BACKGROUND: Previous studies have shown that the neutrophil-to-lymphocyte ratio (NLR) has a significant impact on the prognosis of many malignant tumors such as gastric cancer, colorectal cancer and pancreatic cancer, but the study on the prognosis of patients with resectable lung adenocarcinoma is less. The aim of this study is to investigate the correlation between the NLR and the clinicopathologic features of adenocarcinoma of lung patients who underwent radical pneumonectomy. Furthermore, this study aimed to clarify the predictive and prognostic significance of NLR in patients who underwent pneumonectomy for lung adenocarcinoma. METHODS: This study reviewed the medical records of 163 patients with lung adenocarcinoma who underwent pneumonectomy. The receiver operating characteristic (ROC) curve and Youden index were used to determine the cut-off value of the NLR. Survival curves were described by Kaplan-Meier method and compared by Log-rank test. The univariate and multivariate analyses were performed with the Cox proportional hazard model to identify the prognostic factors. RESULTS: When the NLR value was 2.96, the Youden index was maximal, with a sensitivity of 77.5% and a specificity of 75.9%. The 5-year survival rate in the low NLR group was higher than that in the high NLR group (P<0.05). The univariate and multivariate analyses showed that TNM staging and NLR were independent factors in predicting survival rate. CONCLUSIONS The NLR value was a simple and useful tool to predict the prognosis of lung adenocarcinoma after radical pneumonectomy.
Adenocarcinoma ; diagnosis ; immunology ; pathology ; surgery ; Adenocarcinoma of Lung ; Aged ; Cell Count ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms ; diagnosis ; immunology ; pathology ; surgery ; Lymphocytes ; cytology ; Male ; Middle Aged ; Neoplasm Staging ; Neutrophils ; cytology ; Pneumonectomy ; Prognosis ; ROC Curve ; Retrospective Studies

BACKGROUNDPrimary anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a chronic autoimmune disease associated with multisystem dysfunction. Renal involvement is common and closely associated with outcome. The purpose of this study was to investigate the clinical determinants of mortality of patients with AAV-related renal injury in the first 2 years after diagnosis in a single West Chinese center.

METHODSDemographic and laboratory parameters of 123 consecutive patients with AAV-related renal injury diagnosed in Renal Division and Institute of Nephrology, Sichuan Provincial People's Hospital between 2004 and 2012 were collected retrospectively. All patients were followed up for 2 years after diagnosis. Survivors were compared with nonsurvivors to identify the clinical baseline variables associated with mortality. Multivariate Cox regression model was used to determine the independent predictors of mortality.

RESULTSOf the 123 patients, 46 (37.4%) died by the end of 2 years after diagnosis, with 41 (33.3%) patients dying within the first 12 months. In comparison with the survivors, Birmingham Vasculitis Activity Score (BVAS), the incidence of pulmonary hemorrhage and digestive system (DS) involvement, serum creatinine, and erythrocyte sedimentation rate were significantly higher in nonsurvivors, whereas lymphocyte counts, hemoglobin, and complement 3 (C3) were significantly lower. Renal replacement therapy was more common in nonsurvivors. High BVAS (hazard ratio [HR] = 1.058, 95% confidence interval [CI]: 1.002-1.117; P = 0.042), pulmonary hemorrhage (HR = 1.970, 95% CI: 1.033-3.757; P = 0.04), DS involvement (HR = 2.911, 95% CI: 1.212-6.911; P = 0.017), and serum creatinine >400 μmol/L (HR = 2.910, 95% CI: 1.271-6.664; P = 0.012) were independent predictors of death in patients with AAV-related renal injury.

CONCLUSIONSPatients with AAV-related renal injury have high early mortality. Those with high BVAS (particularly with pulmonary or DS involvement) and serious renal dysfunction should receive aggressive therapy and careful monitoring to reduce the occurrence of adverse events and improve prognosis.

Adult ; Aged ; Aged, 80 and over ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis ; drug therapy ; immunology ; pathology ; Autoantibodies ; immunology ; Autoimmune Diseases ; drug therapy ; immunology ; pathology ; Cyclophosphamide ; therapeutic use ; Humans ; Immunosuppressive Agents ; therapeutic use ; Middle Aged ; Mycophenolic Acid ; therapeutic use ; Neutrophils ; immunology ; Proportional Hazards Models ; Retrospective Studies

