Identifying an immunogenic cell death-related gene signature contributes to predicting prognosis, immunotherapy efficacy, and tumor microenvironment of lung adenocarcinoma.

BACKGROUND: Immunogenic cell death (ICD) is a regulated form of cell death that triggers an adaptive immune response. The objective of this study was to investigate the correlation between ICD-related genes (ICDGs) and the prognosis and the immune microenvironment of patients with lung adenocarcinoma (LUAD). METHODS: ICD-associated molecular subtypes were identified through consensus clustering. Subsequently, a prognostic risk model comprising 5 ICDGs was constructed using Lasso-Cox regression in the TCGA training cohort and further tested in the GEO cohort. Enriched pathways among the subtypes were analyzed using GO, KEGG, and GSVA. Furthermore, the immune microenvironment was assessed using ESTIMATE, CIBERSORT, and ssGSEA analyses. RESULTS: Consensus clustering divided LUAD patients into three ICDG subtypes with significant differences in prognosis and the immune microenvironment. A prognostic risk model was constructed based on 5 ICDGs and it was used to classify the patients into two risk groups; the high-risk group had poorer prognosis and an immunosuppressive microenvironment characterized by low immune score, low immune status, high abundance of immunosuppressive cells, and high expression of tumor purity. Cox regression, ROC curve analysis, and a nomogram indicated that the risk model was an independent prognostic factor. The five hub genes were verified by TCGA database, cell sublocalization immunofluorescence analysis, IHC images and qRT-PCR, which were consistent with bioinformatics analysis. CONCLUSIONS: The molecular subtypes and a risk model based on ICDGs proposed in our study are both promising prognostic classifications in LUAD, which may provide novel insights for developing accurate targeted cancer therapies.

Bioinformatics and Machine Learning Methods Identified MGST1 and QPCT as Novel Biomarkers for Severe Acute Pancreatitis.

Severe acute pancreatitis (SAP) is a life-threatening gastrointestinal emergency. The study aimed to identify biomarkers and investigate molecular mechanisms of SAP. The GSE194331 dataset from GEO database was analyzed using bioinformatics. Differentially expressed genes (DEGs) associated with SAP were identified, and a protein-protein interaction network (PPI) was constructed. Machine learning algorithms were used to determine potential biomarkers. Gene set enrichment analysis (GSEA) explored molecular mechanisms. Immune cell infiltration were analyzed, and correlation between biomarker expression and immune cell infiltration was calculated. A competing endogenous RNA network (ceRNA) was constructed, and biomarker expression levels were quantified in clinical samples using RT-PCR. 1101 DEGs were found, with two modules most relevant to SAP. Potential biomarkers in peripheral blood samples were identified as glutathione S-transferase 1 (MGST1) and glutamyl peptidyltransferase (QPCT). GSEA revealed their association with immunoglobulin regulation, with QPCT potentially linked to pancreatic cancer development. Correlation between biomarkers and immune cell infiltration was demonstrated. A ceRNA network consisting of 39 nodes and 41 edges was constructed. Elevated expression levels of MGST1 and QPCT were verified in clinical samples. In conclusion, peripheral blood MGST1 and QPCT show promise as SAP biomarkers for diagnosis, providing targets for therapeutic intervention and contributing to SAP understanding.

Associations between comorbidities and annual incidence plus frequency of asthma exacerbation hospitalisation during the past year: data from CARN study.

PURPOSE: While asthma comorbidities are associated with higher health care utilisation, lower quality of life and poorer asthma control, the impact of asthma comorbidities on hospitalisation for asthma exacerbation (H-AX) remains less recognised. We aim to analyse the impact of asthma comorbidities on H-AX. METHODS: Based on a national survey on asthma control and disease perception (CARN 2015 study), we analysed the impact of comorbidities on annual incidence and frequency of H-AX in China. Information on demographic characteristics, asthma comorbidities and annual incidence and frequency of H-AX were presented in this study. RESULTS: Among 3875 ambulatory asthma patients, 75.9% (2941/3875) had comorbidities, and 26.4% (1017/3858) experienced H-AX during past year. After adjusting for confounding factors such as demographic data, smoking status and asthma control, COPD [OR = 2.189, 95% CI (1.673, 2.863)] and coronary heart disease [OR = 1.387, 95% CI (1.032, 1.864)] were associated with higher annual incidence, while allergic rhinitis [OR = 0.692, 95% CI (0.588, 0.815)] was associated with lower annual incidence, of H-AX. In terms of frequency, allergic rhinitis [OR = 1.630, 95% CI (1.214, 2.187)], COPD [OR = 1.472, 95% CI (1.021, 2.122)] and anxiety [OR = 2.609, 95% CI (1.051, 6.477)] showed statistically significant correlation with frequent H-AX. CONCLUSIONS: COPD and coronary heart disease were associated with higher annual incidence, while allergic rhinitis was associated with lower annual incidence of H-AX. Allergic rhinitis, COPD and anxiety were associated with frequent H-AX. Comorbidities may have an important role in the risk and frequency of annual hospitalisations due to asthma exacerbation. The goal of asthma control should rely on a multi-disciplinary treatment protocol.

