Serum soluble CD40 ligand expression in children with Kawasaki disease in acute phase and its clinical significance / 中国综合临床

Objective:To investigate the expression of soluble CD40 ligand (sCD40L) in serum of children with Kawasaki disease at acute stage and its diagnostic value in coronary artery disease (CAL).Methods:This study adopts case-control study method. Select 127 children with Kawasaki disease admitted to Xuzhou Children's Hospital affiliated to Xuzhou Medical University from August 2021 to August 2022. They are divided into CAL group and non-CAL group according to the degree of coronary artery involvement. Select 30 healthy children who have physical examination in this hospital at the same time as the healthy control group, and select another 30 children with acute upper respiratory tract infection and fever admitted to this hospital at the same time as the fever control group.Compare the sex, age and laboratory indicators of children with Kawasaki disease with or without CAL, and compare the difference between the serum sCD40L level of children with Kawasaki disease with or without CAL and the fever control group and the healthy control group, the serum sCD40L level of children with different degrees of coronary artery dilation, and analyze the correlation between the serum sCD40L and various laboratory indicators of children with Kawasaki disease and the influencing factors of children with Kawasaki disease complicated with CAL, To evaluate the screening effect of serum sCD40L for Kawasaki disease complicated with CAL. The measurement data with normal distribution is expressed by xˉ± s, the comparison between the two groups adopts independent sample t-test, the comparison between multiple groups adopts one-way ANOVA, and the comparison between two groups adopts LSD method and Bonferroni correction; The measurement data of non-normal distribution is expressed by M( Q1, Q3), and the comparison between the two groups is conducted by Mann-Whitney U test. Pearson method and Spearman mothod were used for correlation analysis. Logistic regression model was used to analyze the influencing factors of children with Kawasaki disease complicated with CAL. The diagnostic value of serum sCD40L level in Kawasaki disease complicated with CAL was analyzed by drawing the ROC curve. Results:All 127 children with Kawasaki disease were divided into CAL group (45 cases) and non-CAL group (82 cases) according to the presence or absence of CAL. The serum level of sCD40L in CAL group was higher than that in non-CAL group, healthy control group and fever control group ((7.03±0.91) μg/L vs (4.66±1.23), (1.73±0.96), (2.21±1.08) μg/L), the difference was statistically significant (all P<0.001). The serum level of sCD40L in children with coronary artery dilation in CAL group was lower than that in children with small CAA, medium CAA and large CAA ((6.04±0.22) μg/L vs (6.95±0.69), (8.02±0.57), (8.23±0.26) μg/L), the difference was statistically significant (all P<0.001). Serum sCD40L level and platelet count (PLT), C-reactive protein (CRP), N-terminal pro brain natriuretic peptide (NT-proBNP), interleukin-6 (IL-6), IL-8 and tumor necrosis factor (TNF-α) in children with Kawasaki disease All were positively correlated ( r=0.31, P<0.001, r=0.32, P<0.001, r=0.26, P=0.003, r=0.58, P<0.001, r=0.27, P=0.002, r=0.39, P<0.001). Serum sCD40L, IL-6 and NT-proBNP were the risk factors of complicated CAL in children with Kawasaki disease (odds ratio 1.21, 1.06 and 1.01, 95% confidence interval 1.03-1.43, 1.01-1.12, 1.00-1.01, P values were 0.022, 0.011 and 0.039, respectively). The area under the curve of serum sCD40L in diagnosing Kawasaki disease complicated with CAL was 0.928 (95% confidence interval: 0.885-0.971), and the optimal critical value was 5.60 μg/L, the sensitivity was 97.8% and the specificity was 79.3%. Conclusions:The level of serum sCD40L increased in children with Kawasaki disease in acute phase, especially in children with CAL. The level of serum sCD40L increased with the severity of CAL, which is a risk factor for Kawasaki disease complicated with CAL, and has certain diagnostic value for Kawasaki disease complicated with CAL.

