Objective To determine the expression of membrane-bound B lymphocyte stimulator (Blys) and Blys mRNA in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE), and investigate the relationship between Blys mRNA expression and SLE activity or lupus nephritis. Methods Measure the expression of Blys mRNA with reverse transcription-PCR (RT-PCR) in PBMCs from patients with SLE, who were separated into active group (n=26) and inactive group (n=20) according to the SLE disease activity index (SLEDAI) and 20 healthy volunteers; analyze the relationship among Blys mRNA and several clinical items; measure the expression of membrane-bound Blys with flow cytometry (FACs) in 20 patients with SLE and 16 healthy controls. Results The expression of Blys mRNA in PBMCs from patients with SLE was significantly elevated compared to healthy controls (P

Objective To evaluate the efficacy of etanercept in active ankylosing spondylitis (AS) pa-tient for 48 weeks by tapering the dosage of etanercept every 12 weeks. Methods 52 patients with active AS were enrolled in this study , and 47 patients finished 48 Weeks of observation. 50 mg etanercept was applied subcutaneously once a week for 12 weeks , and was tapered to 50 mg every two weeks for another 12 weeks , and then 25 mg every two weeks for another 24 weeks. BASDAI, BASFI, BASMI, ASDAS, as well as Serum levels of CRP and ESR were doaunented at week 0, 12, 24 and 48, respectively. Result Among the 47 active AS patients, 40 (85.1%) were male, with mean disease duration of 4.1 ± 3.8 years. After 12 -week treatment with 50 mg etanercept weekly, the scores of BASDAI, BASFI, BASMI, ASDAS, as well as levels of ESR and CRP, declined significantly compared to the baseline (P < 0.05, respectively). Despite of tapering the dosage of etan-ercept gradually, most of the patients (87.2%, 41/47) kept in ASAS 40 response during the following 36 weeks. No severe adverse events were observed during the treatment period. Conclusion This study demonstrat-ed the clinical efficacy of etanercept in patients with active AS. A dosage reduction strategy could maintain the clinical efficacy of etanercept during 48 weeks , which indicates that gradually tapering etanercept might be a po-tential effective, economic and safe way for active AS patients.

Objective To explore the relationship between Adult-onset Still's disease (AOSD) and macrophage activation syndrome (MAS). Methods A total of 78 patients with AOSD who had completed medical information were included in this study. Eleven patients who were diagnosed as rheumatic disease associated hemophagocytic syndrome among 26 patients who had hemophagocytic syndrome with histological evidence consisted of the MAS group. Clinical and laboratory data were analyzed in 78 patients with AOSD and 11 patients with MAS. Results Among 78 cases of AOSD, 9 patients (12%) could be diagnosed as MAS but didn't have hemophagocytic histological evidence. In the 11 MAS cases with hemophagocytic phenomenon, 6 patients fulfilled the diagnostic criteria of AOSD, 2 cases with panniculitis, 1 case with SLE, 1 case of dermatomyositis and 1 case of systemic vasculitis. Logistic analysis showed that splenomegaly (OR =2.13, 95%CI=1.11-3.42), leukopenia (OR=3.57, 95%CI=2.30～4.86), anaemia (OR=0.85, 95%CI=1.03～2.76), thrombocytopenia (OR=2.98, 95%CI=1.17-4.30) and hypertriglyceridemia (OR=1.66, 95%CI=1.02～2.74) were associated with development of MAS in AOSD. Conclusion The development of MAS in AOSD patient is frequent and hemophagocytic histological evidence could be found in severe cases. When splenomegaly and hypocytomsis present in AOSD patients, bone marrow examination should be done and the level of triglyceride and fibrinogen and activity of NK cells should be measured for early diagnosis.

Objective To explore the efficacy of tumor necrosis factor inhibitor in hip joint lesion of ankylosing spondylids (AS). Methods Eight-six patients with hip joint lesion of ankylosing spondylitis were Enrolled in this study. The treatment protocol was: ①Etanercept 25 mg was suncutaneously injected twice a week in the first two months and once a week in the following two months. Then it was injected once every oth-er two weeks in the last two months of the study period.②Methotrexate 15 mg was administered orally or in-travenously once a week.③NSAIDs and prednisone were stopped when symptoms sunsides. Results Twenty-eight cases (33%) stopped NSAIDs because of the disappearance of symptoms in 2 weeks after starting of the study. Forty-three (50%) stopped NSAIDs with in 8 weeks and 36 cases (42%) in them stopped NSAIDs and prednisone. During the 9th and 16th week, etanercept was used once a week and 49 cases (60%) stopped NSAIDs and prednisone. During the 17th and 24th week, etanercept was used once every two weeks, and 38 cases (44%) stopped NSAIDs and prednisone and their disease was stable. Hip Functional Scores of patients were elevated significantly at 2, 4 and 6 months after the treatment (p<0.05) BASDAI and BASFI decreased, and the difference was significant when compared to those before the treatment (P<0.05). For the 19 cases with hip joint synovitis and hydrarthrosis in MRI image but without obvious change in pelvic plain films, syn-ovitis of 11 cases disappeared and 4 cases improved significantly. In 84 hip joints with grade Ⅱ or Ⅲ changes, 13 joints improved for one grade, 16 joints had improvement but less than one grade, and 49 joints had no radiological changes. Conclusion Etanercept, when combined with methotrexate, is effective in treat-ing hip joint lesion of ankylosing spondylitis. The dosage of etanercept can be tapered after the disease is un-der control.

