Aims Abnormal expression of Elabela (ELA) is associated with various diseases, including diabetic nephropathy. However, the roles of ELA on developing diabetic retinopathy (DR) are not known. The aim of this study is to confirm the relationship between serum Elabela (ELA) levels and DR in patients with type 2 diabetes mellitus (T2DM). Methods A total of 90 healthy donors (Control group ) and 270 patients with T2DM were recruited. The were divided into three groups: Normal T2DM without DR, T2DM with nonproliferlative DR and T2DM with proliferative DR, 90 patients including in each group. Basic general clinical characteristics were collected and serum ELA levels were determined using the ELISA kit. Results The results showed that there was no significant difference in serum ELA levels between normal control and T2DM patients, but it significantly decreased in nonproliferlative DR and proliferative DR patients compared with T2DM without DR. Compared with nonproliferlative DR patients, the serum ELA levels further significantly decreased in proliferative DR patients. ELA has a significantly negative correlation with DR, duration of diabetes, age, systolic blood pressure(SBP), Blood urea nitrogen(BUN), serum creatinine(Cre) and urinary albumin/creatinine ratio (ACR), and is positively correlated with body mass index (BMI) and estimated glomerular filtration rate (eGFR). Furthermore, the univariate and multivariate linear regression analysis showed that DR, duration of diabetes and BMI were the risk factors for ELA after adjusting for relevant confounding factors (P < 0.05).According to the ROC curve analysis, ELA could identify subjects with DR with a sensitivity of 54.4% and a specificity of 73.3%. Conclusions With the deterioration of DR, the level of serum ELA decreases gradually. ELA may be involved in the occurrence and development of DR, and ELA may be a potential clinical predictor and therapeutic target of DR.

Introduction and Objective: Diabetic Kidney Disease (DKD) is a leading cause of end-stage renal disease (ESRD). Extensive studies suggest that ferroptosis is a key factor in DKD progression. Our research aims to investigate whether ferroptosis-related factor ZFP36 can alleviate diabetic kidney injury. Methods: We extracted differentially expressed genes from the GEO database and conducted GO enrichment, GSEA, GSVA, plus machine learning techniques like RF, SVM-RFE, and Lasso Cox regression to identify ferroptosis-related genes. Expression differences of ZFP36 and its interacting proteins were validated in HK-2 cells and DKD mouse models. Additionally, ZFP36's interaction with traditional Chinese herbal components was assessed using AutoDock Tools to evaluate their impact on DKD ferroptosis. Results: We identified 9 genes significantly associated with both ferroptosis and DKD. Further machine learning marked ZFP36 as a central gene. In vivo experiments showed that compared to the control group, the expression of ZFP36 is reduced in the DKD model group. In vitro, overexpression of ZFP36 alleviates high-glucose-induced ferroptosis and reduce the formation of extracellular matrix components such as FN1 and α-SMA.ZFP36 interacts with Nrf2, reducing ROS and MDA levels, and increasing GSH levels, indicates that ZFP36 can alleviate oxidative stress. Molecular docking analysis shows that traditional Chinese herbs like Berberine and Jatrorrhizine positively regulating ferroptosis in DKD, exhibit high affinity for ZFP36, suggesting it mediates their renal protective effect. Conclusion: This study illuminates the emerging role of ZFP36 in ferroptosis in DKD, emphasizing its potential as a therapeutic target. This provides new insights for the development of targeted therapies for DKD. A. Li: None. M. Shi: None. W. Gu: None. Y. Chen: None. Y. Liu: None. J. Zhang: None. Y. Yuxuan: None. C. Huimin: None. J. Chen: None. H. Zhang: None. Huai'an Science and Technology Bureau (BE2023745), Jiangsu Provincial Health Commission (H2023137)

