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Objectives: Our study aimed to investigate the distinct clinical patterns of seronegative IgG4‐related disease (IgG4‐RD) patients. Methods: We retrospectively enrolled 698 treatment‐naïve IgG4‐RD patients in this study. Patients were divided into four different subgroups according to their baseline serum IgG4 levels. The distinct clinical patterns of seronegative IgG4‐RD patients were revealed through the comparison of baseline clinical data and disease prognosis among the different subgroups. COX regression analyses were used to investigate the risk factors for disease relapse and to construct the nomogram model. Results: Seronegative IgG4‐RD patients account for a minority of IgG4‐RD patients (49/698, 7.02%). The proportions of seronegative IgG‐RD patients in our study and several Asian cohorts were significantly lower than those of the European and American cohorts. Seronegative IgG4‐RD patients got lower serum IgG levels (p < 0.0001), lower eosinophil count (p < 0.0001), lower serum IgE levels (p < 0.0001)), lower IgG4‐RD responder index (RI) scores (p < 0.0001), and fewer affected organ numbers (p < 0.0001) compared with other subgroups, whereas they were more likely to manifest fibrotic type with some special organ involvement. Younger age at onset, GCs monotherapy, elevated C‐reactive protein level, and elevated erythrocyte sedimentation rate level are the risk factors for the disease relapse of seronegative IgG4‐RD patients. An effective nomogram model predicting disease relapse of seronegative IgG4‐RD patients was constructed. Seronegative IgG4‐RD patients with scores >84.65 at baseline were susceptible to suffering from disease relapse. Conclusions: Distinct clinical features and multiple risk factors for disease relapse of seronegative IgG4‐RD patients have been revealed in this study. A nomogram model was constructed to effectively predict disease relapse during the follow‐up period. [ABSTRACT FROM AUTHOR]

This article develops a framework to demonstrate how employee job satisfaction influences entrepreneurial intentions. Based on new institutional theory, we examine our hypotheses using data from 39,394 employees from 27 countries; the results indicate that job satisfaction has a negative effect on entrepreneurial intentions moderated by uncertainty avoidance at the country level. Furthermore, a cross-level three-way interaction indicates that entrepreneurship legitimacy is an important climate-level variable that influences the entrepreneurial intentions of employees. We conclude by discussing the implications of our findings and future research directions. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a devastating and highly metastatic cancer worldwide. Metformin (MET) is the priority drug for treatment of type 2 diabetes; however, it possesses multiple biological effects like anticancer and hepatoprotective activity. Herein, we examined the effects of aloin (barbaloin) and MET as well as combination treatment in HCC cell line in vitro and in vivo. As a result, aloin and MET alone exhibited inhibitory effects on proliferation and invasion of HepG2 and Bel‐7402 cells. Specially, combination treatment of aloin and MET showed enhanced inhibitory effects in vitro. Aloin and MET alone induced apoptosis and autophagy in vitro. Similarly, aloin and MET cooperated to promote apoptosis and autophagy in HepG2 and Bel‐7402 cells. In the HepG2 xenograft models, aloin in combination with MET confine tumor growth and facilitate apoptosis and autophagy. Both the in vitro and in vivo results showed that aloin and MET alone as well as combination treatment activated the PI3K/AKT/mTOR pathway. Overall, our research demonstrated that the concomitant treatment with aloin and MET enhances the antitumor effect by inhibiting the growth and invasion as well as inducing apoptosis and autophagy in HCC through PI3K/AKT/mTOR pathway. [ABSTRACT FROM AUTHOR]