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Objective To investigate the association between serum alkaline phosphatase (ALP) and type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD). Methods A total of 599 patients with T2DM who were hospitalized in Department of Endocrinology, Affiliated Hospital of Jiangsu University, from July 2016 to December 2018 were enrolled as subjects. According to the presence or absence of NAFLD, the patients were divided into NAFLD group with 286 patients and non-NAFLD group with 313 patients, and according to the results of abdominal ultrasound, the patients with NAFLD were divided into mild group with 111 patients, moderate group with 105 patients, and severe group with 70 patients. General clinical data were compared between groups. The independent samples t - test was used for comparison of normally distributed continuous data between two groups, and an analysis of variance was used for comparison between three groups; the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between three groups; the chi-square test was used for comparison of categorical data between groups. Pearson correlation analysis and Spearman correlation analysis were used to investigate the correlation between ALP and clinical indices, and a logistic regression analysis was used to investigate the influencing factors for NAFLD. Results Compared with the non-NAFLD group, the NAFLD group had significantly higher proportion of patients with history of hypertension ( χ 2 =7.864, P < 0.05), systolic blood pressure ( t =-2.226, P < 0.05), diastolic blood pressure ( t =-3.800, P < 0.05), body mass index (BMI) ( t =-11.842, P < 0.05), waist circumference (WC) ( t =-9.150, P < 0.05), fasting insulin (FINS) ( Z =-6.173, P < 0.05), fasting C-peptide ( t =-5.419, P < 0.05), serum uric acid ( t =-4.957, P < 0.05), low-density lipoprotein cholesterol ( t =-2.702, P < 0.05), triglyceride ( Z =-9.376, P < 0.05), total cholesterol (TC) ( t =-3.016, P < 0.05), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) ( Z =-5.794, P < 0.05), alanine aminotransferase (ALT) ( Z =-6.737, P < 0.05), aspartate aminotransferase (AST) ( Z =-4.389, P < 0.05), gamma-glutamyl transpeptidase (GGT) ( Z =-7.764, P < 0.05), and ALP ( t =-2.833, P < 0.05), as well as significantly lower age ( t =2.184, P < 0.05) and high-density lipoprotein cholesterol ( Z =-5.273, P < 0.05). The severity of NAFLD (mild, moderate or severe) was positively correlated with age ( r s =0.140, P < 0.05), BMI ( r s =0.239, P < 0.05), WC ( r s =0.222, P < 0.05), FINS ( r s =0.191, P < 0.05), HOMA-IR ( r s =0.218, P < 0.05), ALT ( r s =0.188, P < 0.05), AST ( r s =0.279, P < 0.05), GGT ( r s =0.202, P < 0.05), and ALP ( r s =0.361, P < 0.05). In the patients with T2DM and NAFLD, ALP was positively correlated with HbAlc ( r =0.149, P < 0.05), fasting plasma glucose ( r =0.146, P < 0.05), HOMA-IR ( r s =0.132, P < 0.05), TC ( r =0.151, P < 0.05), ALT ( r s =0.210, P < 0.05), AST ( r s =0.192, P < 0.05), and GGT ( r s =0.297, P < 0.05). The logistic regression analysis showed that ALP was an influencing factor for NAFLD in patients with T2DM (odds ratio=1.013, 95% confidence interval: 1.004-1.023, P < 0.05). Conclusion Elevated serum ALP is a risk factor for T2DM with NAFLD and is closely associated with hyperglycemia, insulin resistance, and hyperlipemia, and ALP may play a role in the development and progression of T2DM and NAFLD.
