Cancer immunotherapy using fusion hybrid cells generated from dendritic cells (DCs) and tumor cells may be more effective than other DC-based vaccines. DC-tumor fusion potentially confers not only the DCs' antigen-presenting functionality but also a continuing source of endogenous tumor antigens for major-histocompatibility-complex-restricted T-cell sensitization. In animal models, many investigators demonstrated that vaccination with fusion hybrids was protective against tumor challenge and therapeutic, resulting in the regression of established tumors. In clinical trials for patients with a variety of metastatic diseases, fusion hybrid vaccines were well tolerated, but the overall objective response rate was only 10.9%. Careful scrutiny of a large number of publications revealed that, in most cases, no definitive evidence of heterokaryonic fusion cell formation was found. Further corroboration of this conclusion comes from reports that fusion hybrids generated from autologous (syngeneic) and allogeneic DCs displayed equivalent immunological function and therapeutic effects in vitro and in vivo. This puzzling finding suggests that effective fusion immunotherapy depends on tumor antigen scavenging and presentation by antigen-presenting cells (APCs) of host origin and is in violation of the basic tenet of the principle of DC function. We believe that conclusions drawn from reported clinical trials have not properly evaluated the efficacy of the DC-tumor hybrid vaccine, and therefore, they neither confirm nor disclaim the potential benefits that may be derived from this form of immunotherapy.

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Neonatal sepsis is the main cause of death of newborns, especially premature infants. According to the statistics of epidemiology, the incidence rate of full-term infants is about 1%, the incidence rate of very low birth weight infants is as high as 20%, the mortality rate of early-onset sepsis is 13%, and the mortality rate of late-onset sepsis is 8.9%, which is extremely low, the mortality rate of very low birth weight infants can reach more than 20%. [1][2][3] In recent years, with the completion of the Human Genome Project and the development of

The FK506-binding protein 51 (FKBP51, encoded by FKBP5 gene) has emerged as a critical regulator of mammalian endocrine stress responses and as a potential pharmacological target for metabolic disorders, including type 2 diabetes (T2D). However, in β cells, which secrete the only glucose-lowering hormone—insulin, the expression and function of FKBP5 has not been documented. Here, using human pancreatic tissue and primary human islets, we demonstrated the abundant expression of FKBP5 in β cells, which displayed an responsive induction upon acute inflammatory stress mimicked by in vitro treatment with a cocktail of inflammatory cytokines (IL-1β, IFN-γ, and TNF-α). To explore its function, siRNAs targeting FKBP5 and pharmacological inhibitor SAFit2 were applied both in clonal NIT-1 cells and primary human/mice islets. We found that FKBP5 inhibition promoted β-cell survival, improved insulin secretion, and upregulated β-cell functional gene expressions (MAFA and NKX6.1) in acute-inflammation stressed β cells. In primary human and mice islets, which constitutively suffer from inflammation stress during isolation and culture, FKBP5 inhibition also presented decent performance in improving islet function, in accordance with its protective effect against inflammation. Molecular studies found that FKBP5 is an important regulator for FOXO1 phosphorylation at Serine 256, and silencing of FOXO1 abrogated the protective effect of FKBP5 inhibition, suggesting that it is the key downstream effector of FKBP5 in β cells. At last, in situ detection of FKBP5 protein expression on human and mice pancreases revealed a reduction of FKBP5 expression in β cells in human T2D patients, as well as T2D mice model (db/db), which may indicate a FKBP5-inhibition-mediated pro-survival mechanism against the complex stresses in T2D milieus.

To analyze the influencing factors and outcomes of the different severity of diabetic ketoacidosis (DKA). A total of 50 children with DKA admitted to the Department of Pediatrics, Tianjin Medical University General Hospital from January 2009 to December 2018 were included in this study. The patients were divided into mild group, moderate group, and severe group according to the severity of the disease. We then analyzed the clinical characteristics and outcomes of the 3 groups. Compared to mild and moderate DKA groups, patients with severe DKA were more likely to present chest tightness, and higher levels of blood osmotic pressure, urea, and creatinine ( P < .05). Logistic regression analysis showed that blood osmotic pressure, creatinine, and chest tightness were independent factors for severity of DKA. There was a significant difference in the resolution time of DKA among the 3 groups (mild vs moderate: 9.0 hours vs 15.25 hours; moderate vs severe: 15.25 hours vs 24.5 hours, P < .001). There were statistical differences in the decline of Glasgow score among 3 groups ( P = .004). Patients with severe DKA showed higher osmotic pressure and creatinine, as well as dyspnea. The children with severe DKA were more likely to present progression of neurological symptoms, which was necessary to pay attention to the presence of brain edema.