Objective To determine the effect of atorvastatin on the hypercholesterolemia in-duced lesion in the lung. Methods Fifteen male New Zealand rabbits were randomly assigned into a control group (n=5) , a high-cholesterol forage group (n=5) , and an atrovastatin treatment group (n=5). The control group received normal forage, but the high-cholesterol group and atrovastatin treatment group received high-cholesterol forage. From the 9 th week, the atrovastatin treatment group was added atorvastatin, and the experiment stopped at the end of the 14th week. At the beginning of the experiment and at the 8 th, 14 th week, blood cholesterol and body weight were detected. At the 14th week, bronchial alveolar lavage (BAL) was performed in vitro after the rabbits were executed; pathological examinations were determined in the lung tissues by staining with hamatoxylin-eosin. Oil red 0 and the activities of NF-κB in the alveolar macrophages (AMs) were investigated by immuno-cytochemistry. Proliferative cell nuclear antigen in the lung tissues was adopted by immunohistochem-istry, and the concentrations of IL-6 in the serum, BALF and the culture supematants of AMs were measured by ELISA. Pulmonary tissue paraffin section was stained with hamatoxylin-eosin. Results Atorvastatin reduced inflammatory infiltration, AM NF-κB activation, and cell proliferation in the lung, but raised IL-6 level. Conclusion Hypercholesterolemia-induced pulmonary inflammation is attenuated by atorvastatin.

OBJECTIVE: To investigate the role of focal adhesion kinase (FAK) in extracellular signal-regulated kinase (ERK) signaling pathway mediated invadsion of trophoblasts. METHODS: We established a human extravillous cytotrophoblasts in vitro invasion model. Different concentrations of herbimycin A(FAK inhibitor)and PD98059 (ERK inhibitor) were given to observe the influence on the growth of trophoblast cells, FAK, ERK phosphorylation, and trophoblast invasion abilities. RESULTS: The expression of phosphorylated FAK in the extravillous cytotrophoblasts (EVCT) was inhibited by herbimycin A in a concentration-dependent manner and expression of phosphorylated ERK1/2 was also partially reduced. PD98059 had no effect on the expression of phosphorylated FAK. Herbimycin A and PD98059 suppressed the in vitro invasion of EVCT to various degrees. CONCLUSION ERK signaling pathway may be the common pathway for many invasive signals,and play a key role in the regulation of trophoblast invasion.
Benzoquinones ; pharmacology ; Cell Division ; physiology ; Cell Movement ; physiology ; Extracellular Signal-Regulated MAP Kinases ; antagonists & inhibitors ; metabolism ; Flavonoids ; pharmacology ; Focal Adhesion Protein-Tyrosine Kinases ; antagonists & inhibitors ; metabolism ; Humans ; Lactams, Macrocyclic ; pharmacology ; Phosphorylation ; Rifabutin ; analogs & derivatives ; Signal Transduction ; physiology ; Trophoblasts ; cytology ; physiology

Objective To observe the changes of microRNA‐214 (miR‐214) expression in rat pulmonary artery smooth mus‐cle cells (PASMCs) induced by different hypoxia time ,and lay the foundation to explore the effect and mechanism of regulation of miR‐214 on PASMCs proliferation .Methods The primary cultured PASMCs were cultured under hypoxic 0 h ,6 h ,12 h ,24 h ,48 h ,respectively .The real time quantitative PCR was used to detect miR‐214 expression in each group PASMCs .Results The ex‐pression of miR‐214 in hypoxia group PASMCs was sustained as time increased ,apart from hypoxic hypoxia 6h group and 0h group ,the expression of miR‐214 was no significant difference (P>0 .05);the expression of miR‐214 among other groups PASMCs was significantly different (P<0 .05) .Conclusion The expression of miR‐214 in PASMCs increased after induction of hypoxia .We speculated that miR‐214 may be involved in the regulation of hypoxia induced PASMCs proliferation .

