Objecfive To study T cell subsets distribution in peripheral blood from patients with ankylosing spondylitis(AS)and the role of cell immunity in AS.Methods 30 patients with untreated active phase AS and 30 healthy volunteers were enrolled.The expression of CD4+ and CD8+ T cell subsets were evaluated by flow eytome try.The correlation among T cell subsets and Bath AS function index(BASFI).Bath AS measurement index(BASMI),course of disease,age,ESR,hyper-sensitive C-reactive protein (hs-CRP) were analyzed.Results The level of CD4+ T cell and CD4/CD8+ratio were significantly lower than that of healthy volunteers[(29.24±9.22)% vs.(40.09±6.86) %,(0.96±0.49 ) vs.(1.70±0.67 ),P ＜ 0.01 ],and CD8+ T cell were significantly higher than that of healthy volunteers [(32.91±6.86) % vs.(25.60± 5.97 ) %,P ＜ 0.01 ].The level of CD4+ T cell subsets in peripheral blood of AS patients was negatively correlated with BASMI (r =-0.479,P ＜ 0.01 ),and CD8+ T cell subsets were positively correlated with ESR,hs-CRP,BASFI and BASMI ( r = 0.373,0.430,0.462,0.530,P ＜0.05 ).The ratio of CD4+/CD8+ was negatively correlated with hs-CRP,BASFI and BASMI (r = -0.465,- 0.473,- 0.426,P ＜ 0.05 ).CD4+,CD8+,ratio of CD4/CD8 were not significantly correlated with age and course of disease in patients with AS.Conclusion T cell subsets are significantly abnormal in peripheral blood of patients with AS,and the imbalance degree of T cell is correlated with severity and activity of AS,suggesting that T cell subsets imbalance plays an important role in the pathologensis of AS.

Objective To study the dynamic expression and distribution of high mobility group box 1 (HMGB-1)in diffuse axonal injury (DAI)in rats and to clarify its involvement in the inflammatory reaction after DAI in rats,in order to provide new targets for the clinical treatment of DAI.Methods A DAI model was established using a coronal rotation device and evaluated by HE,Glees-Marsland silver staining,and Mallory phosphotungstic acid hematoxylin staining.Immunohistochemistry,Western blot and RT-PCR were used to detect the expression and distribution of HMGB-1 in the cortex of DAI rats at 6 h,1 d,3 d and 7 d.And TUNEL was used to examine the apoptosis of neurons in DAI rats.Results Immunohistochemical results showed that at 6 h and 1 d after DAI,the number of HMGB-1-positive cells decreased,but at 3 and 7 d it began to increase.Western blot also showed that during the early stage after DAI (6 h and 1 d),the level of HMGB-1 protein in the cortex was significantly lower than that in the control group,but at the late stage (3 and 7 d)after DAI it significantly increased compared with that in the control group until 7 d.RT-PCR showed that at 6 h after DAI there was no significant increase in the level of HMGB-1mRNA,but at 1 d there was a slight increase compared with the control group;at 3 and 7 d,it showed an obvious significance.TUNEL staining indicated that the significant neuronal apoptosis appeared as early as 6 h after DAI,and reached the peak at 3 d;it started to decrease at 7 d but still remained at a relatively high level.Conclusion The dynamic expression and distribution of HMGB-1 showed significant changes with the time course after DAI in rats.They decreased at the early stage but increased at the late stage.At the early stage, HMGB-1 is mainly passively released by the necrotic neurons,and at the late stage it may be actively secreted by the active inflammatory cells.HMGB-1 may mediate the post-DAI neural cell apoptosis by inducing the inflammatory reaction.

Serum p-amyloid peptide(Aβ)40 and Ap42 levels in patients with type 2 diabetes mellitus (T2DM)and atherosclerosis(AS)were detected by ELISA.The results showed that serum Ap40 level in T2DM group was significantly higher than that in the control group[(274.70±159.51 vs 162.63±87.58)pg/ml,P<0.05],especially in the diabetic patients accompanied with AS[(616.95±195.13)pg/m],P<0.01].Serum Ap40 level in simple AS group was also higher than that in control group[(318.52± 188.65)pg/ml,P<0.05].These results suggest that Ap40 is a risk factor of T2DM complicated with AS.However,there was no difference in serum Ap42 levels among various groups.

