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Liang Chen,1 Xiu-Di Han,2 Yan-Li Li,3 Chun-Xiao Zhang,4 Xi-Qian Xing5 1Department of Infectious Diseases, Beijing Jishuitan Hospital, 4th Medical College of Peking University, Beijing, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Qingdao Municipal Hospital, Qingdao City, Shandong Province, People’s Republic of China; 3Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Beijing Huimin Hospital, Beijing, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, The 2nd People’s Hospital of Yunnan Province, Kunming City, Yunnan Province, People’s Republic of ChinaCorrespondence: Liang Chen Tel +8613810438037Email chenliang1995@sina.comPurpose: Respiratory viruses are important etiologies of community-acquired pneumonia (CAP). However, the impact of different RVs on the outcomes of CAP is not well elucidated. This study aims to compare the clinical features and severity of influenza (Flu-p) and non-influenza respiratory viruses-related pneumonia (NIRVs-p) onset in the community among immunocompetent adults.Methods: The data of the patients hospitalized with laboratory-confirmed RVs-p were retrospectively reviewed from five teaching hospitals in China from January 2013 to May 2019. Univariate and multivariate logistic regressions were performed to compare the clinical characteristics and outcomes between Flu-p and NIRVs-p.Results: A total of 1079 patients with Flu-p and 341 patients with NIRVs-p were included in this study. A multivariate logistic regression model revealed chronic pulmonary disease [odd ratio (OR) 0.341, 95% confidence interval (CI) 0.225– 0.515, p < 0.001], solid malignant tumor (OR 0.330, 95% CI 0.163– 0.668, p = 0.002), myalgia (OR 1.697, 95% CI 1.236– 2.330, p < 0.001), lymphocytes < 0.8× 109/L (OR 10.811, 95% CI 6.949– 16.818, p < 0.001) and blood albumin < 35 g/L (OR 0.327, 95% CI 0.242– 0.442, p < 0.001) were predictors for Flu-p. After adjusting for confounders, the multivariate logistic regression analysis confirmed that influenza B-related pneumonia (FluB-p) (OR 0.419, 95% CI 0.272– 0.646, p < 0.001) and NIRVs-p (OR 0.260, 95% CI 0.158– 0.467, p < 0.001) were associated with a decreased risk of 30-day mortality compared with the influenza A-related pneumonia (FluA-p).Conclusion: Our results showed that patients with FluA-p experience a more severe disease than those with FluB-p and NIRVs-p. Some clinical features are helpful to distinguish between NIRVs-p and Flu-p.Keywords: influenza, respiratory virus, pneumonia, clinical characteristics, severity

Respiratory papilloma is a relatively common benign tumor of the respiratory tract, and a few patients may develop malignant changes. The disease has an insidious onset and lacks specific clinical manifestations, and its manifestations are closely related to the growth mode, location and size of the tumor. It can involve multiple parts, such as the larynx, trachea, bronchus, and lung parenchyma, which cause coughing, hoarseness, dysphonia, and, in severe cases, may lead to obstruction of the respiratory tract. At present, the treatment of respiratory papilloma lacks standardization, and there is no effective method to cure the disease. Surgery remains the main treatment for alleviating patients' symptoms and preventing airway obstruction. However, due to the high recurrence rate of respiratory papilloma, multiple surgeries are often needed, which reduces the quality of life of patients and increases their disease burden and economic burden. Bevacizumab, a vascular endothelial growth factor-binding antibody inhibitor, is a promising adjuvant treatment modality that shows good potential for reducing symptoms and the frequency of surgery. This article aimed to review the efficacy and safety of bevacizumab for the treatment of respiratory papilloma and discuss the differences and efficacy of the systemic application and intralesional injection of bevacizumab for the treatment of respiratory papilloma.

Objective: To construct and characterize conditional Src homology region 2 protein tyrosine phosphatase 1 (SHP-1) knockout mice in airway epithelial cells and to observe the effect of defective SHP-1 expression in airway epithelial cells on the emphysema phenotype in chronic obstructive pulmonary disease (COPD). Methods: To detect the expression of SHP-1 in the airway epithelium of COPD patients. CRISPR/Cas9 technology was used to construct SHP-1flox/flox transgenic mice, which were mated with airway epithelial Clara protein 10-cyclase recombinase and estrogen receptor fusion transgenic mice (CC10-CreER +/+ ), and after intraperitoneal injection of tamoxifen, airway epithelial SHP-1 knockout mice were obtained (SHP-1 flox/flox CC10-CreER +/- , SHP-1 Δ/Δ ). Mouse tail and lung tissue DNA was extracted and PCR amplified to discriminate the genotype of the mice; the knockout effect of SHP-1 gene in airway epithelial cells was verified by qRT-PCR, Western blotting, and immunofluorescence. In addition, an emphysema mouse model was constructed using elastase to assess the severity of emphysema in each group of mice. Results: Airway epithelial SHP-1 was significantly downregulated in COPD patients. Genotyping confirmed that SHP-1 Δ/Δ mice expressed CC10-CreER and SHP-1-flox. After tamoxifen induction, we demonstrated the absence of SHP-1 protein expression in airway epithelial cells of SHP-1 Δ/Δ mice at the DNA, RNA, and protein levels, indicating that airway epithelial cell-specific SHP-1 knockout mice had been successfully constructed. In the emphysema animal model, SHP-1 Δ/Δ mice had a more severe emphysema phenotype compared with the control group, which was manifested by disorganization of alveolar structure in lung tissue and rupture and fusion of alveolar walls to form pulmonary alveoli. Conclusions: The present study successfully established and characterized the SHP-1 knockout mouse model of airway epithelial cells, which provides a new experimental tool for the in-depth elucidation of the role of SHP-1 in the emphysema process of COPD and its mechanism.

