1.Aspirin inhibits tumor cell metastasis mediated by HGF/c-Met
Xiao-yang DAI ; Si-kang CHEN ; Jin-xin CHE
Acta Pharmaceutica Sinica 2022;57(10):2985-2994
In this study, we investigated the effect of aspirin on tumor biological effects mediated by hepatocyte growth factor/cellular-mesenchymal-epithelial transition factor (HGF/c-Met) axis, and preliminarily explored the molecular mechanism of inhibiting tumor metastasis by aspirin. The binding of aspirin to c-Met was predicted by molecular docking; cellular thermal shift assay (CETSA) was used to verify the binding of aspirin to c-Met at the cellular level. The inhibitory effect of aspirin on c-Met kinase was detected by kinase activity; Western blot, cell scattering test, cell branching morphogenesis and Transwell test were used to evaluate the cell signal transduction, morphological changes and migration and invasion ability. The results showed that aspirin could effectively inhibit the kinase activity of c-Met with a half inhibitory concentration of 0.95 mmol·L-1. The results of docking showed that aspirin could bind to the ATP pocket of c-Met protein, and the main binding sites were Tyr1230, Tyr1159 and Met1229. The CETSA test also showed that aspirin could form binding complex with c-Met protein. Western blot results showed that aspirin could inhibit the up-regulation of phosphorylated Met stimulated by HGF in a concentration-dependent manner. The results of cell scattering test showed that aspirin could block HGF/c-Met promoted cell scattering in a concentration dependent manner. Aspirin could almost completely block the biological function mediated by c-Met activation at the concentration of 4 mmol·L-1, and this effect was independent of HGF. Similarly, the results of MDCK cell branching morphogenesis experiment showed that aspirin could inhibit HGF/c-Met mediated invasive growth in a concentration dependent manner. The results of Transwell test showed that aspirin could block HGF/c-Met mediated cell migration and invasion in a concentration-dependent manner. Aspirin could almost completely block the biological function mediated by c-Met activation at the concentration of 4 mmol·L-1, and this effect was independent of HGF. The above results indicate that aspirin can bind to c-Met, thereby blocking the biological effects mediated by HGF/c-Met, and inhibiting tumor metastasis. This study revealed the new biological function of aspirin, and provided a new theoretical basis for a comprehensive understanding of the anti-metastatic effect of aspirin.
2.Application of FOCUS-PDCA program in nursing quality management of pressure ulcers
Xianzhen JIN ; Lina QIAO ; Lei YANG ; Hui FAN ; Wenfang CHE ; Xia XIN
Modern Clinical Nursing 2017;16(9):59-64
Objective To investigate the effect of FOCUS-PDCA program on pressure ulcers nursing quality management. Methods By using the 9 steps of FOCUS-PDCA program of exploring, organizing, clarifying, understanding, selecting, planning, enforcing, checking and executing, we looked into the primarily factors for pressure ulcers and modified and improved our pressure ulcer nursing management system. Then training was done to the nurses, and the pressure ulcer management system was used. The effects in implementation of pressure ulcers prevention, mastery of pressure ulcers prevention knowledge among nurses and occurrence of pressure ulcers in the high-risk patients were studied after applying the program. Results After use of FOCUS-PDCA program, the qualification rate of pressure ulcers prevention implementation and mastery of pressure ulcers prevention knowledge were both higher than before the use. The occurrence rate of pressure ulcers in the high-risk patients was lower than before the use (P<0.05). Conclusion By using the FOCUS-PDCA program in the nursing quality management for patients with pressure ulcers, we can effectively improve the implementation of pressure ulcers preventive measures, enhance the nursing staff to master knowledge on pressure ulcers and reduce the incidence of pressure ulcers.
3.Effect of ginsenoside Rg_3 nanostructured lipid carrier modified by pullulan on promoting absorption and its anti-tumor evaluation in vitro.
Qing YANG ; Ning CAI ; Dao-Biao CHE ; Xin JIN
China Journal of Chinese Materia Medica 2020;45(21):5184-5192
Ginsenoside Rg_3 is widely used in clinical practice as an anti-tumor adjuvant drug, but its application is limited due to its poor oral absorption. In this study, we intended to construct a ginsenoside Rg_3 nanostructured lipid carrier modified by the pullulan(PUL-Rg_3-NLC) to improve the adhesion properties of ginsenoside Rg_3, promote the drug uptake and improve the anti-tumor efficacy. PUL-Rg_3-NLC was characterized by morphology, particle size and Zeta potential. In vivo adhesion characteristics were evaluated by oral gavage tests, and the results were verified from multiple perspectives in combination with in vitro uptake behavior and in vitro pharmacodynamics. The results showed that PUL-Rg_3-NLC, with a particle size of(102±1.89) nm, was characterized by gastric adhesion and could be retained in gastric tissues for a long time, and its uptake by BGC-823 cells was promoted mainly through the pathway mediated by the caveolin-mediated endocytosis. In vitro MTT, cell apoptosis, wound-healing assay and invasion assay all showed some anti-tumor effects. Therefore, PUL-Rg_3-NLC can significantly promote the adhesion of Rg_3 in the stomach, promote the uptake of drugs by gastric cancer cells, and improve the anti-tumor effect. This study can provide some reference for the adjuvant treatment of gastric cancer.