Objective To investigate the association between the tumour necrosis factor-α-863(TNF-α-863) polymorphism and gout in Han population from the city of Tangshan.Methods We recruited 80 gout patients and 80 healthy individuals into this study.The polymorphisms of TNF-α-863 site were analyzed by polymerase chain reaction-ligase detection reaction(PCR-LDR).The frequencies of different TNF-α-863 genotypes/alleles were analyzed in the gout group and the control subjects.Results No significant differences were observed in the genotype frequencies(x2=2.8807,P=0.0897) and allelic frequencies(x2=4.2646,P=0.1187) of TNF-α-863 site in the comparison between gout and control groups.Conclusion The result of our study suggests that the polymorphism of TNF-α-863 site may not related to gout in Han population in Tangshan.

Objective:To explore the association between chest high resolution CT (HRCT) scoring and prognostic factors of interstitial lung disease (ILD) in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM).Methods:The patients with DM admitted to Kailuan General Hospital between January 2017 and December 2019 were included into the study including 13 patients with positiveanti-MDA5 antibody (7 survivors, 6 deaths) and 18 patients with anti-synthase (ARS)-antibody positive. All patients underwent chest HRCT prior to treatment. The consolidation, ground-glass opacity (GGO) and fibrosis were scored to assess HRCT findings. The clinical manifestations were compared between the two groups. Cox regression analysis adjusted for age and sex was used to determine the prognostic factors for anti-MDA5 antibody-related ILD.Results:Compared with ARS patients, glutamyl transferase (GGT) and ferritin levels were significantly higher in MDA5-ILD patients [70.0(37.0, 122.5) vs 21.0(16.5, 33.5), Z=-3.37, P=0.001; 977.0(502.5, 1 366.0) vs 307.1(72.3, 546.9) , Z=-3.44, P=0.001]. The cumulative survival rate was significantly lower in patients with positive anti-MDA5 antibody than in those with positive anti-ARS antibody (100% vs 70%, P=0.001). The DM complicated with acute/subacute interstitial pneumonia (A/SIP) were found to significantly relate to death. There were no significant differences in chest HRCT scoringbetween the survivors and the deceased patients [ HR=1.08, 95% CI(0.95, 1.23), P=0.229; HR=0.97, 95% CI(0.72, 1.30), P=0.814]. Conclusion:Anti-MDA5 antibody is an important index for early diagnosis of DM complicated with acute/subacute interstitial pneumonia (A/SIP). The chest HRCT scoreis is not associated with the prognosis of anti-MDA5 antibody-related ILD patients.

Objective To research the effect ofparecoxib on hippocampal nerve cell apoptosis and expressions of B cell lymphoma/lewkmia-2 (Bcl-2),Bcl-2 associated X protein (Bax) and caspase-3 of epilepsy rats.Methods Thirty SD male rats were randomly divided into three groups (n=10):control group,parecoxib treatment group and epilepsy group.The rats in the parecoxib treatment group and epilepsy group were injected with 4 mg/kg of parecoxib and same volume of saline,respectively,and 3 d after that,they both were injected intraperitoneally with 3 mmol/kg of lithium chloride,and then,20 h after that,they were injected intraperitoneally with 30 mg/kg ofhydrochloride pilocarpine; while rats in the control group were only injected intraperitoneally with the same volume of saline.The behavior changes of rats in the three groups were observed.After 7 d,terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) was used to evaluate the neuronal apoptosis and Western blotting was employed to evaluate the expressions of Bcl-2,Bax and caspase-3 in the hippocarnpus of all groups.Results All epilepsy rats were very irritable; spontaneous seizures (SRS) times of precoxib treatment group were significantly reduced as compared with those of epilepsy group (P＜0.05).As compared with those in the control group,the Bcl-2,Bax and caspase-3 expressions and Bcl-2/Bax ratio in the epilepsy group were increased with statistically significant differences (P＜0.05); As compared with those in the epilepsy group,the Bcl-2,Bax and caspase-3 expressions and Bcl-2/Bax ratio in the precoxib treatment group were decreased with statistically significant differences (P＜0.05).As compared with that in the control group,the number of TUNEL positive cells in hippocampus of rats in the precoxib treatment group and epilepsy group were significantly increased (P＜0.05); as compared with that in the epilepsy group,the number of TUNEL positive cells in the hippocampus of precoxib treatment group was statistically reduced (P＜0.05).Conclusion Parecoxib can reduce the apoptosis of hippocampus neurons through inhibiting the protein expressions of Bax and caspase-3 to affect the Bcl-2 protein expression,whose mechanism may be related to the pathways of Bcl-2/Bax and Caspase-3 proteins.