Effect ofXuebijinginjection on the serum soluble CD40 ligand and lipoprotein associated phospholipase A2 of patients with acute coronary syndrome / 国际中医中药杂志

Objective To detect the effect ofXuebijing injection on the serum soluble CD40 ligand (soluble CD40 ligand, sCD40L), lipoprotein associated phospholipase A2 (lipoprotein-phospholipase A2, Lp-PLA2) of patients with acute coronary syndrome (ACS).Methods A total of 120 patients with ACS were randomized divided into the control group and treatment group, 60 in each group.The control group received the routine treatment of Western medicine, and the treatment group receivedXuebijing injectionbased on the intervention of control group. Both groups were treated for 2 weeks. ELISA method was used to detect serum sCD40L, Lp-PLA and IL-6, TNF-α and CRP.Results After treatment, the serum sCD40L(320.62 ± 35.81 pg/Lvs. 401.70 ± 4.84 pg/L, t=10.435), Lp-PLA2 (203.62 ± 33.13μg/L vs. 296.45 ± 4.422μg/L,t=12.831) level was significantly lower than those in the control group (P<0.01); The serum CRP (3.10 ± 2.00 mg/Lvs.4.74 ± 2.04 mg/L,t=4.006), IL-6 (2.10 ± 1.20 pg/Lvs.3.14 ± 1.40 pg/L,t=3.781), TNF (2.81 ± 1.50 pg/Lvs. 3.70 ± 1.70 pg/L,t=3.075) level was significantly lower than thosein the control group (P<0.01 orP<0.05). Compared with the control group, the effect rate (68.3%vs. 50.0%,χ2=4.174) of the treatment group was significantly higher (P=0.041).ConclusionXuebijing injection can improve the therapeutic effectof ACS patients, and reduce CD40L, Lp-PLA2 levels.

Role of cardiovascular disease markers in periodontal infection: Understanding the risk.

Context: Both periodontitis and cardiovascular diseases (CVD) represent chronic inflammatory conditions, and periodontal infections have been postulated to perpetuate the progression of CVD’s. However, limited evidence is available to prove the causal relationship. Aim: An effort in exploring this interrelation has been made in this study. The role of two inflammatory mediators, soluble CD40 ligand (sCD40 L) and monocyte chemoattractant protein‑1 (MCP‑1) has been established in progression and acute precipitation of CVD’s. Due to a close link between these two mediators, the present study was designed to correlate the levels of sCD40 L and MCP‑1 in serum and gingival crevicular fluid (GCF) of patients with chronic periodontitis. Methods: Fifteen healthy and 30 patients of severe chronic periodontitis (diseased) participated in the study. Patients of the diseased group underwent scaling/root planning. The evaluation of plaque index, gingival index, probing depth, clinical attachment level, and a collection of serum and GCF samples was done at baseline and 6 weeks following periodontal therapy. The sCD40 L and MCP‑1 levels were quantified using ELISA. Results: The sCD40 L levels correlated strongly with MCP‑1 levels in both GCF (r = 0.888) and serum (r = 0.861) in patients of chronic periodontitis. The relationship between the levels of the two markers was maintained in GCF (r = 0.868) and serum (r = 0.750) after Phase I periodontal therapy. Conclusions: The positive correlation observed suggests this pathway as one of the mechanisms that may lead to increasing severity of periodontal disease and its systemic effects. Further research efforts should be made in designing appropriate clinical trials, starting at an early stage and monitoring the potential benefits of maintenance of oral hygiene on cardiovascular health.

Soluble CD40L promotes proliferation of orbital fibroblasts and expression of hyaluronan synthase in patients with thyroid associated ophthalmopathy / 第二军医大学学报

