Cuiping Fu

Chronic intermittent hypoxia leads to insulin resistance and impaired glucose tolerance through dysregulation of adipokines in non-obese rats

Background and objectivesThe aim of this study was to determine whether chronic intermittent hypoxia (CIH) could affect the secretion of adipokines, such as resistin, leptin, and adiponectin, in non-obese rats and to investigate the potential mechanisms.MethodsAn established rodent model of CIH was utilized, in which rats were exposed to varying oxygen levels (7–21 %) respectively over a period of 5 weeks. The area under the curve (AUCG) and the insulin resistance index (homeostasis model of assessment for insulin resistance index, HOMA-IR) were calculated. The levels of several secretory factors in the blood were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA levels and protein expression in adipose tissues was measured by reverse transcription-polymerase chain reaction (RT-PCR).ResultsGlucose tolerance and the levels of adiponectin in non-obese rats were decreased in the CIH group both in the serum and adipose tissue compared with the controls, while the insulin resistance index and the levels of resistin and leptin were increased. Moreover, the expressions of hypoxia inducible factor-1α and lactate dehydrogenase A were significantly higher in chronic intermittent hypoxia rats than in control rats, suggesting the presence of adipose tissue hypoxia.ConclusionsThese results show that CIH leads to insulin resistance (IR) and impaired glucose tolerance (IGT) in a non-obese rodent model of obstructive sleep apnea-hypopnea syndrome, and these effects may be due to the dysregulation of adiponectin, resistin, and leptin.

Adaptive servoventilation improves cardiac dysfunction and prognosis in heart failure patients with sleep-disordered breathing: a meta-analysis.

Adaptive servoventilation (ASV) is a new therapeutic modality to treat sleep‐disordered breathing (SDB) especially for central sleep apnoea associated with Cheyne–Stokes respiration, whereas the role of ASV in SDB patients with heart failure (HF) is controversial. The purpose of this study was to evaluate the effects of ASV on these patients through a meta‐analysis of published data.

Association between XPA gene rs1800975 polymorphism and susceptibility to lung cancer: a meta-analysis.

Xeroderma pigmentosum complementation group A (XPA) gene is a key member of nucleotide excision repair pathway. It was reported that XPA rs1800975 polymorphism was associated with susceptibility to lung cancer. However, the conclusions were controversial.

STAT4 knockout protects LPS-induced lung injury by increasing of MDSC and promoting of macrophage differentiation.

The disruption of signal transducer and activator of transcription 4 (STAT4) signal can inhibit the inflammation and protect organs from injury during severe bacterial infection. However, the mechanism of STAT4 signal in lung injury remains poor understood. Here we report that STAT4 deficiency decreased the lethality and protein leakage in STAT4(-/-) mice and protected lipopolysaccharid (LPS)-induced lung injury with ameliorated edema, inflammatory infiltration and hemorrhage. The expression of CD11b(+)Gr-1(+) myeloid derived suppressor cells (MDSCs) markedly increased in the circulation of STAT4(-/-) mice after LPS stimuli, accompanying with increased macrophages infiltration in inflamed lung tissue. In addition, the levels of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 decreased while anti-inflammatory cytokine (IL-10) increased in the bronchoalveolar lavage fluid of STAT4(-/-) mice. Thus, these results indicate that the accumulation of MDSCs and macrophages play a critical role in LPS-induced lung injury. Targeting MDSCs and macrophages polarization through a STAT4 dependent signaling pathway might help to reduce the inflammation and damage of lung tissue.

A meta-analysis: is low-dose computed tomography a superior method for risky lung cancers screening population?

Low‐dose computed tomography (LDCT) has been proposed to be a new screening method to discover lung cancers in an early stage, especially those patients who are in a high risk of lung cancer. The primary objective of this meta‐analysis is to systematically review the effect of LDCT on screening for lung cancers among the risky population who are older than 49 years old and with smoking exposure.

