-OA and anti-lipoic acid (LA) antibody in the peripheral blood of the 3 groups were tested by enzyme linked immunosorbent assay (ELISA).By inhibitive ELISA (iELISA),30 of the 102 PBC patients with anti-PDC-E2 antibody but without anti-2-OA antibody were selected to detect whether there was any new epitope on the PEC-E2 conjugated with 2-OA.The chi-square test and Fisher exact test were taken to analyze the enumeration data.The two-tailed unpaired t test with Welch's correction was used to compare the measurement data.Spearman rank correlation analysis was also employed for proper test.Results The positive rate of anti-PDC-E2,anti-LA and anti-2-OA antibody in PBC patients was 94.1%(96/102),73.5%(73/102) and 53.9%(55/102) respectively,all of which were statistically significantly higher than those in healthy controls group but were of no significant difference between PSC and healthy controls group.There was no significant relevance between the levels of Anti-LA and anti-2-OA antibody in the PBC group (r=-0.065,P=0.520).The iELISA results showed that the antibody,which only identified the epitopes on 2-OA-PDC-E2 induced by the 2-OA conjugation with PDC-E2,existed in 40%(12/30) of the PBC patients,and more interestingly,this antibody was predominantly appeared in PBC patients at their early clinical stage.Conclusion There are anti-LA antibody and anti-2-OA antibody in PBC patients,which have shown no significant association with each other.It is very likely that new antigenic conformational epitopes on PDC-E2 modified by 2-OA would emerge,which might led to the immune response in the individuals who are susceptible to PBC,and thus contribute for the breaking of PDC-E2 immune tolerance,and PBC occurrence finally.
2.Clinical analysis and prognosis of stomal recurrence after laryngectomy
Jiansheng LI ; Jian MA ; Shanyu MU ; Xiujun QIAO ; Xinliang PAN
Chinese Archives of Otolaryngology-Head and Neck Surgery 2006;0(04):-
OBJECTIVE To investigate the causes of stomal recurrence after laryngectomy and the possibility of surgical management.METHODS The clinical data of 13 cases of stomal recurrence were analyzed retrospectively.RESULTS In 13 cases of stomal recurrence after laryngectomy,the survival period of 9 cases treated surgically was longer than that of 4 cases untreated or palliative treatment.CONCLUSION The overall prognosis of stomal recurrence after laryngectomy is poor.A proper surgical treatment in some cases will prolong the patient's lifetime obviously and improve his quality of life.
3.The expression and significance of Krebs von den lungen-6, pulmonary surfactant protein-A, D, interleukin-6 in patients with connective tissue diseases interstitial pulmonary disease
Qin MA ; Jianhua XU ; Fen WANG ; Li LIAN ; Shanyu CHEN ; Jing CAI ; Mu LI ; Hui XIAO
Chinese Journal of Rheumatology 2017;21(1):46-49
Objective To determine the levels and significance of Krebs von den lungen-6(KL-6), pulmonary surfactant protein A (SP-A), SP-D and interleukin (IL)-6 in patients with connective tissue disease interstitial lung disease (CTD-ILD). Methods The serum KL-6, SP-A, SP-D and IL-6 in all subjects were detected and the imaging and pulmonary function were recorded t test, χ2 test, non-parametric test, ANOVA and correlation analysis were used for data analysis. Results ① The levels of serum KL-6, SP-A, SP-D, IL-6 in the CTD-ILD group [551.4 (428.2, 883.5) U/ml, 938.4(435.2, 2324.7) pg/ml, 90.7 (80.7, 100.3) ng/ml and 30.4 (22.9, 41.7) pg/ml; P all<0.05] was significantly higher than that in the CTD group [192.9 (139.2, 266.2) U/ml; 458.0 (372.6, 529.0) pg/ml; 80.0 (71.2, 98.3) ng/ml; 18.6 (4.9, 31.0) pg/ml, Z=-5.383, -3.76, -2.123,-3.903, P all <0.05]; and higher than healthy controls (n=30) [183.2(141.9, 216.6) U/ml; 229.0(162.0, 248.0) pg/ml;50.8(26.1, 96.4) ng/ml;7.1(3.7, 8.7) pg/ml, Z=-5.801,-8.13, 2.272, 3.266;P all<0.05].②The levels of KL-6 in pulmonary HRCT for active ILD group was significantly higher than the non-active ILD group [998.5 (640.3, 1293.3) U/ml vs 565.0(434.0, 799.5) U/ml, Z=2.182, P=0.023], there was no statistical difference in the levels of SP-A, SP-D, IL-6 between the 2 groups. ③ Spearman correlation analysis showed that KL-6 was negatively correlated with forced vital capacity (FVC%);SP-D, IL-6 and diffusing capacity of carbon monoxide (DLCO %). ④ Logistic multiple regression analysis showed that KL-6 [OR=1.017, P=0.002, 95%CI (1.006, 1.028)], SP-A [OR=1.023, P=0.009, 95%CI (1.006, 1.041)], SP-D [OR=1.175, P=0.009, 95%CI (1.075, 1.264)], IL-6[OR=1.213, P=0.001, 95%CI(1.088, 1.354)] were the risk factors for ILD. Conclusion Serum KL-6, SP-A, SP-D and IL-6 are significantly increased and correlate with CTD-ILD. KL-6 is related to the pulmonary inflammatory disease and vital capacity, while SP-D and IL-6 are related to diffusion function.