Background: Non-alcoholic steatohepatitis is closely associated with the progression of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM). We aimed to investigate whether plasma ELABELA, recently identified as a latent biomarker for DKD, is related to the severity of NAFLD. Methods: A total of 362 patients with T2DM were enrolled in this study. Noninvasive clinical markers of hepatic fibrosis including fibrosis-4 (FIB-4) index, NAFLD fibrosis score (NFS) and aspartate aminotransferase-to-platelet ratio index (APRI) were determined. The levels of plasma ELABELA, UACR, creatinine and glucometabolic parameters were measured. The relationships between plasma ELABELA and the clinical markers were statistically evaluated. Results: Based on the median value of the plasma ELABELA, subjects were divided into low and high ELABELA groups. The low ELABELA group showed a significantly longer duration of diabetes, worsened nephropathic indices, and a more enhanced hepatic fibrosis index. A lower ELABELA was associated with a greater odds ratio for the risk of higher hepatic fibrosis stage (OR, 0.98; 95% CI, 0.966 to 0.994). Multiple regression analysis including confounding factors showed that ELABELA independently contributed to decreases in FIB-4 index (P=0.044), NFS (P=0.012). In addition, logistic regression analysis for the prevalence of advanced hepatic fibrosis defined by the cutoff points of the clinical scores showed that ELABELA was the sole and common negative factor for prevalence of advanced hepatic fibrosis (FIB-4 index: P=0.016, NFS: P=0.005). Conclusion: The decline of plasma ELABELA was independently associated with a higher degree of hepatic fibrosis in patients with T2DM. Considering the common metabolic milieu of renal and hepatic fibrosis in T2DM, the potential use of plasma ELABELA as an effective biomarker reflecting hepatic fibrosis in T2DM needs to be validated in the future. Disclosure M. Shi: None. H. Cao: None. Y. Liu: None. W. Gu: None. H. Zhang: None. Funding Jiangsu Province Science and Technology Plan Special Funds (BE2023745); Jiangsu Health Commission Medical Scientific Research Project (H2023137)

Background: The growing evidence has been verified that C1q/TNF-related protein 6 (CTRP6) and CTRP9, secreted by adipose tissue, can regulate glucose and lipid metabolism. However, the effect of CTRP6 and CTRP9 in gestational diabetes mellitus (GDM) is scarcely known. This study aimed to evaluate the potential clinical value of CTRP6 and CTRP9 in GDM. Methods: A total of 35 GDM subjects and 37 healthy controls, between 24 and 28 weeks of gestation, were included in the study. Diagnosis of GDM was made according to American Diabetes Association criteria. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of CTRP6 and CTRP9. Fasting insulin (FINS), IL-6, and TNF-α were detected by Luminex-xMAP technology. The main clinical characteristics, such as Anthropological data and metabolic parameters, were also obtained. Results: Circulating CTRP6, CTRP9, IL-6 and TNF-α were significantly elevated in GDM subjects compared with controls. Pearson correlation analysis showed that CTRP6 and CTRP9 were positively correlated with FPG (r = 0.280, P = 0.017 and r = 0.559, P < 0.001, respectively) and HOMA-IR (r = 0.250, P = 0.035 and r = 0.382, P = 0.001, respectively). Moreover, CTRP9 was also positively correlated with FINS (r = 0.253, P = 0.032), IL-6 (r = 0.283, P = 0.016) and TNF-α (r = 0.266, P = 0.024). The area under the receiver operating characteristic curve (AUC-ROC) indicated that the combination of CTRP6 and CTRP9 was more effective in predicting GDM than single indicators. Conclusion: Elevated CTRP6 and CTRP9 in GDM patients may be related to insulin resistance. And inflammatory factors may mediate the role of CTRP9 in insulin resistance. In addition, CTRP6 and CTRP9 may serve as candidate predictors in patients with early GDM. Disclosure Y.Liu: None. Y.Chen: None. W.Gu: None. L.Yin: None. H.Cao: None. M.Shi: None. Funding National Natural Science Foundation of China (81700723)

