[Analysis of pregnancy outcomes, disease progression, and risk factors in patients with undifferentiated connective tissue disease].

OBJECTIVE: To investigate the fetal and maternal outcomes, risk factors of disease progression and adverse pregnancy outcomes (APOs) in patients with undifferentiated connective tissue disease (UCTD). METHODS: This retrospective study described the outcomes of 106 pregnancies in patients with UCTD. The patients were divided into APOs group (n=53) and non-APOs group (n=53). The APOs were defined as miscarriage, premature birth, pre-eclampsia, premature rupture of membranes (PROM), intrauterine growth restriction (IUGR), postpartum hemorrhage (PPH), and stillbirth, small for gestational age infant (SGA), low birth weight infant (LBW) and birth defects. The differences in clinical manifestations, laboratory data and pregnancy outcomes between the two groups were compared. Logistic regression analysis was performed to analyze the risk factors for APOs and the progression of UCTD to definitive CTD. RESULTS: There were 99 (93.39%) live births, 4 (3.77%) stillbirths and 3 (2.83%) miscarriage, 20 (18.86%) preterm delivery, 6 (5.66%) SGA, 17 (16.03%) LBW, 11 (10.37%) pre-eclampsia, 7 (6.60%) cases IUGR, 19 (17.92%) cases PROM, 10 (9.43%) cases PPH. Compared with the patients without APOs, the patients with APOs had a higher positive rate of anti-SSA antibodies (73.58% vs. 54.71%, P=0.036), higher rate of leukopenia (15.09% vs. 3.77%, P=0.046), lower haemoglobin level [109.00 (99.50, 118.00) g/L vs. 124.00 (111.50, 132.00) g/L, P < 0.001].Multivariate Logistic regression analysis showed that leucopenia (OR=0.82, 95%CI: 0.688-0.994) was an independent risk factors for APOs in UCTD (P=0.042). Within a mean follow-up time of 5.00 (3.00, 7.00) years, the rate of disease progression to a definite CTD was 14.15%, including 8 (7.54%) Sjögren's syndrome, 4 (3.77%) systemic lupus erythematosus (SLE), 4 (3.77%) rheumatoid arthritis and 1 (0.94%) mixed connective tissue disease. Multivariate Cox proportional risk regression analysis showed that Raynaud phenomenon (HR=40.157, 95%CI: 3.172-508.326) was an independent risk factor for progression to SLE. CONCLUSION: Leukopenia is an independent risk factor for the development of APOs in patients with UCTD. Raynaud's phenmon is a risk factor for the progression of SLE. Tight disease monitoring and regular follow-up are the key measures to prevent adverse pregnancy outcomes and predict disease progression in UCTD patients with pregnancy.

A nomogram based on LI-RADS features, clinical indicators and quantitative contrast-enhanced MRI parameters for predicting glypican-3 expression in hepatocellular carcinoma.

Purpose: Noninvasively assessing the tumor biology and microenvironment before treatment is greatly important, and glypican-3 (GPC-3) is a new-generation immunotherapy target for hepatocellular carcinoma (HCC). This study investigated the application value of a nomogram based on LI-RADS features, quantitative contrast-enhanced MRI parameters and clinical indicators in the noninvasive preoperative prediction of GPC-3 expression in HCC. Methods and materials: We retrospectively reviewed 127 patients with pathologically confirmed solitary HCC who underwent Gd-EOB-DTPA MRI examinations and related laboratory tests. Quantitative contrast-enhanced MRI parameters and clinical indicators were collected by an abdominal radiologist, and LI-RADS features were independently assessed and recorded by three trained intermediate- and senior-level radiologists. The pathological and immunohistochemical results of HCC were determined by two senior pathologists. All patients were divided into a training cohort (88 cases) and validation cohort (39 cases). Univariate analysis and multivariate logistic regression were performed to identify independent predictors of GPC-3 expression in HCC, and a nomogram model was established in the training cohort. The performance of the nomogram was assessed by the area under the receiver operating characteristic curve (AUC) and the calibration curve in the training cohort and validation cohort, respectively. Results: Blood products in mass, nodule-in-nodule architecture, mosaic architecture, contrast enhancement ratio (CER), transition phase lesion-liver parenchyma signal ratio (TP-LNR), and serum ferritin (Fer) were independent predictors of GPC-3 expression, with odds ratios (ORs) of 5.437, 10.682, 5.477, 11.788, 0.028, and 1.005, respectively. Nomogram based on LI-RADS features (blood products in mass, nodule-in-nodule architecture and mosaic architecture), quantitative contrast-enhanced MRI parameters (CER and TP-LNR) and clinical indicators (Fer) for predicting GPC-3 expression in HCC was established successfully. The nomogram showed good discrimination (AUC of 0.925 in the training cohort and 0.908 in the validation cohort) and favorable calibration. The diagnostic sensitivity and specificity were 76.9% and 92.3% in the training cohort, 76.8% and 93.8% in the validation cohort respectively. Conclusion: The nomogram constructed from LI-RADS features, quantitative contrast-enhanced MRI parameters and clinical indicators has high application value, can accurately predict GPC-3 expression in HCC and may help noninvasively identify potential patients for GPC-3 immunotherapy.

