OBJECTIVE: To investigate the role and mechanism of the cyclic guanosine monophosphate-adenosine monophosphate synthase/stimulator of interferon gene (cGAS/STING) pathway in oleic acid-induced acute lung injury (ALI) in mice. METHODS: Male wild-type C57BL/6J mice were randomly divided into five groups (each n = 10): normal control group, ALI model group, and 5, 50, 500 μg/kg inhibitor pretreatment groups. The ALI model was established by tail vein injection of oleic acid (7 mL/kg), while the normal control group received no intervention. The inhibitor pretreatment groups were intraperitoneally injected with the corresponding doses of cGAS inhibitor RU.521 respectively 1 hour before modeling. At 24 hours post-modeling, blood was collected, and mice were sacrificed. Lung tissue pathological changes were observed under light microscopy after hematoxylin-eosin (HE) staining, and pathological scores were assessed. Western blotting was used to detect the protein expressions of cGAS, STING, phosphorylated TANK-binding kinase 1 (p-TBK1), phosphorylated interferon regulatory factor 3 (p-IRF3), and phosphorylated nuclear factor-κB p65 (p-NF-κB p65) in lung tissue. Immunohistochemistry was performed to observe STING and p-NF-κB positive expressions in lung tissue. Serum interferon-β (IFN-β) levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the normal control group, the ALI model group exhibited significant focal alveolar thickening, intra-alveolar hemorrhage, pulmonary capillary congestion, and neutrophil infiltration in the pulmonary interstitium and alveoli, along with markedly increased pathological scores (10.33±0.58 vs. 1.33±0.58, P < 0.05). Protein expressions of cGAS, STING, p-TBK1, p-IRF3, and p-NF-κB p65 in lung tissue significantly increased [cGAS protein (cGAS/β-actin): 1.24±0.02 vs. 0.56±0.02, STING protein (STING/β-actin): 1.27±0.01 vs. 0.55±0.01, p-TBK1 protin (p-TBK1/β-actin): 1.34±0.03 vs. 0.22±0.01, p-IRF3 protein (p-IRF3/β-actin): 1.23±0.02 vs. 0.36±0.01, p-NF-κB p65 protein (p-NF-κB p65/β-actin): 1.30±0.02 vs. 0.53±0.02, all P < 0.05], positive expressions of STING and p-NF-κB in lung tissue were significantly elevated [STING (A value): 0.51±0.03 vs. 0.30±0.07, p-NF-κB (A value): 0.57±0.05 vs. 0.31±0.03, both P < 0.05], and serum IFN-β levels were also significantly higher (ng/L: 256.02±3.84 vs. 64.15±1.17, P < 0.05). The cGAS inhibitor pretreatment groups showed restored alveolar structural integrity, reduced inflammatory cell infiltration, and decreased hemorrhage area, along with dose-dependent lower pathological scores as well as the protein expressions of cGAS, STING, p-TBK1, p-IRF3 and p-NF-κB p65 in lung tissue, with significant differences between the 500 μg/kg inhibitor group and ALI model group [pathological score: 2.67±0.58 vs. 10.33±0.58, cGAS protein (cGAS/β-actin): 0.56±0.03 vs. 1.24±0.02, STING protein (STING/β-actin): 0.67±0.03 vs. 1.27±0.01, p-TBK1 protein (p-TBK1/β-actin): 0.28±0.01 vs. 1.34±0.03, p-IRF3 protein (p-IRF3/β-actin): 0.32±0.01 vs. 1.23±0.02, p-NF-κB p65 protein (p-NF-κB p65/β-actin): 0.63±0.01 vs. 1.30±0.02, all P < 0.05]. Compared with the ALI model group, positive expressions of STING and p-NF-κB in lung tissue were significantly reduced in the 500 μg/kg inhibitor group [STING (A value): 0.40±0.01 vs. 0.51±0.03, p-NF-κB (A value): 0.43±0.02 vs. 0.57±0.05, both P < 0.05], and serum IFN-β levels were also markedly reduced (ng/L: 150.03±6.19 vs. 256.02±3.84, P < 0.05). CONCLUSIONS The cGAS/STING pathway is activated in oleic acid-induced ALI, leading to exacerbated inflammatory responses and increased lung damage. RU.521 can inhibit cGAS, thereby down-regulating the expression of pathway proteins and cytokines, and providing protection to lung tissue.
Animals ; Acute Lung Injury/chemically induced* ; Male ; Nucleotidyltransferases/metabolism* ; Mice ; Signal Transduction ; Mice, Inbred C57BL ; Membrane Proteins/metabolism* ; Oleic Acid/adverse effects* ; Transcription Factor RelA/metabolism* ; Lung/pathology* ; Interferon Regulatory Factor-3/metabolism* ; Disease Models, Animal

T cell exhaustion occurs mostly in chronic infections,cancers and autoimmune diseases.Continuous antigenic stimulation leads to the generation of exhausted T cells,which is characterized by progressive loss of effector function,continuous high expression of inhibitory receptors,transcription and epigenetic changes,and metabolic disorders.The in-depth study of the specific mechanism of T cell exhaustion is providing new ideas for the immunotherapy of chronic infection,lung cancer and chronic airway inflammatory disease in respiratory dis-eases.This paper discussed the influencing factors and characteristics of T cell exhaustion and reviewed the current research status of T cell exhaustion and respiratory diseases.