4.Repetitive trans-spinal magnetic stimulation promotes motor function recovery in mice after spinal cord injury
Haiwang SONG ; Guanhua JIANG ; Yingying MU ; Shanyu FU ; Baofei SUN ; Yumei LI ; Zijiang YU ; Dan YANG
Chinese Journal of Tissue Engineering Research 2025;29(11):2252-2260
BACKGROUND:Repetitive trans-spinal magnetic stimulation(rTSMS)can inhibit inflammatory responses following spinal cord injury.rTSMS applies magnetic field stimulation to the spinal cord region to modulate neuronal excitability and synaptic transmission,thereby promoting plasticity and repair of the nervous system. OBJECTIVE:To observe the effects of rTSMS on the Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB/NLRP3 signaling pathway after spinal cord injury and explore its mechanism in promoting motor function recovery. METHODS:Male C57BL/6J mice,SPF grade,were randomly divided into sham surgery group,spinal cord injury group,and rTSMS group.The latter two groups of mice were anesthetized and the T9 vertebral plate was removed using rongeur forceps to expose the spinal cord,and the spinal cord was clamped using a small aneurysm clip for 20 seconds to establish the spinal cord injury model.Mice in the rTSMS group underwent a 21-day rTSMS intervention starting on day 1 after spinal cord injury.The stimulation lasted 10 minutes per day,5 days per week with an interval of 2 days.Basso Mouse Scale scores were used to assess motor function recovery in mice after spinal cord injury at 1,3,7,14,and 21 days after spinal cord injury.Western blot was employed to detect the expression of AQP4,apoptotic factors Bax,Bcl-2,CL-Caspase-3,inflammatory factors tumor necrosis factor-α,interferon-γ,interleukin-6,interleukin-4,and the TLR4/NF-κB/NLRP3 signaling pathway related proteins in the injured spinal cord.Oxidative stress assay kit was used to measure the activity of superoxide dismutase,glutathione peroxidase,and malondialdehyde content at the site of spinal cord injury.Immunofluorescence staining was performed to detect the expression of neuronal nuclei(NeuN). RESULTS AND CONCLUSION:The Basso Mouse Scale score in the rTSMS group was significantly higher than that in the spinal cord injury group(P<0.05).Compared with the spinal cord injury group,the rTSMS group showed a reduction in spinal cord water content.The expression of AQP4 protein,malondialdehyde content,and expression of Bax,Bcl-2,CL-Caspase-3,tumor necrosis factor-α,interferon-γ,interleukin-6,and TLR4/NF-κB/NLRP3 signaling pathway related proteins were all decreased in the rTSMS group,while the activities of superoxide dismutase and glutathione peroxidase,as well as the expression of Bcl-2,interleukin-4,and NeuN,were all increased(P<0.05).These results suggest that rTSMS downregulates the expression of proteins related to the TLR4/NF-κB/NLRP3 signaling pathway,alleviating symptoms after spinal cord injury such as spinal cord edema,oxidative stress,apoptosis,and inflammation,exerting neuroprotective effects,and thereby promoting the recovery of hindlimb motor function after spinal cord injury.