Effects of Crocin on CCL2/CCR2 Inflammatory Pathway in Monocrotaline-Induced Pulmonary Arterial Hypertension Rats.

Pulmonary arterial hypertension (PAH) is a malignant cardiopulmonary disease, in which pulmonary arterial remodeling is regarded as the prominent pathological feature. So far, the mechanism of PAH is still unclear, so its treatment remains a challenge. However, inflammation plays an important part in the occurrence and progression of PAH. It is well known that crocin has anti-inflammatory properties, so we investigated whether crocin could be a potential drug for the treatment of PAH rat models. Rats injected subcutaneously with monocrotaline (MCT) were treated with crocin via a gastric tube daily for four weeks. The results showed that crocin treatment significantly reduced the right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (mPAP) in the PAH rat models. Moreover, crocin treatment reduced the proliferation of pulmonary arteriole smooth muscle cells (PASMCs). In addition, crocin treatment not only relieved inflammatory cell infiltration and collagen fiber hyperplasia in the lung and right ventricle, but also decreased the expression of the CCL2/CCR2 inflammatory pathway in the lung of PAH rat models. Furthermore, crocin treatment reduced the inflammatory cytokines and oxidative stress responses. In summary, crocin may play a protective role in MCT-induced PAH rats by alleviating inflammatory response, improving pulmonary arterial remodeling, and preventing PAH. Therefore, crocin as a new treatment for PAH may be quite worthy of consideration.

Hospitalization Due to Asthma Exacerbation: A China Asthma Research Network (CARN) Retrospective Study in 29 Provinces Across Mainland China.

PURPOSE: Details of patients hospitalized for asthma exacerbation in mainland China are lacking. To improve disease control and reduce economic burden, a large sample survey among this patient population is indispensable. This study aimed to investigate the clinical characteristics and outcomes of such patients. METHODS: A retrospective study was conducted on patients hospitalized for asthma exacerbation in 29 hospitals of 29 regions in mainland China during the period 2013 to 2014. Demographic features, pre-admission conditions, exacerbation details, and outcomes were summarized. Risk factors for exacerbation severity were analyzed. RESULTS: There were 3,240 asthmatic patients included in this study (57.7% females, 42.3% males). Only 28.0% used daily controller medications; 1,287 (39.7%) patients were not currently on inhaled corticosteroids. Acute upper airway infection was the most common trigger of exacerbation (42.3%). Patients with severe to life-threatening exacerbation tended to have a longer disease course, a smoking history, and had comorbidities such as hypertension, chronic obstructive pulmonary disease (COPD), and food allergy. The multivariate analysis showed that smoking history, comorbidities of hypertension, COPD, and food allergy were independent risk factors for more severe exacerbation. The number of patients hospitalized for asthma exacerbation varied with seasons, peaking in March and September. Eight patients died during the study period (mortality 0.25%). CONCLUSIONS: Despite enhanced education on asthma self-management in China during recent years, few patients were using daily controller medications before the onset of their exacerbation, indicating that more educational efforts and considerations are needed. The findings of this study may improve our understanding of hospital admission for asthma exacerbation in mainland China and provide evidence for decision-making.

N-acetyl-l-cysteine ameliorates the PM2.5-induced oxidative stress by regulating SIRT-1 in rats.