Gastric cancer is a malignant tumor with worldwide high incidence and threatening the human health severely. It is a disease induced by multiple factors. Exosomes play an important role in the pathogenesis and development of many malignant tumors including gastric cancer. Exosomes can transport specific contents to regulate local and distant cell communications, and are able to promote or inhibit the development of gastric cancer through regulating the growth and proliferation of tumor cells, relevant immune function and angiogenesis of tumors. This article reviewed the effects of exosomes and their contents on the pathogenesis and development of gastric cancer.

Objective To explore the effect of 5-ethynyl-2'-deoxyuridine (EdU) -labeled adipose-derived stem cells (ADSCs) on lung colonization, TNF-α and IL-4 in rats induced by lipopolysaccharide (LPS) with acute lung injury. Methods Thirty male Sprague-Dawley (SD) rats were randomly divided into the normal control group (n=10), LPS model group (n=10), and LPS+ADSCs intervention group (n=10). The ALI model rats were intraperitoneally injected with 8 mg/kg LPS, rats in the normal control group were intraperitoneally injected with 4 mL/kg physiological saline, and rats in the LPS+ADSCs group were intravenously injected with 300 μL ADSCs by tail vein after 30 minutes for the ALI model establishment, and rats in the normal control group and LPS group were intravenously injected with 300μL physiological saline by tail vein. The time of death in rats was observed, lung tissue and blood from left ventricular were collected, and the serum tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-4) were detected by Enzyme-linked immunosorbent assay (ELISA). Lung wet/dry weight (W/D) ratio was detected by thoracotomy, the pathological changes of lung tissue were observed under optical microscope, and the colonization of ADSCs in the lungs were observed under immunofluorescence microscopy. LSD-t method was used to compare between every two groups. Results There was no significant difference in mortality between the LPS group and LPS + ADSCs group (50％ vs. 70％, P> 0.05); EdU-labeled ADSCs were extensively colonized in the lungs by tail vein injection after 24 h; Compared with the normal control group, the lung injury of the LPS group was heavier, the ratio of lung W/D and TNF-α were significantly increased (all P< 0.01), and IL-4 level was significantly decreased (P< 0.01). Compared with the LPS model group, the degree of lung injury in the LPS + ADSCs group was significantly reduced, lung W/D ratio (5.57±0.27 vs. 5.98±0.28) and TNF-α level of blood [(41.51±4.14)ng/L vs. (45.52±3.74)ng/L] were significantly reduced (all P< 0.05), whereas the IL-4 levels were significantly increased [(7.01±1.11)pg/mL vs. (3.27±0.54)pg/mL, P< 0.05]. Conclusions EdU-labeled ADSCs could be colonized in the lungs of LPS-induced ALI rats, reduce the inflammatory response from TNF-α and improve the anti-inflammatory response from IL-4.

As multidrug resistance related genes and cell factors are discovered one after another,people have a more thorough understanding to the oncological mechanisms of cancer metastasis.Many evidences of the inherent link between the two tips have been found.These researches provide new ideas to further clarify the regulation mechanisms between them.It is revealed that the inherent link maybe occur on the gene expression and transcription,and with complicated regulative factors.Indepth study of the relations between cancer multidrug resistance and metastasis will help to guide the clinical treatment of tumor.

ObjectiveTo analyze the risk factors of complications after laparoscopic gastrectomy.Methods The clinical data of 76 patients who received laparoscopic gastrectomy at the Tenth Hospital of Tangji University from April 2009 to July 2011 were retrospectively analyzed.All patients were divided into complication group (13patients) and non-complication group (63 patients).Seventeen variables,including gender,age,abdominal surgery history,comorbidities (cardiovascular disease,chronic obstructive pulmonary disease,diabetes mellitus,anemia,hypoproteinemia,pyloric obstruction),palliative operation,operative data ( operation time,blood loss,method of alimentary tract reconstruction),postoperative TNM staging,vascular or nerve invasion and number of lymph nodes dissected were analyzed by using the univariate and Logistic regression analysis to screen out the risk factors of postoperative complications.All data were analyzed using the t test or chi-square test.ResultsThere were 67 patients received laparoscopic curative gastrectomy and 9 received laparoscopic palliative gastrectomy.Sixty-three patients received distal gastrectomy ( including 49 received BillrothⅠgastrectomy and 14 received Billroth Ⅱ gastrectomy) and 13 patients received total gastrectomy + Roux-en-Y esophagojejunostomy).The mean operation time,blood loss,number of lymph nodes dissected were ( 263 ± 72) minutes,( 200 ± 191 ) ml and 17 ±8,respectively.There were 25 patients in TNM stage Ⅰ,18 in stage Ⅱ,27 in stage Ⅲ and 6 in stage Ⅳ.The incidence of complications was high in the old patients,but there was no effect of gender and age on the incidence of complications ( x2 =0.68,2.32,P ＞ 0.05 ).The operation time of the complication group was longer than that of non-complication group,but no significant difference was observed ( t =1.44,P ＞ 0.05 ).Preoperative comobidities (cardiovascular disease,chronic obstructive pulmonary disease,diabetes mellitus,anemia,hypoproteinemia,pyloric obstruction),blood loss and number of lymph node disseeted were not the risk factors of postoperative complications ( x2 =3.20,0.58,0.13,0.26,0.01,0.19,t =0.15,0.83,P ＞ 0.05).The results of multivariate Logistic regression analysis showed that Billroth Ⅱ alimentary tract reconstruction,more comorbidites,and advanced TNM stage were correlated with postoperative complications ( OR =5.54,7.02,2.33,P ＜0.05 ).The accuracy rate of multivariate Logistic regression analysis was 8 i.6％.Conclusion Billroth Ⅱ alimentary tract reconstruction,more comorbidities,and advanced TNM stage are the independent risk factors of complicatioas after laparoscopic gastrectomy.