Circular RNAs (circRNAs) are a newly identified type of noncoding RNA molecule with a unique closed-loop structure. circRNAs are widely expressed in different tissues and developmental stages of many species, participating in many important pathophysiological processes and playing an important role in the occurrence and development of diseases. This article reviews the discovery, characteristics, formation, and biological function of circRNAs. The relationship between circRNAs and vascular remodelling, as well as the current status of research and potential application value in pulmonary hypertension (PH), is discussed to promote a better understanding of the role of circRNAs in PH. circRNAs are closely related to the remodelling of vascular endothelial cells and vascular smooth muscle cells. circRNAs have potential application prospects for in-depth research on the possible pathogenesis and mechanism of PH. Future research on the role of circRNAs in the pathogenesis and mechanism of PH will provide new insights and promote screening, diagnosis, prevention, and treatment of this disease., Competing Interests: The authors confirm that there are no conflicts of interest., (Copyright © 2022 Shuang-Lan Xu et al.)

To explore potential critical genes and identify circular RNAs (circRNAs) that act as the competitive endogenous RNA (ceRNA) in a hypoxic pulmonary hypertension (HPH) rat model. Constructed rat model, and a bioinformatics method was used to analyse differentially expressed (DE) genes and construct a circRNA-miRNA-mRNA ceRNA regulatory network. Then, qRT-PCR was used to verify. The significant DEcircRNAs/DEmiRNAs/DEmRNAs was showed, and a ceRNA network with 8 DEcircRNAs, 9 DEmiRNAs and 46 DEmRNAs were constructed. The functional enrichment suggested the inflammatory response, NF-κB signalling, MAPK cascade and Toll-like receptor were associated with HPH. Further assessment confirmed that circ&#95;002723, circ&#95;008021, circ&#95;016925 and circ&#95;020581 could have a potential ceRNA mechanism by sponging miR-23a or miR-21 to control downstream target gene and be involved in the pathophysiology of HPH. The qRT-PCR validation results were consistent with the RNA-Seq results. This study revealed potentially important genes, pathways and ceRNA regulatory networks in HPH., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The reconstruction of pulmonary vascular structure caused by the proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) is the central link in the formation of pulmonary arterial hypertension (PAH). Platelet‑derived growth factor (PDGF) can regulate the proliferation and migration of PASMCs. At the same time, nuclear factor of activated T cells (NFATs) plays an important role in the development of PAH. To the best of our knowledge, there are no reports yet regarding whether PDGF regulates NFATc2 to increase the proliferation of PASMCs. The present study aimed to investigate whether PDGF affects the proliferation and migration of PASMCs by regulating NFAT, and to study the pathogenesis of PAH. PASMCs were treated with recombinant PDGF; Cell Counting Kit‑8 and clone formation experiments showed that PDGF enhanced the cell viability and proliferation of PASMCs. Cell cycle distribution and molecular markers related to cell proliferation (cyclin D1, CDK4 and Proliferating Cell Nuclear Antigen) were detected by flow cytometry, and the results indicated that PDGF promoted the division of PAMSCs. The scratch migration and Transwell migration assays showed that the migratory ability of PASMCs was enhanced following PDGF treatment. Changes in NFATs (NFATc1‑5) after PDGF treatment were evaluated by reverse transcription‑quantitative PCR and western blotting; NFATc2 showed the most significant results. Finally, PDGF‑treated cells were treated with an NFAT pathway inhibitor, cyclosporin A, or a small interfering RNA targeting NFATc2, and changes in cell proliferation and migration were evaluated to assess the role of NFATc2 in PDGF‑induced cell proliferation and migration. In conclusion, PDGF may regulate PASMC proliferation and migration by regulating the expression of NFAT, further leading to the occurrence of PAH. It is proposed that NFATc2 could be used as a potential target for PAH treatment.