18[Formula: see text]-Glycyrrhetinic Acid Inhibits TGF-[Formula: see text]-Induced Epithelial-to-Mesenchymal Transition and Metastasis of Hepatocellular Carcinoma by Targeting STAT3.

18[Formula: see text]-glycyrrhetinic acid (GA) is the active ingredient of the traditional Chinese medicinal herb Glycyrrhizae radix et rhizoma. We previously demonstrated that GA inhibited tumor growth in hepatocellular carcinoma (HCC). However, the effect of GA on transforming growth factor-[Formula: see text] (TGF-[Formula: see text]-induced epithelial-mesenchymal transition (EMT) and metastasis were still unclear. In this study, in vitro transwell assays and immunofluorescence (IF) demonstrated that GA inhibited TGF-[Formula: see text]-induced migration, invasion and EMT of HCC cells. However, it had little effect on the inhibition of proliferation by TGF-[Formula: see text]. Moreover, we confirmed that GA suppressed the metastasis of HCC cells in vivousing an ectopic lung metastasis model. Furthermore, we found that GA inhibited TGF-[Formula: see text]-induced EMT mainly by reducing the phosphorylation of signal transducer and activator of transcription 3 (STAT3), which played an essential role in TGF-[Formula: see text]-induced EMT and cell mobility. Mechanistically, GA inhibited the phosphorylation of STAT3 by increasing the expression of Src homology 2 domain-containing protein tyrosine phosphatases 1 and 2 (SHP1 and SHP2). Therefore, we concluded that GA inhibited TGF-[Formula: see text]-induced EMT and metastasis via the SHP1&SHP2/STAT3/Snail pathway. Our data provide an attractive therapeutic target for future multimodal management of HCC.

GRAMD4 inhibits tumour metastasis by recruiting the E3 ligase ITCH to target TAK1 for degradation in hepatocellular carcinoma.

BACKGROUND: Aberrant TAK1 (transforming growth factor ß-activated kinase 1) activity is known to be involved in a variety of malignancies, but the regulatory mechanisms of TAK1 remain poorly understood. GRAMD4 (glucosyltransferase Rab-like GTPase activator and myotubularin domain containing 4) is a newly discovered p53-independent proapoptotic protein with an unclear role in HCC (hepatocellular carcinoma). RESULTS: In this research, we found that GRAMD4 expression was lower in HCC samples, and its downregulation predicted worse prognosis for patients after surgical resection. Functionally, GRAMD4 inhibited HCC migration, invasion and metastasis. Mechanistically, GRAMD4 interacted with TAK1 to promote its protein degradation, thus, resulting in the inactivation of MAPK (Mitogen-activated protein kinase) and NF-κB pathways. Furthermore, GRAMD4 was proved to recruit ITCH (itchy E3 ubiquitin protein ligase) to promote the ubiquitination of TAK1. Moreover, high expression of TAK1 was correlated with low expression of GRAMD4 in HCC patients. CONCLUSIONS: GRAMD4 inhibits the migration and metastasis of HCC, mainly by recruiting ITCH to promote the degradation of TAK1, which leads to the inactivation of MAPK and NF-κB signalling pathways.

Characteristics and mortality in primary Sjögren syndrome-related interstitial lung disease.

