Objective To detect the expression levels of high mobility group box chromosomal protein 1 (HMGB1) and Th17 cells transcription factors, related cytokines in peripheral blood of rheumatoid arthritis (RA) patients and analyze the relations between HMGB1 and CRP, ESR, RF in RA patients. The other aim of this study is to identify the expression level of HMGBI and the relationship between HMGB1 and Th17 in RA patients. Methods The mRNA levels of HMGB1, RORyt, interleukin (IL)-17 in the peripheral blood mononuclear cells (PBMC) were determined by quantitative real-time PCR (QRT-PCR) from 80 patients with rheumatoid arthritis,including 32 RA patients in stable phase and 48 patients in active phase, and 50 healthy volunteers. The concentration of HMGB1, IL-23, IL-17 in plasma were detected by enzyme linked immunosorbent assay (ELISA), one-way ANOVA and Spearman's correleation were adopted for statistical analysis.Results The mRNAs of HMGBI, RORyt and IL-17 in RA patients were higher than that in healthy control group (P<0.05), especially in active RA patients [ HMGB 1 (0.424±0.262) pg/ml, RORγt (0.34±0.25) pg/ml,IL-17 (1.42±0.38) pg/ml,P<0.01 ] when compared with patients with stable disease. The concentration of HMGB1, IL-23 and IL-17 in the plasma of RA patients was higher than that of the healthy control group (P< 0.05), and was positively correlated with the expression levels of HMGB1, Th 17-associated factors and the level of CRP, ESR, RF in RA patients' plasma(P<0.05). Conclusion The HMGB1 and Thl7 cells levels are higher in active RA patients than those in patients with stable disease, arid there is significant positive correlation between them. Detection of peripheral HMGB1 and Thl7 cell-specific transcription factors or related cytokines can help to understand the development and progress of rheumatoid arthritis and provide clues for new treatment targets for RA.

Medical insurance payment model is transforming from project-based purchases to service bundle-based strategic purchases. The new form of bundled purchases should found on a scientifically-led design process of such bundles. The core to bundled purchase would be the payment standard, and the key to its success would be process control. Establishment of such a foundation, a core, and a key, would promote the current price standards, and lead service providers to a standardized medical service standard, so as to ensure a precise rewarding system of payment and service. The big data diagnosis-intervention packet(DIP)is able to fulfill mentioned ambitions by integrating insurance payment and supervision into one management. DIP is a full-process payment mode that encompasses pre-service estimation, in-service process control, post-service grading, and resource allocation. It is an innovative practice in line with China′s national conditions for the modern governance of medical security and medical services.

Objective:To study the effects of modified citrus pectin (MCP) on the viability and gene expressions of synovial fibroblasts (SF) as well as SF treated by galectin-3 (Gal-3).Methods:Rabbit SF was isolated and cultured in vitro. Then SF was treated with different concentrations of MCP (0, 250, 500, and 750 mg/L). In addition, SF was further treated with the same different concentrations of MCP after treatment with 10 μg/ml Gal-3 for 24 h. The viability of SF was detected by CCK-8 on the first, third, and fifth day after treatment. The mRNA expression of transforming growth factor-β1 (TGF-β1), type I collagen (COL1A2), and Gal-3 in SF was detected by real-time quantitative PCR. The synthesis of type I collagen in SF was investigated by immunofluorescence staining. Results:MCP, especially at a concentration of 500 mg/L can inhibit the proliferation of SF significantly (all P < 0.05) on the first, third, and fifth day after treatment. Compared with the control group, MCP at different concentrations induced different gene expression profiles. In particular, MCP at high concentrations can upregulate the expression of TGF-β1, COL1A2 and Gal-3 in SF. However, MCP shows no significant effect on the synthesis of type I collagen in SF. MCP can down-regulate the expression of TGF-β1, COL1A2, and significantly reduce the synthesis of type I collagen in SF after Gal-3 treatment. Particularly, the effect of MCP at a concentration of 500 mg/L on inhibiting the expression of TGF-β1, COL1A2, and Gal-3 in SF is significant. Conclusions:MCP can inhibit the excessive proliferation of SF and regulate gene expression in SF.