Purpose:To investigate the pathogenesis of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM), we evaluated the effects of short-term glycemic variability (GV) on the profile of T cell subpopulations.Methods:A total of 47 T2DM patients with normoalbuminuria, 47 microalbuminuria, and 49 macroalbuminuria were enrolled. The continuous glucose monitoring (CGM) determined the GV of enrolled patients. Flow cytometry was used to determine the proportion of T cell subpopulations.Results:The frequency of T helper (Th) 17 and Th1 cells significantly increased while regulatory T cells (Tregs) significantly decreased in the macroalbuminuria group compared to normoalbuminuria and microalbuminuria groups (P < 0.01). The suppressive function of Tregs was significantly lower in the macroalbuminuria group than the normoalbuminuria group (P < 0.05). Compared with the normoalbuminuria group, the mean amplitude of glucose excursions (MAGE) of the macroalbuminuria group was significantly higher (P<0.05). Furthermore, there were negative associations between the proportion of Tregs and MAGE.Conclusions:Increased GV could decrease the proportion of Tregs and may impair their function. This may lead to increases in Th1 and Th17 cells, and some inflammatory cytokines, which might contribute to the development and progression of DKD in T2DM.

ELABELA (ELA), an endogenous ligand of the apelin receptor (also known as apelin peptide jejunum [APJ]), has been shown to decrease in the plasma of patients with diabetic kidney disease (DKD). In the current study, we explored the potential function as well as the underlying mechanisms of ELA in DKD. We first found that the ELA levels were decreased in the kidneys of DKD mice. Then, we found that ELA administration mitigated renal damage and downregulated the expression of fibronectin, collagen Ⅳ, and transforming growth factor-β1 in the db/db mice and the high glucose cultured HK-2 cells. Furthermore, the autophagy markers, Beclin-1 and LC3-Ⅱ/LC3-Ⅰ ratio, were significantly impaired in DKD, but the ELA treatment reversed these alterations. Mechanistically, the inhibitory effects of ELA on the secretion of fibrosis-associated proteins in high glucose conditions were blocked by pretreatment with 3-methyladenine (an autophagy inhibitor). In summary, these in vivo and in vitro results demonstrate that ELA effectively protects against DKD by activating high glucose-inhibited renal tubular autophagy, potentially serving as a novel therapeutic candidate for DKD.

Breakdown of tolerance and abnormal activation in B cells is an important mechanism in the pathogenesis of Graves’ disease (GD) and high levels of thyroid hormones (THs) can drive the progression of GD. However, the interactions between THs and abnormal activation of B cells in the context of GD are not well understood. The aim of this study was to investigate B cell-activating factor (BAFF) mediating the cross talk between THs and B cells and the possible underlying mechanisms. A high-level triiodothyronine (T3) mouse model was used to verify T3-mediated induction of overexpression of BAFF and B cell abnormal differentiation. The possible promotion of BAFF overexpression in the mice spleen macrophages during polarization to M1 by T3 was also studied. We showed that high levels of T3 can induce BAFF overexpression and lead to abnormal differentiation of B cells in the mice. While the overexpression of BAFF was observed across many tissue types in the mice, high levels of T3 could induce M1 macrophages polarization by IFN (interferon-gamma)-γ in the spleen of the mice, which in turn generated BAFF overexpression. Our findings provide a novel insight into the interactions between the endocrine and immune systems, as well as provide insight into the role of TH in the pathogenesis of GD.

Objective: Breakdown of tolerance and abnormal activation of B cells is an important mechanism in the pathogenesis of Graves' disease (GD). High levels of thyroid hormones (THs) play important roles in GD progression. However, the interactions between THs and abnormal activation of B cells remain elusive. This study aimed to explore the effect of high levels of THs on TLR4 expression and abnormal B cell differentiation.Materials and Methods: Blood samples were collected from patients with GD and healthy controls (HCs) to evaluate the frequency of B cells, their subsets, and TLR4 expression in B cells. A high-level T3 mouse model was used to study the interaction between THs and the TLR4 signalling pathway.Results: We found that the frequencies of CD19(+), CD19(+) TLR4(+), CD19(+) CD86(+), and CD19(+) CD138(+) B cells were significantly higher, as were the expression levels of MRP8/MRP14 and MRP6 and MRP8, MRP14, and MRP6 messenger RNA (mRNA) in peripheral blood mononuclear cells in patients with GD. In high-level T3 mice models, the serum MRP8/MRP14 and MRP6 levels and the TLR4 mRNA expression in PBMCs were significantly higher. TLR4 mRNA, protein expression, and cytokines downstream of TLR4, such as myeloid differentiation factor 88 (MyD88) and nuclear transcription factor-kappa B, were also increased in mouse spleen mononuclear cells.Conclusion: The present study indicated that high levels of T3 can induce abnormal differentiation and activation of B cells by promoting TLR4 overexpression and provide novel insights into the roles of THs in the pathogenesis of GD.