BACKGROUND/AIMS: Role of autophagy in neutrophil function and the association of autophagy and autophagy related (ATG) gene polymorphisms with asthma susceptibility were suggested. In this study, we investigated the genetic association of ATG5 and ATG7 polymorphisms with asthma risk, severity and neutrophilic airway inflammation. METHODS: We recruited 408 asthma patients and 201 healthy controls. Sputum neutrophil counts were determined by H&E staining. Serum interleukin 8 (IL-8) levels were measured by enzyme-linked immunosorbent assay (ELISA). Genetic polymorphisms of ATG5 (-769T>C, -335G>A, and 8830C>T) and ATG7 (-100A>G and 25108G>C) were genotyped. The functional activities of ATG5 -769T>C and -335G>A variants were investigated by luciferase reporter assays. RESULTS: No associations of ATG5 and ATG7 polymorphisms with asthma susceptibility and severity were found. ATG5 -769T>C and -335G>A were in complete linkage disequilibrium. In the asthma group, GA/AA genotypes at ATG5 -335G>A were associated with higher neutrophil counts in sputum (p < 0.05); CC/TT genotype at ATG5 8830C>T associated with lower FEV1% predicted value (p < 0.05). DNA fragments containing ATG5 -769T and -335G alleles had higher promoter activities compared to those with -769C and -335A in both human airway epithelial cells (A549, p < 0.01) and human mast cell (HMC-1, p < 0.001). GG and CC genotype at ATG7 -100A>G and 25108G>C were significantly associated with high serum levels of IL-8 (p < 0.05 for both variants). CONCLUSIONS: Genetic polymorphisms of ATG5 and ATG7 could contribute to neutrophilic airway inflammation in the pathogenesis of adult asthma.
Adolescent ; Adult ; Asthma/blood/*genetics/immunology/pathology ; Autophagy/*genetics ; Autophagy-Related Protein 5/*genetics ; Autophagy-Related Protein 7/*genetics ; Case-Control Studies ; Cell Line ; Female ; Gene Frequency ; Genes, Reporter ; Genetic Predisposition to Disease ; Haplotypes ; Heterozygote ; Homozygote ; Humans ; Interleukin-8/blood ; Male ; Middle Aged ; Neutrophil Infiltration/*genetics ; Neutrophils/immunology/metabolism/*pathology ; Phenotype ; *Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Risk Factors ; Severity of Illness Index ; Transfection ; Young Adult

OBJECTIVETo evaluate the efficacy of epigallocatechin gallate (EGCG) in treatment of corneal alkali burn injury in mice.

METHODSCorneal alkali burn injury was induced by sodium hydroxide method in C57BL/6J mice. The mice with cornea burns were treated intraperitoneally with EGCG solution or phosphate buffer solution (PBS) respectively. The healing of corneal epithelium, the formation of corneal neovascularization (CNV) and the inflammation reaction were assessed by slit -lamp microscopy and histological examination. Expression of vascular endothelial growth factor (VEGF) mRNA and protein in cornea was evaluated by real -time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively. Myeloperoxidase (MPO) assay was used to quantitatively evaluate the polymorphonuclear neutrophils (PMNs) infiltration in the corneas.

RESULTSThe healing rate of corneal epithelium in EGCG group was significantly higher than that of PBS group at d1, d3 and d7 after treatment (d1: 41.0%±13.0% vs 23.8%±7.6%; d3: 76.6%±7.5% vs 61.2%±6.8%; d7: 87.8%±8.5% vs 74.0%±9.1%; all P <0.05). The CNV scores and the number of CNV in the corneal sections of EGCG group were significantly lower than those of PBS group at d3, d7 and d14 after treatment (CNV score: d3: 1.1±0.5 vs 6.6±1.0; d7: 1.3±0. 3 vs 8.1±1.0; d14: 0.9±0.2 vs 9.2±1.1; CNV number: d3: 1.68±0.61 vs 2.92±0.95; d7: 4.80±1.36 vs 7.92±1.28; d14: 3.64±0.71 vs 5.88±0.76; all P<0.05) . The expression of VEGF protein at d3 (0.19±0.05 vs 0.45±0.08) and d7 (0.42±0.07 vs 0.84±0.09), the expression of VEGF mRNA at d1, d3 and d7 in EGCG group were significantly lower than those in PBS group (all P <0.05). Compared to PBS group, the inflammatory index at d3 (3.2±0.4 vs 3.7±0.5) and d7 (2.3±0.5 vs 4.0±0.0), the number of PMNs in the corneal sections and the MPO values at d3, d7 and d14 in EGCG group were significantly decreased (PMNs: d3: 34.5±15.7 vs 90.0±28.8; d7: 17.1±11.4 vs 54.9±25.9; d14: 12. 8±4.6 vs 39.0±17.9; all P <0.05).

CONCLUSIONIn the murine corneal alkali burn model, intraperitoneal injection of EGCG solution can promote the healing of corneal epithelium, inhibit the formation of CNV and reduce the inflammatory cell infiltration in the corneas.

