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In vivo, the level of cyclic Adenosine Monophosphate (cAMP) and the pathway of the Janus Kinase1/Signal Transducers and Activators of Transcription1 (JAK1/STAT1) were studied. In vitro, the Ca(2+) mobilization in human platelet stimulated by thrombin was observed. In addition, vasomotion of vascular smooth muscle was measured by adding KCl or norepinephrine(NE) under the Ca(2+) contained bath solutions. The effect induced by NE in the presence of N-nitro-L-arginine methyl ester (L-NAME) or indometacin (Indo) was also detected. At last, the levels of tissue plasminogen activator (t-PA) and Plasminogen activator inhibitor-1 (PAI-1) in cultured supernatans in Human umbilical vein endothelial cells (Huvecs) were measured by means of ELISA kit. Results showed that Nattokinase (NK) significantly increased the cAMP level, activated the signal passage of JAK1/STAT1 in injured part and inhibited remarkably the rise of platelet intracellular Ca(2+) ([Ca(2+)]i) in human platelet. Furthermore, NK relaxed rat thoracic aortic artery in the dose-dependent manner and in the endothelium dependent manner and its effect could be attenuated by L-NAME. Also, the secretion of t-PA and PAI-1 were reduced stimulated by Adr on Huvecs. These data indicated that the neuroprotective effect of NK was associated with its antiplatelet activity by elevating cAMP level and attenuating the calcium release from calcium stores; with its anti-apoptotic effect through the activation of JAK1/STAT1 pathway; with its relaxing vascular smooth muscle by promoting synthesis and release of NO, reducing ROC calcium ion influx and with its protection on endothelial cells through increasing fibrinolytic activity and facilitating spontaneous thrombolysis.

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Objective. To study the value of rheumatoid factor (RF) levels in the risk assessment of rheumatoid arthritis (RA) and combined hypertension and diabetes mellitus (DM) and construct RA risk prediction and medical image applications from rheumatoid factor levels. Methods. A total of 249 RA patients who were treated in the First People’s Hospital of Yunnan Province, and another 149 non-RA people were selected as the controls. The clinical data and the detection results of serum circulating RF_IgA, RF_IgG, and RF_IgM were collected. The receiver operating curve (ROC) and logistic regression were used to analyze the value of RF levels in the risk assessment of RA and combined hypertension and DM. Results. After adjusting for age, BMI, smoking, drinking, hypertension, and diabetes, logistic regression analysis showed that RF_IgA positive, RF_IgG positive, and RF_IgM positive were all independent risk factors for RA ( P < 0.05 ). The area under the curve (AUC) of circulating RF_IgA, RF_IgG, and RF_IgM levels in predicting RA was 0.79 (95% CI: 0.74-0.83, P < 0.001 ), 0.73 (95% CI: 0.68-0.78, P < 0.001 ), and 0.87 (95% CI: 0.84-0.91, P < 0.001 ), respectively. The AUC for predicting RA was 0.88 (95% CI: 0.85-0.92, P < 0.001 ) when combined detection of circulating RF_IgA, RF_IgG, and RF_IgM levels in peripheral blood. After adjusting for age and sex, logistic regression analysis showed that RF_IgA positive, RF_IgG positive, and RF_IgM positive were not independent risk factors for DM in RA patients ( P > 0.05 ). Conclusion. The levels of serum circulating RF_IgA, RF_IgG, and RF_IgM are valuable indicators for predicting the risk of RA, but not for the risk of RA complicated with hypertension and DM.