Breakdown of tolerance and abnormal activation in B cells is an important mechanism in Graves’ disease (GD) pathogenesis. However, the mechanism by which B cells are abnormal differentiated and activated in GD remains elusive. Here, we show that elevated BAFF expression is positively correlated with serum thyroid hormone (TH) levels in GD patients and high TH levels can induce BAFF overexpression and lead to the abnormal differentiation of B cells in mice. This BAFF overexpression can be seen in many tissues. In the spleens of mice, high TH levels induce M1 macrophages polarization, which generates BAFF overexpression. Our findings open a new perspective on the interactions between endocrine and immune system and provide insight into the involvement of thyroid hormones in the development and progression of GD.

Objective: Damage to Schwann cells play a crucial role in diabetic peripheral neuropathy (DPN) . To observe whether HMGB1 inhibitor (Glycyrrhizic acid, GA) can prevent diabetic Schwann cells damage and its potential mechanisms. Methods: RSC96 cells were divided into 5 groups: NG group (5.6 mmol/L) and HG group (25.0 mmol/L) , HG+GA (1μM) group, HG+GA (10μM) , HG+GA (100μM) . Small interfering RNA was used to knock out HMGB1. CCK8 assay was used to detect the proliferation of RSC96 cells. The levels of inflammatory factors were determined by ELISA. The mRNA expression of NGF and neuritin-1 was detected by qRT-PCR. The expression levels of NSE, cleaved-caspase-3, RAGE, p38MAPK, ERK, JNK and NF-κBp65 in cells were measured by western blot. Results: GA at the concentration of μM for 24h had significant inhibitory effect on HMGB1 synthesis and secretion (P<0.05) . Schwann cell viability in high glucose was restored due to GA and siHMGB1 (P<0.05) . GA intervention and siHMGB1 potently prevented inflammatory substance generation (TNF-α, IL-1β, IL-6, MCP-1 and ICAM-1) , alleviated the neurotrophic factor reduction (NGF and neuritin-1) , and suppressed cellular apoptosis related protein activation (cleaved caspase-3) in Schwann cells exposed to high glucose ambience (P<0.05) . Moreover, we found that RAGE expression, p38MAPK phosphorylation and nuclear NF-κBp65 expression in high glucose-stimulated Schwann cells was reversed by GA or siRNA interference with HMGB1 (P<0.05) . Conclusions: GA and siHMGB1 can not only inhibit HMGB1 expression in Schwann cells exposed to high glucose, but also enhance cell viability. GA and siHMGB1 restored neurotrophic factors level and reduce cleaved caspase-3 expression in Schwann cell due to its anti-inflammatory ability, which may be related to the inhibition of RAGE/p38MAPK/nuclear NF-κBp65 pathway. HMGB1 may implicate in Schwann cells lesion in high glucose milieu and HMGB1 inhibition protects Schwann cells from high glucose induced cytotoxicity. Funding National Natural Science Foundation of China Grant Award (81700723)

