1.Role of PI3K/Akt Signaling Pathway in the TCP Wear Particles-induced Calvarial Osteolysis in Mice Model
Yudi ZHANG ; Ming YAN ; Lihong YU ; Siye ZHANG ; Jianying ZHUGE ; Jianheng GUO ; Liang DING ; Yun ZHANG
Chinese Journal of Sports Medicine 2017;36(3):212-217
Objective To explore the role of the PI3K/Akt signaling pathway in the calvarial osteolysis induced by TCP wear particles in mice model.Methods Thirty-six male ICR mice were randomly divided into a sham group (n=12),TCP group (n=12)and a LY294002-treated group (n=12).A murine calvarial model of osteolysis was established through implanting 30 mg of TCP particles onto the surface of bilateral parietal bones following the removal of the periosteum.On the second postoperative day,LY294002 (5 mg·kg-1)was locally injected to the calvarium under the periosteum three times a week;mice in the sham group received local injection of normal saline (N.S.)in the calvarium,and the injection time was consistent with that of LY294002.Two weeks later,the calvaria and periostea were obtained after the mice were executed.The calvarial osteolysis,bone mineral density (BMD)and bone mineral content(BMC)were analyzed using Micro-CT,Hematoxylin-Eosin (HE)staining was conducted to observe the inflammatrory response and formation of osteoclasts.Real-time PCR was applied to detect the mRNA level of tartrate-resistant acid phosphatase (TRAP),the marker of osteoclasts formation,cathepsin K (CstK),receptor activator for nuclear factor-κB kigand (RANKL)and c-Fos.The release of tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6)and IL-1β were measured using enzyme-linked immumsorbent assay (ELISA).Results Micro-CT and histological analysis indicated that LY294002,the specific inhibitor of PI3K,significantly prevented TCP wear particles-induced osteolysis and osteoclastogenesis,and increased BMD and BMC in the calvaria of mice.Real-time PCR data revealed LY294002 significantly suppressed the increase in mRNA level of osteoclastogenic genes such as TRAP,CstK,RANKL and c-Fos in the calvaria of TCP wear particles-implanted group.ELISA assay showed that TCP wear particles-induced release of TNF-α,IL-1β and IL-6 was significantly inhibited by LY294002 treatment.Furthermore,LY294002 significantly attenuated TCP wear particles-triggered activation of Akt,and down-regulated the level of p-AktSer473 and p-AktThr308.Conclusion PI3K/Akt signaling pathway contributes to TCP wear particle-induced osteolysis,and can be developed as a new therapeutic target for the prevention and treatment of bone destruction diseases caused by wear debris.
2.Changes of platelet activation markers and platelet ultra-microstructure in the patients with acute myocardial infarction
Deling ZHANG ; Yi ZHUGE ; Yiming JIANG ; Xiaoming TU ; Jianying ZHOU ; Qizhi JIN ; Keyun CHENG ; Guohua LU ; Jiasheng ZHENG ; Qingye YANG ; Zhenyan GAO
Chinese Journal of Emergency Medicine 2011;20(1):74-77
Objective To investigate the expressions of platelet activation-dependent granule membrane protein and platelet-derived growth factor receptor-αB, and the ultra-microstructure changes of platelets in patients with acute ST-segment elevation myocardial infarction(STEMI). Method The expressions of platelet activationdependent granule of glycoprotein (CD62P)and platelet derived growth factor receptor αβ subtype (PDGFR-αβ)of platelets in peripheral blood in 36 patients with acute ST-segment elevation myocardial infarction(STEMI) hospitalized and another 34 healthy subjects over the same period (control group) were investigated by flow cytometry and data were analyzed. The changes of ultra microstructure and activity of blood platelets in those patients and control group were observed under the scanning electron microscope. Results The expressions of CD62P and PDGFR-αβin patients with STEMI group before treatment were (3.65 ± 1.87) % and (0.43 ± 0.39) %, respectively, and those after treatment were (0.96 ± 0.79) % and (0.28 ± 0. 24) %, respectively, whereas those in control group were (0.67 ± 0.35) % and (0.27 ± 0.22) %, respectively, which were much lower in control than those in patients with STEMI before treatment (P < 0.01 or P < 0.05) respectively. There were statistically significant differences in the expressions of CD62P and PDGFR-αβ in patients group between pre-treatment and posttreatment (P <0.01 or P <0.05), respectively. Obvious ultra-microstructure changes of platelet surface in patients with STEMI group were observed. Conclusions Due to platelet activation in AMI, the expressions of CD62P can be used as effective indicators for monitoring coronary heart disease, and the PDGFR-αβ can be used as a reference indicator. The platelet surface ultra-microstructure changes during platelet activation in patients with AMI can be found by scanning electron microscopy.
3.Comparative analysis of endoscopic R0 resection followed by additional chemoradiotherapy for early stage esophageal cancer compared with esophagectomy: A multi-center study from ECETC
HUANG Binhao ; WANG Shengfei ; LIU Zhiguo ; LI Zhigang ; LUO Kongjia ; BAI Jianying ; PENG Xue ; LIU Xiaofeng ; WEI Zhi ; JIN Peng ; CHEN Yanyan ; XIAGN Jiaqing ; ZHANG Yawei ; CHEN Sufeng ; XIE Juntao ; ZHUGE Lingdun ; CHEN Haiquan ; ZHANG Jie
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2018;25(6):466-470
Objective To evaluate the strategy of chemoradiotherapy following endoscopic R0 resection for esophageal cancer in M3-T1b stage. Methods There were 45 esophageal cancer patients with M3-T1b stage with endoscopic R0 resection followed by additional chemoradiotherapy from ECETC (Esophageal Cancer Endoscopic Therapy Consortium) as a trial group with 34 males and 11 females at age of 61.37±7.14 years. There were 90 patients with esophagectomy from Fudan University Shanghai Cancer Center as a control group with 63 males and 27 females at age of 61.04±8.17 years. Propensity score match (1:2) was used to balance the factors: gender, age, position, depth of invasion and lymphovascular invasion (LVI), which may influence the outcomes. Overall survival (OS) rate, relapse free survival (RFS) rate, and local recurrence rate were compared between the two groups. Result There was no statistical difference (HR=2.66 with 95%CI 0.87 to 8.11, P=0.179) in terms of OS rate between the two groups. One, two and three years overall survival rate of patients in the control group was 93%, 86%, and 84%, respectively. Nobody died in the trial group within 3 years after surgery. The RFS rate between the two groups didn’t significantly differ (HR=1.48, 95% CI 0.66 to 3.33, P=0.389). One, two and three years RFS rate of patients in the contorl group was 87%, 78%, and 76%, respectively, while 97%, 93%, and 73% in the trial group, respectively. The local recurrence rates between the two groups didn’t significantly differ either ( HR=0.53,95%CI 0.13 to 2.18, P=0.314). One, two and three years local recurrence rate of patients in the control group was 5%, 6% and 6%, respectively, while 0%, 0% and 21% in the trial group, respectively. Conclusion Similar outcomes are found regarding OS, RFS and local recurrence rates between the two groups. The strategy of endoscopic R0 resection followed by additional chemoradiotherapy has prospect for the treatment of esophageal cancer in M3-T1b stage. And this kind of therapy may be provided for those with risk factors or can not tolerate surgery.