ABSTRACT: Aim of the study was to determine the characteristics and prognosis, and to identify the risk factors for mortality in patients with primary Sjögren syndrome (pSS) with interstitial lung disease (pSS-ILD).A total of 1422 patients with SS were screened and 178 patients with pSS-ILD were recruited. The medical records and outcomes were retrospectively reviewed. Overall survival and case control study were performed to explore the predictors of death.Among 178 pSS-ILD patients, 87.1% were women. Mean age was 61.59 ±â€Š11.69-year-old. Median disease duration was 72.0 (24.0, 156.0) months. Nonspecific interstitial pneumonia was the predominant high-resolution computed tomography pattern (44.9%). Impairment in diffusion capacity was the most common abnormality of pulmonary function test (75.8%) and the most severe consequence. Type 1 respiratory failure and hypoxia were observed in 15.0% and 30.0% patients, respectively. Mean survival time after confirmation of pSS-ILD diagnosis was 9.0 (6.8, 13.0) years. The 10-year survival rate for all patients with pSS-ILD was 81.7%. Forty-four (24.7%) of 178 patients died during the follow-up period. The most predominant cause of death was respiratory failure (n = 27). Twenty-seven patients died of ILD and formed study group. The 78 patients who survived formed control group. Age and smoking were risk factors for mortality in patients with pSS-ILD. In addition, severity of ILD, as reflected by high-resolution computed tomography, pulmonary function test, and arterial blood gas, was an independent risk factor. However, inflammation status (erythrocyte sedimentation rate, C-reactive protein) and anti-Sjögren syndrome-related antigen A and anti-Sjögren syndrome-related antigen B were not.ILD is a severe complication of pSS. Age, smoking, and severity of lung involvement are more critical for prognosis rather than inflammation status and autoantibodies.

Elevated serum Dickkopf-1 is a biomarker for bone erosion in patients with psoriatic arthritis.

BACKGROUND: Psoriatic arthritis (PsA) is an inflammatory arthropathy characterized by psoriasis and bone erosion on radiology. Dickkopf-1 (Dkk-1) is considered to be the main inhibitor of the Wnt signaling pathway and results in reduced osteoblast proliferation. The aim of this study was to investigate the serum level of Dkk-1 and its association with bone erosion in PsA patients. METHODS: Serum Dkk-1 levels were measured by enzyme-linked immunosorbent assay (ELISA) in 69 patients with PsA and 60 controls, including 39 rheumatoid arthritis (RA) patients, and 21 healthy controls (HCs). Rheumatoid factor and anti-cyclic citrullinated peptide levels were also determined by ELISA. The association of Dkk-1 level with clinical and laboratory features of PsA was analyzed. Logistic regression analysis was used to analyze the risk factors for bone erosion in PsA. RESULTS: Dkk-1 was elevated in 68.1% (47/69) of the patients with PsA, 46.2% (18/39) of RA patients, and 9.5% (2/21) of HCs. Serum Dkk-1 concentration was significantly higher in PsA patients compared with that in HCs. The level of serum Dkk-1 was correlated with a swollen joint count, and levels of complement components 3 and 4. Elevated Dkk-1 level (odds ratio = 4.440, 95% confidence interval: 1.246-15.817, P = 0.021) was identified as the risk factor for bone erosion in PsA. CONCLUSIONS: The serum level of Dkk-1 is abnormally elevated in PsA patients. The elevation of Dkk-1 might be involved in the mechanism of bone erosion in patients with PsA.

Recovery and identification bioactive peptides from protein isolate of Spirulina platensis and their in vitro effectiveness against oxidative stress-induced erythrocyte hemolysis.

BACKGROUND: Spirulina platensis is recognized as one of the most nutritious foods, containing a high protein content of up to 70%. Meanwhile, he interest in using natural protein resources to develop bioactive peptides is steadily increasing. Therefore, this study released the bioactive peptides from S. platensis by enzymatic hydrolysis using pepsin (1:3000 U g-1 ), and their amino acid sequences were determined by de novo sequencing. On this basis, the antioxidant activities of synthesized bioactive peptides were comprehensively evaluated by 2,2'-azinobis-3-ethylbenzothiazolin-6-sulfonic acid assay, 1,1-diphenyl-2-picryhydrazyl assay, and cell hemolysis assay induced by 2,2'-azobis-(2-amidino-propane) dihydrochloride (AAPH). RESULTS: The degree of hydrolysis and recovery percentage of pepsin hydrolysis were 172 and 825 g kg-1 respectively, and FFEFF (P1: m/z 736.4, 8%), EYFDALA (P2: m/z 828.4, relative intensity 18.5%), and VTAPAASVAL (P3: m/z 899.5, relative intensity 17.3%) were purified and identified. P2 possessed an excellent radical scavenging activity compared with P1, P3, and vitamin C, which was contributed to by its high ß-sheet conformation and specific amino acid compositions. Moreover, P2 significantly attenuated AAPH-induced oxidative hemolysis of erythrocytes and protected the erythrocytes, because it reduced the formation of malondialdehyde and increased the enzyme activities of superoxide dismutase, catalase, and glutathione peroxidase in erythrocytes. CONCLUSION: This study provided insights into the potential antioxidant function of the synthesized peptides originated from the bioactive peptides of S. platensis proteins, which would contribute to the development of natural antioxidant from new protein resources. © 2020 Society of Chemical Industry.

