ObjectiveTo investigate the possible mechanism of Jishe Qushi Capsule （脊蛇祛湿胶囊， JQC） in treating rheumatoid arthritis （RA） from the perspective of macrophage polarization mediated by neutrophil extracellular traps （NETs）. MethodsTwenty-four female SD rats were randomly divided into four groups， blank control group， model group， JQC group， and peptidylarginine deiminase 4 （PAD4） inhibitor group with 6 rats in each group. All groups but the blank control group were subjected to the induction of collagen-induced arthritis （CIA）. After successful model establishment， rats in the JQC group received intragastric administration of JQC 1.47 g/kg daily； rats in the PAD4 inhibitor group received intraperitoneal injections of the PAD4 inhibitor 4 mg/kg weekly. Rats in the blank， model， and PAD4 inhibitor groups received 2 ml of pure water daily by gavage. All treatments lasted 4 weeks. Joint lesions of each group were assessed on day 7， 14， 21， 28， and 35 after model establishment， and arthritis index （AI） scores were recorded. At 24 h after the final administration， histopathology of knee joints， including HE staining， safranin O-fast green staining， and TRAP staining， was performed. Flow cytometry was used to detect the counts of M1 and M2 macrophages in peripheral blood. ELISA was used to determine serum levels of TRACP， NETs， TNF-α， IL-1β， and iNOS. Western Blotting and qRT-PCR were used to measure MPO， NE， RANKL， OPG， and p65 protein and mRNA expression in knee cartilage tissue. ResultsCompared with the blank control group， the model group showed increased AI scores （P＜0.05）， marked synovial inflammatory infiltration， angiogenesis， and bone-cartilage destruction， increased TRAP-positive osteoclasts， increased M1 macrophages and decreased M2 macrophages， elevated serum TRACP， NETs， TNF-α， IL-1β， and iNOS （P＜0.05）， elevated MPO， NE， RANKL， and p65 protein/mRNA expression and decreased OPG protein/mRNA expression in knee cartilage tissue （P＜0.05）. Compared with the model group， the JQC group exhibited improved synovial inflammation， angiogenesis， and bone-cartilage damage， reduced AI scores on day 21， 28， and 35， decreased osteoclast counts， decreased M1 macrophages and increased M2 macrophages， reduced serum TRACP， NETs， TNF-α， IL-1β， and iNOS （P＜0.05）， decreased MPO， NE， RANKL， and p65 protein/mRNA expression and increased OPG expression （P＜0.05）. Compared with the PAD4 inhibitor group， the JQC group showed significantly lower AI scores， reduced M1 macrophages， increased M2 macrophages （P＜0.05）， reduced serum TRACP， TNF-α， IL-1β， and iNOS， decreased MPO， RANKL， and p65 expression， and increased OPG levels （P＜0.05）. ConclusionThe therapeutic mechanism of JQC for RA may involve inhibition of NETs formation， downregulation of the RANKL/NF-κB signaling pathway， and regulation of macrophage M1/M2 polarization imbalance， thereby suppressing osteoclastogenesis and inflammatory bone destruction.

Metabolic associated fatty liver disease （MAFLD） is a chronic liver disease with a rapidly increasing incidence rate worldwide， and its complex pathogenesis is closely associated with O-linked β-N-acetylglucosamine （O-GlcNAc） modification. As a dynamic and reversible post-translational modification of proteins， O-GlcNAc modification is mainly regulated by O-GlcNAc transferase and O-GlcNAcase. O-GlcNAc modification can drive hepatic steatosis， exacerbate insulin resistance， and impair mitochondrial function， thereby leading to the aggravation of metabolic disorders， promoting inflammation response， and driving the progression of MAFLD to metabolic associated steatohepatitis and hepatic fibrosis. This article systematically reviews the latest research advances in the role of O-GlcNAc modification in the development and progression of MAFLD， in order to provide theoretical support and research direction for a deeper understanding of the pathological mechanism of MAFLD and the development of effective therapeutic strategies.

Objective To establish a rat model of acute antibody-mediated rejection (AMR) in kidney transplantation and investigate the preventive effect of dihydroartemisinin (DHA) on acute AMR. Methods BN rats were used as donors and Lewis rats as recipients. Kidney transplantation was performed 2 weeks after skin transplantation for sensitization. After establishing the acute AMR model in rat kidney transplantation, the recipients of experimental groups included the syngeneic kidney transplantation group (6 rats), the allogeneic kidney transplantation group (6 rats), the syngeneic skin transplantation followed by kidney transplantation group (12 rats), and the allogeneic skin transplantation followed by kidney transplantation group (24 rats). The groups for investigating the preventive effect of DHA on acute AMR included the control group (allogeneic skin transplantation followed by kidney transplantation) and the DHA group (allogeneic skin transplantation followed by kidney transplantation + DHA), with 12 rats in each group. The survival time of recipient rats, serum donor-specific antibody (DSA) levels and graft pathological changes were used to identify the acute AMR model. On this basis, DSA levels, pathological changes in the transplant kidneys and peripheral blood B-cell levels were detected to assess the preventive effect of DHA on acute AMR. Results Compared with the allogeneic kidney transplantation group, skin transplantation sensitization significantly shortened the survival time of recipient rats (P<0.01). Compared with the syngeneic skin transplantation followed by kidney transplantation group, the allogeneic skin transplantation followed by kidney transplantation group showed significantly elevated serum DSA-IgG levels from 7 days after skin transplantation to 5 days after kidney transplantation (P<0.01), and significantly elevated DSA-IgM levels at 7 and 14 days after skin transplantation(all P<0.01). The transplant kidneys in the allogeneic skin transplantation followed by kidney transplantation group showed a small number of inflammatory cell infiltrations, tubular necrosis, capillaritis, and C4d deposition starting from 1 day after kidney transplantation, with these pathological changes worsening as the post-transplantation days increased. The kidney damage became significant starting from 3 days after transplantation. The above pathology manifestations were consistent with the characteristics of acute AMR. On the basis of establishing the acute AMR model, DHA treatment significantly prolonged the survival time of recipient rats (P<0.01) , and reduced serum DSA-IgG and DSA-IgM levels. DHA treatment significantly alleviated the pathological manifestations of acute AMR, including kidney damage, inflammatory cell infiltration, capillaritis and tubular necrosis, and also reduced C4d deposition in the transplant kidneys, inflammatory cell infiltration and peripheral blood CD19⁺ B-cell levels. Conclusions An acute AMR model is established by performing kidney transplantation 2 weeks after allogeneic skin transplantation in rats. It is discovered that DHA has immunosuppressive effects and may effectively prevent acute AMR, which provides a new strategy for the management of clinical AMR.

