Objective To investigate the feasibility and plan quality of the image-guided volumetric modulated arc therapy (VMAT) based voluntary deep exhale breath-holding technique in the stereotactic ablative body radiotherapy (SABR) for liver tumors.Methods Fifteen patients with liver tumors were involved in this study.All patients were immobilized with voluntary deep exhale breath hold (vDEBH) combined with real-time position management (RPM) respiratory gating system.Treatment was planned using VMAT with 2 modified partial arc and re-planned using intensity modulated radiation therapy (IMRT) technique for comparison.Dosimetric parameters were calculated for plan quality assessment.Quality assurance studies included absolute dose and multiple planar dose verifications,total monitor units and delivery time analysis.Daily cone beam computed tomography imaging was used to verify the motions.Results There were no significant dosimetric differences between VMAT and conventional IMRT plans (P ＞0.05).Both techniques were able to minimize doses to organs at risk including normal liver,kidneys,spinal cord,and stomach.However,the average monitor units with VMAT were significantly lower 28.1％ than those with IMRT(t =3.064,P ＜0.05).The average beam-on time in VMAT plans was 31.6％ shorter than that in IMRT plans(t =2.278,P ＜ 0.05).Conclusions The utilization of VMAT in the treatment planning of SABR for liver tumors under breath control mode has better dosimetrics.In comparison to conventional IMRT plans,VMAT plans have higher efficiency and feasibility.

Acute respiratory distress syndrome (ARDS), characterized by acute hypoxic respiratory dysfunction or failure, is a manifestation of multiple organ failure (MOF) in the lung, which often caused by various non-cardiac reasons, included severe trauma, infection, shock; and the most common risk factor is sepsis which would cause uncontrolled host response to infecting factors. As a strong stressor during sepsis, the severe infectious state of the body triggers serious stress reaction. The hypothalamus-pituitary-adrenal cortical (HPA) axis and sympathetic-adrenal medulla axis were activated and participated the initiation and progression of the stress response through the production of adrenocorticotropic hormone (ACTH), glucocorticoid (GC), epinephrine and norepinephrine (NE). As the main hormones during sepsis, catecholamines (CA), including epinephrine and NE, could bind to adrenergic receptor (AR). After the binding, CA could play its role through the complicated signal way. Therefore, to explore the signal transduction pathway of α-AR, during sepsis, is important for revealing the mechanism of sepsis-induced ARDS.

Objective To explore the effects and mechanism of α2A-adrenergic receptor (α2A-AR) antagonist BRL-44408 maleate on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Methods Sixty male C57BL/6 mice were randomly divided into three groups (n = 20): sham group, LPS group and BRL-44408 maleate pre-treated group (BRL+LPS group). The model of ALI was replicated by intratracheally administrated of LPS (5 mg/kg), and the mice in the sham group were received an equal volume of saline. Mice in the BRL+LPS group were treated with additionally BRL-44408 maleate (5 mg/kg, i.p) at 4 hours before LPS administration. The mice were sacrificed at 6 hours and 24 hours after LPS administration in each group. Among them, 5 mice were used to collect the bronchoalveolar lavage fluid (BALF) and the other 5 mice were sacrificed for lung tissues. The levels of norepinephrine (NE), tumor necrosis factor-α (TNF-α), interleukins (IL-6, IL-10) in BALF were measured by enzyme linked immunosorbent assay (ELISA). The level of protein in BALF was measured by bicinchoninic acid (BCA) method. The histopathological changes and wet/dry (W/D) ratio of lung tissue were observed. The expression of lung phosphorylated mitogen-activated protein kinase kinase (p-MEK) and phosphorylated extracellular regulated protein kinases (p-ERK) were detected by Western Blot. Results Compared with the sham group, the lung histopathological injury was significantly aggravated, and the histopathological injury score was significantly increased, the lung W/D ratio, and total protein content, NE, TNF-α, IL-6, IL-10 in BALF, and p-MEK and p-ERK expressions were significantly increased in LPS group at 6 hours after model setup [the lung histopathological injury score: 0.70±0.04 vs. 0.14±0.13,W/D ratio: 4.79±0.15 vs. 4.35±0.17, protein content (g/L): 1.51±0.36 vs. 0.46±0.13, NE (ng/L): 85.02±11.28 vs.47.18±10.30, TNF-α (ng/L): 186.61±21.93 vs. 9.18±2.86, IL-6 (ng/L): 193.45±26.54 vs. 13.58±2.54, IL-10 (ng/L): 113.46±31.23 vs. 25.66±9.41, p-MEK/β-actin: 0.246±0.019 vs. 0.178±0.030, p-ERK/β-actin:0.257±0.013 vs. 0.175±0.014, all 1 < 0.05], and increase with time after model setup. Compared with the LPS group,BRL-44408 maleate pretreatment for 6 hours could significantly improve the degree of lung injury and reduce the lung histopathological injury score (0.61±0.05 vs. 0.70±0.04), reduce lung W/D weight ratio (4.51±0.22 vs. 4.79±0.15);the expression of NE, TNF-α, IL-6 in BALF were inhibited [NE (ng/L): 55.77±15.86 vs. 85.02±11.28, TNF-α (ng/L): 54.79±12.68 vs. 186.61±21.93, IL-6 (ng/L): 67.66±20.08 vs. 193.45±26.54], in addition, the up-regulation of p-MEK, p-ERK were significantly inhibited (p-MEK/β-actin: 0.204±0.008 vs. 0.246±0.019, p-ERK/β-actin:0.186±0.024 vs. 0.257±0.013), with statistically significant differences (all 1 < 0.05). The protein content and the expression of IL-10 in BALF showed no significant difference. Conclusion α2A-AR blocker BRL-44408 maleate could alleviate endogenous ALI induced by LPS in mice by inhibiting the MEK/ERK pathway.

Acute?lung?injury?(ALI)?and?its?severe?form,?acute?respiratory?distress?syndrome?(ARDS),?are?common?critical?syndromes.?The?causes?of?the?syndrome?are?complex?and?diverse.?The?main?pathological?features?are?the?diffuse?inflammatory?and?protein-rich?pulmonary?edema?caused?by?destruction?of?the?blood-air?barrier.?Reactive?oxygen?species?(ROS)?mediate?oxidative?damage?by?oxidizing?bio-macromolecules,?including?lipids,?proteins?and?nucleic?acid.?Among?many?systems?producing?ROS,?nicotinamide-adenine?dinucleotide?phosphate?(NADPH)?oxidase-mediated?ROS?is?the?main?source,?and?its?functional?subunit?is?the?transmembrane?subunit?NOX?family.?The?distribution?of?NOX?family?proteins?in?lung?tissue?is?cell?type?dependent.?NOX-derived?ROS?is?involved?in?the?defense?function?of?lung?tissue?and?related?to?the?occurrence?and?development?of?ALI/ARDS.?This?review?mainly?describes?the?cell?distribution,?activation?factors,?and?its?relationship?with?the?occurrence?and?development?of?ALI?of?the?NOX?family.