Type-2 11ß-hydroxysteroid dehydrogenase promotes the metastasis of colorectal cancer via the Fgfbp1-AKT pathway.

Type-2 11ß-hydroxysteroid dehydrogenase (HSD11B2) is a key enzyme which converts cortisol to inactive cortisone and is involved in tumor progression and metastasis. Several studies have shown that the promotion of tumor progression and metastasis by HSD11B2 resulted from its physiological function of inactivating glucocorticoids (GC). However, the underlying molecular mechanisms by which HSD11B2 drives metastasis, in addition to inactivating GC, are still unclear. In our study, a series of in vivo and in vitro assays were performed to determine the function of HSD11B2 and the possible mechanisms underlying its role in CRC metastasis. mRNA transcriptome array analysis was used to identify the possible downstream targets of HSD11B2. We found that the ectopic expression of HSD11B2 significantly promoted the migration, invasion and metastasis of colorectal cancer (CRC) cells both in vitro and in vivo, while it did not affect their proliferation in either case. Mechanically, HSD11B2 appeared to enhance cell migration and invasion by upregulating the expression of fibroblast growth factor binding protein 1 (Fgfbp1), and subsequently increasing the phosphorylation of AKT. Furthermore, AKT activation partially mediated the increased expression of Fgfbp1 induced by HSD11B2. HSD11B2 expression was positively correlated with Fgfbp1 and p-AKT expression in clinical samples of CRC. Additionally, knockdown of either Fgfbp1 or AKT impaired the migration and invasion capability of CRC cells with HSD11B2 overexpression, suggesting that HSD11B2 promoted the migration, invasion and metastasis of CRC cells via the Fgfbp1-AKT pathway. Therefore, targeting HSD11B2 or Fgfbp1 may be a novel treatment strategy for inhibiting the metastasis of CRC.

Glucose-6-phosphate isomerase is associated with disease activity and declines in response to infliximab treatment in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA), a systemic autoimmune disease characterized by synovial inflammation, can cause cartilage and bone damage as well as disability. The aim of this study was to explore whether serum glucose-6-phosphate isomerase (GPI) is correlated with disease activity and the value of GPI in the evaluation of infliximab treatment in patients with RA. METHODS: Sixty-two patients with RA who had an inadequate response to methotrexate (MTX) were enrolled in Peking University People's Hospital from July 1, 2016 to July 31, 2018. Infliximab (3 mg/kg, intravenous at weeks 0, 2, and 6 and then every 8 weeks) was administered to patients with stable background MTX therapy. Serum samples were obtained at baseline and week 18. Serum GPI levels were determined using enzyme-linked immunosorbent assay. The associations between serum GPI levels and clinical features were analyzed. RESULTS: Serum GPI was positively correlated with Disease Activity Score in 28 joints (DAS28), swollen joint count, tender joint count and C-reactive protein level (P < 0.001, P < 0.001, P < 0.001, and P = 0.033, respectively). The change of DAS28 in GPI-positive patients was greater than that in GPI-negative patients (P < 0.001). Compared with those for patients receiving MTX monotherapy at baseline, the GPI levels were significantly declined when MTX was combined with infliximab (P < 0.001). CONCLUSION: Serum GPI is related to disease activity and clinical response to infliximab treatment.

Activity of fibroblast-like synoviocytes in rheumatoid arthritis was impaired by dickkopf-1 targeting siRNA.