Drug Carriers
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Ginsenosides
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Glucans
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Lipids
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Nanostructures
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Particle Size
4.Comparison of MRI and CT for target volume delineation and dose coverage for partial breast irradiation in patients with breast cancer
Yuchun SONG ; Xin XIE ; Shunan CHE ; Guangyi SUN ; Yu TANG ; Jianghu ZHANG ; Jianyang WANG ; Hui FANG ; Bo CHEN ; Yongwen SONG ; Jing JIN ; Yueping LIU ; Shunan QI ; Yuan TANG ; Ningning LU ; Hao JING ; Yong YANG ; Ning LI ; Jing LI ; Shulian WANG ; Yexiong LI
Chinese Journal of Radiation Oncology 2021;30(3):244-248
Objective:To compare magnetic resonance imaging (MRI)-based and computed tomography (CT)-based target volume delineation and dose coverage in partial breast irradiation (PBI) for patients with breast cancer, aiming to explore the application value of MRI localization in PBI after breast-conserving surgery.Methods:Twenty-nine patients with early breast cancer underwent simulating CT and MRI scans in a supine position. The cavity visualization score (CVS) of tumor bed (TB) was evaluated. The TB, clinical target volume (CTV), planning target volume (PTV) were delineated on CT and MRI images, and then statistically compared. Conformity indices (CI) between CT- and MRI-defined target volumes were calculated. PBI treatment plan of 40 Gy in 10 fractions was designed based on PTV-CT, and the dose coverage for PTV-MRI was evaluated.Results:The CVS on CT and MRI images was 2.97±1.40 vs. 3.10±1.40( P=0.408). The volumes of TB, CTV, PTV on MRI were significantly larger than those on CT, (24.48±16.60) cm 3vs. (38.00±19.77) cm 3, (126.76±56.81) cm 3vs. (168.42±70.54) cm 3, (216.63±81.99) cm 3vs. (279.24±101.55) cm 3, respectively, whereas the increasing percentage of CTV and PTV were significantly smaller than those of TB. The CI between CT-based and MRI-based TB, CTV, PTV were 0.43±0.13, 0.66±0.11, 0.70±0.09( P<0.001), respectively. The median percentage of PTV-MRI receiving 40 Gy dose was 81.9%(62.3% to 92.4%), significantly lower than 95.6%(95.0%~97.5%) of PTV-CT. Conclusions:The CVS between CT and MRI is not significantly different, but the MRI-based TB, CTV, PTV are significantly larger than CT-based values. The PTV-MRI is of underdose if PBI treatment plan is designed for PTV-CT. As a supplement of CT scan, MRI can enhance the accuracy of TB delineation after breast-onserving surgery.
5.Minimally invasive cardiac surgery for cardiac atrioventricular valve reoperation
Weilai HE ; Xin LI ; Hong CHE ; Chaolong JIN ; Wenpeng DONG ; Feng LI ; Yanli LI ; Min LIN ; Shenglin GE ; Ruyuan ZHOU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2022;29(06):755-760
Objective To summarize the clinical experiences of minimally invasive cardiac surgery (MICS) for cardiac atrioventricular valve reoperation. Methods Perioperative data of 32 patients who underwent MICS for cardiac atrioventricular valve reoperation from 2009 to 2019 in the First Affiliated Hospital of Anhui Medical University were retrospectively reviewed, including 13 males and 19 females with a mean age of 51.0±12.6 years. All patients were given combined intravenous and inhalation anesthesia, and a double-lumen tube for mechanical ventilation. Cardiopulmonary bypass was established in all patients by femoral artery and venous cannulation or combined with percutaneous superior vena cava cannulation, without aortic cross-clamping. The MICS approaches included right anterolateral small incision surgery, thoracoscopic assisted small incision surgery and total thoracoscopic surgery. The clinical data of the 32 patients were compared with the perioperative indicators of 24 patients undergoing reoperation with conventional median thoracotomy during the same period. Results Among them, 21 patients underwent isolated tricuspid valve replacement, 4 isolated tricuspid valvuloplasty, 1 combined tricuspid valve replacement and atrial septal defect repair and 6 combined mitral valve replacement and tricuspid valvuloplasty. Twenty-seven patients completed the operation in a beating heart, and 5 under the condition of ventricular fibrillation. Operation time (3.23±1.56 h vs. 5.46±2.13 h, P<0.001), postoperative mechanical ventilation time (9.19±5.40 h vs. 43.23±21.74 h, P<0.001), ICU stay (35.03±18.26 h vs. 79.15±22.43 h, P<0.001) and hospital stay of patients with minimally invasive surgery (9.35±6.43 d vs. 15.85±7.56 d, P=0.001) were shorter than those with median thoracotomy. And the extracorporeal circulation time was not significantly prolonged. There were 4 perioperative complications in patients with minimally invasive surgery, and 1 died in hospital after operation. Conclusion MICS for cardiac atrioventricular valve reoperation can avoid the risk of median sternotomy and separation of cardiac scar adhesion. Especially, total thoracoscopic surgery has more advantages when compared with other operations, including less trauma, less myocardial ischemia reperfusion injury, more rapid recovery and fewer postoperative complications. Total thoracoscopic surgery may be the development direction of MICS for cardiac atrioventricular valve reoperation. However we should take effective and feasible measures to solve the problems caused by cardiopulmonary bypass.