Alkalies ; Animals ; Burns, Chemical ; drug therapy ; Catechin ; analogs & derivatives ; therapeutic use ; Cornea ; drug effects ; pathology ; Corneal Neovascularization ; prevention & control ; Disease Models, Animal ; Eye Burns ; drug therapy ; Inflammation ; drug therapy ; immunology ; Mice ; Mice, Inbred C57BL ; Neutrophils ; cytology ; RNA, Messenger ; Vascular Endothelial Growth Factor A ; metabolism

Sweet's syndrome (SS), also known as acute febrile neutrophilic dermatosis, is characterized by the sudden onset of painful erythematous skin lesions together with fever and neutrophilia. SS can be associated with several disorders, such as malignancy, autoimmune disease, and infections. However, SS associated with liver cirrhosis is uncommon. We report a case of SS in a patient who was diagnosed with liver cirrhosis caused by chronic hepatitis B.
Hepatitis B, Chronic/complications/*diagnosis ; Humans ; Liver Cirrhosis/*diagnosis/etiology ; Male ; Middle Aged ; Neutrophils/immunology/pathology ; Skin Diseases/*diagnosis/pathology ; Sweet Syndrome/*diagnosis/pathology ; Tomography Scanners, X-Ray Computed

OBJECTIVETo investigate immune state in lung of BALB/c mice with ovalbumin (OVA) allergy and the effects of fulvotomentoside (Ful) on lungs of the mice and provide some clues for the mechanism that patients with food allergies were prone to asthma and observe the effects of the treatment with traditional Chinese medicine.

METHODNinety-six female BALB/c mice were randomly divided into 6 groups. Mice in group 1 and group 2 were sensitized intraperitoneally and challenged intragastrically with OVA and were exposed to phosphate buffer solution and OVA respectively by nebulized inhalation. Mice in group 3 and group 4 were treated with Ful, other processes were the same as the mice in group 1 and group 2, respectively. Mice in group 5 were not challenged intragastrically with OVA and other processes were the same as the mice in group 2. Group 6 was the control group. The number of total leukocytes and cell classification in bronchoalveolar lavage (BALF) were counted, and inflammatory characteristic of lung was scored by staining with hematoxylin and eosin. The protein expressions of transforming growth factor (TGF-β1), interleukin-6 (IL-6), interleukin-17 (IL-17A) in lung of the mice were detected by immunohistochemical method. The activation of neutrophils in lung was assayed by the level of myeloroxidase (MPO).

RESULTThere was no inflammatory cells infiltration in lung of the mice in group 1. Compared with group 6, numbers of total leukocytes and erythrocytes as well as the percentage of neutrophils and lymphocytes were increased in group 2. Inflammatory score and protein expressions of TGF-β1 [(75 437 ± 3 638) vs. (6 118 ± 1 978)], IL-6 [(121 650 ± 25 389) vs. (15 726 ± 9 360)], IL-17A [(252 105 ± 31 651)vs. (72 644 ± 12 285)] in lung were increased, too. Inflammatory score and TGF-β1 (11 054 ± 1 468), IL-6 (50 877 ± 11 744), IL-17A (137 864 ± 28 986) expressions in group 5 were lower than those in group 2. Eosinophils infiltration was significant in group 5. After the treatment with Ful, TGF-β1 expression did not change and IL-6, IL-17A expressions were decreased in lung of the mice that inhaled OVA. It was not enough for Ful to relieve the neutrophil aggregation and improve inflammatory reaction in lung.

CONCLUSIONThe expressions of TGF-β1, IL-6, IL-17A in lung of the mice with OVA allergy were increased markedly after they inhaled specific antigen, which caused serious inflammation that was induced by neutrophil infiltration in lung. Ful could decrease the expressions of IL-6, IL-17A to some extent, but it was not enough to improve pathologic state in lung.

Administration, Inhalation ; Animals ; Bronchoalveolar Lavage Fluid ; cytology ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Female ; Food Hypersensitivity ; immunology ; metabolism ; pathology ; Immunohistochemistry ; Inflammation ; Interleukin-17 ; metabolism ; Interleukin-6 ; metabolism ; Lung Diseases ; immunology ; pathology ; prevention & control ; Mice ; Mice, Inbred BALB C ; Neutrophils ; drug effects ; immunology ; Oleanolic Acid ; analogs & derivatives ; pharmacology ; Ovalbumin ; adverse effects ; immunology ; Saponins ; pharmacology ; Transforming Growth Factor beta1 ; metabolism