Silent information regulator 1 (SIRT1), a class III histone deacetylase, plays a major role in combating cellular oxidative stress injury. However, the role of SIRT1 in oxidative stress induced by particulate matter remains unclear. A total of 32 healthy male Sprague-Dawley rats were divided into PM2.5, PM2.5+NAC, filtered air (control), and filtered air+NAC (NAC control) groups. The expressions of MnSOD, SIRT1, and FOXO3a were examined at both transcriptional and protein levels. The expression levels of MnSOD, SIRT1, and FOXO3a reduced significantly (P<0.05) in the PM2.5 group as compared to the control group. However, their expression levels were increased after NAC intervention. These results suggested that SIRT1 exerted a protective effect against PM2.5-induced respiratory oxidative damage by regulating the expression of FOXO3a. NAC can activate SIRT1 and exert an anti-oxidative role in PM2.5-induced oxidative injury.

Analysis of the first therapeutic-target-achieving time of warfarin therapy and associated factors in patients with pulmonary embolism.

The present study aimed to investigate the factors affecting the first therapeutic-target-achieving (TTA) time of warfarin therapy in patients with acute pulmonary embolism (PTE). Between January 2008 and June 2013, patients with PTE confirmed by transpulmonary arterial enhanced computed tomographic pulmonary angiography or pulmonary ventilation perfusion scanning were included in the present study. Data collected included demographic information, history of tobacco and alcohol intake, basic diseases (stable and unstable hypertension, diabetes, heart failure, cancer/cerebral infarction, old myocardial infarction and atrial fibrillation), liver and kidney function, the haemoglobin and platelet count of the blood, international normalized ratio monitoring, warfarin dosage adjustment and medication combinations. Dynamic changes in international normalized ratio, anticoagulant efficacy, and adverse events within 90 days were monitored and analyzed. Univariate analysis demonstrated that the following factors affect the first TTA time: Initial dose, body mass index (BMI), liver function, heart failure, and the administration of levofloxacin, cephalosporins, and blood circulation-activating drugs. Logistic regression analysis revealed that the following were independent factors of the first TTA time: Initial dose, BMI, liver function, heart failure and levofloxacin. Therefore, the results of the present study demonstrated that various factors may affect the first TTA time of warfarin therapy, including the initial dose, BMI, liver function, heart function and concomitant medication.

[Effects of estrogen on ACE-Ang II-AT1 axis in ovariectomy and hypoxic pulmonary hypertension rats].

OBJECTIVE: To explore the effects of estrogen (E2) on angiotensin converting enzyme-angiotensin II-angiotensin type 1 receptor (ACE-Ang II-AT1) axis in hypoxic pulmonary hypertension rats. METHODS: A total of 60 healthy female Sprague-Dawdley (SD) rats were divided randomly into 6 groups (n = 10 each) of sham operation, pure ovariectomy (OVX), pure hypoxia,OVX+hypoxia,OVX+E2 and OVX+hypoxia+E2. Abdominal cavity was opened for sham operation group and bilateral ovaries were left intact without any other procedure. The pure OVX group underwent oophorectomy. The pure hypoxia group were placed into a low-oxygen environment (24 hour, 8 weeks). The OVX+hypoxia group were placed into a low-oxygen environment after bilateral oophorectomy. The OVX+E2 group received a subcutaneous injection of E2 (20 µg×kg(-1)×d(-1)) after bilateral oophorectomy. The OVX+hypoxia+E2 group had an injection of E2 and was placed into a low-oxygen environment after bilateral oophorectomy. The rats were feed continuously for 8 weeks to establish hypoxic pulmonary hypertension model. The mean pulmonary artery pressure (mPAP) was measured after bloodletting. Then right ventricle hypertrophy index (RVHI) and hematoxylin-eosin pulmonary artery remodeling (HPSR) were observed. And electron microscope was employed to observe pulmonary arteriolar ultrastructure. The methods of radio-immunity assay, ultraviolet spectroscopy, Western blot and reverse transcription PCR were used to measure the levels of CE,Ang II and AT1 in sera, lung and pulmonary artery. RESULTS: The vascular walls of pure hypoxia and OVX+hypoxia groups became thickened and lumen narrowed.mPAP and RVHI were (32.4 ± 2.2) mmHg (1 mmHg = 0.133 kPa),0.331 ± 0.032 and (37.9 ± 1.6) mmHg,0.433 ± 0.033. Both were significantly higher than those of Sham operation group ((12.6 ± 1.8) mmHg,0.233 ± 0.029) (both P < 0.05); the above parameters of OVX+Hypoxia+E2 group changed little. And mPAP ((26.1 ± 1.4) mmHg) was significantly higher than that in sham operation group (P < 0.05) while the difference in RVHI between OVX+ Hypoxia+ E2 (0.267 ± 0.040) and sham operation groups had no statistical significance (P > 0.05). Compared with Sham operation group, the expression levels of ACE,Ang II and AT1 in pure OVX, pure hypoxia and OVX+ hypoxia groups rose markedly (all P < 0.05).However, the OVX+E2 and OVX+ hypoxia+E2 groups had no obvious change (all P > 0.05). CONCLUSION: The intervention effect of E2 for hypoxic pulmonary hypertension may be partly mediated by the down-regulated expressions of ACE and AT1 in lung tissue resulting in the reduced activity of ACE-AngII-AT1 axis.