Objective To explore the relationships between metabolic syndrome (MS) and rheumatoid arthritis (RA).Methods Two hundred and forty RA patients who fulfilled the 1987 revised American College of Rheumatology (ACR) classification criteria,and 250 age and sex matched healthy controls were enrolled.The frequency of metabolic syndrome was assessed using three Metabolic Syndrome definitions (Guidelines on Prevention and Treatment of Blood Lipid Abnormality in Chinese Adults 2016,International Diabetes Federation 2005,National Cholesterol Education Program 2005).Data were analyzed by Chi-square test and t test,risk factors were identified by Logistic regression.Results ① According to the definition used,the frequency of metabolic syndrome varied from 28.3％ to 35％ in RA,which was significantly higher than controls.② In RA with MS group defined by guidelines on Prevention and Treatment of Blood Lipid Abnormality in Chinese Adults 2016,the age,the diseases duration,erythrocyte sedimentation rate (ESR),DAS28,health assessment questionnaire (HAQ) scores and dose of glucocorticoid used were higher than controls [(12±6) years vs (10±7) years,t=6.96,P=0.01,(32±9) mm/1 h vs (26±6) mm/1 h,t=4.66,P=0.008,(3.7±1.2) vs (2.6±1.0),t=3.78,P=0.01,(1.6±0.5) vs (1.2±0.5),t=3.42,P=0.017],the percentage of patients who received anti-tumor necrosis factor α therapy was lower than the control group (39.7％ vs 23.7％,x2=6.881,P=0.009).③ In multivariate analysis,long disease duration,high ESR and HAQ scores were independently associated with the presence of MS [OR(95％CI):1.489(0.382,0.624),1.555(0.423,0.729),1.603(0.423,0.858),P＜0.01].Being treated with anti-tumor necrosis factor α was an independent protector of the presence of metabolic syndrome in RA patients [OR=0.582,95％CI(0.453,0.742),P＜0.01].Conclusion The frequency of metabolic syndrome in RA is higher compared to controls,while diseases duration,ESR,and HAQ are independent predictors for the presence of metabolic syndrome in patients with RA,anti-TNF-α therapy may be protective factor for the presence of metabolic syndrome in patients with RA.

Objective To investigate the relationship between serum uric acid ( UA) level and brachial?ankle pulse wave velocity ( baPWV) in patients with systemic lupus erythematosus ( SLE) and lupus nephritis (LN)??Methods A total of 110 hospitalized,out?patient and healthy examinees from January 2017 to September 2017 were selected from Kailuan General Hospital??They were divided into three groups:(1)Fifty?five healthy controls were examined at the same time,and those who had no history of hypertension, myocardial infarction and stroke were excluded by physical examination??(2)Thirty?four SLE patients without LN were diagnosed according to the SLE classification standard revised by the American Society of Rheumatology ( ACR) in 1997,excluding those with lupus nephritis??( 3) 21 SLE patients with LN were diagnosed according to the SLE classification standard revised by the American Society of Rheumatology (ACR) in 1997??Pearson correlation coefficient and multivariate linear regression model were used to analyze the related factors affecting baPWV??Results The level of baPWV and the proportion of baPWV (≥1400 cm／s) in SLE without LN group and SLE with LN group were higher than those in healthy control group (all P＜0??05)??In SLE without LN group, baPWV was positively correlated with age, systolic blood pressure (SBP) and total cholesterol ( CHOL) ( r＝ 0??623,0??528,0??402, P＜0??01 or P＜0??05), and negatively correlated with blood uric acid(UA) ( r＝－0??371,P＜0??05),but the correlation was not significant??The correlation between UA and baPWV disappeared after after correction of age,SBP,diastolic blood pressure (DBP) by partial correlation analysis??In SLE with LN group,baPWV was positively correlated with SBP, DBP and serum creatinine ( Cr) ( r＝0??815, 0??725, 0??464, P＜0??01 or P＜0??05)??Multivariate stepwise regression analysis showed that SBP was independently correlated with baPWV in SLE group ( t＝2??54,P＝0??026); UA in SLE group without LN was independently negatively correlated with baPWV(t＝－2??96,P＝0??042); UA(t＝4??24,P＝0??013) and SBP(t＝7??70,P＝0??002) were independently positively correlated with baPWV in SLE group with LN??Logistic regression analysis showed that SLE was a risk factor for baPWV (≥1 400 cm／s),and the OR (95% CI) was 4??31 ( 1??56－11??88),P＝0??005,and there was statistical significance after adjusting for age,SBP,DBP,body mass index ( BMI)??However,UA was not a risk factor for baPWV (≥1 400 cm／s) (P values were 0??163 and 0??519,respectively)??Conclusion The degree of arteriosclerosis in SLE patients is higher than that in normal subjects,and the level of UA in SLE patients may be related to baPWV??