Aim: To analyze the relationship between serum Elabela (ELA) levels and type 2 diabetic retinopathy (DR) . Methods: A total of 81 patients with type 2 diabetes were collected. According to the stages of diabetic retinopathy, the patients were divided into three groups: group 1: no diabetic retinopathy stage, group 2: non-proliferative diabetic retinopathy (NPDR) and group 3: proliferative diabetic retinopathy (PDR) , with 27 patients in each group. Serum ELA levels were detected by ELISA. Relevant clinical datas were recorded and analyzed. Results: There were no statistical significance in age, BMI, FPG, HbA1c, t-chol, TG, LDL-C, HDL-C among 3 groups (all P> 0.05) . The duration of diabetes in group 1 was significantly shorter than that in groups 2 and 3 (all P<0.05) , and there were significant differences in SBP, DBP, eGFR and Cre in groups 3 compared with those in groups 1 and 2 (P<0.05) . From group 1 to group 3, the levels of ELA decreased gradually, with statistical significance among the three groups (P<0.05) . Correlation analysis showed that serum ELA levels were negatively correlated with the course of diabetes, DR, SBP, Cre (P<0.05) , and positively correlated with eGFR (P<0.05) . Stepwise multiple linear regression analysis showed that the most relevant variables for ELA were age, BMI and DR (P=0.005; P = 0.000; P = 0.001) . According to ROC curve analysis, the sensitivity and specificity of ELA in the diagnosis of diabetic retinopathy were 59.3%, 83.3%, and the area under the curve was 0.753 (95%CI: 0.638, 0.869, P=0.000) . Conclusions: With the progressive of diabetic retinopathy, the level of serum ELA decreases gradually. ELA may be a potential clinical predictor and therapeutic target of diabetic retinopathy. Disclosure W.Gu: None. M.Shi: None. Y.Chen: None. Y.Liu: None. J.Song: None. H.Zhang: None. Funding National Natural Science Foundation of China Grant Award (81200595/81400807/81700723) , Six High-peak Talents Project of Jiangsu Province (WSN-101) , Research Project of Jiangsu 333 engineering (BRA2016232) and Research Project of Jiangsu Provincial Commission of Health and Family Planning (F201549/H201667) , and International Science and Technology Cooperation Project of Huaian (HAC201707) .

Objective: Damage to Schwann cells play a crucial role in diabetic peripheral neuropathy (DPN) . To observe whether HMGB1 inhibitor (Glycyrrhizic acid, GA) can prevent diabetic Schwann cells damage and its potential mechanisms. Methods: RSC96 cells were divided into 5 groups: NG group (5.6 mmol/L) and HG group (25.0 mmol/L) , HG+GA (1μM) group, HG+GA (10μM) , HG+GA (100μM) . Small interfering RNA was used to knock out HMGB1. CCK8 assay was used to detect the proliferation of RSC96 cells. The levels of inflammatory factors were determined by ELISA. The mRNA expression of NGF and neuritin-1 was detected by qRT-PCR. The expression levels of NSE, cleaved-caspase-3, RAGE, p38MAPK, ERK, JNK and NF-κBp65 in cells were measured by western blot. Results: GA at the concentration of μM for 24h had significant inhibitory effect on HMGB1 synthesis and secretion (P&lt;0.05) . Schwann cell viability in high glucose was restored due to GA and siHMGB1 (P&lt;0.05) . GA intervention and siHMGB1 potently prevented inflammatory substance generation (TNF-α, IL-1β, IL-6, MCP-1 and ICAM-1) , alleviated the neurotrophic factor reduction (NGF and neuritin-1) , and suppressed cellular apoptosis related protein activation (cleaved caspase-3) in Schwann cells exposed to high glucose ambience (P&lt;0.05) . Moreover, we found that RAGE expression, p38MAPK phosphorylation and nuclear NF-κBp65 expression in high glucose-stimulated Schwann cells was reversed by GA or siRNA interference with HMGB1 (P&lt;0.05) . Conclusions: GA and siHMGB1 can not only inhibit HMGB1 expression in Schwann cells exposed to high glucose, but also enhance cell viability. GA and siHMGB1 restored neurotrophic factors level and reduce cleaved caspase-3 expression in Schwann cell due to its anti-inflammatory ability, which may be related to the inhibition of RAGE/p38MAPK/nuclear NF-κBp65 pathway. HMGB1 may implicate in Schwann cells lesion in high glucose milieu and HMGB1 inhibition protects Schwann cells from high glucose induced cytotoxicity. Funding National Natural Science Foundation of China Grant Award (81700723)

