Objective:To investigate the role of the angiopoietin (Ang)/tyrosine kinase receptor 2 (Tie2) pathway in mediating histone-induced coagulation activation in mice with acute lung injury, and the protective mechanism of unfractionated heparin (UFH).Methods:Twenty-four mice were randomly divided into three groups ( n=8 per group): Control group, Histone group, and Histone + UFH group using the random number table method. The Histone group and Histone + UFH group were administered 50 mg/kg histone via the tail vein. One hour later, UFH was given at a dosage of 400 U/kg by the same way. The Control group was administered an equivalent volume of sterile saline solution. Four hours after modeling, tissue samples were collected. HE staining was performed to observe the pathology of lung tissue. Lung lobe wet and dry weights were measured to assess the degree of pulmonary edema. Immunohistochemistry was used to observe the expression of fibrinogen (FIB) in lung tissue. ELISA was used to detect the levels of thrombin-antithrombin complex (TAT), plasminogen activator inhibitor type-1 (PAI-1), and D-dimer (D-D) in plasma. The qRT-PCR was used to measure the mRNA expression levels of tissue factor (TF), FIB, PAI-1, angiopoietin (Ang)-1, Ang-2, and Tie2 in lung tissue. Western blot was used to measure the protein expression levels of TF, FIB, Ang-1, Ang-2, and pTie2 in lung tissue. Results:The HE staining results revealed that, compared to the Control group, the Histone group exhibited thickened alveolar walls, significant neutrophil infiltration, and alveolar congestion with edema, indicating histone-induced ALI ( P<0.001). In contrast, the Histone + UFH group exhibited milder lung injury ( P<0.001), suggesting that UFH mitigated the lung damage induced by histones. The lung wet/dry weight ratio and lung water content percentage were significantly higher in the Histone group than in the Control group ( P<0.001), while UFH reduced the severity of pulmonary edema ( P<0.01). Immunohistochemistry revealed intravascular thrombus formation and fibrin deposition in the Histone group, which were reduced by UFH. ELISA results showed significantly elevated levels of TAT, PAI-1, and D-D in the Histone group ( P<0.001), and UFH decreased the levels of these parameters stimulated by histone ( P<0.05). The qRT-PCR showed increased mRNA expression of TF, FIB, PAI-1, and Ang-2, and decreased expression of Ang-1 and Tie2 in lung tissues in the Histone group, while UFH mitigated the effects of histones on mRNA expression of these parameters. Western blot analysis indicated increased protein expression of TF, FIB, and Ang-2 ( P<0.01), and decreased expression of Ang-1 and Tie2 in lung tissues in the Histone group ( P<0.01), and UFH reduced the impact of histones on the protein expression of these parameters ( P<0.05). Conclusions:Histones can cause lung injury, pulmonary edema, and coagulation activation in mice lung tissue. UFH can effectively alleviate histone induced lung injury, and coagulation activation in by histones via the Ang/Tie2 signaling pathway.

Objective:To explore the clinical significance of recurrent laryngeal nerve inlet zone(RLNIZ) lymph node metastasis in papillary thyroid cancer(PTC).Methods:The clinical data of the clinicopathologic characteristics of 738 cases with papillary thyroid cancer at our centers from Jul 2017 to Jun 2018 was retrospectively reviewed. 108 cases with RLNIZ lymph node dissection for pathological examination were included. The relationship between metastasis of RLNIZ lymph node and clinicopathologic characteristics was analyzed.Results:RLNIZ lymph node was detected in 12.3%(91/738)cases, the mean lymph node number in RLNIZ was 1.5±0.7, and 30.8%(28/91) cases suffered RLNIZ lymph node metastasis. RLNIZ lymph node metastasis(LNM) is associated with tumor size( P=0.028), capsular invasion( P=0.019), No. of central compartment LNM( P<0.001) and lateral neck LNM( P<0.001). No. of central compartment LNM was found to be the independent risk factor of RLNIZ lymph node metastasis. The incidence of dysphagia and inferior parathyroid damage was 0.9%(1/108)respectively. Conclusions:RLNIZ lymph node metastasis is common among PTC patients , therefore, RLNIZ lymph node should be routinely removed especially in patients with tumor size over 1cm、suspected capsular invasion and lateral neck lymph node metastasis confirmed by preoperative imaging examination.