Pluripotency makes human pluripotent stem cells (hPSCs) promising for regenerative medicine, but the teratoma formation has been considered to be a major obstacle for their clinical applications. Here, we determined that the downregulation of miR-302 suppresses the teratoma formation, hampers the self-renewal and pluripotency, and promotes hPSC differentiation. The underlying mechanism is that the high endogenous expression of miR-302 suppresses the AKT1 expression by directly targeting its 3'UTR and subsequently maintains the pluripotent factor OCT4 at high level. Our findings reveal that miR-302 regulates OCT4 by suppressing AKT1, which provides hPSCs two characteristics related to their potential for clinical applications: the benefit of pluripotency and the hindrance of teratoma formation. More importantly, we demonstrate that miR-302 upregulation cannot lead OCT4 negative human adult mesenchymal stem cells (hMSCs) to acquire the teratoma formation in vivo. Whether miR-302 upregulation can drive hMSCs to acquire a higher differentiation potential is worthy of deep investigation.

Background The use of mesh is controversial in the treatment of female pelvic organ prolapse. Objectives To systematically review the outcomes of sacrocolpopexy compared with transvaginal mesh surgery and to provide evidence-based suggestions. Search strategy The MEDLINE, EMBASE, Cochrane Library and clinicaltrials.gov databases were searched on 21 November 2018. Selection criteria Randomised controlled trials and prospective and retrospective cohort studies were included. Data collection and analysis Data were extracted by one reviewer and examined by a second reviewer for accuracy. Odds ratios and 95% CI were calculated using random-effects models. Main results Twenty comparative studies were included. The metaanalysis was performed with subgroups. The summary odds ratios of the randomised controlled group were 1.84 (95% CI 0.79-4.29, I 2 = 75%) for anatomical success, 1.41 (95% CI 0.47-4.24, I 2 = 38%) for subjective success, 0.42 (95% CI 0.18-0.98, I 2 = 0%) for mesh complications, 0.61 (95% CI 0.20-1.91, I 2 = 0%) for prolapse reoperation and 0.44 (95% CI 0.23-0.88, I 2 = 0%) for de novo dyspareunia. The mean differences were 0.77 (95% CI 0.31-1.23, I 2 = 66%) for total vaginal length and À1.28 (95% CI À2.00 to À0.55, I 2 = 66%) for point C after surgery. Conclusions Very-low-quality evidence indicated that the anatomical and subjective success rates of sacrocolpopexy were similar to those of transvaginal mesh surgery; sacrocolpopexy might be more beneficial than transvaginal mesh surgery in terms of mesh-related complication rates, prolapse recurrence and de novo dyspareunia. However, additional high-quality randomised trials with long-term follow-up durations are needed.

Immune checkpoint blockade (ICB) targeting PD-1/PD-L1 has been used for the treatment of head and neck squamous cell carcinoma (HNSCC). However, the overall response rate to ICB therapy for HNSCC remains less than 20%. It has recently been reported that the appearance of tertiary lymphoid structures (TLSs) in tumor tissue is correlated with better prognosis and response to ICB treatment. Here, we demonstrated an immune classification for the tumor microenvironment (TME) of HNSCC by analyzing The Cancer Genome Atlas (TCGA)–HNSCC data set and found that immunotype D with TLS enrichment had a better prognosis and response to ICB treatment. Furthermore, we observed that TLSs were present in a part of tumor samples of human papillomavirus (HPV) infection negative HNSCC (HPV− HNSCC) and were associated with the densities of dendritic cell (DC)–LAMP+ DCs, CD4+ T cells, CD8+ T cells, and progenitor T cells in TME. We established an HPV− HNSCC mouse model with TLS-enriched TME by overexpressing LIGHT in a mouse HNSCC cell line. We found that the induction of TLS formation enhanced the response to PD-1 blockade treatment in the HPV− HNSCC mouse model, accompanied by increases in DCs and progenitor exhausted CD8+ T cells in the TME. Elimination of CD20+ B cells attenuated the therapeutic effect of PD-1 pathway blockade in TLS+ HPV− HNSCC mouse models. These results indicate that TLSs contribute to the favorable prognosis and antitumor immunity of HPV− HNSCC. Inducing TLS formation in HPV− HNSCC tumors is a potential therapeutic method for improving the ICB response rate in patients with HPV− HNSCC.