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Purpose In colorectal cancer (CRC), whether the immune score can be used to predict the clinical prognosis of the patient has not been completely established. Besides, the prognostic values of tumor-infiltrating lymphocytes (TILs) in different anatomical locations, counting sites, and subtypes have been controversial. The purpose of this meta-analysis is to analyze and determine the prognostic value of TILs indices including TIL subsets, infiltrating sites, and anatomical sites. Methods Relevant literature was obtained by searching PubMed and Google Scholar. The pooled hazard ratio (HR) of the overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) was computed to investigate the prognostic significance of CD3+, CD8+, CD45RO+, and FOXP3+ T cells. Results A total of 22 studies involving 5108 patients were included in the meta-analysis. In CC, based on T cell subtypes analysis, the final results indicated that CD8+ and FOXP3+ infiltrating cells, but not CD3+ T cells were prognostic markers for DFS and OS. In addition, with regard to the counting location of TILs, subgroup analysis revealed that only high FOXP3+ infiltrates in the tumor stroma (ST) were significantly associated with OS (HR = 0.38, 95% confidence interval (CI) = 0.22–0.67, P = 0.0007), whereas in invasive margin (IM), high density of CD3+ infiltrating cells indicated increased DFS (HR = 0.76, 95% CI = 0.62–0.93, P = 0.008). At the tumor center (TC), high CD8+ T cells infiltration was associated with improved DFS (HR = 0.50, 95% CI = 0.38–0.65, P < 0.00001). In RC, whether CSS or OS, high-density TIL was associated with improved prognosis. Conclusion In a single counting site, high-density TILs reflect favorable prognostic value in CC or RC. For CC, more prospective studies are needed to verify whether different anatomical sites affect the distribution of TILs and thus the prognosis of patients. For RC, further studies should analyze the prognostic value of the immune score. Electronic supplementary material The online version of this article (10.1186/s12957-019-1621-9) contains supplementary material, which is available to authorized users.

BACKGROUND Bilaterality is common in papillary thyroid cancer (PTC), but its clinical and prognostic implications are still controversial, and it remains unclear whether its behavior is more aggressive than multifocality. METHODS The clinicopathologic features of 2211 consecutive patients with PTC who underwent surgical treatment at the authors’ institute between 1997 and 2011 were reviewed. Among these surgical patients, 425 (19.2%) had bilateral PTCs, and 1786 had unilateral PTCs. The patients who had unilateral PTCs were subdivided into a group with unilateral‐multifocal PTCs (210 patients) and a group with solitary PTCs (1576 patients). The 10‐year disease‐free survival (DFS) rates were calculated to compare the prognosis between groups. B‐Raf proto‐oncogene, serine/threonine kinase (BRAF) mutation status was examined by direct DNA sequencing. RESULTS Patients who had bilateral PTCs were likely to have larger tumors, higher rates of extrathyroid extension and lymph node metastasis, and more advanced tumor stage than those who had unilateral‐multifocal PTCs. Multivariate analysis identified only lymph node metastasis as an independent risk factor for PTC recurrence (P < .001). The 10‐year DFS rate for patients with bilateral PTCs was much lower than that for those with unilateral‐multifocal and solitary PTCs (78.8% vs 85.7% and 89.3%, respectively; P = .005). It is noteworthy that patients who had bilateral PTCs with lymph node metastasis had the worst prognosis in terms of DFS. Incidence of the BRAF V600E mutation (valine to glutamic acid mutation at position 600) was higher in the bilateral PTC group than that in the unilateral and unilateral‐multifocal PTC groups. CONCLUSIONS The current results provide initial evidence that bilateral PTCs are more aggressive than unilateral‐multifocal PTCs, and patients who have bilateral disease have more advanced stage and shorter DFS. The poorer outcome of patients with bilateral PTCs may be caused in part by their high incidence of lymph node metastasis. Cancer 2016;122:198–206. © 2015 American Cancer Society.

Our data demonstrate that vemurafenib induces ER stress response-mediated autophagy in thyroid cancer and autophagy inhibition may be a beneficial strategy to sensitize BRAF-mutant thyroid cancer to vemurafenib.

Sesamol, an antioxidant lignan from sesame oil, possesses neuroprotective bioactivities. The present work was aimed to elucidate the systemic protective effects of sesamol on cognitive deficits and to determine the possible link between gut and brain. Wildtype and ApoE–/– mice were treated with a high-fat diet and sesamol (0.05%, w/v, in drinking water) for 10 weeks. Behavioral tests including Morris-water maze, Y-maze, and elevated plus maze tests indicated that sesamol could only improve cognitive deficits and anxiety behaviors in wildtype. Consistently, sesamol improved synapse ultrastructure and inhibited Aβ accumulation in an ApoE-dependent manner. Moreover, sesamol prevented dietary-induced gut barrier damages and systemic inflammation. Sesamol also reshaped gut microbiome and improved the generation of microbial metabolites short-chain fatty acids. To summarize, this study revealed that the possible mechanism of neuroprotective effects of sesamol might be ApoE-dependent, and its beneficial effects on gut microbiota/metabolites could be translated into neurodegenerative diseases treatment.

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Background A study has shown that miR-423-5p is highly expressed in proliferative diabetic retinopathy. However, the exact biological functions and mechanisms of miR-423-5p in diabetic retinopathy (DR) progression are currently unclear. This study aimed to investigate the role of miR-423-5p in DR and the underlying mechanism. Results Our data demonstrate that the expression of miR-423-5p is significantly increased in HG-induced RPE cells and DR patient plasma. Moreover, the overexpression of miR-423-5p exacerbates HG-induced apoptosis. Mechanistically, our results provide evidence that miR-423-5p directly targets TFF1. MiR-423-5p exerts its effect on HG-induced apoptosis in RPE cells through TFF1, and the NF-κB pathway is involved in the regulatory mechanism. Further analysis revealed that the transcription factor NFE2 regulates miR-423-5p promoter activity. In addition, NFE2 regulates the levels of TFF1 and NF-κB pathway-associated proteins by regulating the expression of miR-423-5p. Conclusion The NFE2-miR-423-5p-TFF1 axis is a novel molecular mechanism and provides a new direction for the study and treatment of DR.