BACKGROUND: Fibroblast-like synoviocytes (FLSs), resident mesenchymal cells of synovial joints, play an important role in the pathogenesis of rheumatoid arthritis (RA). Dickkopf-1 (DKK-1) has been proposed to be a master regulator of bone remodeling in inflammatory arthritis. Here, potential impairation on the activity of FLSs derived from RA to small interfering RNAs (siRNAs) targeting DKK-1 was investigated. METHODS: siRNAs targeting DKK-1 were transfected into FLSs of patients with RA. Interleukin (IL)-1ß, IL-6, IL-8, matrix metalloproteinase (MMP) 2, MMP3, MMP9, transforming growth factor (TGF)-ß1, TGF-ß2 and monocyte chemoattractant protein (MCP)-1 levels in the cell culture supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Invasion assay and H incorporation assay were utilized to investigate the effects of siRNAs targeting DKK-1 on FLSs invasion and cell proliferation, respectively. Western blotting was performed to analyze the expression of nuclear factor (NF)-κB, interleukin-1 receptor-associated kinase (IRAK)1, extracellular regulated protein kinases (ERK)1, Jun N-terminal kinase (JNK) and ß-catenin in FLSs. RESULTS: DKK-1 targeting siRNAs inhibited the expression of DKK-1 in FLSs (P < 0.01). siRNAs induced a significant reduction of the levels of IL-6, IL-8, MMP2, MMP3 and MMP9 in FLSs compared to the control group (P < 0.05). DKK-1 targeting siRNAs inhibited the proliferation and invasion of FLSs (P < 0.05). Important molecules of pro-inflammatory signaling in FLSs, including IRAK1 and ERK1, were decreased by the inhibition of DKK-1 in FLSs. In contrast, ß-catenin, a pivotal downstream molecule of the Wnt signaling pathway was increased. CONCLUSIONS: By inhibiting DKK-1, we were able to inhibit the proliferation, invasion and pro-inflammatory cytokine secretion of FLSs derived from RA, which was mediated by the ERK or the IRAK-1 signaling pathway. These data indicate the application of DKK-1 silencing could be a potential therapeutic approach to RA.

Association between musculoskeletal ultrasonography and bone remodelling markers and its role in disease monitoring of gout and hyperuricaemia.

OBJECTIVES: To evaluate associations between bone destruction markers and musculoskeletal ultrasonography (MU) findings in patients with gout and hyperuricaemia and clarify the role of MU in treatment responsiveness. METHODS: One-hundred and fifty patients with gout and 100 patients with hyperuricaemia were divided into five groups according to MU manifestations. Circulating Dickkopf-1 (DKK-1) and receptor activator of nuclear factor-κB ligand (RANKL) levels were measured. Thirty patients from the gout group and 10 from the hyperuricaemia group, were treated for 1 year with urate-lowering therapy (ULT). RESULTS: Patients with gout and tophus and/or bone erosion had the highest DKK-1 and RANKL levels. Patients with gout and MU-evidenced aggregates and/or double-contour signs had higher DKK-1 and RANKL levels than the normal MU group (p<0.001). Patients with hyperuricaemia and abnormal MU findings had significantly higher DKK-1 and RANKL levels than those with normal MU findings. DKK-1 and RANKL levels positively correlated with disease duration in patients with gout (r=0.430, p<0.001; r=0.359, p<0.001, respectively) and hyperuricaemia (r=0.446, p<0.001; r=0.379, p<0.001, respectively). After ULT, MU abnormalities disappeared in 12 and 8 patients with gout and hyperuricaemia, respectively. The largest tophus diameter decreased in patients with gout (t=6.092, p<0.001). DKK-1 and RANKL concentrations significantly decreased in all patients. Lower serum urate levels corresponded with higher ratios of normal MU features in all patients. CONCLUSIONS: In patients with gout and hyperuricaemia, MU manifestations were associated with DKK-1 and RANKL levels and were ameliorated after ULT. Thus, MU could be a useful tool in assessing bone remodelling and monitoring disease responsiveness.

Interstitial lung disease in non-sicca onset primary Sjögren's syndrome: a large-scale case-control study.

