Relationship between programmed death-ligand 1 and clinicopathological characteristics in non-small cell lung cancer patients / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the correlation between programmed death-ligand 1 (PD-L1) expression in primary lung cancer cells, tumor associated macrophages (TAM) and patients' clinicopathological characteristics.</p><p><b>METHODS</b>From 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.</p><p><b>RESULTS</b>Positive 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).</p><p><b>CONCLUSION</b>PD-L1, secreted from TAM, might induce cancer cells apoptosis, and decrease lymph node metastasis.</p>

Use of real-time polymerase chain reaction for the diagnosis of Pneumocystis pneumonia in immunocompromised patients: a meta-analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The diagnosis of Pneumocystis pneumonia (PCP) in immunocompromised patients is still challenging today due to the absence of an in vitro culture system and the low diagnostic accuracy of microscopic examinations. Herein, we performed a meta-analysis to evaluate the accuracy of real-time polymerase chain reaction (PCR) in the diagnosis of PCP.</p><p><b>METHODS</b>We searched Web of Knowledge and Medline from 1990 to May 2010 for studies reporting diagnostic accuracy data regarding the use of real-time PCR in the diagnosis of PCP in immunocompromised patients.</p><p><b>RESULTS</b>Ten individual studies were included. Overall, the sensitivity of real-time PCR was 97% (95%CI: 93% - 99%); the specificity was 94% (95%CI: 90% - 96%). The area under the HSROC curve (95%CI) for real-time PCR was 0.99 (0.97 - 0.99). In a subgroup analysis regarding studies involving HIV patients among the study population, the sensitivity and specificity were 97% (95%CI: 93% - 99%) and 93% (95%CI: 89% - 96%), respectively. Regarding studies using Bronchoalveolar lavage (BAL) samples only: sensitivity = 98% (95%CI: 94% - 99%); specificity = 93% (95%CI: 89% - 96%), respectively. Regarding studies using microscopy as a reference standard: sensitivity = 97% (95%CI: 92% - 99%); specificity = 93% (95%CI: 88% - 96%). However, high between-study statistical heterogeneity was observed in all analyses.</p><p><b>CONCLUSIONS</b>Real-time PCR has a good diagnostic accuracy and may provide a useful adjunctive tool for the diagnosis of PCP in immunocompromised patients. Further studies are needed in order to identify any differences in the diagnostic performance of real-time PCR in HIV and non-HIV immunocompromised patients.</p>

Effects of N(omega)-nitro-L-arginine methyl ester and aminoguanidine on lipopolysaccharide-induced airway hyperresponsiveness in guinea pigs / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The down-regulation of constitutive nitric oxide synthase (cNOS) and up-regulation of inducible nitric oxide synthase (iNOS) are associated with the allergen-provocated airway hyperresponsiveness (AHR). This study aimed to determine whether their alteration also plays an important role in the AHR induced by lipopolysaccharide (LPS).</p><p><b>METHODS</b>Hartley male guinea pigs, weighing between 250 g and 350 g, were injected with LPS at a dose of 1 mg/kg every 24 hours for three days. A non-selective NOS inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), or a selective inducible NOS inhibitor, aminoguanidine (AG), were used thirty minutes before each injection of LPS. Airway reactions, nitric oxide (NO) production and inflammatory changes were detected 24 hours after the last dose of LPS.</p><p><b>RESULTS</b>AG significantly decreased the NO production in the bronchoalveolar lavage fluid (BALF) and sharply reduced the intensity of bronchoconstriction to histamine challenge. L-NAME also significantly decreased the NO production in the BALF, but had no effect on airway reactions or, perhaps, a tendency to enhance the intensity of AHR.</p><p><b>CONCLUSIONS</b>The data suggest that inducible NOS contributes to the AHR induced by repetitive intraperitoneal LPS, and constitutive NOS was also involved.</p>

Impaired upregulation of keratinocyte growth factor in injured lungs induced by Pseudomonas aeruginosa in immunosuppressed rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The 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.</p><p><b>METHODS</b>Immunosuppression 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.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSIONS</b>Compared 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.</p>

A study on inflammatory reaction induced by N-protein of severe acute respiratory syndrome-CoV in human alveolar type Ⅱ epithelial cell(A549) / 中华传染病杂志

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

Lung immunohistochemical study on the changes of ICAM-1,MMP-2 and MMP-9 in an immunocompromised rat model infected with Pseudomonas aeruginosa pneumonia / 中华传染病杂志

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.