High dose Vitamin C inhibits PD-L1 by ROS-pSTAT3 signal pathway and enhances T cell function in TNBC.

Vitamin C (VitC) presents excellent anti-tumor effect for long time. Recently, high dose VitC achieved by intravenous administration manifests superior anti-tumor effect. However, the functions and detailed mechanisms of high dose VitC's role in cancer immunity are not fully understood. This study investigates the effect of high dose VitC on PD-L1 expression in triple negative breast cancer (TNBC) and the potential mechanism. Results showed VitC inhibited PD-L1 expression in breast cancer cell lines and enhanced anti-tumor effects of T cells. Furthermore, we found VitC inhibited PD-L1 transcription through ROS-pSTAT3 signal pathways. Consistent with in vitro results, in vivo study showed VitC suppressed tumor growth in immunocompetent mice and enhanced CD8+ T cells infiltration and function in tumor microenvironment. Our findings identify the effects of high dose VitC on PD-L1 expression and provide a rationale for the use of high dose VitC as immunomodulator for cancer therapy.

Relationships between job satisfaction, organizational commitment, burnout and job performance of healthcare professionals in a district-level health care system of Shenzhen, China.

Background: Existing research indicates that job satisfaction has effects on job performance, but little evidence exists about the mechanism through which the satisfaction-performance association operates. This study aims to examine the effect of job satisfaction on job performance in a district-level health care system of China and to explore the effect mechanism mediated by organizational commitment and burnout. Methods: Cluster sampling was used in this study. All healthcare professionals in the Nanshan Medical Group, who were at work in the last 3 months and able to complete online questionnaire independently were invited to participate the anonymous online survey. Job satisfaction, organizational commitment, burnout and job performance were measured by tools, which have been validated in China. Descriptive statistics were used for the socio-demographic variables and the four job psychological variables. Pearson correlation coefficients was used to determine associations among each of the psychological variables. Linear regression was used to examine association between job performance and other three psychological variables. PROCESS macro was used to examine the mediation effects of organizational commitment and burnout on the association between job satisfaction and performance. Results: In total, 1,200 healthcare professionals completed the anonymous online survey. Job satisfaction, organizational commitment, and job performance were positively correlated with one another, with burnout negatively correlated with them. Linear regression revealed that demographic characteristics, job satisfaction, organizational commitment, and burnout explained 5, 6, 2, and 9% of the variance in job performance. Path analysis showed that the coefficient of the direct effect of job satisfaction on job performance was 0.18, the coefficients of the indirect effects of job satisfaction on job performance through organizational commitment and burnout were 0.17 and 0.37, respectively. The coefficients of the indirect effects of organizational commitment on job performance through burnout was -0.04, but it was not significant. Conclusion: It is promising to improve job performance of providers in Chinese healthcare systems by improving job satisfaction and reducing burnout. Tailored support policies for female healthcare professionals, appropriate incentive mechanisms and improving multidisciplinary healthcare delivery are potential to improve job performance of healthcare professionals in integrated healthcare systems.

Analysis of immunological mechanisms exerted by HBsAg-HBIG therapeutic vaccine combined with Adefovir in chronic hepatitis B patients.

An HBsAg-HBIG therapeutic vaccine (Yeast-derived Immune Complexes, YIC) for chronic hepatitis B (CHB) patients has undergone a series of clinical trials. The HBeAg sero-conversion rate of YIC varied from 21.9% to 14% depending on the immunization protocols from 6 to 12 injections. To analyze the immunological mechanisms exerted by 6 injections of YIC, 44 CHB patients were separately immunized with YIC, alum as adjuvant control or normal saline as blank control, with add on of antiviral drug Adefovir in all groups. Kinetic increase in Th1 and Th2 cells CD4+ T cell sub-populations with association in decrease in Treg cells and increase of Tc1 and Tc17 cells in CD8+ T cells were observed in YIC immunized group. No such changes were found in the other groups. By multifunctional analysis of cytokine profiles, significant increase of IL-2 levels was observed, both in CD4+ and CD8+ T cells in the YIC immunized group, accompanied by increase in IFN-gamma and decrease of inhibitory factors (IL-10, TGF-ß and Foxp3) in CD4+ T cells. In the alum immunized group, slight increase of IL-10, TGF-ß and Foxp3 in CD4+ T cells was found after the second injection, but decreased after more injections, suggesting that alum induced early inflammatory responses to a certain extent. Similar patterns of responses of IL-17A and TNF-α in CD8+T cells were shown between YIC and the saline group. Results indicate that add on of Adefovir, did not affect host specific immune responses.