Background: GLP-1R agonists can exhibit a direct renoprotective effect in patients with diabetic nephropathy (DN) beyond the hypoglycemic effect, but the underlying mechanisms remain unknown. Recent studies have suggested that high mobility group box 1 (HMGB1) contributes to the development and progression of DN. In this study, we assessed whether GLP-1R agonists acts through HMGB1 and explored its downstream signaling pathways in DN. Methods: Rat glomerular mesangial cells (GMCs) were divided into four groups: normal control (NG), normal control with 10 nmol/L exendin-4 treatment (GLP-1 analog) (NGE), high glucose (HG), and high glucose with 10 nmol/L exendin-4 treatment (HGE) groups. GMCs were transfected with GLP-1R-siRNA using Lipofectamine TM2000 and divided as HG, HGE, HGE + GLP-1R-siRNA, or HGE + scrambled siRNA. FN and type IV collagen (COL-IV) were evaluated by enzyme-linked immunosorbent assay (ELISA). GLP-1R, HMGB1, TGF-β1, phosphorylated and total extracellular signal-regulated kinases (ERK), c-Jun NH2-terminal kinases (JNK), p38 mitogen-activated protein kinases (p38MAPK), and NF-κB p65 were measured by western blot analysis. Results: FN and COL-IV were higher in the HG group than NG group (P<0.05). Compared with NG group, the level of GLP-1R was decreased, HMGB1 and TGF-β1 were increased in the HG group (P<0.05). Additionally, NF-κB p65, the phosphorylation levels of ERK, JNK, and p38MAPK were all significantly elevated in the HG group (P<0.05). However, all these effects were reversed by Exendin-4 treatment (P<0.05), except phosphorylated p38MAPK (P>0.05). Moreover, the protective effects of Exendin-4 were abolished by GLP-1R knockdown (P<0.05). Conclusion: These results suggest that GLP-1 receptor agonists attenuates the ECM secretion of GMCs induced by high glucose. The potential mechanism involves it binding to and activating GLP-1R, which prevents ECM production by inhibiting HMGB1 and its signaling pathways. Disclosure W. Gu: None. M. Shi: None. H. Zhang: None. Funding National Natural Science Foundation of China (81200595, 81400807, 81700723)

目的 探讨T2DM患者血清Elabela(ELA)水平与DKD的关系.方法 选取2014年1月至2016年12月于我院内分泌科住院治疗的80例T2DM患者.ELISA法检测血清ELA水平,根据血清ELA水平分为高ELA组和低ELA组,检测两组患者HbA1c、TC、Scr、UACR等指标.结果 血清ELA总体水平为(7.18±3.17)ng/ml.与高ELA组比较,低ELA组UACR、Scr水平升高,eGFR降低(P<0.05);低ELA组DKD及DR患病率高于高ELA组(P<0.05).Pearson相关分析显示,血清ELA水平与eGFR、Ccr呈正相关(r=0.319、0.236,P<0.05),与UACR、Scr、SBP、DBP呈负相关(r=-0.561、-0.270、-0.249、-0.261,P<0.05).Logistic回归分析显示,UACR、BUN和LDL-C是血清ELA的影响因素.受试者工作特征曲线分析显示,ELA诊断DKD的敏感度为76.7％,特异度为80.0％,曲线下面积为0.803(95％CI 0.702～0.904,P=0.000).结论 T2DM合并白蛋白尿患者血清ELA较低,ELA可能是DKD潜在临床预测指标或治疗药物.

