Adult ; Betacoronavirus ; Clinical Laboratory Techniques ; Coronavirus Infections ; diagnosis ; epidemiology ; etiology ; prevention & control ; therapy ; Diagnosis, Differential ; Extracorporeal Membrane Oxygenation ; Humans ; Pandemics ; prevention & control ; Pneumonia, Viral ; epidemiology ; etiology ; prevention & control ; therapy ; Practice Guidelines as Topic ; Respiration, Artificial

Objective To observe the immunohistochemical changes of ICAM-1,MMP-2 and MMP-9 in the lungs of immunocompromised rats with Pseudomonas aeruginosa pneumonia and their relationships with lung inflammation.Methods After the establishment of pseudomonas aeruginosa pneumonia infected immunocompromised rat mode,the pathological changes of lungs were observed, lung wet/dry ratios and total protein concentration in bronchial alveolar lavage fluid were tested,and imunnohistochemical study of ICAM-1,MMP-2 and MMP 9 in lung tissue were performed.Results 1.The staining intensity of ICAM-1 in alveolar epithelial cells turned stronger in rats with pulmonary infection than those without of both groups(P＜0.05);2.The staining intensity of MMP-2 in lung tissue was stronger in rats with pulmonary infection than those without infection in both groups,and reached peak at 6～9 h after inoculation.Immunohistochemical changes of MMP-9 exhibited a similar pattern,4.Immunohistochemical changes of ICAM-1,MMP-2 and MMP-9 showed some correlation with numbers of polymorphonuclears in lung tissue(P＜0.05);5.A correlation between the stai- ning intensity of MMP-9 in bronchial epithelial eells and total protein concentrations were observed(r_s =0.484,P＜0.05),similar association were found between the staining intensity of MMP-2 in alveolar epithelial cells,endothelium of arterioles and venules and tissues beneath endothelium and to- tal protein eoncentrations in bronchial alveolar lavage fluid(r_s were 0.457,0.492 and 0.429,respec- tively,P＜0.05).Conclusion In immunocompromised rats,the staining intensity of ICAM-1, MMP-2 and MMP-9 in lung tissue of those with pseudomonas aeruginosa pneumonia were stronger than those without infection,and the changes were demonstrated some correlation with the levels of polymorphonuclears infiltration or severity of lung injury.

Adult ; Carcinogens ; Epoxy Compounds ; poisoning ; Female ; Humans ; Lymphocytes ; drug effects ; metabolism ; Male ; Multivariate Analysis ; Mutation ; drug effects ; Occupational Exposure ; analysis ; Regression Analysis ; Sister Chromatid Exchange ; drug effects

Objective To study inflammatory reaction induced by N-protein of severe acute respiratory syndrome(SARS)-coronavirus(CoV)in human alveolar typeⅡepithelial cell(A549). Methods Effects on growth of A549 cell by N-protein of SARS-CoV:activity of A549 cells was determined by thiazylyl blue colorimetry assay at 24,48,72 and 96 h,respectively.Effects on cyto- kine production by A549 cells exposed to N-protein of SARS-CoV:interleukin(IL)-6,IL-10 and transforming growth factor-?1(TGF-?1)concentration in culture supernatant were determined by enzyme-linked immunosorbent assay(ELISA).Effects on mRNA expression of cytokine of A549 cells and matrix metalloproteinases-9(MMP-9)exposed to N-protein of SARS-CoV:total RNA of A549 cells was extracted using Rneasy mini kit;RT-PCR was employed to measure the mRNA expression of IL-6,IL-10,TGF-?1 and MMP-9 semiquantitatively.Results Different concentrations of N-protein could all inhibit the growth of A549 cells(after 48 h)and the inhibition by 20?g/mL pro- tein was the strongest.Compared with the control group(0.737?0.024,0.968?0.007),the A val- ues of experimental groups at 72 h and 96 h(0.672?0.027,0.799?0.092)decreased obviously (P

Objective To investigate the relationship between the polymorphisms of both aldose reductase (AR) and endothelial nitric oxide synthase (eNOS) genes in chromosome 7q35 and the susceptibility to diabetic nephropathy (DN) in type 2 diabetes of Han nationality in North China. Methods The C(-106)T in the promoter region of AR gene as well as the G894T in exon 7 and the 27 bp repeat polymorphism in intron 4 of the eNOS gene were investigated in 85 healthy controls and 134 type 2 diabetics with or without DN. The C(-106)T as well as the G894T genotype were determined by PCR RFLP method and sequencing the PCR products. The 27 bp repeat polymorphism alleles were determined by PCR combined with agarose gel electrophoresis and sequencing the PCR products. Results The frequencies of the C allele and C/C genotype in AR gene as well as T allele and T/G genotype in exon 7 and the 4a allele and 4a/4b genotype in intron 4 of eNOS gene were significantly higher in DN+ group than those in DN-group (all P