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Objective:To identify key genes and their potential biological mechanisms in the progression of non-alcoholic fatty liver disease (NAFLD) using bioinformatics technology.Methods:Genes differentially expressed in simple non-alcoholic fatty liver disease (NAFL) and non-alcoholic steatohepatitis (NASH) were analyzed by integrating NAFLD-related sequencing datasets GSE135251 and GSE167523 from the Gene Expression Omnibus (GEO) datebase. Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome signaling pathway analysis were performed. Key genes were identified by STRING database and Cytoscape3.7.2 software, and the expression of key genes under different fibrosis grades and activity scores was observed. In addition, the expression of key genes in different cell clusters was observed based on the single-cell RNA-seq dataset of NAFLD mice.Results:Bioinformatics methods were used to obtain 97 common differential genes in NAFLD from two datasets. GO functional enrichment analysis was mainly performed in Extracellular Matrix (ECM) tissues. The main signaling pathway is ECM-receptor interaction. Five key genes were identified based on PPI network and Cytoscape software: COL1A1, THBS2, CXCL8, THY1 and LOXL1. The expression of key genes was significantly positively correlated with fibrosis grade and activity score, indicating that they were closely related to the progression of NAFLD. These key genes are highly expressed in hepatic stellate cells (HSCs) and natural killer/T cells (NK/T cells).Conclusion:In this study, bioinformatics technology was used to identify five key genes that may be involved in the NAFL-NASH transformation, suggesting that the ECM-receptor interaction signaling pathway may be a key molecular mechanism of NAFLD disease progression.
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Oxytocin is a classic neuropeptide hormone. In recent years, basic and clinical researches have shown that oxytocin is involved in the regulation of blood glucose homeostasis by protecting islet β cells, promoting insulin secretion and peripheral tissue glucose uptake. This article reviews the recent evidence of the linkage between oxytocin and diabetes mellitus.
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Oxytocin is a classic neuropeptide hormone. In recent years, basic and clinical researches have shown that oxytocin is involved in the regulation of blood glucose homeostasis by protecting islet β cells, promoting insulin secretion and peripheral tissue glucose uptake. This article reviews the recent evidence of the linkage between oxytocin and diabetes mellitus.
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Objective To explore the effect of the position of the biliary stents on the short?term and long?term effects of the patients with low malignant obstructive jaundice after treatment.Methods Seventy?eight patients with low?grade malignant obstructive jaundice diagnosed in Jiangyin Hospital Affiliated to Medical College of Southeast University who underwent biliary stenting were enrolled as the study object.According to the placement of the biliary stents,the stents were divided into the spanning group and the non?crossing group.The baseline data and related serological indexes were recorded,and the changes of jaundice between the two groups were compared by repeated measurements.All patients were followed up for 48 weeks.Multivariate Cox regression analysis was applied on the risk factors that might affect the prognosis of patients, and the degree of influence of various factors on the prognosis of patients was further evaluated.Results Repeated measures analysis showed that the biochemical indicators of the spanning group and the non?crossing group showed a significant downward trend and the difference was statistically significant (TBil: Fintra?group＝9.392,Pintra?group＝0.000; DBil: Fintra?group＝7.581,Pintra?group＝0.001).Among them,the total bilirubin (TBil) (Preoperative: (318.69±101.13) μmol／L,1 week after surgery: (135.98 ±63.61) μmol／L,2 weeks after surgery: (60.21±24.81) μmol／L) was lower than the non?crossing group preoperative: (309.07±109.97) μmol／L,1 week after surgery: (158.87±66.92) μmol／L,2 weeks after surgery: (75.91 ± 20.46) μmol／L), and the difference was statistically significant ( Finter?group ＝3.362, Pinter?group＝0.041).The direct bilirubin ( DBil) ( Preoperative: (171.93 ± 73.01) μmol／L,1 week after surgery: (90.38± 57.33) μmol／L,2 weeks after surgery:(36.64± 18.95) μmol／L) was lower than the non?crossing group ( Preoperative: ( 174.53 ± 82.74) μmol／L,1 week after surgery: ( 107.85 ± 49.07) μmol／L,2 weeks after surgery: ( 37.87 ± 14.55 ) μmol／L.The difference was statistically significant (Finter?group＝6.284,Pinter?group＝0.003).There was