Objective:To investigate the effect of hUCMSC-exos on the expression levels of HDAC in different isotypes of RA FLSs, and to elucidate the possible mechanism of hUCMSC-exos on the apoptosis of RA FLSs by regulating HDAC.Methods:hUCMSC and hUCMSC-Exos were isolated and identified. RT-qPCR was used to detect the changes in HDAC mRNA expression levels in FLSs after hUCMSC-Exos intervention, and the most affected HDAC types were identified. Western blot was used to detect the levels of FLS HDAC1 protein and the expression levels of NF-κB p65 and phospho-NF-κB p65 (Ser 536) in the blank control group, hUCMSC group, hUCMSC-Exos group, Trichostatin A (TSA) group and HDAC1 Inhibitor (Pyroxamide) group. To investigate the effects of hUCMSC-Exos on HDAC expression and NF-κB activity in FLSs. Flow cytometry was used to detect the effect of hUCMSC-Exos on the apoptosis of FLSs. ELISA was used to detect the effects of hUCMSC-Exos on the secretion of TNF-α, IL-6, IL-1β and IL-8 by FLSs. Flow cytometry and ELISA were used to detect the apoptosis level and pro-inflammatory cytokine secretion level of RA FLSs in the blank control group, NF-κB Inhibitor (pyrrolidine dithiocarbamate (PDTC) group, hUCMSC-Exos group and PDTC+hUCMSC-Exos co-intervention group. Whether inhibition of NF-κB affects the regulatory effect of hUCMSC-Exos on RA FLSs was further explored. All experimental data conforming to the normal distribution were compared by one-way ANOVA. LSD- t test was used for pin-group comparison, and independent sample t test was used for two-sample comparison. Results:Cultured primary hUCMSC were adherently grown spindle-shaped cells, and hUCMSC-Exos were saucer-shaped membranous vesicles, both of which met the identification criteria. hUCMSC-Exos reduced the expression level of HDCA1 mRNA [(0.932±0.091), t=2.19, P<0.001] and protein [(0.204±0.012), t=8.28, P<0.001] in RA FLSs, and the inhibitory effect was stronger than that of hUCMSC ( t=1.09, P=0.009) and HDAC1 ( t=11.29, P=0.013) Inhibitor. hUCMSC-Exos increased the apoptosis rate of RA FLSs [(48.68±0.84)%, t=12.33, P<0.001]. hUCMSC-Exos reduced the secretion levels of TNF-α [(29.6±1.0)pg/ml, t=10.78, P<0.001], IL-6 [(20.1±0.7)pg/ml, t=7.96, P<0.001], IL-1β [(9.28±0.23)pg/ml, t=6.14, P<0.001] and IL-8 [(108.0±3.8)pg/ml, t=1.21, P<0.001] in the supernatant of RA FLSs. hUCMSC-Exos reduced the expression level of p-NF-κB-p65/NF-κB-p65 in RA FLSs(0.351±0.024, t=17.67, P<0.001), and its inhibitory effect was stronger than that of hUCMSC (0.515±0.064, t=8.07, P=0.009) and HDAC1 inhibitor(0.411±0.033, t=2.44, P=0.04). After use of NF-κB inhibitors, hUCMSC-Exos weakened the promotion of apoptosis of RA FLSs [(29.0±0.5)%, t=10.63, P<0.001] and weakened the inhibitory effect of IL-8 secretion in the supernatant of RA FLSs [(125.5±3.2)pg/ml, t=2.63, P=0.002]. Conclusion:hUCMSC-Exos can mimic maternal cells to effectively inhibit the aberrant expression of HDAC1 in RA FLSs. hUCMSC-Exos may affect the apoptosis of RA FLSs and the secretion of pro-inflammatory cytokines by inhibiting the HDAC1/NF-κB pathway.