ABSTRACT
Pulmonary vascular remodeling (PVR) is not only the main pathophysiological feature of Pulmonary Artery Hypertension (PAH) but also the main reason for the progressive aggravation of PAH. Its central link is the excessive proliferation of pulmonary artery smooth muscle cells (PASMCs), which leads to the imbalance of proliferation/apoptosis, leads to the formation of PAH. At present, we found that hypoxia can up-regulate the expression of mitophagy protein PINK1/Parkin, induce the proliferation of PASMCs, and inhibit apoptosis. Knocking down PINK1-/- and/or Parkin-/-, found that the proliferation of PASMCs was significantly inhibited compared with that of PINK1/Parkin, while the proliferation of cells under PINK1-/- Parkin-/- was significantly lower than that of PINK1-/- Parkin+/+or PINK1+/+ Parkin-/-. These results suggest that hypoxia can activate the PINK1/Parkin-mediated mitophagy pathway, induce the excessive proliferation of PASMCs, eventually lead to PVR, leading to HPH. Our team is further exploring which substances in HPH can induce mitotic response, which molecules specifically mediate the activation of mitotic pathways, and what role they play in the occurrence and development of HPH disease.
Subject(s)
Protein Kinases/genetics , Protein Kinases/physiology , Pulmonary Artery/pathology , Pulmonary Artery/physiopathology , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/physiology , Vascular Remodeling/genetics , Vascular Remodeling/physiology , Animals , Apoptosis/genetics , Apoptosis/physiology , Cell Proliferation/genetics , Cell Proliferation/physiology , Cells, Cultured , Disease Models, Animal , Gene Knockdown Techniques , Humans , Hypoxia/complications , Hypoxia/pathology , Hypoxia/physiopathology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Mitophagy/genetics , Mitophagy/physiology , Protein Kinases/deficiency , Pulmonary Arterial Hypertension/etiology , Pulmonary Arterial Hypertension/pathology , Pulmonary Arterial Hypertension/physiopathology , RNA, Small Interfering/genetics , Ubiquitin-Protein Ligases/deficiencyABSTRACT
Objective To investigate the surgical approach of Siewert Ⅱ and Ⅲ gastroesophageal junction adenocarcinoma.Methods A total of 148 cases with Siewert Ⅱ,Ⅲ type patients were prospectively studied.The patients were divided into two groups,including transthoracic approach group (58 cases) and transabdominal approach group(90 cases).The results of surgery were compared.Patients were followed up for 2 years and survival rate were compared.Results In transthoracic approach group and transabdominal approach group,operative time ((329.5 ± 84.3) min vs.(202.4± 84.5) min,t =15.431,P ＜ 0.001),the positive rate margin stump (8.62％ vs.1.11％,x2 =5.763,P =0.012),pleural effusion (13.79％ vs.2.22％,x2 =10.462,P ＜0.001) and pulmonary infection rate (15.52％ vs 1.11％,x2 =12.574,P＜ 0.001) were significantly higher than transabdominal approach group,and number of lymph node dissection ((16.7 ± 4.3) vs.(22.6± 5.5),t =6.321,P =0.004) was significantly less than transabdominal approach group.In incidence of blood loss,tumor diameter,anastomotic leakage (or bleeding) and discharge time,there was no significant difference (P ＞0.05).One-year survival rate of transthoracic approach group was 73.24％,and 2-year survival rate was 53.43％.Oneyear survival rate of transabdominal approach group was 78.42％,and 2-year survival rate was 57.51％.Survival rate of two groups showed no significant difference (P =0.453,0.311).Conclusion Transabdominal surgical approach in Siewert Ⅱ,Ⅲ patients is better than transthoracic approach,can better carry out abdominal lymph node dissection,does not destroy the integrity of the chest,and avoid the occurrence of related complications.
