Objective To formulate a ZIF-8 nano mimetic enzyme conjugated with platinum metal(ZIF-8@Pt)that can scavenge reactive oxygen species(ROS)and to explore its potential applications in the treatment of rheumatoid arthritis(RA).Methods The ZIF-8@Pt nanozyme was created by in situ reduction.Characterization of the nanozyme was then performed and its ability to mimic enzymes was investigated.Cell experiments were conducted using RAW264.7 cells,which were divided into three groups,including the untreated group(UT),the positive control group receiving lipopolysaccharide(LPS),which was designated as the LPS group,and the ZIF-8@Pt group receiving ZIF-8@Pt and LPS treatment.The cell experiments were conducted to evaluate the anti-inflammatory properties of ZIF-8@Pt through scavenging intracellular ROS.On the other hand,a collagen-induced arthritis(CIA)model was induced in rats.Similar to the group designations in the cell experiments,the rats were assigned to three groups,including a healthy control group(the UT group),a positive control group receiving a local injection of PBS solution in the knee joint,which was referred to as the control group,and a treatment group receiving a local injection of ZIF-8@Pt solution in the knee joint,which was referred to as the ZIF-8@Pt group.General evaluation,imaging observation,assessment of inflammatory factors,and pathological evaluation were performed to assess the therapeutic efficacy of ZIF-8@Pt against RA.Results The in vitro experiment revealed significant difference in the levels of intracellular ROS and LPS-induced M1-type macrophage polarization between the LPS group and the ZIF-8@Pt group(P＜0.05).The in vivo experiment showed that significant difference in the levels of inflammatory factors,including interleukin-1β(IL-1β),C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),and arginase-1(Arg-1)in the knee joints of the CIA rats between the LPS group and the ZIF-8@Pt group(P＜0.05).Comparing the findings for the ZIF-8@Pt group and the control group,pathology assessment revealed that ZIF-8@Pt reduced local hypoxia and suppressed osteoclastic activity,neovascularization,and M1-type macrophage polarization(P＜0.05).Conclusion The ZIF-8@Pt enzyme mimetic inhibits macrophage inflammatory polarization by ROS scavenging,thereby improving inflammation in RA.Furthermore,the ZIF-8@Pt nanozyme improves the hypoxic environment and inhibits angiogenesis and bone destruction,demonstrating promising therapeutic efficacy for RA.

Objective To investigate whether follicular helper T(Tfh) cells were involved in the development of Henoch-Sch?nlein purpura(HSP) and Henoch-Sch?nlein purpura nephritis(HSPN) in chil-dren through affecting CD40/CD40L axis. Methods Fifty-five subjects were enrolled in this study and di-vided into four groups as follows:22 children with HSP but without renal involvement(Group A),11 chil-dren with HSPN presenting with microhematuria(Group B),11 children with HSPN presenting with micro-hematuria and proteinuria (Group C) and 11 healthy children (control group). Flow cytometry was per-formed to detect the percentages of CD19+B cells and their subsets,CD19+B cells and CD19+CD38+B cells secreting different Ig classes,CD19+CD40+B cells and their subsets and Tfh cells expressing CD40 ligand (CD40L). Results Compared with the control group,the percentages of CD19+CD86+B,CD19+CD138+B and CD40L+Tfh cells significantly increased in Group C(P<0.05) and slightly increased in Groups A and B (P>0.05). No significant difference in the percentages of CD19+B cells, CD19+CD27+B cells, CD19+B cells or CD19+CD38+B cells expressing IgG, IgM, IgD, CD19+B cells or CD19+B cell subsets secreting CD40 was found between the control group and Groups A,B and C(P>0.05). Moreover,the percentages of CD19+B and CD19+CD38+B cells secreting IgA and IgE in Groups A,B and C were higher than those in the control group(P<0.05). Secretion of IgA by CD19+B and CD19+CD38+B cells were positively correla-ted with the expression of CD40L by Tfh cells(P<0.05). Conclusion Tfh cell-mediated abnormal expres-sion of CD40/CD40L might play an important role in the development of HSP and be related to the clinical severity of renal involvement in HSPN.

Objective To explore the role of CD4~+CD25~+CD127~(lo) regulatory T cells (Tregs) and inter-leukin (IL)-6, transforming growth factor beta (TGF-β), IL-17 in the pathogenesis of lupus nephritis (LN) by detecting the levels of IL-10, IL-6, TGF-β, IL-17, CD4~+CD25~+CD127~(lo) Tregs in the peripheral blood of patients with active and inactive LN. Methods Three-colour flow cytometry was used to quantitatively measure proportions of Treg cells, the levels of TGF-β, IL-17 were detected by ELISA, and the levels of IL-10, IL-6 in the peripheral blood were detected by Cytometric Bead Array System. Results ① Compared with the inactive LN and the normal controls (P<0.01), the level of CD4~+CD25~+CD127~(lo) Tregs from patients with active LN was lower(P<0.01). When compared with the normal controls, the level of CD4~+CD25~+CD127~(lo) Tregs from LN inactive patients had no significant difference (P>0.05). ② Compared with patients with inactive LN, the levels of IL-10, IL-6 was higher (P<0.01) in patients with active LN. ③ Compared with the patients with inactive LN and the normal controls, the levels of TGF-β, IL-17 was not significantly different (P>0.05). ④ The level of CD4~+CD25~+CD127~(lo) T cell was correlated negatively with the levels of IL-10, IL-6 and SLEDAI (P<0.05), and was not correlated with C3 and C4. ⑤ SLEDAI was correlated positively with the levels of IL-10 and IL-6 (P<0.01). SLEDAI and the level of IL-10 were correlated negatively with C3 and C4 (P<0.01 for both). ⑥ The level of CD4~+CD25~+CD127~(lo) Tregs from LN was not correlated with TGF-β and IL-17. ⑦ TGF-β was correlated positively with the level of IL-17. Conclusion ① The level changes of Tregs and IL-10, IL-6, TGF-β in the peripheral blood of LN can be used as the indicators for the activity status of lupus nephritis. ② Tregs and IL-10, IL-6 in the peripheral blood of LN patients is negatively correlated. ③ The glucocorticoid hormone is helpful to elevate the level of Tregs but decrease IL-17. T cell level can vary in different body status, different microenvironmental and immune status.

Objective To prepare the pH-dependent Yuchangning Tablet for colon-specific delivery(PYTCSD) used in treating the ulcerative colitis and evaluating the releasing property in vivo and in vitro.Methods The coating prescription was screened by the in vitro delivery of matrine and oxymatrine.The in vitro releasing property of the preparation was examined by the method of in vitro delivery. The in vivo releasing property of the preparation was evaluated by the shadowgraph technique of barium sulfate.Results The preparation method of the PYTCSD was obtained.The core of the tablet was coated by the alcohol solution mixed with 3.70%(g/mL) Eudragit Ⅲ,0.37%(g/mL) DEP,and 0.93%(g/mL) talcum power.The weight of the core was increased 8%.From the in vitro delivery,matrine and oxymatrine were not detected in the simulated gastric fluid after 2 h.The quantities of matrine and oxymatrine were less 10% in the simulated intestinal fluid after 4 h.The quantities of matrine and oxymatrine were 86.5% and 86.8% in the simulated colon fluid after 1 h.On the basis of the in vivo delivery by treating eight volunteers,the PYTCSD could completely get to the ileocecum or ascending colon and disintegrate in that part.Conclusion The PYTCSD can be prepared and the preparation is significantly delivered in the specific colon.