Age Factors ; Animals ; Cytokines ; physiology ; Humans ; RNA, Messenger ; analysis ; Sepsis ; etiology ; Signal Transduction ; Toll-Like Receptors ; genetics ; physiology

BACKGROUNDThe solitary pulmonary nodule (SPN) is one of the most common findings on chest radiographs. The objectives of clinical practice are to differentiate malignant nodules from benign nodules in the least invasive way and to make a specific diagnosis. This study was aimed to evaluate the correlation between perfusion imaging features and microvessel density (MVD) and vascular endothelial growth factors (VEGF) in SPNs using multi-slice computed tomography (MSCT); and to provide the theoretical basis for SPN blood flow pattern and blood flow quantitative features. Also, the study called for the discussion of the method's clinical application value in the differential diagnosis of benign and malignant SPNs.

METHODSSixty-eight patients with SPN underwent multi-location dynamic contrast enhanced (nonionic contrast material was administrated via the antecubital vein at a rate of 4 ml/s) MSCT. Precontrast and postcontrast attenuations on every scan was studied. Perfusion, peak height, and the ratio of the peak height of the SPN to that of the aorta were analyzed. Perfusion was calculated using the maximum gradient of the time-density curves (TDC) and the peak height of the aorta. The quantitative parameters (perfusion, peak height, ratio of peak height of the SPN to that of the aorta) of the blood flow pattern were compared with MVD and the VEGF expression of immunohistochemistry.

RESULTSThe perfusion peak heights of malignant ((96.15 +/- 11.55) HU) and inflammatory ((101.15 +/- 8.41) HU) SPNs were significantly higher than those of benign ((47.24 +/- 9.15) HU) SPNs (P < 0.05, P < 0.05). Ratios of SPN-to-aorta of malignant and inflammatory SPNs were significantly higher than those of benign SPNs (P < 0.05, P < 0.05). No significant differences were found between the peak height and SPN-to-aorta ratio of malignant SPNs and inflammatory SPNs (P > 0.05, P > 0.05). The precontrast densities of inflammatory SPNs were lower than those of malignant SPNs (P < 0.05). Perfusion values of malignant and inflammatory SPNs were significantly higher than those of the benign SPNs (P < 0.05, P < 0.05). The VEGF positive expressions appeared in 32 patients with malignant SPNs and 2 patients with benign SPNs, and the average value of the MVD was higher in patients with malignant SPNs (36.88 +/- 6.76) than in patients with either benign (4.51 +/- 0.60) or inflammatory (26.11 +/- 5.43) SPNs (P < 0.05, P < 0.05). There were statistically significant correlations between the CT perfusion feature and the MVD. The highest correlation was between the peak height of SPN and the MVD (r = 0.657, P < 0.05).

CONCLUSIONSTumor microvessel density and VEGF expression facilitate the exploration of the pathophysiological basis of CT perfusion in SPNs. Multi-slice CT perfusion has shown strong positive correlations with angiogenesis in SPNs.

Adult ; Aged ; Female ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Lung ; diagnostic imaging ; metabolism ; pathology ; Male ; Microvessels ; pathology ; Middle Aged ; Neovascularization, Pathologic ; Perfusion Imaging ; Solitary Pulmonary Nodule ; diagnostic imaging ; metabolism ; pathology ; Tomography, X-Ray Computed ; methods ; Vascular Endothelial Growth Factor A ; analysis

OBJECTIVETo evaluate the correlation between programmed death-ligand 1 (PD-L1) expression in primary lung cancer cells, tumor associated macrophages (TAM) and patients' clinicopathological characteristics.

METHODSFrom 2008 to 2010, 208 non-small cell lung cancer patients who underwent surgery or CT-guided biopsy were recruited from Huadong Hospital, Fudan University. Immunohistochemistry staining was performed to evaluate the PD-L1 expression in both primary lung cancer cells and CD68 positive TAM. The relationship between PD-L1 expression and the clinical pathology was evaluated using χ(2) test. Spearman's rank correlations were used to determine the correlation between PD-L1 expression in tumor cells and macrophages.

RESULTSPositive PD-L1 expression in primary cancer cells was found in 136 (65.3%) patients, which were negatively correlated with lymph node metastasis (P=0.009) and smoking history (P=0.036). Besides, TAM with PD-L1 expression (found in 116 patients) was positively associated with smoking history (P=0.034), well-differentiation (P=0.029) and negative lymph node metastasis (P=0.0096). A correlation between PD-L1 expression in primary tumor cells and non-small cell lung cancer associated macrophages was found (r=0.228, P=0.021).