Objective To investigate the effects of soluble CD40L (sCD40L) on proliferation of orbital fibroblasts (OFs) and the expression of three types of hyaluronan synthase (HAS) in vitro, so as to explore the role of sCD40L in the pathogenesis of thyroid-associated ophthalmopathy (TAO). Methods OFs obtained from 5 patients with TAO and 3 normal controls were primarily culutred. The effect of different concentrations of sCD40L (6.25,12.5,25,50,100 and 200 ng/mL) on proliferation of OFs of different sources were examined by MTS after 48 h exposure. OFs were also cultured with different concentrations of sCD40L (12.5, 25, 50 and 100 ng/mL) for 3,6,12 and 24 h, and then the expression levels of HAS 1-3 mRNA were determined by real-time RT-PCR. Results Treatment with sCD40L at concentrations higher than 25 ng/mL for 48 h obviously promoted the proliferation of OFs in patients with TAO (P<0.05). In contrast, treatment with sCD40L only at concentrations higher than 50 ng/mL for 48 h could promote proliferation of OFs from normal control, and the effect was comparatively weak. HAS3 mRNA expression of OFs in TAO patients was increased after exposed to sCD40L (P<0.05), and the increase was in a concentration- and time-dependent manner. Conclusion sCD40L can promote the proliferation of OFs and expression of HAS3 mRNA in patients with TAO, which implies that sCD40L plays an important role in the pathogenesis of TAO.

The role of platelet TLR4 expression in the pathogensis of thrombocytopenia in sepsis / 中华急诊医学杂志

Objective To unravel the relationship between Toll-like receptor 4 (TLR4) expression in platelets and the activation of platelet in thrombocytopenia (TCP) in case of sepsis. Method A total of 64 patients with sepsis were prospectively studied with control. Platelet count (PC), mean platelet volume (MPV),platelet distribution width (PDW),platelet TLR4 expression, platelet PAC-1 expression, sCD40L and TNF-α concentrations were compared between healthy control group (15 cases) and sepsis group on admission and 3 d,Sd,and 9 days after admission. The changes of MPV and PDW in TCP and non-TCP subgroups of sepsis before and after treatment were recorded. Prognostic index was analyzed. Results The PC was lower in sepsis group (P=0.006), and MPV and PDW were higher in sepsis group than those in healthy control group (P = 0.046, P =0.001). Platelet TLR4 and PAC-1 expressions, and sCD40L and TNF-α levels also increased more significantly in sepsis group (P ＜ 0.001). PAC-1 expression and TNF- level were higher in TCP group than those in non-TCP group before and after treatment (P = 0.023, P = 0.011). The sCD40L concentration and platelet TLR4 expression were significantly higher in treated TCP groups than in non-TCP group (P = 0.047, P = 0.001). Compared with non-TCP,the rate of bleeding was higher (P = 0.024) and the length of ICU stay was longer (P = 0.013).The APACHE Ⅱ score and the 28-day mortality were higher in TCP group (P ＜ 0.01, P = 0.048). Conclusions The elevation of platelet TLR4 expression in sepsis along with platelet activation is closely related to the incidence of thrombocytopenia. The occurrence of TCP is a poor prognosis sign of sepsis.

The effect of TLR4 expression in platelets and activation of platelets on the pathogenesis of thrombocytopenia induced by lipopolysaccharide in mice / 中华急诊医学杂志

Objective To determine the role of the platelet activation and the expression of platelet Toll-like receptor 4 (TLR4) in thrombocytopenia induced by lipopolysaccharide (LPS) in mice.Methods ICR mice were randomly (random number) divided into control group,model 3,6,12,24,48,72h groups and neutrocytopenia syndrome (NEP) group.The blood samples of mice in model groups were detected 3,6,12,24,48,and 72 hours after intravenous injection of LPS respectively.Anti- neutrophil monoclonal antibody was administered in the mice of NEP group 24 h before injection of LPS,and blood samples were collected 24 h after injection of LPS.The determination of platelet count (PC),mean platelet volume (MPV) and platelet distribution width (PDW) was carried out with full automatic hemocyte analyzer.The plasma tumor necrosis factor- α (TNF- α),macrophage colony stimulating factor (M-CSF) and soluble CD40 ligand (sCD40L) levels were measured by using ELISA.The rate of platelet TLR4 expression was detected by flow cytometry.Comparison between groups was carried out by using ANOVA statistical methods.Results PC was reduced by 30％ 3 h after intravenous injection of LPS,and reached the lowest level within 24 h (P ＜0.01 ).MPV and PDW were increased compared with healthy controls (P ＜0.01 ).Plasma TNF - α,M - CSF and sCD40L were significantly increased after LPS stimulation (P ＜0.01 ),and reached the peak during 6 ～ 24 h after LPS administration.PC had correlation with plasma levels of M - CSF ( r =- 0.746) and sCD40L ( r =- 0.573 ).The platelet TLR4 expression was significantly increased 6 h after LPS stimulation.The platelet TLR4 expression in NEP group was significantly lower than that in 24 h model group ( P ＜ 0.01 ).Conclusions The excessive activation platelet represented by increase in sCD40L,MPV,PDW and high levels of M-CSF in macrophages along with platelet TLR4 expression participate in the pathogenesis of thrombocytopenia.The up - regulation of the platelet TLR4 expression is dependent on neutrophils in case of thrombocytopenia induced by LPS.