AIM: This study investigated the common initial clinical presentations of primary Sjögren's syndrome (pSS) with interstitial lung disease (ILD) and explored differences between sicca and non-sicca onset pSS-ILD patients. METHOD: A total of 1341 SS patients hospitalized between 2003 and 2012 were retrospectively reviewed. Of them, 102 were analyzed and recruited to examine the differences between non-sicca and sicca onset. RESULTS: Fifty-one percent of pSS-ILD patients presented with non-sicca onset. Although the mean diagnosis time was equal, only 4% of non-sicca onset patients were diagnosed with pSS at onset versus 34% with sicca onset (P = 0.000). Hyperglobulinemia, elevated rheumatoid factor (RF) titer, and anti-SSA and/or anti-SSB presence were less predominant in patients with non-sicca onset (immunoglobulin G, 16 [12-21] vs. 21 [15-28] g/L, P = 0.032; RF, 22 [20-171] vs. 104 [20-237] IU/mL, P = 0.048; anti-SSA and/or anti-SSB presence, 33% vs. 72%, P = 0.000). The usual interstitial pneumonia pattern was more commonly seen in non-sicca onset patients (20.0% vs. 14.3%). The high-resolution computed tomography score was higher (12 [88-15] vs. 8 [5-13], P = 0.070) and predicted total lung capacity and forced vital capacity were lower (87 ± 23% vs. 97 ± 20%, P = 0.050; 88 ± 28% vs. 100 ± 27%, P = 0.089) in non-sicca patients. CONCLUSION: Non-sicca is a common initial manifestation in pSS-ILD. Anti-SSA presence, elevated RF titer and hyperglobulinemia were less predominant, and pulmonary complications were more progressive and severe in non-sicca onset patients than sicca onset patients.

Prevalence, risk factors, and prognosis of interstitial lung disease in a large cohort of Chinese primary Sjögren syndrome patients: A case-control study.

To determine the prevalence of pulmonary complications in primary Sjögren syndrome (pSS), and to identify the risk factors and the prognosis associated with pulmonary involvement in pSS patients.A total of 1341 hospitalized patients (853 with pSS and 488 with secondary Sjögren syndrome [sSS]) were retrospectively reviewed. Of these, 165 hospitalized patients with pSS-associated interstitial lung disease (ILD) were analyzed and recruited as a study group. Eighty-four pSS patients without organ damage were included as a control group.One hundred and sixty-five patients (19.34%) from the pSS group and 126 patients (25.82%) from the sSS group presented with lung involvement. Of the 165 pSS patients with lung complications, 151 (91.5%) were women. The mean age was 61.25 ±â€Š9.79 years, and the median disease duration was 84 (24-156) months. Non-specific interstitial pneumonia (NSIP; 39.1%) was the predominant pattern on high-resolution computed tomography (HRCT). The total HRCT score was 9.71 ±â€Š4.77. Impairment in diffusion capacity was the most common (74.3%) and severe complication (predicted value of TLCO was 57.5 ±â€Š21.2%). The 5-year survival rate for all patients with pSS-ILD was 88.5%. Age, disease duration, rheumatoid factor (RF), and C-reactive protein (CRP) were significantly higher than in controls, whereas anti-SSA was less common. Age, RF, and CRP were independent predictors of ILD after adjustment for confounders.Lung involvement is a common and severe complication of Sjögren syndrome. Age and disease activity are correlated with pulmonary involvement in pSS patients.

Expression of circulating Semaphorin3A and its association with inflammation and bone destruction in rheumatoid arthritis.

To determine the expression of Semaphorin3A (Sema3A) in rheumatoid arthritis (RA) patients, and analyze the correlation between serum Sema3A and the pathogenesis of RA. The concentration of serum Sema3A and its mRNA expression level were detected in RA patients. The association of serum Sema3A level with clinical and laboratory features of RA were analyzed. Serum Sema3A of 130 RA patients (15.89 ± 8.58 ng/ml) was significantly higher than that of 150 HC (6.96 ± 2.62 ng/ml) and 215 patients with other rheumatic diseases (P < 0.05). Consistent with the serum level, the Sema3A mRNA level was also higher in RA patients' PBMC than that in HC (1.8-fold increase, P < 0.01). The serum level of Sema3A was correlated with platelet counts (r = 0.229), ESR (r = 0.172), RF (r = 0.230), IgM (r = 0.254) and Sharp score (r = 0.254), and bone mineral density (BMD) of lumbar spine (r = 0.263). Serum Sema3A was also fundamentally higher in AKA-, APF-, anti-CCP-positive groups compared with negative groups (P < 0.05). The ROC curve showed that the optimum diagnostic cutoff value for Sema3A was 10.881 ng/ml. RF level and antibodies (anti-CCP, APF, AKA, and GPI) positive rates were significantly higher in Sema3A positive group. Sharp score was also higher, although without significance. The expression of Sema3A is significantly elevated in RA patients. The level of serum Sema3A is positively correlated with inflammatory factors (including ESR, IgM, and RF) and is associated with auto-antibody production and bone destruction.

Identification of a novel autoantibody against self-vimentin specific in secondary Sjögren's syndrome.