AIM: To determine the expression of membrane-bound B lymphocyte stimulator((BLyS)) and its mRNA in peripheral blood mononuclear cells(PBMCs) from individuals with systemic lupus erythematosus(SLE),and to investigate the effect of dexamethasone on(BLyS) expression.METHODS: PBMCs were obtained from 25 individuals with SLE(mean age of 31.40?14.23) and 20 female healthy volunteers(mean age of 28.20?10.36).They were randomized into dexamethasone((1 ?mol/L)) group and media group.PBMCs were gathered at 0,6,12 and 24 h for(BLyS) mRNA assessment using reverse transcription-PCR(RT-PCR).PBMCs were also collected at 72 h for membrane-bound(BLyS) protein detection using flow cytometry(FACS) and direct immunofluorescence.RESULTS:(1) The expression of(BLyS) mRNA and membrane-bound protein were significantly higher in PBMCs from individuals with SLE than that in PBMCs from healthy controls(0.40?0.18 vs 0.27?0.20,P

AIM: To examine whether Akt signal pathway proteins, including Akt, NF-?B and I?B?, are activated in kidney tissue of murine chronic graft-versus -host disease (GvHD) lupus nephritis in vivo , and whether prednisone suppres ses activation of them. METHODS: Akt activity and phosphorylated I?B? were detected by Weste rn-blot. Activation of NF-?B was detected by electropheretic mobilit y shift assay (EMSA). RESULTS: Activity of Akt, NF-?B and phosp horylated I?B ? were significantly increased in kidney tissue of murine chronic graft-versus -ho st disease (GvHD) in 8th week and 12th week after monocell injection, respective ly. However, they were no significant elevation in 16th week, when compared with controls. Prednisone treatment significantly prevented the increase in serum an ti-dsDNA antibody level, urinary protein excretion and glomerular cell prolif eration in GvHD mice, indicating the beneficial effects of prednisone on t his model. Prednisone also significantly suppressed the increase in the activities o f glomerular Akt, NF-?B and phosphorylated I?B?. CONCLUSION: T his study provides t he first evidence of marked increase in glomerular Akt-NF-?B signal pathway act ivities in murine chronic graft-versus-host disease lupus nephritis. The benefic ial effect of prednisone on this lupus nephritis model may be partially mediated by the suppression of abnormal Akt- NF-?B activation.

Endovascular aneurysm repair (EVAR) of combined abdominal and iliac aneurysm requires exclusion of the hypogastric artery for prevention of endoleak. However, exclusion of the hypogastric artery is often associated with significant ischemic complications such as hip or buttock claudication, gluteal necrosis and bowel ischemia. Several techniques have been introduced to preserve the flow of the hypogastric artery. We report a successful case of external iliac artery-to-hypogastric artery bypass with artificial graft combined with EVAR.
Aneurysm ; Aortic Aneurysm, Abdominal ; Arteries ; Buttocks ; Endoleak ; Hip ; Humans ; Iliac Aneurysm ; Ischemia ; Necrosis ; Transplants

OBJECTIVETo understand the pathogenic effect and the correlation between the genotype and phenotype of the 4 novel missense mutations (G247S, E280G, P362T and A434D) of phenylalanine hydroxylase gene (PAH).

METHODS(1) The enzyme activity of the 4 mutants was assessed by using transient protein expression in mammalian cells. (2) The PAH amino acid sequences among different animal species were alignmented. (3) The effects of the 4 missense mutations on the protein structure were analyzed. (4) The clinical phenotype of the patients with PKU were analyzed, according to their blood Phe levels prior to treatment and the Phe tolerance.

RESULTS(1) The residual enzyme activity expressed in vitro of G247S, E280G, P362T and A434D were 3.1%, 0.4%, 8.2% and 21.7% of the wild-type PAH respectively; (2)Gly247, Glu280 and Pro362 were among the highly conserved amino acids, while Ala434 was only moderately conserved; (3) As revealed by 3D structural analysis, G247S and E280G, being located at the active center of the enzyme, interfered with the binding of PAH to BH4 and ferrousion respectively, while P362T and A434D affected the formation and stability of the dimer and the tetramer of PAH; (4) As shown by clinical phenotypic analysis, classical PKU were observed in patients carrying G247S and E280G, moderate PKU were observed in patients carrying A434D, whereas both classical and moderate PKU were observed in patients carrying P362T.

