CX3CR1 participates in pulmonary angiogenesis in experimental hepatopulmonary syndrome mice through inhibiting AKT/ERK signaling pathway and regulating NO/NOS release.

OBJECTIVE: Hepatopulmonary syndrome (HPS) is a kind of pulmonary microvascular disease and occurs in 15%-30% cirrhosis. This study aimed to investigate the effects of pulmonary CX3CR1 on angiogenesis and associated mechanisms in HPS animal models. MATERIALS AND METHODS: CX3CR1GFP/GFP mice were constructed by replacing CX3CR1 with GFP. Common bile duct ligation (CBDL) mouse model was established with surgery. Release of nitric oxide (NO) was evaluated. Hematoxylin-eosin (HE) staining was employed to examine the inflammation of lung tissues. CD31 expression was detected with immunohistochemistry assay. Western blotting was used to evaluate the expression of CX3CL1, CX3CR1, phosphorylated-AKT (p-AKT), phosphorylated-ERK (p-ERK). Quantitative Real Time-PCR (qRT-PCR) assay was used to examine VEGF, PDGF, iNOS, eNOS, and HO-1 expression. RESULTS: CX3CR1-deficiency (CX3CR1GFP/GFP-sham or CX3CR1GFP/GFP-CBDL mice) significantly reduced NO release compared to wide type (WT)-mice or WT-CBDL mice (p<0.05). CX3CR1-deficiency significantly alleviated inflammation compared to wide type (WT)-mice or WT-CBDL mice (p<0.05). CX3CR1-deficiency significantly reduced CD31 expression compared to WT-sham and WT-CBDL mice, respectively (p<0.05). CX3CR1 also participated in anti-angiogenesis efficacy of Bevacizumab. CX3CR1-deficiency significantly down-regulated the ratio of p-AKT/AKT and p-ERK/ERK and inhibited the secretion of VEGF and PDGF compared to WT-mice (p<0.05). CX3CR1-deficiency significantly reduced iNOS, eNOS, and HO-1 expression compared to WT-mice (p<0.05). CONCLUSIONS: CX3CR1 deficiency reduced VEGF and PDGF production, inhibited p-AKT, and p-ERK activation and down-regulated iNOS, eNOS, and HO-1 expression. Therefore, CX3CR1 participates in pulmonary angiogenesis in the experimental HPS mice via inhibiting AKT/ERK signaling pathway and regulating NO/NOS release. These findings would provide a potential insight for clarifying the pathological mechanisms of HPS.

[A comparison of leak compensation in six acute care ventilators during non-invasive ventilation].

Objective: To compare the ability of leak compensation in 6 medical ventilators during non-invasive ventilation. Methods: Six medical ventilators were selected, including 3 non-invasive ventilators (V60, Flexo and Stellar150), and 3 invasive ventilators(Avea, Servo I and BellaVist). Using a lung simulator, the ability of leak compensation was evaluated during triggering and cycling in 2 respiratory mechanics conditions (high airway resistance condition and high elastance resistance condition), and each condition was performed under 2 PEEP levels (4, and 8 cmH(2)O, 1 mmHg=0.098 kPa) at 4 air leak level conditions (L0: 2-3 L/min, L1: 8-10 L/min, L2: 22-27 L/min, L3: 35-40 L/min). Results: In the high elastance resistance condition (L2, L3)with different leak levels, the number of auto-triggering and miss-triggering of the non-invasive ventilator Flexo was significantly less than those of the others (L2: 1, 1; L3: 1.67, 1.33, P<0.01), and had better synchronization (L2: 2.33, 2.33; L3: 3.33, 3.33, P<0.01). In the high airway resistance condition with PEEP 4 cmH(2)O, V60 had less number of auto-triggering than other ventilators (P<0.01), while in the high airway resistance condition with PEEP 8 cmH(2)O, Stellar150 had less number of miss-triggering than other ventilators (1, 0.67, 0, P<0.01). Flexo had a shorter trigger delay time than other ventilators in both high airway resistance and high elastance resistance conditions with L0 and L1 leak levels and PEEP levels [ARDS, PEEP=4: (109.8±1.8) ms, (112.0±0.6) ms; ARDS, PEEP=8: (103.1±0.7) ms, (109.7±0.7) ms; COPD, PEEP=4: (207.3±1.1) ms, (220.8±1.1) ms; COPD, PEEP=8: (195.6±6.7) ms, (200.0±1.2) ms , P<0.01]. Stellar150 had the shortest trigger delay time in high airway resistance condition with PEEP 4 cmH(2)O and high leak level L3[(262.8±0.8) ms , P<0.01]. V60 had a good performance on trigger delay time in high elastance resistance condition with PEEP 4 and 8 cmH(2)O, and also was most stable in increasing leak levels. Conclusion: In high airway resistance and high elastance resistance conditions with different PEEP levels and leak levels, V60, Stellar150, Flexo and BellaVista ventilators could be synchronized, among which V60, Stellar150 and Flexo presented a good performance features in specific conditions.

Tissue inhibitor of metalloproteinase-2 G-418C polymorphism is associated with an increased risk of gastric cancer in a Chinese population.

AIMS: To examine the effect of the TIMP-2 G-418C polymorphism on gastric cancer risk. METHODS: We conducted a hospital-based, case-control study using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 412 individuals (206 gastric cancer patients and 206 age, sex matched cancer-free controls). RESULTS: The genotype and allele frequencies were significantly different (P = 0.007 and 0.005, respectively) between cases and controls. Further analysis showed that the variant TIMP-2 genotypes (CC+GC) had a 51% increased risk of gastric cancer compared with GG [adjusted odds ratio (OR) 1.51, 95% confidence interval (CI) 1.00-2.26, P = 0.049]. The elevated gastric cancer risk was especially evident in younger individuals (age < 58 years old) (adjusted OR 2.21, 95% CI 1.18-4.16) and smokers (adjusted OR 2.61, 95% CI 1.01-6.72). However, no significant association was observed between the variant genotypes and clinicopathological features of gastric cancer. CONCLUSIONS: These findings suggest that the TIMP-2 G-418C polymorphism is a genetic predisposing factor for gastric cancer.