BACKGROUND: Sjögren's syndrome (SS) is a primary autoimmune disease (pSS) or secondarily associated with other autoimmune diseases (sSS). The mechanisms underlying immune dysregulation in this syndrome remain unknown, and clinically it is difficult to diagnose owing to a lack of specific biomarkers. METHODS: We extracted immunoglobulins (Igs) from the sera of patients with sSS associated with rheumatoid arthritis (RA) and used them to screen a phage display library of peptides with random sequences. RESULTS: Our results show that an sSS-specific peptide, designated 3S-P, was recognized by sera of 68.2% (60 of 88) patients with sSS, 66.2% of patients with RA-sSS, and 76.5% of patients with systemic lupus erythematosus (SLE)-sSS. The anti-3S-P antibody was scarcely found in patients with pSS (1.8%), RA (1.3%), SLE (4.2%), ankylosing spondylitis (0%), and gout (3.3%), as well as in healthy donors (2%). The 3S-P-binding Igs (antibodies) were used to identify antigens from salivary glands and synovial tissues from patients with sSS. A putative target autoantigen expressed in the synovium and salivary gland recognized by anti-3S-P antibody was identified as self-vimentin. CONCLUSIONS: This novel autoantibody is highly specific in the diagnosis of sSS, and the underlying molecular mechanism of the disease might be epitope spreading involved with vimentin.

Clinical features of new-onset systemic lupus erythematosus in pregnant patients.

AIM: This study was conducted to examine the clinical characteristics of new-onset systemic lupus erythematosus (SLE) during pregnancy. METHODS: We performed a retrospective study of all pregnancies in patients with SLE managed at The People's Hospital of Peking University from 2008 to 2015. In total, 97 pregnancies were identified and studied, 22 of which were first diagnosed with SLE during pregnancy or puerperium. RESULTS: New-onset SLE mainly occurred during the first and second pregnancy trimesters. Blood and multi-organ involvement were detected in 95.45% and 45.45% of new-onset patients, respectively, and both had a higher incidence than in active patients. Thrombocytopenia was the most common blood involvement in new-onset patients. All three maternal deaths occurred in new-onset patients. There were nine (40.91%) fetal losses, three (13.64%) low birth weight infants, one (4.54%) fetal malformation and two (9.09%) cases of neonatal lupus in new-onset patients. CONCLUSION: New-onset pregnant SLE patients were characterized with blood system involvement and generally experienced more adverse maternal outcomes than active patients with SLE history. However, adverse fetal outcomes in new-onset patients were the same as those of active patients with an SLE history.

TTF1-NPs Induce ERS-Mediated Apoptosis and Inhibit Human Hepatoma Cell Growth In Vitro and In Vivo.

Previous studies have shown that 5,2',4'-trihydroxy-6,7,5'-trimethoxyflavone (TTF1) is the primary anticancer constituent of the traditional Chinese medicinal plant Sorbaria sorbifolia (SS), which has been applied to treat cancer in China. In this study, we investigated the in vitro and in vivo antitumor effects and biological mechanisms of small-molecule TTF1 nanoparticles (TTF1-NPs). The effects of TTF1-NPs on cell growth and apoptosis were investigated using human hepatoma cells. The molecular changes associated with the effects of TTF1-NPs were analyzed by immunocytochemistry and Western blot analysis. The in vivo effect of TTF1-NPs was investigated using the HepG2 tumor xenograft model. We found that TTF1-NPs exhibited antitumor effects in vitro accompanied by induction of apoptosis in human hepatoma cells. Mechanistically, our data showed that TTF1-NPs induced apoptosis via endoplasmic reticulum stress (ERS) pathway in hepatoma cells. Moreover, inhibition of ERS activation blocked TTF1-NP-induced apoptosis in HepG2 cells. Finally, TTF1-NPs inhibited the growth of HepG2 xenograft tumors. Taken together, our results demonstrated that TTF1-NP-induced apoptosis was mediated at least in part by the ERS pathway and thus inhibited hepatoma tumor growth.

Mixed hemimicelles solid-phase extraction based on sodium dodecyl sulfate-coated nano-magnets for selective adsorption and enrichment of illegal cationic dyes in food matrices prior to high-performance liquid chromatography-diode array detection detection.