Objective To investigate the correlation between cumulative serum uric acid (cumUA) and brachial-ankle pulse wave velocity (baPWV).Methods Among the workers who participated in the four health check-up of Kailuan Group from 2010 to 2017,subjects who completed one PWV test were selected.The subjects who met the selection criteria were 20 688,subjects who lacked the first three uric acid tests and sex data were excluded.The subjects who had ischemic stroke (excluding lacunar infarction),transient ischemic attack and myocardial infarction were excluded.Decreased subjects were excluded and the extreme value were also excluded,20 295 subjects eventually meet the inclusion criteria and were included for statistical analysis.Stepwise linear regression,multivariate logistic regression and natural spline function were used to analyze the relationship between cumUA and baPWV and the influence of cumUA on baPWV.Results Among 20 295 subjects,the incidence of baPWV ≥ 14 m/s (criteria for judging atherosclerosis) increased with the increase of cumUA.There was significant difference in the incidence of baPWV ≥ 14 m/s (53.07％,54.35％,56.42％,58.41％,61.91％) among different cumUA partition groups (β=0.11,P＜0.01).In stepwise linear regression analysis,after adjusting for other confounding factors,it was found that cumUA was positively correlated with baPWV.In multivariate logistic regression analysis,after adjusting for other confounding factors,the results showed that baPWV ≥aPWVm were all risk factors for the third,fourth and fifth subgroups of cumUA compared with the first subgroup,and the OR05％CI) was 1.35(1.13,1.62) (P=0.01),1.60(1.29,1.97) (P＜0.01) and 2.14(1.64,2.80) (P＜0.01),respectively.Natural spline analysis exhibited a similar J curve relationship between cumUA and increased baPWV.Conclusion CumUA is a risk factor for increased baPWV.

BACKGROUNDThe mechanisms underlying diabetic encephalopathy are largely unknown, and no effective treatments are available. Catalpol has received much attention due to its numerous biological effects, especially in neuroprotective studies. The aim of this study was to investigate the effects of catalpol on cognitive functions in diabetic rats and the underlying mechanisms.

METHODSA rat model of diabetes was established by streptozotocin injection, followed by intraperitoneal infusion of catalpol after 10 weeks. Two weeks later, the Morris water maze was used to test the spatial learning performance. Nissl staining was performed to evaluate the morphological changes in the hippocampus. Expression of protein kinase Cγ (PKCγ) and caveolin-1 (Cav-1) in the hippocampus were assessed by reverse transcription PCR and Western blotting. Activities of anti-oxidative enzymes such as glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) and levels of malonaldehyde (MDA) were measured using commercial kits.

RESULTSSignificant hippocampal neuronal injury was observed in rats with streptozotocin-induced diabetes. Moreover, cognitive dysfunction was associated with markedly increased oxidative stress in the brain. Catalpol treatment significantly attenuated cognitive deficits, neuronal damage, and oxidative stress in the brain of diabetic rats. Biochemical analyses showed that catalpol reversed the down-regulation of PKCγ and Cav-1 expression in the diabetic rats.

CONCLUSIONSSpatial memory in diabetic rats is associated with the expression of PKCγ and Cav-1. Catalpol treatment markedly attenuated oxidative stress, reversed the alteration of PKCγ, Cav-1 and spatial memory deficits.

Animals ; Caveolin 1 ; metabolism ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; physiopathology ; Hippocampus ; drug effects ; metabolism ; Iridoid Glucosides ; therapeutic use ; Male ; Neuroprotective Agents ; therapeutic use ; Oxidative Stress ; drug effects ; Protein Kinase C ; metabolism ; Rats ; Spatial Memory ; drug effects ; physiology