Neutrophil adhesion and migration are critical in hepatic ischemia/reperfusion (I/R) injury. Despite very strong preclinical data, recent clinical trials failed to show a protective effect of anti-adhesion therapy in reperfusion injury. Therefore, the aim of this study was to assess the role of CD44 in neutrophil infiltration and liver injury from hepatic I/R. In this study, using a partial hepatic ischemic model in vivo, we determined the potential role of CD44 in neutrophil infiltration and liver injury from I/R. Reperfusion caused significant hepatocellular injury as it was determined by plasma ALT levels and liver histopathology. The injury was associated with a marked neutrophil recruitment and CD44 expression into the ischemic livers. Administration of anti-CD44 antibody to mice reduced the infiltration of neutrophil into the ischemic tissue, associated with liver function preservation. These results support crucial roles of CD44 in neutrophil recruitment and infiltration leading to liver damage in hepatic I/R injury. Moreover, they provide the rationale for targeting to CD44 as a potential therapeutic approach in liver I/R injury.
Alanine Transaminase/blood ; Animals ; Antibodies/immunology/pharmacology ; Antigens, CD44/immunology/metabolism/*physiology ; Cytokines/metabolism ; Disease Models, Animal ; Liver/*metabolism/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Neutrophils/immunology/physiology ; Reperfusion Injury/metabolism/pathology/*prevention & control

Autoimmune pancreatitis (AIP) has two distinct subsets. Type 1 AIP or lymphoplasmacytic sclerosing pancreatitis is systemic disease with the elevation in serum levels of the IgG4. Type 2 AIP, also called duct-centric pancreatitis, features granulocyte epithelial lesions with duct obstruction in the pancreas without systemic involvement. Here, we report a case of type 2 AIP diagnosed by pathology, which is the first report in Korea. The case is a 56-year-old woman who presented with anorexia and vomiting. Computed tomography revealed mass-like lesion in the pancreatic head and the compression of the distal common bile duct and the head portion of the main pancreatic duct. Serum levels of the IgG4 were normal. Histologic examination revealed a dense neutrophil infiltration in the pancreatic parenchyme associated with extensive fibrosis, thereby confirming the diagnosis of type 2 AIP. The abnormalities in the clinical, laboratory, and radiological findings improved after oral steroid treatment.
Autoimmune Diseases/blood/immunology/*pathology ; Female ; Fibrosis ; Humans ; Immunoglobulin G/blood ; Magnetic Resonance Imaging ; Middle Aged ; Neutrophils/immunology ; Pancreas/pathology ; Pancreatitis/*drug therapy/immunology/pathology ; Steroids/*therapeutic use ; Tomography, X-Ray Computed

OBJECTIVETo explore the protective effects and mechanism of ethanol extract of Inonotus obliquus (EEIO) injection on asthmatic mice.

METHODOVA was injected intraperitoneally and inhaled to produce the asthmatic model. Thirty two mice were randomly divided into four groups: control group, asthma group and I. obliquus groups of high and low dose. The concentrations of IL-4, IL-5, IL-13 and IFN-gamma in BALF, the phosphor-p38 MAPK in lung tissues were respectively measured by ELISA and Western blotting. The number of inflammatory cells in BALF and histopathology changes were observed.

RESULTIn asthmatic group, the number of inflammatory cells and the concentrations of IL-4, IL-5, IL-13 in BALF and phospho-p38 MAPK in lung tissue were higher, while IFN-gamma were lower than those in normal control mice (P < 0.05). In I. obliquus group, the number of inflammatory cells, the concentrations of IL-4, IL-5, IL-13 in BALF and phosphor-p38 MAPK in lung tissue were lower, but were higher than those in normal control mice (P < 0.05), and histropathology damage was alleviated significantly. There was no significant difference observed among the efficacies in the I. obliquus groups of high and low dose.

CONCLUSIONp38 MAPK may play a role in pathological process of asthma. I. obliquus effectively treats asthma by inhibiting the expression of phosphor-p38 MAPK, correcting the unbalance of IFN-gamma/IL-4 and decreasing the number of inflammatory cells.

Animals ; Anti-Asthmatic Agents ; isolation & purification ; pharmacology ; Asthma ; drug therapy ; metabolism ; pathology ; Basidiomycota ; chemistry ; Basophils ; drug effects ; metabolism ; Bronchoalveolar Lavage Fluid ; cytology ; immunology ; Disease Models, Animal ; Interferon-gamma ; drug effects ; metabolism ; Interleukin-13 ; metabolism ; Interleukin-4 ; metabolism ; Interleukin-5 ; metabolism ; Lung ; pathology ; Lymphocytes ; drug effects ; metabolism ; Mice ; Mice, Inbred BALB C ; Neutrophils ; drug effects ; metabolism ; Phytotherapy ; Plant Extracts ; pharmacology ; p38 Mitogen-Activated Protein Kinases ; drug effects ; metabolism

Aged ; Antibodies, Antineutrophil Cytoplasmic ; blood ; Comorbidity ; Glomerulonephritis ; etiology ; immunology ; physiopathology ; Humans ; Male ; Neutrophils ; pathology ; Thrombotic Microangiopathies ; diagnosis ; physiopathology