Background: The overexpression of TSLP and DNA methylation in asthma were both risk factors the relationship was not clear., Objective: This study aimed to investigate the relationship between methylation status of TSLP promoter and mRNA/protein expression in asthmatic airway epithelial cells., Methods: Human bronchial epithelial cells were cultured in vitro and divided into: Control group, treated with PBS, model group, sensitized with LPS (10 μg/mL) for 12 h (37 °C, 5% CO 2 ). Other groups were cultured with the pCMV3 plasmid (M + NC/pCMV), pGPH1 plasmid (M + NC/pGPH), DNMT1/pCMV3 plasmid (M + DNMT1/pCMV), and DNMT1/pGPH1 plasmid (M + DNMT1/pGPH) for 48 h. The expression of DNA methyltransferase 1 and TSLP were measured using real-time PCR and western blotting., Results: Compared with the control group, TSLP mRNA (1.00 ± 0.00 vs. 2.82 ± 0.81 vs. 1, P < 0.001) and protein (1.07 ± 0.04 vs. 1.46 ± 0.11, P < 0.01) were significantly greater, and the methylation of promoter was lower (92.75 ± 1.26 vs. 58.57 ± 3.34, P < 0.05) in the model group. Compared with the model group, TSLP mRNA (2.82 ± 0.81 vs. 1.17 ± 0.10, P < 0.001) decreased, but TSLP promoter methylation increased (58.57 ± 3.34 vs. 92.58 ± 7.30, P < 0.05) in M + DNMT1/pCMV. TSLP mRNA and protein were higher (2.82 ± 0.81 vs. 5.32 ± 0.21, P < 0.001; 1.46 ± 0.11 vs. 1.94 ± 0.11, respectively, P < 0.01), TSLP promoter methylation was lower (58.57 ± 3.34 vs. 33.57 ± 4.29, P < 0.05) in M + DNMT1/pGPH., Conclusions: Overexpression of TSLP in asthmatic airway epithelial cells may be regulated by DNA demethylation.

The separation of actinides has a vital place in nuclear fuel reprocessing, recovery of radionuclides, and remediation of environmental contamination. Here we propose a new paradigm of nanocluster-based actinide separation, namely, nanoextraction, that can achieve efficient sequestration of uranium in an unprecedented form of giant coordination nanocages using a cone-shaped macrocyclic pyrogallol[4]arene as the extractant. The U 24 -based hexameric pyrogallol[4]arene nanocages with distinctive [U 2 (PG) 2 ] binuclear units (PG = pyrogallol) that rapidly assembled in situ in monophasic solvent were identified by single-crystal X-ray diffraction, MALDI-TOF mass spectrometry, NMR spectroscopy, and small-angle X-ray and neutron scattering. Comprehensive biphasic extraction studies showed that this novel separation strategy has enticing advantages such as fast kinetics, high efficiency, and good selectivity over lanthanides, thereby demonstrating its potential for efficient separation of actinide ions.

The synergistic anti-tumor effect of schisandrin B (Sch.B) and apatinib was investigated in vitro. The CCK-8 assay revealed that Sch.B enhanced the inhibition of apatinib on cell proliferation by arresting cell cycle in G0/G1 phase. Sch.B also potentiated the suppression of apatinib on cell migration and invasion, by means of wound-healing and transwell invasion assay. Flow cytometry results showed that Sch.B enhanced apoptosis induced by apatinib. The results were confirmed by western blot analysis of the proteins MMP-9, and Bax caspase-9, and -12. These results suggest that combining apatinib and Sch.B is an effective therapeutic strategy for preventing GC progression. [Formula: see text].

Background: Inconsistencies exist regarding the severity of illness caused by different influenza strains. The aim of this study was to compare the clinical outcomes of hospitalized adults and adolescents with influenza-related pneumonia (Flu-p) from type A and type B strains in China., Methods: We retrospectively reviewed data from Flu-p patients in five hospitals in China from January 2013 to May 2019. Multivariate logistic and Cox regression models were used to assess the effects of influenza virus subtypes on clinical outcomes, and to explore the risk factors of 30-day mortality for Flu-p patients., Results: In total, 963 laboratory-confirmed influenza A-related pneumonia (FluA-p) and 386 influenza B-related pneumonia (FluB-p) patients were included. Upon adjustment for confounders, multivariate logistic regression models showed that FluA-p was associated with an increased risk of invasive ventilation (adjusted odds ratio [aOR]: 3.824, 95% confidence interval [CI]: 2.279-6.414; P <  0.001), admittance to intensive care unit (aOR: 1.630, 95% CI: 1.074-2.473, P = 0.022) and 30-day mortality (aOR: 2.427, 95% CI: 1.568-3.756, P <  0.001) compared to FluB-p. Multivariate Cox regression models confirmed that influenza A virus infection (hazard ratio: 2.637, 95% CI: 1.134-6.131, P = 0.024) was an independent predictor for 30-day mortality in Flu-p patients., Conclusions: The severity of illness and clinical outcomes of FluA-p patients are more severe than FluB-p. This highlights the importance of identifying the virus strain during the management of severe influenza.

