Adrenal Cortex Hormones ; blood ; Adult ; Exercise ; physiology ; Gonadal Hormones ; blood ; Humans ; Luteinizing Hormone ; blood ; Male ; Pituitary-Adrenal System ; Serum ; metabolism ; Students ; Testosterone ; blood

Objective To investigate the serum levels of soluble human leukocyte antigen (sHLA)-G in patients with polymyositis (PM) or dermatomyositis (DM),and to analyze its association with clinical features and possible role in the pathogenesis of PM/DM.Methods Serum sHLA-G levels of 26 patients with PM,70 patients with DM and 35 matched healthy controls were measured by ELISA.The relationship between the sHLA-G levels and clinical features or seroimmunological data in the patients with PM/DM was analyzed.Results Serum levels of sHLA-G in PM/DM patients were significantly higher compared to healthy controls [(44±70) U/ml vs (4±5) U/ml,P＜0.01].There was statistically significant difference between DM patients and PM patients [(54±81) U/ml vs (27±41) U/ml,P=0.004].The incidence of dysphagia was significantly higher in sHLA-G elevated group than those in sHLA-G normal group (P=0.001).Additionally,Spearman rank correlation analysis showed that the serum sHLA-G levels were positively correlated with serum C3 (r=0.284,P=0.021),but negatively correlated with CD3+ T cells (r=-0.233,P=0.047) and CD4+ T cells (r=-0.287,P=0.015) in the peripheral blood in patients with PM/DM.Serum levels of sHLA-G in non-treated PM/DM patients were significantly higher compared to treated patients [(77±99) U/ml vs (34±52) U/ml,P=0.021].No relationship between serum sHLA-G levels and PM/DM disease activity,or different drug therapy was found.Conclusion Serum levels of sHLA-G are increased in PM/DM patients.The increased production of sHLA-G,paralleled with higher incidence of dysphagia and lower level of CD3+ T cells and CD4+ T cells,indicates that sHLA-G may play an important role in the pathogenesis of PM/DM.

Virus infection is a serious threat to human health and social development. The increase in pandemics caused by emerging and re-emerging viruses highlights the urgent need for broad-spectrum antivirals. In this perspective, we highlight recent case studies and summarize the universal strategies and methodologies in broad-spectrum antiviral drug discovery from common targets, common steps in viral life cycle, universal strategies, and broad-spectrum molecules, hoping to provide valuable guidance for the current and future development of antiviral drugs.

New drug research and development is a technology-intensive industry with high investment, high cycle and high risk. In recent years, with the rapid development of modern disciplines such as omics technology, bioinformatics, high-throughput and high-content screening, and artificial intelligence, the research and development of small-molecule drugs has presented a new paradigm characterized by "integrated medicinal chemistry". This review summarizes new enabling drug discovery technologies, the emergence of new subfields formed through integration innovations and practical chemistry toolbox in the field of medicinal chemistry.

Although current synthetic anti-gout drugs have significant therapeutic effects in reducing serum uric acid levels, they have serious side effects such as allergic reactions and liver and kidney damage. Natural products with a wide range of uric acid-lowering and high safety have played a critical role in anti-gout drug discovery and development. This paper reviews the natural products with uric acid-lowering or anti-gout pharmacological effects and the investigation on their mechanisms of action, to provide information for drug discovery and development.

Objective To identify the prevalence of anti-transcriptional intermediary factor (TIF)1-γ antibody in Chinese patients with idiopathic inflammatory myositis and to define its role in the assessment of early diagnosis of cancer associated myositis (CAM) in a large cohort.Methods Sera from 96 Chinese patients with dermatomyositis(DM),50 patients with polymyositis (PM),33 patients with systemic lupus erythem-atosus (SLE),54 patients with rheumatoid arthritis (RA),8 patients with systemic sclerosis (SSc),and 40 healthy controls were examined by immunoprecipitation assays followed by Western blotting.The distribution of these antibodies in each group was assessed and the association between this autoantibody and CAM in a large cohort was further revealed.T test,Mann-Wittney U test,Chi-square test and Fisher exact test were used for statistical analysis.Results Sera from 17 of 96 DM patients (18％),including 1 with juvenile dermatomyositis (JDM) (17％),2 with clinical amyopathic dermatomyositis (CADM) (25％),and 9 with CAM (64％) were found to have anti-TIF1-γ antibody by immunoprecipitation assays followed by Western blotting.Only 1 patient with PM (2％) was observed with anti-TIF1-γ autoantibody,and no patients with other connective tissue disease patients as well as healthy controls were positive for this autoantibody.The risk of -developing CAM in anti-TIF1γ-positive patients was significantly increased compared to the anti-TIF1-γnegative group,with an OR of 17.74 (95％CI,5.68-55.40).In DM,the negative and positive predictive value of anti-TIF1-γ autoantibody for the diagnosis of CAM was 90.8％ and 56.3％,respectively.Anti-TIF1γ-positive DM patients were significantly older than anti-TIF1-γ-negative DM patients (63±11 vs 48 ±14,P＜0.01).Notably,three of the anti-TIF1γ-positive patients had ILD,one patient was classified as having CAM and the other two were DM patients without cancer,but anti-TIF1γ-positive patients still had a significantly lower incidence of interstitial lung disease (19％ vs 54％,P＜0.05).In contrast to anti-TIF1-γγ-negative DM patients,anti-TIF1-γ antibody-positive patients were more frequently (81％ vs 50％,P＜0.01).There was no significant difference between these groups in terms of other clinical and laboratory parameters.Conclusion Anti-TIF1-γ antibodies may act as a useful diagnostic serological marker for early diagnosis of CAM in Chinese patients.For patients with DM,anti-TIF1-γ antibodies should be assessed at the time of disease diagnosis.This antibody may have impo-rtant significance in the early diagnosis of tumor and improving prognosis.