In this study, mixed hemimicelles solid-phase extraction (MHSPE) based on sodium dodecyl sulfate (SDS) coated nano-magnets Fe3O4 was investigated as a novel method for the extraction and separation of four banned cationic dyes, Auramine O, Rhodamine B, Basic orange 21 and Basic orange 22, in condiments prior to HPLC detection. The main factors affecting the extraction of analysts, such as pH, surfactant and adsorbent concentrations and zeta potential were studied and optimized. Under optimized conditions, the proposed method was successful applied for the analysis of banned cationic dyes in food samples such as chili sauce, soybean paste and tomato sauce. Validation data showed the good recoveries in the range of 70.1-104.5%, with relative standard deviations less than 15%. The method limits of determination/quantification were in the range of 0.2-0.9 and 0.7-3µgkg(-1), respectively. The selective adsorption and enrichment of cationic dyes were achieved by the synergistic effects of hydrophobic interactions and electrostatic attraction between mixed hemimicelles and the cationic dyes, which also resulted in the removal of natural pigments interferences from sample extracts. When applied to real samples, RB was detected in several positive samples (chili powders) within the range from 0.042 to 0.177mgkg(-1). These results indicate that magnetic MHSPE is an efficient and selective sample preparation technique for the extraction of banned cationic dyes in a complex matrix.

Practical Synthesis, Antidepressant, and Anticonvulsant Activity of 3-Phenyliminoindolin-2-one Derivatives.

Herein, a series of 3-phenyliminoindolin-2-one derivatives were designed, synthesized, and screened for their antidepressant and anticonvulsant activities. The IR spectra of the compounds afforded NH stretching (3340-3346 cm(-1)) bands and C=O stretching (1731-1746 cm(-1)). In the (1)H-NMR spectra of the compounds, N-H protons of indoline ring were observed at 10.65-10.89 ppm generally as broad bands, and (13)C-NMR spectra of the compounds C=O were seen at 161.72-169.27 ppm. Interestingly, compounds 3o, 3p and 3r significantly shortened immobility time in the The forced swimming test (FST) and The tail suspension test (TST) at 50 mg/kg dose levels. In addition, compound 3r exhibited higher levels of efficacy than the reference standard fluoxetine but had no effect on locomotor activity in the open-field test. Compound 3r significantly increased serotonin and norepinephrine and the metabolite 5-hydroxyindoleacetic acid in mouse brain, suggesting that the effects of compound 3r may be mediated through these neurotransmitters. In the seizure screen, 15 compounds showed some degree against PTZ-induced seizure at a dose of 100 mg/kg, and the tested compounds did not show any neurotoxicity at a dose of 300 mg/kg in the rotarod test.

[Mechanism of TTF1-NP induced implanted hepatoma tumor apoptosis in nude mice by endoplasmic reticulum stress pathway].

This study was designed to investigate the effect of 5,2',4'-trihydroxy-6,7,5'-trimethoxy flavone nanoparticle(TTF1-NP) on inducing apoptosis of implanted tumour cells in nude mice and the mechanism of endoplasmic reticulum stress pathway. The implanted hepatoma model was established in nude mice, and used to test the drug TTF1-NP in five groups(vehicle, 5 µmol·kg(-1) TTF1-NP, 10 µmol·kg(-1) TTF1-NP, 20 µmol·kg(-)1TTF1-NP and adriamycin). The nude mice were killed after the treatment to determine the tumor growth inhibition rate(IR). Morphological changes of implanted tumor cells were observed by HE staining; apoptosis of tumor cells was detected by TUNEL; the protein expression of GRP78, p-JNK and caspase 12 were analyzed using immunocytochemistry staining and Western blotting. We tested the effects of TTF1-NP on implanted Hep G-2 cell tumor growth in nude mice. TTF1-NP-treated mice showed volume of tumor smaller than that of the vehicle-treated mice. The tumor mass of the TTF1-NP-treated mice were significantly reduced than those of the vehicle-treated mice. In addition, the tumor growth rate of the TTF1-NP-treated mice was significantly lower than that of the vehicle-treated mice, and the tumor growth inhibition ratio of the TTF1-NP-treated mice was significantly higher than that of the vehicle-treated mice. TTF1-NP exhibited an inhibitory effect on implanted tumor cells in the model. The IR was 51.2%, 54.2%, 61.8% and 65.9%, respectively. In comparison with the vehicle group, the treated groups exhibited alteration in cell morphology and apoptosis of tumor cells, and expression of GRP78, p-JNK and caspase 12, which were observed by immunocytochemistry staining and Western blotting. Taken together, our results suggest that TTF1-NP induces apoptosis of implanted tumor cells in nude mice and the main mechanism is related to activation of endoplasmic reticulum stress.