Objective: To explore the incidence, risk factors of cardiovascular events (CVE) and their impact on 30-day mortality in patients hospitalized with community-acquired pneumonia (CAP). Methods: This is a multicenter, retrospective study. Patients hospitalized with CAP from 5 teaching hospitals in Beijing, Shandong and Yunnan provinces during 1 January 2013 to 31 December 2015 were included and clinical data were retrieved from the Hospital Information System (HIS), and patients were divided into CVE group and non-CVE group. Age, sex, comorbidities, pneumonia severity index(PSI)/CURB-65 score, routine blood test, biochemical examinations, radiological findings on admission and mortality on 30-day after admission were analyzed. The primary endpoint was acute CVE during hospitalization, the secondary endpoint was 30-day death after admission. Multivariate Cox regression analysis was used to explore the risk factors for CVE. Kaplan-Meier survival curve was used to compare the difference on 30-day mortality between CVE patients and non-CVE patients by Log-rank test. Multivariate Cox regression model was used to assess the impact of CVE on the 30-day mortality among CAP patients after adjustment with age, sex, comorbidities, PSI/CURB-65 score. Results: A total of 3 561 CAP patients were included into the final analysis, including 210 (5.9%) patients in CVE group and 3 351 (94.1%) patients in non-CVE group. Compared with patients in non-CVE group, patients in CVE group were older ( P< 0.001), prevalence of hypertension, coronary heart disease, chronic heart failure, cerebrovascular disease, chronic obstructive pulmonary disease, chronic kidney disease, aspiration risk and bedrid were significantly higher (all P< 0.001); prevalence of CURB-65 score 3-5 and PSI risk class Ⅳ/Ⅴ were also significantly higher (both P< 0.001). The proportion of axillary temperature<36 ℃, respiratory rate≥30 beats/minutes, confusion, leukocytes>10×10(9)/L, hemoglobin < 100 g/L, platelets>300×10(9)/L, albumin < 35 g/L, blood urea nitrogen > 7 mmol/L, fasting blood glucose>11 mmol/L, serum C-reaction protein > 100 mg/L, serum procalcitonin≥2 μg/L, arterial pH<7.35, arterial PO(2)/FiO(2)≤300 mmHg (1 mmHg=0.133 kPa), and multilobar infiltrates and pleural effusion on chest X-ray or CT scan were significantly higher in CVE group than in non-CVE group(all P< 0.05); the 30-day mortality was significantly higher in CVE group than in non-CVE group( P< 0.001). The incidence of CVE was significantly higher in patients with cardiovascular and cerebrovascular disease(CVD) than in patients without CVD (13.9%(150/1 079) vs. 2.4%(60/2 482), χ(2)=178.737, P< 0.001). Meanwhile, the incidence of CVE increased with PSI in patients with Ⅰ/Ⅱ, Ⅲ and Ⅳ/Ⅴ class, respectively(χ(2)=228.350, P< 0.001); and CURB-65 score 0-1, 2 and 3-5, respectively (χ(2)=387.154, P< 0.001). Cox regression analysis revealed that age ( HR =1.05, 95 %CI 1.02-1.09, P= 0.002), coronary heart disease ( HR =1.88, 95 %CI 1.01-3.51, P= 0.048), chronic heart failure ( HR =4.25, 95 %CI 1.89-9.52, P< 0.001), PSI risk class ( HR =1.66, 95 %CI 1.50-2.62, P= 0.029) and serum procalcitonin≥ 2 μg/L ( HR =3.72, 95 %CI 1.60-8.66, P= 0.002) were independent risk factors for CVE in CAP patients. Kaplan-Meier curve showed that the survival probability of patients with CVE was significantly lower than patients without CVE ( P< 0.001). After adjustment for age, sex, comorbidities and PSI/CURB-65 score, Cox regression model showed that CVE was associated with increased 30-day mortality in CAP patients ( HR =6.05, 95 %CI 3.11-11.76, P< 0.001). Conclusions: Although the incidence of CVE is not high in Chinese patients hospitalized with CAP, CVE is common in patients with severe pneumonia and in patients with CVD. Age, cardiovascular disease, PSI risk class and serum procalcitonin are the risk factors for CVE in this patient cohort. CVE is related to increased 30-day mortality in CAP patients.

BACKGROUND miR-214-3p has been found to inhibit proliferation and migration in cancer cells. The objective of this study was to determine whether ARHGEF12 is involved in miR-214-3p-mediated suppression of proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). MATERIAL AND METHODS PASMCs were cultured under normoxia or hypoxia. miR-214-3p mimics or inhibitors were transiently transfected into PASMCs. Proliferation, apoptosis, and migration of PASMCs were evaluated using MTT assay, flow cytometry, and Boyden chamber apparatus. Western blot analysis was used to examine expression of Rho guanine nucleotide exchange factor 12 (ARHGEF12), c-fos, c-jun, and caspase-3. Luciferase reporter assay was used to test the direct regulation of miR-214-3p on the 3'-untranslated region (UTR) of ARHGEF12. RESULTS miR-214-3p was significantly upregulated in hypoxia-treated PASMCs. Knockdown of miR-214-3p significantly attenuated hypoxia-induced proliferation and migration in PASMCs and promoted apoptosis, whereas this effect was aggravated by overexpression of miR-214-3p. In addition, dual-luciferase reporter assay demonstrated that ARHGEF12 is a direct target gene of miR-214-3p. The protein levels of ARHGEF12 were downregulated after knockdown of miR-214-3p in PASMCs. Rescue experiment results indicated that decreased proliferation of PASMCs resulted from knockdown of miR-214-3p were partially reversed by silencing of ARHGEF12 by siRNA. Furthermore, knockdown of miR-214-3p reduced expression of c-jun and c-fos, but increased expression of caspase-3 in PASMCs under hypoxia. CONCLUSIONS In conclusion, these results indicate that miR-214-3p acts as a novel regulator of hypoxia-induced proliferation and migration by directly targeting ARHGEF12 and dysregulating c-jun and c-fos in PASMCs, and may be a potential therapeutic target for treating pulmonary hypertension.