Bone-marrow-derived mesenchymal stem cells inhibit gastric aspiration lung injury and inflammation in rats

Gastric aspiration lung injury is one of the most common clinical events. This study investigated the effects of bone‐marrow‐derived mesenchymal stem cells (BMSCs) on combined acid plus small non‐acidified particle (CASP)‐induced aspiration lung injury. Enhanced green fluorescent protein (EGFP+) or EGFP− BMSCs or 15d‐PGJ2 were injected via the tail vein into rats immediately after CASP‐induced aspiration lung injury. Pathological changes in lung tissues, blood gas analysis, the wet/dry weight ratio (W/D) of the lung, levels of total proteins and number of total cells and neutrophils in bronchoalveolar lavage fluid (BALF) were determined. The cytokine levels were measured using ELISA. Protein expression was determined by Western blot. Bone‐marrow‐derived mesenchymal stem cells treatment significantly reduced alveolar oedema, exudation and lung inflammation; increased the arterial partial pressure of oxygen; and decreased the W/D of the lung, the levels of total proteins and the number of total cells and neutrophils in BALF in the rats with CASP‐induced lung injury. Bone‐marrow‐derived mesenchymal stem cells treatment decreased the levels of tumour necrosis factor‐α and Cytokine‐induced neutrophil chemoattractant (CINC)‐1 and the expression of p‐p65 and increased the levels of interleukin‐10 and 15d‐PGJ2 and the expression of peroxisome proliferator‐activated receptor (PPAR)‐γ in the lung tissue in CASP‐induced rats. Tumour necrosis factor‐α stimulated BMSCs to secrete 15d‐PGJ2. A tracking experiment showed that EGFP+ BMSCs were able to migrate to local lung tissues. Treatment with 15d‐PGJ2 also significantly inhibited CASP‐induced lung inflammation and the production of pro‐inflammatory cytokines. Our results show that BMSCs can protect lung tissues from gastric aspiration injury and inhibit lung inflammation in rats. A beneficial effect might be achieved through BMSC‐derived 15d‐PGJ2 activation of the PPAR‐γ receptor, reducing the production of proinflammatory cytokines.

G4-Tetra DNA Duplex Induce Lung Cancer Cell Apoptosis in A549 Cells

The specific DNA is typically impermeable to the plasma membrane due to its natural characters, but DNA tetra structures (DTNs) can be readily uptake by cells in the absence of transfection agents, providing a new strategy to deliver DNA drugs. In this research, the delivery efficiency of tetrahedral DNA nanostructures was measured on adenocarcinomic human alveolar basal epithelial (A549) cells via delivering AS1411 (G4). The DNA tetra-AS1411 complex was rapidly and abundantly uptake by A549 cells, and the induced apoptosis was enhanced. Furthermore, biodistribution in mouse proved the rapid clearance from non-targeted organs in vivo. This study improved the understanding of potential function in DNA-based drug delivery and proved that DTNs-AS1411 could be potentially useful for the treatment of lung cancer.

Predictors of mid-term prognosis and adverse factors in acute pulmonary embolism.

Background: To explore the differences in short and middle term adverse factors of pulmonary embolism (PE) outcome. Methods: This was a single-center retrospective study of inpatients admitted from Zhongshan Hospital, Fudan University, with first-time PE. Clinical data were collected from patients with objectively confirmed PE, and a 2-year follow up was conducted. Results: The sample contained 310 patients with PE, ranging in age from 18 to 86 years old (mean 63.28 ± 15.30) and including 165 men (53.2%) and 145 women (46.8%). Successful treatment was achieved in 285 cases (91.9%) and unsuccessful treatment turned out in 25 cases (8.1%). Logistical regression analysis showed that massive PE [odds ratio (OR) = 23.625, 95% confidence interval (CI) 6.248–89.333], hypoxemia (OR = 11.915, 95% CI 1.900–74.727), leukocytosis (OR = 9.120, 95% CI 2.227–37.349) and active cancer (OR = 6.142, 95% CI 1.233–30.587) were associated with a poor prognosis for acute PE in the short term (in hospital). Seventy-seven PE cases with complete electronic records were finally included in the follow up. Cox regression analysis showed that elevated pulmonary artery systolic pressure (PASP, ⩾50 mmHg) (HR = 9.240, 95% CI, 2.307–37.013) and active cancer with PE (HR = 3.700, 95% CI, 1.010–13.562) were associated with an increased risk of mid-term mortality after a follow-up period of 2 years. Conclusions: Massive PE, hypoxemia, leukocytosis and active cancer may contribute to a poor prognosis for patients with acute PE in hospital. Elevated PASP and active cancer may negatively impact survival time and increase the risk of death for patients with acute PE after 2-year follow up. Short-term adverse factors of acute PE are not exactly the same as the mid-term risk factors of acute PE.