an interaction between the treatment regimen and treatment time (1 week after surgery and 2 weeks after surgery) (TBil: Finteraction＝12.262,Pinteraction＝0.000; DBil:Finteraction＝10.254,Pinteraction＝0.000).The results of the multi factor Cox proportional hazard model of the spanning group and the non?crossing group showed that the ALP, DBil, TBil and lymphatic metastasis of malignant tumor were the two independent risk factors that affect the prognosis.However, the pancreatic cancer,ALT and age in the spanning group across the ampulla also have a certain effect on the prognosis of the patients.Conclusion The effect of the placement of biliary stents across the Vater ampullary was more obvious in the short term on the decline of bilirubin.But in the long term,there was no significant difference in the prognosis of patients with biliary stenting position.ALP,TBil,DBil,and disease classification were all important risk factors affecting the prognosis of two groups of patients
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Objective To compare the safety and efficacy of insulin degludec (IDeg) with those of insulin glargine (IGlar) in insulin-naive subjects with type 2 diabetes (T2DM).Methods This was a 26-week,randomized,open-label,parallel-group,treat-to-target trial in 560 Chinese subjects with T2DM (men/women:274/263,mean age 56 years,mean diabetes duration 7 years) inadequately controlled on oral antidiabetic drugs (OADs).Subjects were randomized 2:1 to once-daily IDeg (373 subjects) or IGlar(187 subjects),both in combination with metformin.The primary endpoint was changes from baseline in glycosylated hemoglobin(HbA1c) after 26 weeks.Results Mean HbA1c decreased from 8.2％ in both groups to 6.9％ in IDeg and 7.0％ in IGlar,respectively.Estimated treatment difference (ETD) of IDegIGlar in change from baseline was-0.10％ points (95％ CI-0.25-0.05).The proportion of subjects achieving HbA1c ＜ 7.0％ was 56.3％ and 49.7％ with IDeg and IGlar,respectively [estimated odds ratio of IDeg/IGlar:1.26 (95 ％ CI 0.88-1.82)].Numerically lower rateof overall confirmed hypoglycaemia and statistically significantly lower nocturnal confirmed hypoglycemia were associated with IDeg compared with IGlar,respectively [estimated rateratio of IDeg/IGlar 0.69 (95％ CI 0.46-1.03),and 0.43 (95％ CI 0.19-0.97)].No differences in other safety parameters were found between the two groups.Conclusions IDeg was non-inferior to IGlar in terms of glycaemic control,and was associated with a statistically significantly lower rate of nocturnal confirmed hypoglycaemia.IDeg is considered to be suitable for initiating insulin therapy in Chinese T2DM patients on OADs requiring intensified treatment.Clinical trail registration Clinicaltrials.gov,NCT01849289.
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Objective There are few researches for the serum betatrophin level and diabetic nephropathy (DN) recently.The aim of this study was to investigate the change of serum betatrophin level and the correlation of serum betatrophin and urinary albumin-to-creatintine ratio (UACR) in patients with type 2 diabetes mellitus (T2DM).Methods A total of 150 Chinese subjects from Mar 2013 to Jul 2016 were enrolled in the study, including 90 patients with type 2 diabetes and 60 healthy controls.According to the level of UACR, the diabetic patients were divided into two groups:normal UACR group (UACR30 mg/g, n=30).Serum betatrophin was measured by enzyme linked immunosorbent assay (ELISA).UACR was measured by turbidimetric inhibition immune assay.Blood glucose blood lipid were measured simultaneously.Results The serum betatrophin level was significantly higher in abnormal UACR group than that in normal UACR group[677.37±59.02 vs 486.13±41.22 pg/mL, P<0.05];Serum betatrophin level in T2DM patients was positively correlated with age (r=0.246), waist hip ratio (WHR) (r=0.240), fasting blood glucose (FPG) (r=0.234), 2 hour plasma glucose (2hPG) (r=0.363), glycosylated hemoglobin (HbA1c) (r=0.346), fasting insulin (FINS) (r=0.249), insulin resistance index (HOMA-IR) (r=0.309), blood urea nitrogen (BUN) (r=0.223), creatinine (CREA) (r=0.277) and UACR (r=0.244) (P<0.05),and negatively correlated with glomerular filtration rate (GFR) (r=0.308) (P<0.01).Serum betatrophin level in normal UACR group was positively correlated with age, HbA1c and UACR (P<0.05);Serum betatrophin level in abnormal UACR group was positively correlated with WHR (r=0.504), 2hPG (r=0.600), HbA1c (r=0.449), HOMA-IR (r=0.395) (P<0.05).The WHR, HbA1c, HOMA-IR and GFR were the influential factors of the serum betatrophin level.Conclusion The level of serum betatrophin was significantly increased in T2DM patients with albuminuria, which suggests that the betatrophin might play an important role in the pathogenesis of DN.