Retrospective analysis of docetaxel, oxaliplatin plus fluorouracil compared with epirubicin, cisplatin and fluorouracil as first-line therapy for advanced gastric cancer.

The purpose of this retrospective study was to evaluate the safety and efficacy of docetaxel, oxaliplatin plus fluorouracil (DOF) regimen in comparison with epirubicin, cisplatin and fluorouracil (ECF) regimen in treating AGC. A total of 88 AGC patients were treated with DOF regimen (N = 45) and ECF regimen (N = 43) respectively. The end points of this study were response rate, survival, and toxicity. The overall response rates for DOF and ECF were 42·2% and 37·3%, and the respective tumour control rates were 80% and 60·6%, respectively. While the median progression-free survival (PFS) approached 6·7 and 5·0 months for DOF and ECF, the overall survival (OS) was 11·4 and 9·8 months respectively. Although both groups showed acceptable level of toxicity, compared with ECF, DOF group was associated with less nausea/vomiting and alopecia but more peripheral neuropathy and neutropenia. Although DOF and ECF exhibit similar efficacy, DOF may broaden the spectrum of chemotherapeutically treatable patients and deserve further investigation.

[Meta-analysis of risk factors for all-cause mortality of pulmonary thromboembolism].

OBJECTIVE: To evaluate the causes of death and risk factors of pulmonary thromboembolism. METHODS: Pubmed, English Medical Current Contents, Chinese Conference Data and Chinese Biomedical Database were searched from January 1995 up to May 2011. And the references of these studies were also examined. Observational studies were assessed according to suggestion of quality assessment with references. Randomized control trials (RCT) were assessed with Jadad scale. Software RevMan 5.1 was used to examin the heterogeneity of trials. The fixed or random effect model was employed to pool the risk ratio and 95%CI. The results were expressed with risk ratio and 95%CI. RESULTS: Thirty-five studies with a total number of 19 613 cases of pulmonary thromboembolism (PTE) were included for final analysis. The average mortality rate was (10.7 ± 7.6)% (range 0.5%-30.0%). And the following factors increased the total mortality of pulmonary embolism: right ventricular hypokinesis or dysfunction (2.18(1.64-2.89), P = 0.000), elevated D-dimer (5.19(1.93-13.96), P = 0.001), elevated cardiac troponin (cTnI) (4.01(2.77-5.81), P = 0.000), hypotension (2.76(1.25-6.09), P = 0.010), malignancy (2.65(2.01-3.50), P = 0.000), congestive heart failure (1.90(1.62-2.22), P = 0.000), chronic lung disease (1.40(1.18-1.66), P = 0.000), tachycardia (1.65(1.23-2.20), P = 0.000), immobility (1.74(1.36-2.21), P = 0.000) and age > 65 years (1.24 (1.13-1.37), P = 0.000), etc. When multiple factors co-existed, the risk of death became more obvious. CONCLUSION: Elevated D-dimer, elevated cTnI, hypotension, malignancy, right ventricular hypokinesis or dysfunction, immobility, congestive heart failure, tachycardia, chronic lung disease, age > 65 years influence the mortality rate of pulmonary embolism.

[Inhibitory effects of celecoxib combined with capecitabine on H22 hepatoma mice and its mechanism].