Objective:To investigate the protective effects of Elabela(ELA) on the renal injury of db/db mice and its possible mechanism.Methods:Sixteen eight-week-old male db/db mice were intraperitoneally injected with ELA(5 mg·kg -1·day -1) or equivalent normal saline( n=8) for 8 weeks. Eight age-matched male db/m mice received equivalent normal saline injection as normal control. At the end of the experiment, blood and urine samples were obtained for HbA 1C and urinary albumin/creatinine(ACR) measurements. Immunohistochemistry was used to observe the expression of ELA. Histopathological changes in kidney tissue were observed by HE staining and Masson staining. The levels of collagen type Ⅳ(Col-Ⅳ) and transforming growth factor-β1(TGF-β1) as well as Yes-associated protein(YAP) phosphorylation in kidney tissue were examined by western blot. Results:Immunohistochemistry results showed that ELA expression was decreased in the renal tissue of db/db mice as compared with that of db/m mice( P<0.05). After ELA treatment, ACR and blood pressure were markedly decreased in db/db mice( P<0.05), but without significant changes in the body weight and HbA 1C. Renal tubular epithelial cells edema, basement membrane thickening, and increased collagen fiber in db/db were improved by ELA administration. Compared with db/m mice, the levels of TGF-β1 and Col-Ⅳ expression, as well as YAP phosphorylation were significantly increased in renal tissue of db/db mice(0.98±0.08 vs 0.68±0.10, 1.10±0.14 vs 0.51±0.08, 3.38±0.72 vs 0.81±0.13, all P<0.05), which were down-regulated after ELA administration(0.80±0.06, 0.51±0.05, 2.21±0.22, all P<0.05). Conclusion:ELA may improve the renal injury of db/db mice by regulating the signaling pathway of YAP, thereby delaying the development of diabetic nephropathy.

BACKGROUNDMyeloid-related protein 8/14 (MRP8/14) is secreted by macrophages and formed by MRP8 and MRP14, which is closely related to vascular inflammation. Chronic vascular inflammation plays a significant role in the development and progression of diabetic kidney disease (DKD). This study aims to investigate the relationship between MRP8/14 and DKD.METHODSA total of 80 individuals with type 2 diabetes were divided into four groups, according to the baseline urinary albumin/creatinine ratio (ACR) levels Serum concentrations of MRP8/14 were measured by ELISA. The clinical variables were obtained through physical examination, illness history, or laboratory evidence.RESULTSAs DKD worsened, the level of serum MRP8/14 increased gradually, and MRP8/14 has a significantly positive correlation with ACR (r = 0.349, P = 0.002), body mass index (BMI) (r = 0.288, P = 0.009), serum creatinine (Cre) (r = 0.392, P < 0.001), blood urine nitrogen (BUN) (r = 0.333, P = 0.003), systolic blood pressure (SBP) (r = 0.301, P = 0.007), and a negative correlation with the estimated glomerular filtration rate (eGFR) (r = -0.478, P < 0.001). Logistic regression analysis showed that age, Cre, eGFR, ACR, and MRP8/14 were associated with the progression of DKD (P < 0.05).CONCLUSIONSThe serum MRP8/14 is correlated significantly with the progression of DKD, suggesting that MRP8/14 may be an independent predictor of the progression of DKD.

目的 分析髓系相关蛋白8/14复合物(MRP 8/14)与2型糖尿病患者甲状腺功能的相关性.方法 搜集2014年12月～2016年9月在南京医科大学附属淮安第一医院内分泌代谢科住院的2型糖尿病患者80例,根据MRP 8/14的中位数分为A组(MRP 8/14≤5.41 μg/mL)和B组(MRP 8/14＞5.41 μg/mL),每组各40例.记录所有被纳入者的性别、年龄、体重指数(BMI)、糖尿病病史、收缩压、舒张压、空腹血糖、糖化血红蛋白(HbA1c)、总胆固醇、三酰甘油、低密度脂蛋白胆固醇,高密度脂蛋白胆固醇、血清肌酐、尿白蛋白/肌酐比值(ACR)、促甲状腺激素(TSH)、甲状腺激素[血清游离三碘甲腺原氨酸(FT3)、血清游离甲状腺素(FT4)]和MRP 8/14等临床资料并对其进行分析.结果 A、B两组患者的性别、年龄、BMI、糖尿病病史、收缩压、舒张压、空腹血糖、HbA1c、总胆固醇、三酰甘油、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、FT3、FT4等指标比较,差异均无统计学意义(均P＞ 0.05).A组血清肌酐,ACR和TSH明显低于B组,差异均有统计学意义(均P＜ 0.05).血清MRP 8/14水平与BMI、收缩压、血清肌酐、ACR、TSH呈正相关(P＜0.05).结论 血清MRP 8/14与2型糖尿病患者的TSH水平呈正相关,故MRP 8/14可能参与2型糖尿病患者甲状腺功能的变化.