CONCLUSIONPD-L1, secreted from TAM, might induce cancer cells apoptosis, and decrease lymph node metastasis.

Adult ; Aged ; Aged, 80 and over ; Apoptosis ; B7-H1 Antigen ; secretion ; Carcinoma, Non-Small-Cell Lung ; pathology ; secretion ; Cell Line, Tumor ; Female ; Humans ; Lung Neoplasms ; pathology ; secretion ; Lymphatic Metastasis ; Macrophages ; pathology ; secretion ; Male ; Middle Aged ; Retrospective Studies

BACKGROUNDThe number of immunosuppressed patients has increased in the past decades. Among them Pseudomonas aeruginosa (P. aeruginosa) is one of the leading bacteria for pneumonia that are associated with poor prognosis. However, the pathogenesis of P. aeruginosa pneumonia in immunosuppressed patients is not understood completely. Previous reports showed keratinocyte growth factor (KGF) is associated with lung injury in immunocompetent hosts. In this study, we investigated the different reactions of lung injury, lung pathology and KGF expressions in P. aeruginosa pneumonia between immunosuppressed and immunocompetent rats.

METHODSImmunosuppression of male rats was induced by injecting immunosuppressive subcutaneously. Pneumonia was established by instilling P. aeruginous tracheally. The immunocompetent rats were the control group. Survival rate, lung histopathology, pulmonary permeability and oedema, KGF mRNA and protein expressions in lungs of both groups were investigated.

RESULTSThe survival rate of immunosuppressed group was lower than that of immunocompetent group (33.3% vs 83.3%). After exposure to bacteria, pulmonary permeability and wet/dry ratio in immunosuppressed group were higher than those in immunocompetent group. Pulmonary congestion and haemorrhage were more intensive in immunosuppressed group compared to immunocompetent group. Apoptosis and necrosis were also observed in infected lungs of immunosuppressed rats. Although we detected KGF expressions in lungs of both groups after infection, the expressions of KGF protein and mRNA gene in immunosuppressed group were much lower than in immunocompetent group.

CONCLUSIONSCompared with immunocompetent group, there was more intensive lung injury in immunosuppressed group. Severe lung injury may contribute to the poor prognosis of pneumonia. KGF expressions of pneumonia in immunosuppressed rats were less than those in immunocompetent ones.

Animals ; Capillary Permeability ; Fibroblast Growth Factor 7 ; analysis ; genetics ; Immune Tolerance ; Leukocyte Count ; Lung ; metabolism ; pathology ; Male ; Pneumonia, Bacterial ; metabolism ; Pseudomonas Infections ; metabolism ; mortality ; pathology ; Pulmonary Edema ; etiology ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Survival Rate ; Up-Regulation

Hyperglycemia, advanced glycation end products (AGEs), hyperinsulinemia and dyslipidemia may play roles in the development of diabetes-associated atherosclerosis and post-angioplasty restenosis. Clinically, their effects seem to be synergic. However, few studies have focused on the synergistic action of these factors. In the present study, we investigated whether glycated serum albumin (GSA) has a synergistic effect with insulin on the proliferation of vascular smooth muscle cells (VSMCs). VSMCs were isolated from rat thoracic aortas and cultured in fetal bovine serum (FBS)-free medium for 24 h, then exposed to GSA, insulin or GSA + insulin for 48 h with or without pretreatment of mitogen-activated protein kinase (MAPK) inhibitors or the antioxidant N-acetylcysteine (NAC). Cell growth rate was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay or cell counting. The changes of phosphorylated-p38 MAPK and phosphorylated-C-Jun N-terminal kinase 1/2 (JNK1/2) were measured by Western blot analysis. The results showed that only p38 MAPK, but not JNK was activated by GSA and insulin co-incubation. VSMC proliferation was increased by insulin (10-1000 nmol/L) or GSA (10, 100 microg/mL). Co-incubation of insulin (100 nmol/L) and GSA (100 mug/mL) caused a more potent increase in VSMC proliferation than insulin or GSA incubation alone. p38 MAPK inhibitor, SB203580, as well as NAC, could inhibit the VSMC proliferation induced by co-incubation of GSA and insulin. The results show that insulin enhances GSA-induced VSMC proliferation, which may be mediated through a reactive oxygen species (ROS)-p38 MAPK pathway. The synergism of AGEs and insulin may play a detrimental role in the pathogenesis of diabetic atherosclerosis and post-angioplasty restenosis.
Animals ; Aorta, Thoracic ; cytology ; Cell Proliferation ; drug effects ; Cells, Cultured ; Drug Synergism ; Insulin ; pharmacology ; physiology ; Male ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; cytology ; drug effects ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Serum Albumin ; pharmacology ; physiology ; p38 Mitogen-Activated Protein Kinases ; metabolism