OBJECTIVE: To evaluate the inhibitory effect and its mechanism of celecoxib combined with capecitabine on the growth of implanted H22 hepatoma in mice. METHODS: Tumor model was established by hypodermical injection of H22 cells in BALB/c nude mice. Forty mice were equally randomly divided into 4 groups: control group, celecoxib group (receiving 100 mg/kg celecoxib), capecitabine group (receiving 755 mg/kg capecitabine), and combined treatment group (receiving 100 mg/kg of celecoxib and 755 mg/kg of capecitabine). From the third post-implantation day, each mouse was given relevant drug (or normal saline) by oral gavage. Fifteen days later, all mice were sacrificed and the tumor tissues were measured. The mRNA and protein levels of nuclear factor kappa-B (NF-ΚB) p65 and cyclooxygenase (COX)-2 in tumor tissues were detected by the quantitative polymerase chain reaction (qPCR)and Western blotting, respectively. RESULTS: The tumor inhibition rate was 30.2% in celecoxib group and 49.9% in capecitabine group, which was significantly lower than that (75.4%) in the combined treatment group (P<0.01,P<0.05, respectively). qPCR showed a significant decrease of the mRNA expression of COX-2 in celecoxib group and combined treatment group when compared with control group (P<0.001), but no significant change in NF-ΚB p65.Capecitabine had no significant effects on the mRNA expression of COX-2 and NF-ΚB p65. Western blotting showed that celecoxib and combined treatment significantly inhibited the protein expression of COX-2 and NF-ΚB p65(P<0.05), but not capecitabine. CONCLUSION: Celecoxib can enhance the antitumor effect of capecitabine by inhibiting the expressions of COX-2 and NF-ΚB p65 in mice bearing H22 implanted tumor.

[Association of genetic polymorphisms of angiotensin converting enzyme and matrix metallo proteinase-1 with idiopathic pulmonary fibrosis].

OBJECTIVE: To investigate the correlation between angiotensin converting enzyme (ACE) and matrix metallo proteinase (MMP)-1 gene polymorphisms and the risk of idiopathic pulmonary fibrosis (IPF) in a Han Chinese population from Hebei Province. METHODS: Eighty-four IPF patients and 100 controls were enrolled from the Second Hospital of Hebei Medical University. Polymerase chain reaction (PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to detect ACE gene insertion/deletion (I/D) polymorphism and MMP-1 polymorphism respectively. The MMP-1 polymorphism was genotyped by DNA sequence analysis. Radioimmunoassay and ELISA were used to analyzed AngII, MMP-1 and TIMP-1 levels in IPF patients and healthy controls. RESULTS: There was a significant difference between the 2 groups in allele and genotype frequency distribution of ACE Insertion/Deletion polymorphism; frequency distribution of DD genotype and D allele of IPF patients were higher than those of the healthy control group (χ(2) = 11.227, 4.318, P < 0.05). There was no difference from different genders and ages on allele and genotype frequency distribution of ACE Insertion/Deletion polymorphism. (χ(2) = 0.03 - 1.069, P > 0.05). There was no significant difference between the 2 groups in genotype and allele frequency distribution of MMP-1 1G/2G polymorphism (χ(2) = 0.94 and 0.001, P > 0.05). The AngII levels from DD genotype of both IPF patients and healthy controls were the highest, followed by the DI genotype and the II genotype. The AngII level of any genotype for ACE Insertion/Deletion polymorphism in the IPF group was higher than that in the healthy control group (all P < 0.05). The serum level of AngII, MMP-1 and TIMP-1, as well as MMP-1/TIMP-1 ratio in the IPF group were higher than those in the healthy control group (all P < 0.05). CONCLUSIONS: The ACE polymorphism might be associated with IPF, and the serum level of AngII was affected not only by the genetic background of ACE insertion/deletion polymorphism but also the environmental factors. The MMP-1 1G/2G polymorphism might be weakly associated with IPF.

[Effects of PM2.5 exposure on Klebsiella pneumoniae clearance in the lungs of rats].