Autophagy is an important mechanism for cellular self-digestion and basal homeostasis. This gene- and modulator-regulated pathway is conserved in cells. Recently, several studies have shown that autophagic dysfunction is associated with pulmonary hypertension (PH). However, the relationship between autophagy and PH remains controversial. In this review, we mainly introduce the effects of autophagy-related genes and some regulatory molecules on PH and the relationship between autophagy and PH under the conditions of hypoxia, monocrotaline injection, thromboembolic stress, oxidative stress, and other drugs and toxins. The effects of other autophagy-related drugs, such as chloroquine, 3-methyladenine, rapamycin, and other potential therapeutic drugs and targets, in PH are also described., (© 2019 Wiley Periodicals, Inc.)

Phosphatase and tensin homolog (PTEN) plays an important role in the pathogenesis of hypoxic pulmonary hypertension (HPH). A decrease in PTEN expression is associated with the hypermethylation of its promoter. However, whether the demethylation of the PTEN gene could attenuate HPH remains unknown. 5-Aza-2'-deoxycytidine (5-Aza-dC) is a DNA methyltransferase (DNMT) inhibitor. The present study was designed to investigate the effects and mechanisms of 5-Aza-dC on HPH. The proliferation, migration and apoptosis of rat pulmonary artery smooth muscle cells (PASMCs) induced by hypoxia and treated with 5-Aza-dC were detected. The expression of PTEN and DNMTs and the PTEN methylation status of PASMCs were detected. SD rats were randomly divided into normal group, hypoxia group and hypoxia + 5-Aza-dC group. The expression of PTEN was decreased, the expression of DNMTs was increased, and the methylation status of PTEN was increased in hypoxia-induced PASMCs. However, 5-Aza-dC can rescue the decreased PTEN, inhibit DNMT levels in a dose-dependent manner and suppress PTEN methylation. Furthermore, the demethylation of PTEN, which was induced by 5-Aza-dC, inhibited the proliferation, migration and promoted apoptosis in PASMCs. In vivo studies further demonstrated that the expression of PTEN, mean pulmonary artery pressure and right ventricular hypertrophy index in HPH rats was attenuated by 5-Aza-dC. 5-Aza-dC also suppressed the expression of DNMTs and PTEN methylation in the lungs of HPH rats. These results indicated that PTEN promoter methylation status is involved in HPH. 5-Aza-dC, as a DNMT inhibitor, has the potential to attenuate HPH via demethylation of the PTEN promoter., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To determine the association of serum cardiac troponin (cTn) with the mortality of pulmonary hypertension (PH) patients via a meta-analysis., Date Source: We searched PubMed and EMBASE from inception to October 25, 2017., Study Selection: The reference lists of the retrieved articles were also consulted. The Q test and I 2 test were used for to assess heterogeneity. The relationship between cTn elevation and mortality was analysed. Studies were stratified according to type of troponin (cTnT vs cTnI), region (Europe vs America) and follow-up length (≤3 years vs >3 years)., Results: Eight studies with 739 patients were included in the meta-analysis. Cardiac troponin elevation ranged from 14.3% to 94.5%. Overall, 48.8% (39/80) of patients with elevated cTn died compared to 18.6% (45/242) of patients with normal cTn levels. These findings showed cTn elevation was significantly related to an increased mortality risk in PH patients [hazard ratio (HR) = 3.05, 95% confidence interval (95% CI) = 2.16-4.32, I 2  = 24.9%]. cTnI was better at predicting mortality than cTnT (HR = 3.37, 95%CI = 2.05-5.55 vs HR = 2.80, 95%CI = 1.97-3.98, respectively). American populations had increased mortality compared to European populations (HR = 4.23, 95%CI = 2.29-7.80 vs HR = 2.70, 95% CI = 1.95-3.74, respectively). This finding was independent of the follow-up length of the studies (≤3 years: HR = 2.36, 95%CI = 1.65-3.38; >3 years: HR = 4.55, 95%CI = 2.80-7.39)., Conclusions: Although different studies detected the expression cTnT or cTnI by various methods, the mortality in the cTn-positive group was higher than that in the cTn-negative group. Serum cTn elevation emerged as an independent predictor of increased risk of mortality in PH patients., (© 2019 John Wiley & Sons Ltd.)