Platelet Toll-like receptor expression modulates lipopolysaccharide-induced cytokines production / 中华微生物学和免疫学杂志

Objective To affirm the expression of Toll like receptor 4 (TLR4) on the surface membrane of platelet and to explore the immunomodulatory factors[(interlukine-8(IL-8),β-thromboglobulin(β-TG), soluble CD40 ligand(sCD40L)] released by platelets after platelets stimulated by TLR4 ligand.Methods TLR4 expressed on the platelet was detected by flow cytometry. Monoclonal anti-human FcγRⅡantibody(Ⅳ.3)-treated human platelets were cultured with LPS in the presence or absence of blocking monoclonal antibody to human TLR4. The release of IL-8, β-TG, sCD40L were measured by specific enzymelinked immunosorbent assay. Results Human platelets could express functional TLR4. The detection rate of TLR4 on platelets were decreased after LPS involvement(P<0.01). It was noted that sCD40L and β-TG were present in large concentration in the release of platelets stimulated by TLR4 ligand but the release of IL-8 was independent of platelet activation after TLR4 engagement. The concentration of sCD40L and β-TG had no statistical difference between 1-5 μg/ml LPS. The effects of LPS on the modulation of secretory factors were attenuated by preincubation of platelets with an anti-TLR4 monoclonal antibody. Conclusion The TLR4 on platelet could recognize and link LPS, induce the release of sCD40L, β-TG by platelet, but could not influence IL-8.

The changes of plasma soluble CD40 and soluble CD40L in patients with chronic renal failure and their clinical significance / 中华急诊医学杂志

Objective To investigate the changes of plasma soluble CD40 (sCD40) and soluble CD40L (sCD40L) in patients with chronic renal failure( CRF) and their potiential mechanisms in renal injury and immunodeficiency. Method From September to December 2006, 30 CRF patients without hemodialysis (CRF group) in department of Nephrology and 30 uremic patients receiving maintenance hemodialysis for more than 3 months ( HD group) in dialysis center in Beijing TongRen Hospital of Capital Medical University, were enrolled in this study. The normal control group consisted of 20 healthy volunteers who matched with study subjects for age and gender. The levels of plasma sCD40 and sCD40L were measured by the method of enzyme linked immunosorbent assay (ELISA). The relationship between sCD40, sCD40L and related factors were analyzed, and the influence of hemodialysis on sCD40 and sCD40L were observed. ANOVA and Pearson correlation analysis were used in statistical analysis. Results (1) The sCD40 levels in CRF group and HD group were significantly higher than those in control group(P ＜ 0.01). The sCD40 levels in HD group were also higher than those in CRF group(P ＜ 0.01). (2) The sCD40L levels in CRF group and HD group were significantly higher than those in control group (P ＜ 0.01). The sCD40L levels in HD group were slightly higher than those in CRF group, but without significant difference (P ＞ 0.05). (3) In CRF group, the sCD40 levels correlated positively with serum creatinine (Scr) and C-reactive protein(CRP) (r = 0.637,P ＜ 0.01,r = 0.551,P ＜ 0.05). The correlations between sCD40L and Scr and CRT were also seen (r = 0.553, P ＜ 0.05, r = 0.686,P ＜ 0.01), whereas the correlation with blood pressure,hemoglobin (Hb), platelet(PLT), white blood cell(WBC), serum albumin(Alb), glucose (Glu),blood urea nitrogen(Bun)and serum lipid was no seen (P ＞ 0.05). In HI) group, there were no correlations between sCD40,sCD40L and above parameters (P ＞ 0.05), there were also no correlations between sCD40, sCD40L and duration of the treatment by dialysis and dialysis adequacy(Kt/V) (P ＞ 0.05). (4)After one HD session, the post-HD levels of sCD40 were slightly higher than pre-HD levels, but without statistical difference ( P ＞ 0.05). The post-HD levels of sCD40L were obviously lower than pre-HD levels, with significant difference (P ＜ 0.01). Conclusions The levels of sCD40 and sCLMOL in CRF patients,particularly in HD patients, were significantly higher than those of controls, which may participate in pathogenesis of renal injury and immunodeficiency.