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[Abstract ] Objective C reactive protein (CRP), an in-flammatory maker, increased significantly among diabetes mellitus and other metabolic diseases.Meanwhile, adiponectin plays a vital role in anti-atherogenic, anti-inflammatory and anti-diabetic poten-tials.Further, it decreased in diabetes mellitus.To investigate the effects of C-reactive protein in the expression of high-molecular-weight adiponectin ( HMWA) and adiponectin multimerization. Methods The fully differentiated 3T3-L1 cells were respectively treated with 50μg/mL CRP for 0 h、6 h、12 h and 24 h , and different doses of CRP with 0μg/mL、5μg/mL、25μg/mL、50μg/mL for 24 h.The expres-sion of HMWA was further detected by Western blot.Additionally, the mRNA expressions of adiponectin assembly related genes ( Ero1-L、DsbA-L、ERp44 ) were detected by Real time PCR after 50μg/mL CRP treatment for 24 h. Results After 24 h treatment, 25μg/mL CRP and 50μg/mL CRP resulted in a substantial reduction ( [70 ±7]%vs [44 ±7]%, P<0.05) while 5μg/mL CRP revealed no change.With the dose of 50μg/mL CRP treated, the ex-pression of HWMA were both inhibited after the 12 h and 24 h CRP treatment ([71 ±6]%vs [48 ±11]%, P<0.05), but for the 6 h CRP treatment group, HWMA remained unchanged.Additionally, CRP inhibited Ero1-L(86 ±10)%and DsbA-L(72 ±6)%gene expression and upregulated the expression of ERp44(141 ±23)%. Conclusion CRP decreases HMWA expression in a dose and time-dependent manner and inhibits the multimerization of adiponectin, thus weaken the benefits of adiponectin in diabetes.
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Objective To detect serum oxytocin and highly sensitive C-reactive protein (hs-CRP) levels in obese and type 2 diabetes mellitus(T2DM) subjects and investigate the relationships between serum oxytocin levels and hs-CRP, glycolipid metabolism, insulin resistance and pancreas β cell function. Methods A total of 176 subjects were enrolled in the study, including 88 patients with newly-diagnosed type 2 diabetes ( T2DM) and 88 subjects with normal glucose tolerance(NGT). NGT and T2DM groups were further divided each into normal weight (NW) and obese(OB) subgroups. Obesity was defined as body mass index(BMI)≥25 kg/ m2 according to the WHO-Western Pacific Region diagnostic criteria (2000). 75g oral glucose tolerance test ( OGTT) was performed in all subjects. Fasting plasma glucose ( FPG), 2 h postprandial plasma glucose (2hPG), fasting insulin ( FINS), 2h postprandial serum insulin(2hINS), HbA1C and lipids were also determined. Insulin resistance and pancreas β-cell function were determined by homeostasis model assessment ( HOMA-IR, HOMA-β). Highly sensitive C-reactive protein(hs-CRP) level was determined by chemiluminescence immunoassay and fasting serum oxytocin level was determined by ELISA. Results Serum oxytocin level was lower in T2DM group than that in NGT group(P<0. 01), while serum hs-CRP level was higher in T2DM group than that in NGT group(P<0. 01). The level of serum oxytocin in subjects with obesity was also lower than that in subjects with NW in both NGT and T2DM groups [7. 16(6. 45-8. 82) vs 7. 98(7. 03-9. 17) ng/ L and 9. 23(8. 16-10. 36) vs 9. 86(8. 77-12. 06) ng/ L, P<0. 05]. The level of serum hs-CRP in subjects with obesity was higher than that in subjects with NW in both NGT and T2DM groups [0. 99(0. 25-1. 97) vs 0. 54(0. 19-0. 91) mg/ L and 3. 47(1. 63-6. 20) vs 1. 65(0. 81-3. 81) mg/ L, P<0. 05]. Serum oxytocin level was negatively correlated with hs-CRP, BMI, WC, WHR, HbA1C , FPG, 2hPG, FINS, 2hINS, total cholesterol, triglycerides, LDL-C and HOMA-IR, while was positively correlated with HOMA-β(P<0. 05). Subjects within the upper serum hs-CRP tertile had lower level of oxytocin when compared to subjects in the middle or lower serum hs-CRP tertiles(P<0. 05 ). Conclusion Serum oxytocin level was decreased in subjects with type 2 diabetes as well as with obesity. Serum oxytocin level was closely correlated with inflammation, glycolipid metabolism, insulin resistance, and pancreas β cell function. It may play an important role in the pathogenesis of obesity and T2DM.