Objective: To explore the clinical features, etiological features and prognostic risk factors of long-term glucocorticoid users with community-acquired pneumonia (CAP). Methods: A retrospective study included 100 long-term glucocorticoid users with CAP (G-CAP group) from 11 hospitals of China between January 2014 and December 2014, while 100 non-immunocompromised patients with community-acquired pneumonia were enrolled as controls (nICH-CAP group). Characteristics including age, gender, underlying diseases, corticosteroids, symptoms, disease severity, imaging manifestations, etiology, respiratory failure, mechanical ventilation, whether the application of vasoactive drugs, antibiotics application, hospital mortality rate between the two groups were compared, and the prognostic factors of G-CAP were investigated using Logistic regression. Results: The peripheral blood lymphocytes[1.06(0.70, 1.68) vs 1.44 (0.87, 1.98)]in G-CAP group was less than nICH-CAP group ( P <0.05). CT with pulmonary interstitial change (28.6% vs 9.9%), the proportion of patients with respiratory failure (25.0% vs 7.0%), mechanical ventilation (9.0% vs 2.0%), noninvasive mechanical ventilation (12.0% vs 2.0%), septic shock (9.0% vs 2.0%), and the hospital mortality rate (13.0% vs 3.0%) in G-CAP group were significantly higher than in nICH-CAP group (all P <0.05). Bacterial infection accounted for the highest proportion of infection (61.3%) in G-CAP group, but also virus infection (19.4%) and mixed infection (16.1%). Pseudomonas accounted for the highest proportion (47.4%) in bacterial infection of G-CAP. Logistic regression analysis showed that peripheral blood lymphocytes ( OR =0.004, 95% CI: 0.000-0.234; P <0.05) and respiratory failure ( OR =17.766, 95% CI: 4.933-131.0; P <0.05) were independent predictors of death in G-CAP group. Conclusions: The proportion of severe pneumonia and the mortality rate of patients with G-CAP are higher than the patients with nICH-CAP. Lymphopenia and respiratory failure are associated with poor outcome of patients with G-CAP.

Pulmonary hypertension is characterized by extensive vascular remodelling, leading to increased pulmonary vascular resistance and eventual death due to right heart failure. The pathogenesis of pulmonary hypertension involves vascular endothelial dysfunction and disordered vascular smooth muscle cell (VSMC) proliferation and migration, but the exact processes remain unknown. Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid involved in a wide spectrum of biological processes. S1P has been shown to regulate VSMC proliferation and migration and vascular tension via a family of five S1P G-protein-coupled receptors (S1P1-SIP5). S1P has been shown to have both a vasoconstrictive and vasodilating effect. The S1P receptors S1P1 and S1P3 promote, while S1P2 inhibits VSMC proliferation and migration in vitro in response to S1P. Moreover, it has been reported recently that sphingosine kinase 1 and S1P2 inhibitors might be useful therapeutic agents in the treatment of empirical pulmonary hypertension. The sphingosine kinase 1/S1P signalling pathways may play a role in the pathogenesis of pulmonary hypertension. Modulation of this pathway may offer novel therapeutic strategies.

The wastewater containing polyvinyl alcohol (PVA) was characterized with poor biodegradability, and was difficult to remove. In order to find an economically reasonable and practical technology, the research on the removal efficiency of different concentration wastewater containing PVA by ozonation-activated sludge process was studied, and the result was compared with the traditional activated sludge process. The results showed that the ozonation-activated sludge process was not suitable for treating influent with COD below 500 mg x L(-1) and the wastewater PVA concentration was 10-30 mg x L(-1). When the influent COD was between 500-800 mg x L(-1) and the PVA concentration was 15-60 mg x L(-1), the system had advantages on dealing with this kind of wastewater, and the average removal efficiency of COD and PVA were 92.8% and 57.4%, which were better than the traditional activated sludge process 4.1% and 15.2% respectively. In addition, the effluent concentrations of COD could keep between 30-60 mg x L(-1). When the influent COD was 1 000-1 200 mg x L(-1) and the PVA concentration was 20-70 mg x L(-1), the average removal efficiencies of COD and PVA were 90.9% and 45.3%, which were better than the traditional activated sludge process 12.8% and 12.1% respectively, but the effluent should to be further treated. Compared with the traditional activated sludge process, ozonation-activated sludge process had high treatment efficiency, stable running effect, and effectively in dealing with industrial wastewater containing PVA.

Accumulating evidence suggests that statins possess anti-inflammatory properties and may decrease C-reactive protein (CRP) levels in plasma. However, no studies have as yet addressed whether or not statins regulate the expression of CRP in human lung epithelial cells (A549). In this study, we determined whether atorvastatin modulates the lipopolysaccharide (LPS)-induced expression of CRP in A549 cells. A549 cells were incubated in Dulbecco's modified Eagle's medium containing LPS in the absence or presence of various concentrations of atorvastatin. After incubation, the medium was collected and the amount of CRP was measured by an enzyme-linked immunosorbent assay. The cells were harvested and CRP messenger ribonucleic acid (mRNA) was analyzed by reverse transcription polymerase chain reaction. Incubation with LPS induced a significant time- and dose-dependent increase in CRP mRNA expression and CRP production in A549 cells, whereas atorvastatin significantly decreased LPS-induced CRP mRNA expression and CRP production in a dose-dependent manner. The present study revealed that A549 cells are capable of LPS-induced CRP expression, and that atorvastatin down-regulates the LPS-induced expression of CRP in cultured A549 cells. Our results suggest that statins ameliorate lung inflammation by regulating CRP production in human lung epithelial cells.

