Objective To examine the plasma β-catenin and DKK1 levels in patients with rheumatoid arthritis (RA) and to explore their relationship with bone and joint damage in RA.Methods One hundred and thirteen patients with RA and 120 healthy individuals were recruited into this research.Bone mineral density (BMD) in the femur and lumbar spine were measured with dual-energy X-ray absorptiometry (DEXA).Radiographs for two hands were evaluated according to the Sharp's method.Serum levels of β-catenin and DKK1 in all patients with RA and healthy controls were detected by enzyme-linked immunosorbent assay (ELISA).The 2-tailed independent samples t test was used for measurement data.Chi-square test was used for the enumeration data.Correlation analysis,linear regression and Logistic regression analysis were used as appropriate statistical analysis.Results ① Significantly higher serum levels of DKK1 were observed in RA patients than that in healthy controls [(8±7) vs(6±4) μg/ml,t=2.552,P=0.012],while there was no sinnificant difference with regard to the levels of β-catenin between the two groups.② Compared to control groups,patients with RA had lower BMDs at femur and lumbar spine (P＜0.01).Furthermore,incidence of osteoporosis (OP) in RA (31.9％,36/113) was remarkablely higher than that in healthy subjects (15.0％,18/120) (x2=9.290,P=0.002).③ There were obvious discrepancies in age,swollen joint count (SJC),swollen joint count index (SJI),alkaline phosphatase (AKP),joint narrowing space score,joint erosion score,Sharp score between patients with osteoporosis and without osteoporosis (P＜0.05).④ In RA group,DKK1 level was posi-tively related with plasma erythrocyte sedimentation rates (ESR),28-jonit disease activity score (DAS28),AKP,joint narrowing space score (P＜0.05).Serum β-catenin level was associated with ESR,AKP in RA (P＜0.05).⑤ Multiple linear regression analysis indicated that in the RA group,disease duration (b=0.709,t=9.560,P＜0.01,95％CI:2.154-3.286),HAQ (b=0.151,t=2.052,P=0.043,95％CI:0.234-15.243),DKK1(b=0.286,t=2.057,P=0.043,95％CI:0.034-2.028)were the contributors for joint space narrow score(R2=0.580,F=24.745,P＜0.01).⑥ Multiple Logistic regression analysis showed that the Sharp score (OR=1.018,P＜0.01,95％CI:1.008-1.028) was the risk factor for the occurrence of osteoporosis at femur in RA,while age (OR=1.087,P=0.012,95％CI 1.019-1.159) was the risk factor for osteoporosis at lumbar spine.Conclusion Serum DKK1 levels in RA increase significantly,while there is no apparent alteration in plasma β-catenin.Serum DKK1 is correlated with disease activity and joint space narrow score.

Objective To investigate the relationship between single-nucleotide polymorphism (SNP)in receptor activator for nuclear factor-κB ligand (RANKL),osteoprotegerin (OPG) gene and rheumatoid arthritis (RA).Methods In our study,3 SNPs in the genes of OPG (2 SNP:rs2073618,rs3102735) and RANKL (1 SNP:rs2277438) by ligase detection reactions from 200 RA and 201 controls were examined.BMD values of different areas were assessed using dual-energy X-ray absorptiometry.Clinical and laboratory parameters were collected.Analysis of variance,t-test and x2 test were used for statistical analysis.Results No signi-ficant differences in the distribution of the alleles and genotypes were observed between case group and the control group (P＞0.05).The haplotype analysis for RANKL and OPG SNPs showed that the rs2073618/rs2277438/rs3102735 GGG haplotype could reduce the risk of RA (1.5％ vs 6.0％,P=0.008; OR 0.216;95％CI:0.081 to 0.575) and the GAG haplotype increased the risk of RA (14.5％ vs 8.4％,P=0.007; OR 1.862,95％CI:1.179 to 2.943).Patients with RANKL-rs2277438 AA or GG genotypes (n=6) had significantly higher BMD values compared to those with AG genotypes (n=39) at spine lumber 3 (1.05±0.22 vs 0.93±0.26,t=2.314,P=0.023),spine lumber 4 (1.06±0.24 vs 0.94±0.28,t=2.27,P=0.030),spine lumber 2-4 (1.04±0.21 vs 0.89±0.28,t=2.788,P=0.007).The tender joint counts (13±7 vs 10±6),tender joint index (19±11 vs 13±9),and VAS score (5.7±1.9 vs 4.8±1.8) differed significantly between patients with the OPG-rs2073618 CC or GG genotypes (n=60) and GC genotypes (n=40).Conclusion The rs2073618/rs2277438/rs3102735GGG haplotype may be protective against RA,while GAG haplotype may increase the susceptibility to RA.RANKL gene SNP rs2277438 may affect BMD value at spine lumber,and OPG gene SNP rs2073618 may influence the disease activity of RA patients.

Objective:To investigate the effect and mechanism of local gastric hypothermia in rats with pancreatitis based on a GC?MS and LC?MS dual metabolomics strategy.Methods:Eighteen SD rats were randomly divided into the sham operation (SO), acute pancreatitis (AP) and acute pancreatitis hypothermia (APH) groups. The AP model was established by retrograde injection of 3.5% sodium taurocholate solution into the pancreaticobiliary duct in the AP and APH groups. In the APH group, gastrotomy was performed near the cardia, and a cooling balloon with 2 silicone catheters was placed in the stomach. After the successful establishment of the rat pancreatitis model in the APH group, the speed of ice water circulation was controlled and the output power of the heating pad was adjusted to achieve pancreatic surface temperature reduction while avoiding systemic hypothermia. Temperatures were not monitored and controlled in the SO and AP groups. Serum amylase was detected by ELISA. Pancreatic tissues were stained with HE and histopathologically scored. The expression of NF-κB, IL-6, TNF-α and IκBα in pancreatic tissue was detected by Western blotting. The AP and APH groups were compared by full-scan analysis, and the serum differential metabolites and metabolic pathways were detected by GC?MS- and LC?MS-based metabolomics strategies.Results:Compared with the SO group, the serum amylase level in the AP group and APH group were increased (all P<0.05). Compared with the AP group, the amylase levels at 3 h and 5 h after the operation were decreased in the APH group (both P<0.05). The pathological scores of the AP and APH groups were higher than those of the SO group (both P<0.05), and the pathological damage to pancreatic tissue in the APH group was less than that in the AP group ( P<0.05). IL-6, TNF-α and NF-κB were decreased and IκBα was increased in the APH group compared with the AP group by Western blotting (all P<0.05). A total of 53 differential metabolites were identified by GC?MS, and 236 differential metabolites were identified by LC?MS in the serum samples of the APH group compared with the AP group. The differential metabolites obtained from the blood samples of the APH group and AP group were imported into MetaboAnalyst 4.0 software for analysis, and the root data-log ( P value)>2, P<0.05, three major metabolic pathways were obtained, including ascorbate and aldarate metabolism, pentose and glucuronate interconversions and tryptophan metabolism. Conclusions:Local gastric hypothermia has a protective effect on the expression of inflammatory factors and alleviates pathological damage in rats with acute pancreatitis, which may be related to ascorbate and aldarate metabolism, pentose and glucuronate interconversions and tryptophan metabolism.