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Replenishing the insulin-producing β cell mass is considered to be a hot topic in the field of diabetes treatment.It has long been known that pancreatic β cells are generated primarily by self-duplication in adults.However,insulin resistance can induce dramatic compensatory β cell mass expansion in the pancreas.Therefore,it is of great value to investigate the etiology and pathogenesis of β cell proliferation under insulin resistance.The recent study has shown that betatrophin,a protein secreted by the liver,modulates β cell growth in response to insulin resistance.We published one article in Diabetes Care titledIncreased circulating levels of betatrophin in newly diagnosed type 2 diabetic patientsto elaborate the relationship between diabetes and betatrophin.
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Objective To investigate the association of single nucleotide polymorphisms (SNPs) in the SCGB3A2(secretoglobin family 3A member 2) gene promoter with susceptibility of Graves' disease.Methods One-hundred and seventy-nine SNPs within a 3.0 Mb region surrounding marker D5s2090 were scanned in a case-control study.The size of the region(s) associated with GD was then narrowed.Results Total 179 SNPs within a 3.0 Mb region surrounding marker D5s2090 were analyzed.The most significant association signal was found at SNP rs1368408 (P =3.69 × 10-5).Subsequent association analysis was then performed and the results suggested that the SNP76 (P =4.11 × 10-8) and SNP75 (P =1.37 × 10-8) in the promoter of SCGB3A2 gene may be the causal variants of GD.Logistic regression analysis suggested these 2 SNPs in this region may contribute to GD susceptibility.Conclusion A significant association seems to exist between GD with the SCGB3A2 gene.
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Objective To detect serum Vaspin level in subjects with normal glucose regulation(NGR)and newly-diagnosed type 2 diabetes mellitus (T2DM) ,and to investigate the association between serum Vaspin and body mass index (BMI), age, gender, glycometabolism and lipemetabolism and insulin sensitivity index. Methods The fasting serum levels of Vaspin were measured in 48 normal controls and 66 T2DM patients using enzyme linked immunosorbent assay ( ELISA ). BMI, waist-hip ratio (WHR) and % body fat were measured,as well as fasting blood glucose (FBG), HBA1C, lipids and insulin levels. Results The fast serum Vaspin concentrations in the obese T2DM patients was ( 1.13 ±0. 25 ) μg/L,which were significantly higher than that in the non-obese T2DM patients (0. 65 ± 0. 13 ) μg/L (P ＜ 0. 01 ). In the NGR group, the fast serum Vaspin concentrations in the obese was (0. 95 ± 0. 11 ) μg/L, which were significantly higher than that in the non-obese (0. 38 ± 0. 18) μg/L( P ＜ 0. 01 ). In the T2DM group, serum Vaspin concentration in females ( [0. 92 ± 0. 35]μg/L) was higher than in males ([0.76 ± 0. 22] μg/L) (P ＜ 0.01 ). In the NGR group, serum Vaspin concentration in females was also higher than that in males ( [1.05 ± 0. 21] μg/L vs [0. 48 ± 0. 14] μg/L) )(P＜0. 01 ). Serum Vaspin level was positively correlated with BMI,WHR,% Body Fat,fasting insulin(FINS)and insulin sensitivity index (ISI) (r = 0. 365,0. 214,0. 238,0. 183 and 0. 147, respectively, Ps ＜ 0. 05 ). The multiple stepwise regression analysis showed that gender( R2 = 0. 161, P ＜ 0. 01 ), ISI ( R2 = 0. 183, P ＜ 0. 01 )and WHR( R2 = 0. 216, P ＜ 0. 01 ) were independent variables associated with Vaspin. Conclusion Serum vaspin level significantly increases in subjects with obesity, and independently associated with gender, ISI,WHR. These findings suggest that serum Vaspin may be involved in the pathophysiology of insulin resistance syndrome.