OBJECTIVE To study the toxicity-reducing effects and mechanisms of Niuhuang Jiedu Tablets(NHJDT)by gas chromatography-mass spectrometry(GC-MS)metabolomics.METHODS 24 mice were randomly divided into control,realgar(1.0 g·kg-1)and NHDJT(1.0 g·kg-1)groups with 8 mice in each group.The liver and kidney of mice were collected for patho-logic examination after 14 d oral administration to mice.The content of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in liver and creatinine(Cr)and uric acid(UA)in kidney was also determined.The differences of endogenous metabolites in liver and kidney were further analyzed by GC-MS metabolomics.RESULTS The contents of ALT and AST in the liver as well as the Cr and UA in kidney of mice were significantly changed after NHJDT intervention(P<0.05).NHJDT alleviated the pathological dam-age of liver and kidney in mice.A total of 17 biomarkers related to detoxification were screened,including citric acid,ascorbic acid,asparagine,levodopa and phenylalanine.The changes of metabolites mainly involved in glutamine and glutamate metabolism,arginine biosynthesis,tryptophan metabolism,tyrosine and tryptophan biosynthesis,and phenylalanine metabolism.CONCLUSION NHJDT with compound compatibility could reduce the hepatorenal toxicity of realgar.The detoxification mechanism may be related to the regu-lation of amino acid metabolism.

Objective:A kinetic model of the clearance of protein-bound uremic toxins (PBUTs) in maintenance hemodialysis patients is established to evaluate the effects of adding sorbents with different sorption efficiency to dialysate on the clearance rate of PBUTs, and to predict the sorption efficiency of sorbents using the model.Methods:The kinetic model was established by integrating the parameters of plasma flow rate ( Qp), dialysate flow rate ( Qd), free plasma fraction of PBUTs ( f1), free dialysate fraction of PBUTs ( f2), mass transfer coefficient of dialyzer ( K) and surface area of dialysis membrane ( A), and using the mass balance equation and Fick's first law. The model was also used to evaluate the relationship between the clearance rate of different PBUTs and the parameters of dialyzer and the sorption efficiency of sorbents. Results:The kinetic model of PBUTs clearance (CL): ?CL=Qp1-f1-f2γφf1-f2γ,?γ=QpQd,?φ=eKAf1Qp-f2Qd. The model was used to analyze the dialysis parameters of indoxyl sulfate and p-cresol sulfate dialysis.The clearance rate of PBUTs increased with the decrease of its binding capacity to albumin in plasma and the increase of plasma flow rate in dialyzer, dialysate flow rate, mass transfer coefficient of dialyzer, surface area of dialysis membrane, and sorption capacity of sorbents in dialysate. The increasing trend of PBUTs clearance rate was particularly obvious after applying sorbents. Further analysis of the dialysate flow rate and the sorption efficiency of sorbents in the dialysate showed that the increase of the dialysate flow rate could make up for the difference of the sorption efficiency of sorbents. When the dialysate flow rate tended to be infinite, the sorption efficiency of sorbents in the dialysate had no effect on the clearance rate of PBUTs. Conclusion:Adding sorbents of PBUTs to the dialysate during dialysis can significantly improve the clearance rate of PBUTs, suggesting a promising clinical application value.

Objective To investigate the consistency of fetal gallbladder volume (FGV) during middle-late pregnancy with three-dimensional ultrasonic virtual organ computer-aided analysis (VOCAL) technique at different rotation angles,and to analyze the correlation between FGV and gestation age.Methods A total of 157 healthy pregnant women underwent prenatal screening were included.The reference range of FGV was measured with three-dimensional ultrasonic VOCAL at 30°,18° and 12° rotation angle,respectively.The correlation between FGV and gestation age was observed,and the consistency of FGV values measured with VOCAL at different rotation step angles was compared.Results The correlations between FGV values measured with VOCAL at 30°,18°,12° rotation step angles and gestation age were all excellent (r=0.92,0.88,0.90;all P＜ 0.001).The consistency of FGV values measured with VOCAL at different rotation step angles was very good (30° and 18°,ICC=0.94;30° and 12°,ICC=0.97;18° and 12°,ICC=0.94).Conclusion Three-dimensional ultrasonic VOCAL can be used to establish the reference range of fetal gallbladder volume in middle-late pregnancy.The consistency of FGV values measured with VOCAL at different rotation step angles was very good,and the correlation between FGV and gestation age was excellent.