To observe a PPAR-alpha agonist effect of N-oleoylethanolamine (OEA) on CB2 (cannabinoid receptor 2), an anti-inflammatory receptor in vascular endothelial cell, healthy HUVECs and TNF-alpha induced HUVECs were used to establish a human vascular endothelial cell inflammatory model. Different doses of OEA (10, 50 and 100 micromol x L(-1)) had been given to HUVECs, cultured at 37 degrees C for 7 h and then collected the total protein and total mRNA. CB2 protein expression was detected by Western blotting and CB2 mRNA expression was assayed by real-time PCR. As the results shown, OEA (10 and 50 micromol x L(-1)) could induce the CB2 protein and mRNA expression, but not 100 micromol x L(-1). To detect if anti-inflammation effect of OEA is partly through CB2, CB2 inhibitor AM630 was used to inhibit HUVEC CB2 expression, then the VCAM-1 expression induced by TNF-alpha was detected, or THP-1 adhere to TNF-alpha induced HUVECs was examined. OEA (50 micromol x L(-1)) could inhibit TNF-alpha induced VCAM-1 expression and THP-1 adhere to HUVECs, these effects could be partly inhibited by a CB2 inhibitor AM630. The anti-inflammation effect of OEA is induced by PPAR-alpha and CB2, suggesting that CB2 signaling could be a target for anti-atherosclerosis, OEA have wide effect in anti-inflammation, it may have better therapeutic potential in anti-inflammation in HUVECs, thus achieving anti-atherosclerosis effect.

Child ; Contracture ; congenital ; therapy ; Humans ; Male ; Neck Muscles ; pathology ; Torticollis ; congenital

Objective To evaluate 99tcm-DTPA nuclear dynamic imaging in distinguishing the renal occupied disease.Methods A total of 164 in-patients with renal occupied disease who underwent surgery were included.According to the pathological diagnosis,119 patients had malignant tumors,and 45 patients had benign diseases.All patients’ imaging was retrospectively analyzed.Application of 99Tcm-DTPA nuclear dynamic imaging in renal occupied disease was compared with ultrasonography (US),computed tomography (CT),magnetic resonance imaging (MRI),intravenous pyelogram (IVP),and positron emission tomography (PET)-CT.Results The accuracy rates of different imaging methods in distinguishing between renal malignant and benign disease were 99Tcm-DTPA (84 ％,45 ％),US (72 ％,64 ％),CT ( 91％,92 ％),MRI (50 ％,67 ％),IVP (50 ％, 17 ％), respectively.The diagnostic accuracy rate of PET-CT for malignant tumors was 67 ％.The accuracy rates of 99Tcm-DTPA in distinguishing different phases of renal cell carcinoma were statistically significant (x 2 =83.4, P ＜ 0.01), while the accuracy rates in distinguishing renal cyst from renal angiomyolipoma were not statistically different.With the greater diameter, the diagnostic accordance rate is higher (x 2 =16.05,P ＜ 0.05).Conclusion 99Tcm-DTPA could be used not only to evaluate the renal function quantificationally,but also be helpful to distinguish renal malignant tumor from benign disease.

Objective To study the relationship between anti-transcription intermediary factor 1 family proteins (TIF1) autoantibodies profiles and cancer-associated dermatomyositis (CAM) and to define the diagnostic value of different subtypes of anti-TIF1 aotuantibodies for CAM.Methods The sera from 156 patients with dermatomyositis (DM),55 with polymyositis (PM),70 with systemic lupus erythematosus (SLE),60 with rheumatoid arthritis (RA),46 with primary Sj(o)gren syndrome (pSS),14 with systemic sclerosis (SSc),49 with kinds of malignancies and 40 healthy subjects were examined by immunoprecipitation assays followed by western blotting.Statistical analysis were performed using ANOVA,t test Mann-Wittney U and x2 test or Fisher exact test,nonparametric method was used to evaluate the sensitivity and specificity through calculating the area under the receiver operating characteristic curve (ROC).Results In summary,32 of 156 sera from patients with DM (20.5％) were positive for at least one anti-TIF1 autoantibodies.There are four subtypes of anti-TIF1 autoantibodies profiles existed in patients with DM,including 4 patients with only positive anti-TIF1-α (12.5％),20 with only positive anti-TIF1-γ (62.5％),7 with both positive anti-TIF1-α and anti-TIF1-γ (21.9％) and 1 with both positive anti-TIF1-β and anti-TIF1-γ (3.1％).However,only positive anti-TIF1-α (7.3％) was observed in 4 patients with PM.No patients with other CTDs as well as malignancy and healthy subjects were positive for these autoantibodies.The sensitivity and specificity of presence of anti-TIF1-α antibodies for the diagnosis of CAM were 42.9％ and 96.5％,respectively and those of anti-TIF1-β antibodies were 0 and 99.3％,respectively and those of anti-TIF-1-γ antibodies were 64.3％ and 86.6％,respectively.Application of areas of ROC to identify the best performance of test of anti-TIF1 antibodies profiles were 0.70,0.50,0.76,0.74 and 0.71,respectively.Conclusion Joint detection of antiTIF1 autoantibodies profiles can improve the diagnostic capbility for CAM.