OBJECTIVE: To investigate the effects of PM2.5 exposure on susceptibility to Klebsiella infection and bacterial clearance, and to discuss its possible mechanisms. METHODS: Eighty-six healthy male SD rats were randomly divided into 4 groups: a control group, a Klebsiella pneumoniae infection group(infection group), a PM2.5 group and a PM2.5+ Klebsiella pneumoniae infection group (combined group) .We developed a rat model in which the animals were given Klebsiella pneumoniae, PM2.5 exposure and PM2.5 exposure followed by infection with Klebsiella pneumoniae respectively. The clinical scores were evaluated. The total mortality of each group was assessed. Bacterial load in the BALF was quantified and the infection rate of each group was assessed.Lung histopathological changes were detected by HE staining. The concentrations of IL-6 and TNF-α in serum were detected by ELISA. Cells in the BALF were counted for each group by microscopy. The changes of tracheal membrane epithelial cells were observed by scanning electron microscope. RESULTS: The total mortality in the combined group (n = 14) was higher than that in the control group (n = 0), infection group(n = 4) and PM2.5 group(n = 4). The infected cases in the combined infection group (n = 13) was higher than that in the infection group (n = 6). The total number of WBC in BALF in the combined group on the first day[(11.96 ± 0.56)×10(5)/L] and seventh day [(15.68 ± 0.81)×10(5)/L] was higher than that in the control group, the infection group and the PM2.5 group. The neutrophil number in BALF in the combined group on the first day[(5.76 ± 0.44)×10(5)/L] and seventh day [(9.41 ± 0.64)×10(5)/L] was higher than that in the control group, the infection group and the PM2.5 group. The lung pathological changes were much more severe in the combined group as compared to those in the control, the infection and the PM2.5 groups. Concentrations of TNF-α in serum in the combined group on the first day [(829 ± 90) ng/L] and the seventh day [(1055 ± 91) ng/L] were higher than those in the control group and the PM2.5 group. Concentrations of IL-6 in serum in the combined group on the first day [(1.26 ± 0.16) ng/L] and seventh day [(1.95 ± 0.18) ng/L] was higher than those in the control, the infection and the PM2.5 groups. Tracheal cilia in the PM2.5 group showed signs of disorderly arrangement, adhesion and ecclasis. CONCLUSIONS: PM2.5 exposure increased the susceptibility of the rats to Klebsiella pneumoniae infection and decreased bacterial clearance.Its mechanism may be related to impairment of the bronchial mucociliary system and interaction of cytokines.

Plasminogen activator inhibitor-1 promotes the proliferation and inhibits the apoptosis of pulmonary fibroblasts by Ca(2+) signaling.

AIM: Our previous investigation demonstrated that plasminogen activator inhibitor-1 (PAI-1) siRNA ameliorated bleomycin (BLM)-induced rat lung fibrosis. The present study was undertaken to explore the effect and the mechanism of PAI-1 siRNA and plasmid pcDNA on the proliferation and apoptosis of cultured fibroblasts from BLM-induced fibrotic lung tissues. MATERIALS AND METHODS: The fibroblasts from BLM-induced fibrotic lung tissue were isolated and transfected using PAI-1 siRNA and plasmid pcDNA-PAI-1. The techniques of real time RT-PCR and/or western blot were used to determine the expression of PAI-1, α-smooth muscle actin (α-SMA) (real time RT-PCR only), collagen type-1 and type-3 (real time RT-PCR only), and the levels of caspase-3, ERK and AKT signal molecules. The proliferation of fibroblasts was measured by cell cycle with flow cytometry. The intracellular concentration of Ca(2+) was examined by confocal laser microscopy. RESULTS: PAI-1 siRNA downregulated the PAI-1 mRNA expression by 70%±7% at 24h and protein expression by 73.5%±10% and 42%±3% at 48h and 72h compared to Non-specific siRNA group. Flow cytometry showed that the fibroblasts at the G(2)M+S phase were significantly reduced by 20.56±1.03% after transfecting PAI-1 siRNA and were significantly increased by 43.8±1.21% after transfecting plasmid pcDNA-PAI-1. The mRNA expressions of α-SMA, collagen type-1and type-3 were downregulated after transfecting the PAI-1 siRNA, while upregulated after the transfection of pcDNA-PAI-1. PAI-1 siRNA increased the level of caspase-3, inhibited the expressions of p-ERK and p-AKT protein molecules, while the pcDNA-PAI-1 transfection showed a reversal effect on these expressions. Intracellular Ca(2+) concentration was decreased after transfecting PAI-1 siRNA, whereas increased after transfecting pcDNA-PAI-1. CONCLUSION: PAI-1 promotes the proliferation, transforming into myofibroblasts, collagen synthesis, and inhibits apoptosis of pulmonary fibroblasts by activating Ca(2+), ERK and AKT signaling pathway. Decreasing PAI-1 expression is an available strategy in inhibiting the progression of pulmonary fibrosis.