Objective:To evaluate the impact of short-term low-medium dose of corticosteroids on the clinical outcomes of patients with community-acquired pneumonia due to influenza A (FluA-CAP).Methods:This was a multicenter, retrospective study, including 693 patients hospitalized with FluA-CAP from Beijing Jishuitan Hospital, Qingdao Municipal Hospital, Beijing Huimin Hospital, Beijing Chao-Yang Hospital and the 2nd People′s Hospital of Yunnan Province during January 1, 2013 to December 31, 2018. The clinical characteristics of patients with or without corticosteroids administration were compared. The first dose of corticosteroids was administrated within 72 hours after admission, with the average dose of methylprednisolone (0.6±0.3) mg/(kg·d) and duration of (4.0±1.2) days. An adjusted logistic regression model was performed to assess the impact of corticosteroids treatment on the clinical outcomes (noninvasive ventilation, invasive ventilation, vasopressor use, admittance to intensive care unit (ICU), 30-day mortality, hyperglycemia needing insulin treatment and gastrointestinal bleeding). Mann-Whitney test and χ2 test were used for the statistical analysis. Results:Among the 693 patients, 132 patients received corticosteroids. Logistic regression analysis revealed that asthma (odd ratios ( OR)=15.528, 95% confidence interval ( CI) 1.953-123.484, P=0.01), chronic obstructive pulmonary disease ( OR=21.904, 95% CI 4.548-105.504, P<0.01) and arterial partial pressure of oxygen (PaO 2)/fraction of inspired oxygen (FiO 2)<300 mmHg (1 mmHg=0.133 kPa, OR=2.701, 95% CI 1.513-4.822, P<0.01) were independent risk factors for corticosteroids use in the FluA-CAP patients. An adjusted logistic regression model showed that low-medium dose corticosteroids administration was associated with decreased risks for early (defined as zero to three days after the first dose of corticosteroids) noninvasive ventilation ( OR=0.342, 95% CI 0.156-0.750, P<0.01), and increased risk for late (defined as four to 14 days after the first dose of corticosteroids) vasopressor use ( OR=2.651, 95% CI 1.913-6.306, P<0.01), late hyperglycemia which needed insulin treatment ( OR=9.739, 95% CI 2.174-21.769, P=0.019), ICU admission ( OR=3.075, 95% CI 1.166-8.143, P<0.01) and the 30-day mortality ( OR=2.372, 95% CI 1.337-4.549, P<0.01). In patients with asthma or chronic obstructive pulmonary disease ( OR=2.343, 95% CI 1.145-4.073, P<0.01) and PaO 2/FiO 2<300 mmHg ( OR=1.961, 95% CI 1.029-4.212, P<0.01), corticosteroids administration increased the risk of 30-day mortality. Conclusion:Low-medium corticosteroids treatment is associated with poor outcomes of FluA-CAP patients, and is not recommended to be used routinely.

OBJECTIVE: To determine the effect of atorvastatin on lipopolysaccharide-induced expression of C-reactive protein in cultured A549 cells. METHODS: A549 cells were incubated in DMEM medium containing lipopolysaccharide in the absence or presence of various concentrations of atorvastatin. After the incubation, the medium was collected and the level of C-reactive protein was measured by enzyme-linked immunosorbent assay. The cells were harvested and C-reactive protein mRNA was analyzed by reverse transcription polymerase chain reaction. RESULTS: Incubation with lipopolysaccharide significantly induced a time and dose dependent increase in the mRNA expression and the production of C-reactive protein in A549 cells (P<0.05). Atorvastatin significantly decreased the lipopolysaccharide induced the mRNA expression and the production of C-reactive protein in a dose dependent manner in A549 cells (P<0.05). CONCLUSION Atorvastatin downregulates lipopolysaccharide-induced expression of C-reactive protein in cultured A549 cells, which may be its mechanism of anti-inflammation.
Atorvastatin ; C-Reactive Protein ; genetics ; metabolism ; Cell Line ; Down-Regulation ; drug effects ; Epithelial Cells ; metabolism ; pathology ; Heptanoic Acids ; pharmacology ; Humans ; Lipopolysaccharides ; antagonists & inhibitors ; Lung ; metabolism ; pathology ; Pyrroles ; pharmacology ; RNA, Messenger ; genetics ; metabolism