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Objective To investigate the relationship of carotic intimal-medial thickness (IMT) to high sensitive C-reative protein (hs-CRP) and homocysteine (Hcy) in IGT patients. Methods Seventy patients with IGT were divided into two groups by carotic IMT levels: IMT normal group( IMT≤0.9 mm) and IMT increased group(IMT>0.9 mm). Sixty healthy people were chosen as controls. Blood-lipid, hs-CRP, Hcy, BMI, SBP and DBP were measured in all subjects. Results The Hcy and hs-CRP levels in IGT group were higher than those in controls (P<0.01) ,and also the carotic SBP,DBP,TG and TC levels were higher than those in controls(P<0.05). The Hcy and hs-CRP levels in carotic IMT increased group were higher than those in IMT normal group(P<0.05). The levels of the carotic IMT is positively correlated with hs-CRP(r=0.616, P<0.01), Hcy(r=0.557 ,P<0.01), TC (r=0.351,P<0.05), SBP(r=0.252, P<0.05). Hcy is positively correlated with hs-CRP in IMT increased group (r=0.364, P<0.05). Conclusions Compare with controls, the IMT was higher in IGT patients, and it had the early stage of atherosclerosis (AS). Hcy and hs-CRP levels may predict the early stage of AS in IGT. The high level of Hcy may increase the level of hs-CRP,then lead to the early stage of AS.
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Objective To explore the possible correlation between serum highly sensitive C reactive protein (hs CRP) and blood glucose, insulin, lipids ,insulin sensitivity index (SI),acute insulin response(AIR), and adiponectin in subjects with impaired glucose tolerance (IGT) or newly diagnosed type 2 diabetes mellitus(DM). Methods SI and AIR were assessed by the reduced sample number of Bergman′s minimal model method by intravenous glucose tolerance test in subjects. Meanwhile body mass index (BMI), waist hip ratio (WHR), the serum lipid profile, hs CRP, adiponectin levels were measured. Results Compared with normal control (NC) group[SI(6.6?2.4) 10 -4 (min?mU/L) -1 ,adiponectin7.77(6.35 10.70 mg/L),hs CRP0.40(0.21 1.67mg/L)], the SI and serum adiponectin in IGT group [(1.5?1.1) 10 -4 (min?mU/L) -1 , 4.29(3.59 6.22 mg/L) respectively] and type 2 DM group [(1.5?1.0)?10 -4 (min?mU/L) -1 , 3.46(2.37 4.72 mg/L) respectively] were significantly decreased (all P
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Objective To prepare rabbit antibody against mouse AD-004 by AD-004 expressed in the prokaryotic expression system and to identify its distribution in the testis and adrenal. Methods The full-length cDNA of mouse AD-004 was cloned into PET28 plasmid, and the protein was induced in E. coli BL21 bacteria by adding IPTC and then purified by Ni2+ -NTA column. The purified protein was used as an immunogen to prepare polyclonal antibody ( pAb) of AD-004. The specificity of the antibody was detected by Western blotting. Immunohistochemical staining was performed in the mouse adrenal and testis via pAb of AD-004. Results Hisfused AD-004 was expressed efficiently in the prokaryotic system. Western blot analysis showed that the polyclonal antibody was duly bound to purified AD-004 with high specificity and sensitivity. AD-004 could be abundantly identified in the adrenal medulla and mainly expressed in the Leydig cells of testis. Conclusion The mouse protein of AD-004 is obtained from the prokaryotic expression system. The rabbit anti-AD-004 antibody has been prepared successfully. AD-004 protein is mainly localized in the interstitium of testis, suggesting that AD-004 may play a role in the synthesis of sex-steroid hormone.