[Association between genetic polymorphism of erythrocyte CR1 and the susceptibility of idiopathic pulmonary fibrosis].

OBJECTIVE: To explore the association between the erythrocyte CR1 genomic density polymorphism, A3650G site polymorphism and the susceptibility of idiopathic pulmonary fibrosis (IPF); and to investigate the correlation between the HindIII density polymorphism of CR1 gene and the quantitative levels of E-CR1 in IPF patients. METHODS: Blood samples from IPF patients (n = 64) and ethnically matched healthy controls (n = 54) were taken from a population-based case-control association study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to identify the genotype of the HindIII restriction fragment length polymorphism of CR1 gene and SNP A3650G in two groups. Quantitative expression of CR1 on RBC membrane surface was detected by flow cytometry. RESULTS: The genotype frequencies of HH, HL and LL were 32.8% (21/64), 46.9% (30/64) and 20.3% (13/64) respectively in the IPF group, and 72.2% (39/54), 25.9% (14/54) and 1.9% (1/54) respectively in the controls. The distribution of genotype between the two groups was significantly different (χ(2) = 15.516, P < 0.05). HL + LL genotype for the HindIII polymorphism was more common in patients with IPF compared to the controls with an OR = 5.32 (χ(2) = 18.20, P < 0.05). Compared the allele frequency of A3650G sites in the IPF group with that in the control group, there was no difference from distribution in the two groups (χ(2) = 1.094, P > 0.05). The mean CR1/E numbers observed in the IPF patients was 13.46 ± 3.86, and the mean CR1/E in normal individuals was 24.33 ± 3.84 (t = 15.288, P < 0.05 vs IPF group). The levels of E-CR1 in both IPF patients and healthy controls HH genotype for E-CR1 HindIII-RFLP were significantly higher than HL genotype for E-CR1 HindIII-RFLP (t = 9.973, P < 0.05), and the levels of E-CR1 in both groups HL genotype for E-CR1 HindIII-RFLP were significantly higher than LL genotype for E-CR1 HindIII-RFLP (t = 9.973, P < 0.05). The levels of HH, HL and LL genotypes for E-CR1 HindIII-RFLP in the IPF group were significantly lower than those in the control group, respectively (P < 0.05, on average). CONCLUSION: The quantitative levels of CR1 on erythrocyte membrane was not only determined by the genetic background of E-CR1 HindIII-RFLP but also by the acquired predisposition. HL and LL genotypes of CR1 gene may be associated with IPF, and as a result individuals carrying the L allele might be a susceptible population for IPF.

[A study on viral infections in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To study the relation between viral infection and chronic obstructive pulmonary disease (COPD), and the role of viral infection in the pathogenesis of COPD. METHODS: (1)Serum samples from 91 patients with acute exacerbation of COPD (Group A), 42 patients with stable COPD (Group B) and 25 healthy subjects (Group C) were tested for specific IgM and IgG for respiratory syncytial virus (RSV) herpes simplex virus type 1 (HSV-1) parainfluenza virus(PIV),adenovirus (ADV) and cytomegalovirus (CMV) with an indirect enzyme linked immunosorbent assay (ELISA). (2) T lymphocyte subsets (CD(3) CD(4) and CD(8)) were studied by flow cytometry in patients with IgM positivity (Group D n = 28) and patients in Group C. RESULTS: (1) The positive rates of IgM were significantly different (P < 0.001) in group A (12%, 8%, 6%, 2%, 3% for RSV HSV-1 PIV ADV and CMV) as compared to group B (0%, 0%, 0%, 0%, 0%) and group C (0%, 0%, 0%, 0%, 0%). There was no significant difference in the positive rate of IgG between group A (47%, 41%, 12%, 14%, 10%) and group B (43%, 33%, 12%, 7%, 7%, P > 0.05), but the positive rates of IgG in group A and group B were significantly different (P < 0.01) as compared to group C (0%, 8%, 0%, 0%, 0%) (2)In group D the expression of CD(4) and CD(4)/CD(8) were significantly lower, the expression of CD(8) was significantly higher (P < 0.01) than those in group C but the expression of CD(3) was not significantly different (P > 0.05). CONCLUSION: Viral infection was common in acute exacerbation of COPD, and related to the pathogenic mechanism of COPD.