Objective: Electrical and structural remodeling are of importance for the occurrence and maintenance of atrial fibrillation. We observed association between atrial connexin protein expression and fibrosis in a canine model of prolonged rapid atrial pacing., Methods: "J"-type electrodes were placed in the right atrial appendage under the guidance of X-ray in 16 dogs, Animals in model group (n = 8) received fast pacing (400 beats/min) for 10 weeks while animals in control group (n = 8) maintained at sinus rhythm. Limb-lead ECGs were recorded at 2, 4, 6, 8 weeks respectively. Burst stimulation was applied to induce atrial fibrillation in all animals after 10 weeks, animals were sacrificed thereafter and the left atrial tissues were taken for myocardial collagen measurement (Masson staining) and myocardial ultrastructure examination and detection of protein expression of connexin (Cx) 40 and 45 (immune staining). Procollagen type III N-terminal peptide and type IV collagen in serum were also detected by radioimmunoassay., Results: Two dogs died in model group due to atrial rupture induced cardiac tamponade or lung emboli. Spontaneously atrial fibrillation was not observed in all animals, but two dogs developed atrial flutter and atrial premature beats. Atrial fibrillation was induced by burst stimulation in 4 out of 6 dogs in model group and in none of the dogs in control group. Atrial myocardial collagen volume fraction was significantly increased in model group compared with the control group (P < 0.05). Ultrastructure examination in atrial tissue evidenced disorder, fracture, collagen fiber proliferation, mitochondrial swelling, blurred cristae, and intercalated disc distortion, expansion, part of gap junction disappears in model group. The serum levels of procollagen type III N-terminal peptide and type IV collagen in model group were significantly higher than in the control group (P < 0.05). The protein expression of Cx 40 in atrial myocardium in model group was significantly higher than in control group (P < 0.05), while Cx 45 protein expression was similar between two groups (P > 0.05). The left atrial CVF was positively correlated with Cx 40 (r = 0.671, P < 0.01)., Conclusion: Increased myocardial fibrosis is positively correlated with upregulation of myocardial Cx 40 protein expression in left atrium in rapid atrial paced canine.

Objective: To investigate the effects of simvastatin(Sim) and losartan(Los) on cardiac fibrosis and myocardial expression of MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA in pressure overloaded rat hearts., Methods: The pressure overload model was induced by descending aortic constriction (DAC) in rats. SD rats were randomized into 6 groups (n = 20 each): normol control group, control sham group, DAC group, Los group (DAC + Los, 5 mg/kg), Sim group (DAC + Sim, 2 mg/kg), Los + Sim group (DAC + Los + Sim, Los 5 mg/kg, Sim 2 mg/kg). Water, Los or Sim drug was administrated by gavage daily beginning from day 5 after operation for 30 days. Collagen was measured on Masson stained myocardial sections, and the level of MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA in left ventricle were detected by RT-PCR., Results: Collagen volume fraction (CVF) in DAC group was significantly higher than the normal control and sham groups (P < 0.01) which could be significantly reduced by Los and Sim (P < 0.05), especially in DAC + Los + Sim group (P < 0.01). The levels of myocardial MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA were also significantly higher in DAC group than in normal control and sham groups (P < 0.01). Treatment Sim and Los alone and especially in combination significantly decreased the TIMP-1 mRNA, TIMP-2 mRNA expressions (P < 0.01) while MMP-2 mRNA, MMP-9 mRNA levels remained unchanged (P > 0.05)., Conclusion: Upregulation of myocardial MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA expressions might contribute to myocardial fibrosis in this model, Sim and Los significantly inhibited myocardial fibrosis possibly by downregulating myocardial TIMP-1 mRNA, TIMP-2 mRNA expressions in this model.

A lattice Boltzmann method-based single-phase free surface model is developed to study the interfacial dynamics of coalescence, droplet formation and detachment phenomena related to surface tension and wetting effects. Compared with the conventional multiphase models, the lattice Boltzmann-based single-phase model has a higher computational efficiency since it is not necessary to simulate the motion of the gas phase. A perturbation, which is given in the same fashion as the perturbation step in Gunstensen's color model, is added to the distribution functions of the interface cells for incorporating the surface tension into the single-phase model. The assignment of different mass gradients along the fluid-wall interface is used to model the wetting properties of the solid surface. Implementations of the model are demonstrated for simulating the processes of the droplet coalescence, the droplet formation and detachment from ceiling and from nozzles with different shapes and different wall wetting properties.