CONCLUSION(1) The E280G, G247S, P362T and A434D are all disease-causing mutations, with those located at the center of the enzyme displaying the most marked pathogenic effect; (2)The results of the structural analysis of the 3D molecule are consistent with the activity assessment of the enzyme expressed in vitro; (3) The consistency is observed between the genotype, the enzymatic activity expressed in vitro and the clinical phenotype.

Amino Acid Sequence ; Animals ; Child ; Child, Preschool ; Female ; Gene Expression ; Genotype ; Humans ; Infant ; Infant, Newborn ; Male ; Models, Molecular ; Molecular Sequence Data ; Mutant Proteins ; chemistry ; genetics ; metabolism ; Mutation, Missense ; Phenotype ; Phenylalanine Hydroxylase ; chemistry ; genetics ; metabolism ; Phenylketonurias ; enzymology ; genetics ; Protein Conformation ; Sequence Alignment ; Structure-Activity Relationship

Purpose: The gene expression test (GET) was used to predict the response to chemotherapy and the recurrence risk.Several randomized clinical trials have demonstrated that some patients with node-positive disease can achieve favorable survival outcomes even without adjuvant chemotherapy. This study aimed to predict the results of Oncotype DX (Genomic Health) and MammaPrint (Agendia) using traditional clinicopathological factors. Methods: We reviewed the records of 311 patients who underwent GET for hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative primary invasive breast cancer with node-positive disease between 2015 and 2022 at Severance Hospital and Gangneung Asan Medical Center. Univariate and multivariate logistic regression analyses assessed the relationships between clinicopathological variables and risk stratification using the GET results. Results: A simple scoring system was created by assigning integer values to each variable. A score of 3 was assigned for histological grade 3, a score of 2 for pathologic T2 or above, and a score of 1 for a lower progesterone receptor (1–20 or Alled score 3–6), HER2 2-positive, and high Ki-67 (>20). In the validation cohort, overall accuracy was 0.798 (95% confidence interval, 0.744–0.844). Conclusion The high GET risk results can be predicted using traditional clinicopathological factors: tumor size, progesterone receptor, histological grade, HER2, and Ki-67. These results will be useful for treatment decision-making among clinically high-risk patients with HR-positive/HER2-negative and node-positive disease, helping to identify patients to whom the GET assay may not apply.

Objective: To explore the activity of auranofin against ovarian cancer cells and its possible molecular mechanism． Methods : The dose-response survival curve and IC50 of auranofin on ovarian cancer cell lines ，SKOV3，Caov3 and SW626 cells and immortalized normal human embryonic kidney HEK-293T cells were determined by CCK-8 method．Cell cycle was determined by flow cytometry．The levels of total glutathione ( GSH) ，reduced GSH and glutathione disulfide ( GSSG) ，thioredoxin reductase (TrxR) and reactive oxygen species (ROS) in cells were determined by microplate reader，and the reduced GSH / GSSG ratio was calculated．Western blot was used to determine the expression of cyclin dependent kinases( CDK) 4，CDK6，Cyclin D1，P53，p-P53 and MDM2 in SKOV3 and Caov3 ovarian cancer cells. Results : Compared with HEK-293T cells，the dose-response survival curves and IC50 values of SKOV3，Caov3 and SW626 cells showed that ovarian cancer cells were more sensitive to auranofin (P＜0. 05) ．After SKOV3 and Caov3 cells were treated with the dose of respective IC50 concentrations of auranofin，compared with the untreated cells group，the Auranofin IC50 group cells' intracellular levels of GSH，the ratio of reduced GSH / GSSG and the activity of TrxR decreased (t = 25. 11 /31. 18，14. 72 /19. 92，43. 30 /10. 74， all P＜0. 05) ，and the levels of ROS increased (t = 23. 82 /27. 71，P＜0. 05) ; cells number at G0 / G1 phases increased，with cells number at S and G2 phases decreased (P＜0. 05) ; and the expression levels of cell cycle-related proteins CDK4，CDK6，Cyclin D1 and the P53-specific E3 ubiquitin ligase MDM2 were down-regulated (t = 7. 51 /15. 59，17. 32 /11. 26，20. 78 /20. 78，24. 25 /17. 32，all P＜0. 05) ，while the expression levels of P53 and p-P53 were up-regulated (t = 17. 32 /24. 25，12. 12 /10. 39，all P ＜0. 05) ． Conclusion Auranofin causes oxidative stress in ovarian cancer cells by inhibiting TrxR activity，and by partially degrading MDM2 to stabilize and acti- vate P53，so as to block the cancer cells in G0 / G1 phase，and exert anti-ovarian cancer activities.