The clinical significance of CD40L level in the diagnosis of ACS / 中国实用内科杂志

Objective To observe the difference of sCD40L level in different subtypes of coronary heart disease,and to explore the clinical value of CD40 ligand in identification for the acute coronary syndrome(ACS).Methods The patients with coronary heart disease(CHD)and the heathy controls in the First Affiliated Hospital of Harbin Medical University from Jan,2006 to June,2006 were enrolled in the study.CHD group included ACS and stable angina patients.Enzyme-linked immunosorbent assay was used to measure the serum sCD40L level in three groups;t-test and receiver operateing characteristic curve were used to analyze the results.Results sCD40L level was significantly higher in patients with ACS[(2.39?0.37)?g/L]than stable angina patients[(1.89?0.16)?g/L,P0.05.The ROC curve demonstrated that using the concentration of sCD40L 2.01 ?g/L as the boundary to diagnose ACS,sensitivity of this marker was 0.91 and specificity was 0.80 respectively,and area under the curve(AUC)was 0.907.Conclusion sCD40L level which is more than 2.01 ?g/L has important significance for the diagnosis of ACS.

Changes of serum inflammatory mediators,lipid profile and left ventricular structure and their correlations in patients with essential hypertension / 医学研究生学报

Objective: Accumulating evidence shows that hypertension is a chronic low-grade inflammatory disease,and inflammatory reaction is involved in the formation and progress of target-organ damage in hypertension.The authors aimed to explore the changes in the serum levels of interleukin-6(IL-6),soluble CD40 ligand(sCD40L),metalloproteinase-9(MMP-9),tissue inhibitor of metalloproteinase-1(TIMP-1),lipid profile and left ventricular structure in patients with essential hypertension.Methods: The serum levels of IL-6,sCD40L,MMP-9 and TIMP-1,along with blood lipids were determined and echocardiography was performed to evaluate the cardiac structure and function of 158 hypertension patients and 22 age-and sex-matched controls.Results: The hypertension patients exhibited higher levels of IL-6(P

Serum Soluble CD40L Level and its Application in Coronary Heart Disease / 昆明医科大学学报

Objective To investigate the serum of soluble CD40 ligand(sCD40L) in coronary heart disease and its relationship with serum lipid levels and the extent of coronary stenosis,whether upregulation of CD40L system is related to stability of atherosclerotic plaque in patients with acute coronary syndrome.Methods Enzyme-linked immunosorbent assay(ELISA) was used to measure the level of sCD40L in 64 patients with coronary heart disease(18 with acute myocardial infarction,19 with unstable angina pectoris and the other 27 with stable angina pectoris) and 20 matched healthy controls.Coronary stenosis of 29 patients were assessed by angiographic coronary stenosis morphology.Results sCD40L level was significantly higher in patients with acute coronary syndrome(ACS)((19.8?3.0)、(19.6?4.3)ng/mL in acute myocardial infarction and unstable angina pectoris group,respectively)than that of those with stable coronary heart disease and that of controls((8.3?3.2)ng/mL and(2.6?1.9)ng/mL,respectively P