Screening for obstructive sleep apnea syndrome in asthma patients: a prospective study based on Berlin and STOP-Bang questionnaires

BACKGROUND The bidirectional relationship of asthma and obstructive sleep apnea (OSA) has been confirmed in recent years. However, in the clinical practice, majority of asthma patients did not pay adequate attention to their sleep apnea condition. Berlin questionnaire (BQ) and STOP-Bang questionnaire (SBQ) are two most common OSA screening questionnaires to screen high-risk patients for OSA. This study aimed at evaluating the predictive performance of BQ and SBQ for OSA in asthma patients. METHODS Asthma outpatients of Zhongshan Hospital were enrolled into the study. All patients were asked to fill in the BQ and SBQ and clinical characteristics and asthma characteristics were recorded. Univariate and multivariate logistic regression analyses were applied to identify risk factors of OSA in asthma patients. With the gold standard of laboratory-based overnight polysomnography (PSG), the predictive performance of SBQ and BQ was evaluated and compared. The probability of OSA severity was predicted by various SBQ scores in asthma patients. RESULTS A total of 123 asthma patients (average age 47.56±12.12 years; 57.72% males) were enrolled and underwent PSG diagnosis overnight at Sleep Center. Logistic regression analyses showed that rhinitis (adjusted OR =4.30; 95% CI: 1.50-12.37, P=0.007) and dyslipidemia (adjusted OR =2.75; 95% CI: 1.16-6.51, P=0.021) were associated with OSA in asthma patients after adjusting for known OSA risk factors. No asthma functional characteristic differences were found to be associated with OSA severity in the study. The prevalence of moderate-to-severe OSA (AHI ≥15) in the asthmatic population sample was 36.59% (45/123). Questionnaires predictive results showed that compared with BQ, SBQ has higher diagnostic sensitivity (84.4% vs. 60%), lower specificity (79.5% vs. 91%) lower positive predictive value (PPV): (70.4% vs. 79.4%) and higher negative predictive value (NPV) (90% vs. 80%) to detect moderate-to-severe OSA at the cut-off as AHI of 15/h. OSA probability results showed that with the increasing of the questionnaire scores, the moderate and severe OSA probability of SBQ rose significantly. CONCLUSIONS SBQ is a preferable sleep questionnaire better than BQ for detecting moderate and severe OSA in asthma patients which should be validated in larger population sample.

2-Methoxyestradiol attenuates chronic-intermittent-hypoxia-induced pulmonary hypertension through regulating microRNA-223: HAO et al.

Pulmonary hypertension (PH) is prevalent in patients with obstructive sleep apnea (OSA) syndrome, and coexistence of PH and OSA indicates a worse prognosis and higher mortality. Chronic intermittent hypoxia (CIH) is the key pathogenesis of OSA. Also, microRNA‐223 (miR‐223) plays a role in the regulation of CIH‐induced PH process. However, the detailed mechanism of CIH inducing PH is still unclear. This study aimed to investigate the pathological process of CIH associated PH and explore the potential therapeutic methods. In this study, adult Sprague–Dawley rats were exposed to CIH or normoxic (N) conditions with 2‐methoxyestradiol (2‐Me) or vehicle treatment for 6 weeks. The results showed that 2‐Me treatment reduced the progression of pulmonary angiogenesis in CIH rats, and alleviated proliferation, cellular migration, and reactive oxygen species formation was induced by CIH in pulmonary artery smooth muscle cells (PASMCs). CIH decreased the expression of miR‐223, whereas 2‐Me reversed the downregulation of miR‐223 both in vivo and in vitro. Furthermore, the antiangiogenic effect of 2‐Me observed in PASMCs was abrogated by miR‐223 inhibitor, while enhanced by miR‐223 mimic. These findings suggested that miR‐223 played an important role in the process of CIH inducing PH, and 2‐Me might reverse CIH‐induced PH via upregulating miR‐223.