Objective To assess the impact of short-term, low-dose systemic glucorticosteroids treatment on the clinical outcomes in patients with severe community-acquired pneumonia (SCAP). Methods A multi-center retrospective study was conducted. Data of patients hospitalized with SCAP in five teaching hospitals from Beijing, Shandong and Yunnan Provinces from January 1st, 2013 to December 31st, 2015 were reviewed. Patients were divided into steroids group and non-steroids group according to whether treated with glucorticosteroids during the disease course or not. Data of patients were reviewed, including gender, age, underlying disease, blood routine, biochemical examination and radiology findings (the worst value was recorded if there were more than one value), supportive treatment, complications (hyperglycemia needing insulin treatment and gastrointestinal bleeding) and clinical outcomes [early (0-3 days) treatment failure, late (4-14 days) treatment failure and 30-day mortality, treatment failure was defined as one of the followings: needing noninvasive or invasive ventilation, needing vasopressor use or death]. Univariate and multivariate Logistic regression was performed to evaluate the impact of short-term, low-dose systemic glucorticosteroids on the clinical outcomes in SCAP patients. Results Overall, 3 561 immunocompetent adult and adolescent patients with community-acquired pneumonia (CAP) were screened, 132 SCAP patients were entered into final analysis, including 24 patients in steroids group and 108 patients in non-steroids group. The patients in steroids group were prescribed with methylprednisolone (0.6±0.1) mg·kg-1·d-1 for (4.0±1.7) days. Compared with patients in non-steroids group, patients in steroids group showed younger age [years old: 70.5 (59.0, 75.0) vs. 80.0 (76.0, 85.0)], less frequency of male [41.7% (10/24) vs. 72.2% (78/108)], less comorbidities with cardiovascular [16.7% (4/24) vs. 42.6% (46/108)] and cerebrovascular disease [0% (0/24) vs. 40.7% (44/108)], less confusion [16.7% (4/24) vs. 40.7% (44/108)]; more frequency of chronic obstructive pulmonary disease [COPD, 41.7% (10/24) vs. 13.0% (14/108)], asthma [25.0% (6/24) vs. 1.9% (2/108)], chronic hepatic disease [8.3% (2/24) vs. 0% (0/108)] and respiratory rate≥30 times/min [33.3% (8/24) vs. 9.3% (10/108)] with significant differences (all P < 0.05), the proportion of guideline-based empirical antimicrobial therapy, early needing noninvasive ventilation, late gastrointestinal bleeding, early and late hyperglycemia needing insulin treatment were higher in steroids group than non-steroids group [50.0% (12/24) vs. 21.3% (23/108), 33.3% (8/24) vs. 7.4% (8/108), 20.8% (5/24) vs. 4.6% (5/108), 20.8% (5/24) vs. 1.9% (2/108), 37.5% (9/24) vs. 2.8% (3/108), all P < 0.05]. Adjusted by gender, age, comorbidities and empirical antimicrobial therapy, Logistic regression confirmed short-term, low-dose systemic glucorticosteroids was associated with higher risk for vasopressor usage [odds ratio (OR) = 3.369, 95% confidence interval (95%CI) = 1.369-6.133, P = 0.035], hyperglycaemia needing insulin treatment (OR = 4.738, 95%CI = 1.890-8.652, P = 0.017) in late stage and 30-day mortality (OR = 2.187, 95%CI = 1.265-4.743, P = 0.002). Conclusion Adjunctive treatment with short-term, low-dose systemic glucorticosteroids worsen the clinical outcomes and should not be used to SCAP patients routinely.

Objective: To explore the value of B-type natriuretic peptide (BNP) be used as a prognostic factor for community-acquired pneumonia. Methods: This was a multicenter, retrospective study. Data of patients hospitalized with community-acquired pneumonia during 2014/1/1 to 2015/12/31 from four tertiary hospitals were reviewed, including demographic and clinical features, and outcomes. Univariate analysis and logistic regression analysis were performed to determine risk factors for 30-day mortality. Receiver operating characteristic curves (ROCs) was performed to verify the accuracy of BNP>1 000 pg/ml, CURB-65 score and BNP>1 000 pg/ml+ CURB-65 score (B-CURB65) as 30-day mortality predictors in the study patients. Results: 1 786 patients hospitalized with community-acquired pneumonia (CAP) were entered into the final analysis. The 30-day mortality was 4.7%. Logistic regression analysis confirmed blood BNP>1 000 pg/ml was an independent risk factor associated with 30-day mortality of CAP patients. The area under the curve (AUC) of B-CURB65 was 0.774, which was higher than CURB-65 score (AUC=0.625, P=0.002). Conclusions Blood BNP is a valuable biomarker related to the 30-day mortality of CAP patients, which can increase the predicting accuracy of CURB-65 score.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*