Statins are the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors that function as potent inhibitors of cholesterol biosynthesis and have been used for many years for the treatment of hypercholesterolemia. However, accumulating experimental and clinical studies have revealed that the health benefits associated with statins treatment, particularly those conferred on the cardiovascular system, were the cholesterol-independent. Because statins inhibit an early step in the cholesterol biosynthetic pathway, they also inhibit the synthesis of isoprenoids such as farnesylpyrophosphate and geranylgeranylpyrophosphate, which are important postranslational lipid attachments for intracellular signaling molecules such as the Rho GTPases. The isoprenylation of Rho is a prerequisite for Rho activation, facilitating its interaction with the plasma membrane, undergoing GDP-GTP exchange and be activated. Inhibition of RhoA geranylgeranylation by statins decreases membrane GTP-bound active RhoA and subsequent Rho-kinase activity. Activated RhoA via its downstream effector Rho-kinase is involved in a wide range of cellular functions, such as cell migration, proliferation and apoptosis. Recently, rising evidences suggested that RhoA/Rho-kinase pathway was essentially involved in various models of pulmonary hypertension and statins effectively ameliorated pulmonary hypertension. Based on this findings, we hypothesis that statins attenuate pulmonary hypertension via RhoA/Rho-kinase signaling pathway in vivo.

Pulmonary hypertension (PH) is a cardiovascular disorder characterized by vasoconstriction and vascular remodeling. Recently, rapidly increasing evidence from various rat models of PH and patients with PH suggest that small GTPase Rho and its downstream effector, Rho-kinase, play a key role in the pathogenesis of PH. Activation of the Rho/Rho-kinase pathway is important for pulmonary endothelial dysfunction, pulmonary vascular smooth muscle cell contractility, proliferation and apoptosis in PH. A greater Rho-kinase expression and an enhanced Rho-kinase activity have been observed in pulmonary arteries of PH rats, such as hypoxia-induced, monocrotaline-induced and genetic spontaneous PH rats. Moreover, Y-27632 or fasudil, the selective Rho-kinase inhibitors, significantly attenuated PH in various pulmonary hypertensive model rats and patients with PH, but did not reduce systemic blood pressure. Therefore, Rho-kinase inhibitors may have therapeutic potential for the treatment of PH., (Copyright 2006 Prous Science. All rights reserved.)

Incubating plasma membranes prepared from pig liver with varying concentrations of insulin (50-1000 microU/ml) resulted in the release of at least two insulin chemical mediators. One of them was fraction 1 of insulin mediator (M. W. 3700-4000 daltons) which had a significant lipogenesis-stimulating activity. The other was fraction 2 of insulin mediator (M. W. about 1000 daltons) which exhibited a lipogenesis-inhibitory activity. The ratio of yield between the two mediators produced from the membranes was not only dependent on the concentration but also on the potency of insulin and its analogs added. The result showed that there was more production of fraction 2 than fraction 1 with the inducer at low concentration (100 microU/ml), while the production of fraction 1 from the plasma membranes incubated with high concentration of insulin (300 microU/ml) was higher than fraction 2. On the other hand, insulin and its analogs which have different biological activities and receptor binding activities have been used to induce the insulin mediators. The results obtained were similar to those mentioned above. This suggested that the generation of the mediators was dependent on the biological potences but not the binding activities.

Plasma membranes prepared from pig liver incubated with insulin (50-300 microU/ml) resulted in the release of at least two insulin chemical mediators. They appeared to modulate the activity of adenylate cyclase in liver plasma membranes of pig. One of them was fraction 1 of insulin mediator (M. W. about 3700-4000 dalton) which markedly stimulated the activity of the enzyme, the other was fraction 2 of insulin mediator (M. W. about 1000 dalton) which inhibited the enzyme activity. The results showed that the inhibitor of fraction 2 generated was significantly higher than that of fraction 1 when the membranes were incubated with insulin of low concentration (50-100 microU/ml). On the other hand, the generation of stimulator of fraction 1 from plasma membranes incubated with insulin of high concentration (200 microU/ml) was higher than that of fraction 2. So the ratio of yield between two mediators produced from the membranes was dependent on the concentration of insulin added. The results also showed that the effect of fraction 1 of insulin mediator on adenylate cyclase activity in liver cell plasma membranes was biphasic while fraction 2 of insulin mediator showed an inhibitory effect only even though it was at very high concentration. The results that both mediators combined with Gpp(NH)p and forskolin to affect the enzyme activity show that the action of insulin mediators likely resides in the GTP regulatory component of adenylate cyclase.

Plasma membranes prepared from pig, mouse and rat liver incubated with insulin resulted in the release of at least two insulin chemical mediators. These mediators, identified as fractions 1 and 3, were found to inhibit cAMP level in response to lipolytic hormone and forskolin and to enhance lipogenesis in adipocytes of rat. Fractions 1 and 3 have been estimated to have molecular weights of 3700-4000 and 1000-1500 dalton, respectively. This initial report will focus on fraction 1. Interestingly, liver membranes from diabetic animals were found not to release mediators in the presence of insulin. However, following in vivo treatment of diabetic animals with insulin, the liver membranes appeared to restore its ability in generating chemical mediators in response to insulin.