Our current understanding of how sugar metabolism affects inflammatory pathways in macrophages is incomplete. Here, we show that glycogen metabolism is an important event that controls macrophage-mediated inflammatory responses. IFN-γ/LPS treatment stimulates macrophages to synthesize glycogen, which is then channeled through glycogenolysis to generate G6P and further through the pentose phosphate pathway to yield abundant NADPH, ensuring high levels of reduced glutathione for inflammatory macrophage survival. Meanwhile, glycogen metabolism also increases UDPG levels and the receptor P2Y 14 in macrophages. The UDPG/P2Y 14 signaling pathway not only upregulates the expression of STAT1 via activating RARβ but also promotes STAT1 phosphorylation by downregulating phosphatase TC45. Blockade of this glycogen metabolic pathway disrupts acute inflammatory responses in multiple mouse models. Glycogen metabolism also regulates inflammatory responses in patients with sepsis. These findings show that glycogen metabolism in macrophages is an important regulator and indicate strategies that might be used to treat acute inflammatory diseases.

Standard use of cool-tip RFA was dangerous for pancreatic head cancer close to portal vein, in which a 5-mm minimum safe distance between RFA site and major peripancreatic vessels might not be enough to avoid injury to the vessels.

Malignant pleural effusion (MPE) is a frequent complication of various cancers and often leads to a poor quality of life, prognosis, and life expectancy, and its management remains palliative. New approaches that can effectively treat MPE are highly desirable. Here, we show that methotrexate (MTX)packaging tumor cell-derived microparticles (MTX-MP) act as an effective immunotherapeutic agent to treat patients with MPE by mobilizing and activating neutrophils. We find that MTX-MP perfusion via a pleural catheter elicits the recruitment of neutrophils in patients through macrophage-released CXCL1 and CXCL2. By performing ex vivo experiments, we find that the recruited neutrophils are activated and release reactive oxygen species (ROS) and neutrophil extracellular trap (NET) to kill tumor cells. Neutrophil-released NETs were also able to seal off the damaged endothelium, facilitating MPE resolution in vitro and in tumor-bearing mice. These findings reveal the potential for use of cell-derived materials to package drugs as an immunotherapeutic agent against MPE.

Aim: The goal of this retrospective study was to analyze the strategy for the surgical management of insulinomas. Methods: From May 2000 to October 2006, the medical records of 52 patients with insulinomas were retrospectively studied. Results: All tumors were localized precisely by imaging techniques combined with intraoperative palpation. Forty-eight patients with benign lesions underwent surgical treatment: 41 patients open and 7 patients laparoscopic procedures. Four patients with malignant insulinomas underwent tumor resection; 3 of them underwent metastatic lesion and/or lymph node dissection. There were no discrepancies regarding operation time, blood loss, and complication rate between open enucleation and laparoscopic surgery. The mean hospital stay was 11.8 ± 3.4 days after laparoscopic surgery, shorter than the 17.0 ± 6.0 days after the open approach. Twenty-two complications occurred in 17 patients (32%) following resection. On follow-up, 86% of the patients were free from symptoms, and surgical cure was achieved in 95% of the patients with benign insulinomas. Conclusions: The choice of the surgical strategy for the treatment of pancreatic insulinomas depends on size and location of the tumor and the risk of malignancy. The optimal surgical procedure is key to prevent postoperative complications. The laparoscopic approach is safe and feasible for patients with benign tumors located in body or tail of the pancreas.

Objectives Infectious disease knowledge and behaviors are key elements that ensure student health and safety. This study explores the impact of health education on student knowledge and behaviors toward infectious diseases and determines the factors affecting infectious diseases knowledge and behaviors among students in Gansu, China. Methods A cross-sectional study and three sampling methods were used in two counties, 12 schools, and 32 classes in Gansu, China, from 2012 to 2013. Collected data included the following: (1) sociodemographic characteristics of 2002 students (1001 participants in the intervention group and 1001 in the control group); (2) accuracy of student knowledge and behaviors toward infectious diseases based on comparison of intervention and control groups through X2 test; and (3) mean scores on knowledge and behavior of students with different characteristics toward infectious diseases, as analyzed through analysis of variance (ANOVA). Multiple linear regression was conducted to analyze factors affecting student knowledge and behaviors toward infectious diseases. Results Statistically significant differences were observed among eight items of infectious disease transmission and treatment knowledge between intervention and control groups (P < 0.001). Average accuracies of knowledge and behaviors toward infectious diseases reached 72.23% and 60.03%. Significant differences were observed in six items on student behavior in rural and urban areas (P < 0.001). Health education, household register, and county affected scores of student knowledge and behaviors toward infectious diseases (P < 0.05). Gender and education level also affected scores of student behaviors toward infectious diseases (P < 0.001). Conclusions Health education contributes to student knowledge and behaviors toward infectious diseases. Students in the control group need intensified health education on infectious diseases. Health education needs to pay particular attention to rural students, all male students, and students at senior high school level living on campus.

Despite their mutual antagonism, inflammation and immunosuppression coexist in tumor microenvironments due to tumor and immune cell interactions, but the underlying mechanism remains unclear. Previously, we showed that tumor cell-derived microparticles induce an M2 phenotype characterized by immunosuppression in tumor-infiltrating macrophages. Here, we further showed that lung cancer microparticles (L-MPs) induce macrophages to release a key proinflammatory cytokine, IL-1β, thus promoting lung cancer development. The underlying mechanism involves the activation of TLR3 and the NLRP3 inflammasome by L-MPs. More importantly, tyrosine kinase inhibitor treatment-induced L-MPs also induce human macrophages to release IL-1β, leading to a tumor-promoting effect in a humanized mouse model. These findings demonstrated that in addition to their antiinflammatory effect, L-MPs induce a proinflammatory phenotype in tumor-infiltrating macrophages, promoting the development of inflammatory and immunosuppressive tumor microenvironments.

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Clinical applications of antiangiogenic agents profoundly affect tumor cell behaviors via the resultant hypoxia. To date, how the hypoxia regulates tumor cells remains unclear. Here, we show that hypoxia promotes the growth of human breast tumorigenic cells that repopulate tumors [tumor-repopulating cells (TRCs)] in vitro and in vivo. This stimulating effect is ascribed to hypoxia-induced reactive oxygen species (ROS) that activates Akt and NF-κB, dependent on the attenuated tricarboxylic acid (TCA) cycle. We find that fumarate is accumulated in the TCA cycle of hypoxic TRCs, leading to glutathione succination, NADPH/NADP + decrease, and an increase in ROS levels. Mechanistically, hypoxia-increased HIF-1α transcriptionally downregulates the expression of mitochondrial phosphoenolpyruvate carboxykinase (PCK2), leading to TCA cycle attenuation and fumarate accumulation. These findings reveal that hypoxia-reprogrammed TCA cycle promotes human breast TRCs growth via a HIF-1α-downregulated PCK2 pathway, implying a need for a combination of an antiangiogenic therapy with an antioxidant modulator.