1.Effect of Dexmedetomidine on Proliferation and Angiogenesis of Human Hepatocellular Carcinoma Cell Cultured in Hypoxia Condition and Possible Mechanism
Yonghua CHEN ; Dongtai CHEN ; Jiahao PAN ; Yan YAN ; Yunfei YUAN ; Weian ZENG
Journal of Sun Yat-sen University(Medical Sciences) 2017;38(2):229-236
[Objective]This study was conducted to examine the effects of dexmedetomidine on the proliferation and angiogenesis of MHCC97H and SMCC7721 human hepatocellular carcinoma(HCC)cell lines cultured in hypoxia condition in vitro,and investigated the possible mechanism involved.[Methods]MHCC97H and SMCC7721 human HCC cell lines under hypoxia culture condition were treated with presence or absence of dexmedetomidine(100 μmol/L). Cell viability,colony formation,vasculogenic mimicry(VM) formation were assessed. The effects of dexmedetomidine on α-2A adrenergic receptor(α2A),hypoxia induced factor-1a(HIF-1a),and vascular endothelial growth factor(VEGF)protein expression were evaluated with Western blot analysis.[Results]Cell proliferation assay and colony formation assay indicated that hypoxia obviously promoted the proliferation of MHCC 97H and SMCC7721 cells(CoCl2 group vs corresponding control group,the proliferation rate of MHCC97H and SMCC7721:Day 3,142.2%and 133.8%;Day 4,134.7%and 131.0%;Day 5,133.5%and 136.2%;all P<0.05),and VM formation assay suggested that hypoxia increased angiogenesis of MHCC97H and SMCC7721 cells. Whereas dexmedetomidine significantly inhibited the proliferation(Dex+CoCl2 group vs CoCl2 group,the proliferation rate of MHCC97H and SMCC7721:Day 3,55.7%vs 60.7%;Day 4,46.9%vs 58.1%;Day 5,46.4%vs 57.0%,all P<0.05)and angiogenesis of MHCC97H,SMCC7721 cells induced by hypoxia. Dexmedetomidine may exert these functions by activating α-2A adrenergic receptor,causing an decrease in HIF-1a and VEGF protein,while hypoxia activated HIF-1a and VEGF protein to promote the growth and angiogenesis of cells.[Conclusion]The findings provide evidence that hypoxia could promote the proliferation and angiogenesis of MHCC97H and SMCC7721 cells,while dexmedetomidine might inhibit these effects by down-regulating HIF-1a and VEGF protein expression through activatingα-2A adrenergic receptor.
2.Intention and satisfaction of people aged 18 to 25 years to seek medical advice in primary medical institutions in Zhejiang Province
XU Yunhan ; PAN Jiahao ; HE Yusa ; YE Bingqi ; XIE Renxiang ; MAIHEMUTI Tunishaguli ; XU Xin ; WANG Dina ; WANG Daosen ; YU Linjie ; CHEN Minhe ; YAN Ruochen ; XUE Kexin ; FU Yajing ; YE Huaizhuang ; WU Xifeng ; LI Xiuyang
Journal of Preventive Medicine 2020;32(8):767-773
Objective :
To analyze the status and influencing factors of the intention of people aged 18 to 25 years to primary medical institutions and their satisfaction for health services in Zhejiang Province, so as to provide basis for the improvement of health services in primary medical institutions.
Methods:
During November and December in 2019,the 18-25 year-old people in Zhejiang Province were recruited to investigate the general information, intention to seek medical advice and satisfaction for health services in primary medical institutions through WeChat. Logistic regression was performed to analyze the influencing factors of the intention and the satisfaction. Importance matrix was used to analyze the key drivers of the satisfaction.
Results:
Among the 620 people surveyed, with a response rate of 93.37%, 142 (22.90%) chose primary medical institutions for advice. Actually 516 (83.23%) people went to primary medical institutions last year, and 384 ( 74.42% ) of them were satisfied with the health services. The results of multivariate logistic regression analysis showed that the people aged 18-25 years who were under the new rural cooperative medical care system ( OR=3.062, 95%CI: 1.745-5.373 ) and who had records in community health centers ( OR=0.547, 95%CI: 0.308-0.970 ) were more likely to go to primary medical institutions for medical advice; the ability of doctors ( OR=1.478, 95%CI:1.168-1.871 ) ,the drug notification by medical staff ( OR=1.308, 95%CI: 1.065-1.606 ) , routine examination items ( OR=1.523, 95%CI: 1.227-1.889 ) , the ways of payment ( OR=1.168, 95%CI: 1.017-1.340 ) , the comfort of environment ( OR=1.785, 95%CI: 1.437-2.219 ) and the bulletin boards of health knowledge ( OR=1.302, 95%CI: 1.086-1.561 ) were associated with the satisfaction. The results of importance matrix analysis showed that the ability of doctors and routine examination items were the priorities to improve, followed by the drug notification by medical staff; the comfort of environment had competitive advantages; the ways of payment and the bulletin boards of health knowledge needed to be further analyzed.
Conclusions
The 18-25-year-old people in Zhejiang Province were less intended to seek medical advice in primary medical institutions, which was associated with the type of medical insurance and records in community health centers. They were satisfied with the health services, the ability of doctors and routine examination items were the key drivers.
3.Clinical application of autologous platelet separation in different time courses of cardiovascular surgery
Yuxin ZENG ; Cong NIE ; Jiahao PAN ; Jiawen LUO ; Ming WU ; Fei CHEN ; Daling YI ; Chunfang TANG ; Wenwu ZHOU
Journal of Chinese Physician 2022;24(4):577-581
Objective:To investigate the clinical significance of autologous platelet separation (APS) in different time courses of cardiovascular surgery.Methods:The relevant data of 75 patients with cardiovascular surgery from September 2019 to August 2021 in Hunan Provincial Peoples′ Hospital were collected retrospectively. They were divided into two groups according to whether APS was used during the operation: group A used APS (37 cases) and group B did not use APS (38 cases). The two groups were divided into subgroups according to the length of cardiopulmonary bypass (CPB): A1 and B1 were medium and short-term groups (CPB bypass time ≤200 min), and A2 and B2 were long-term groups (CPB bypass time >200 min). Blood routine, postoperative drainage volume, postoperative blood product infusion volume and thromboelastogram at different time points were recorded and compared.Results:The postoperative drainage volume, red blood cell infusion volume and ventilator assisted time in group A were less than those in group B (all P<0.05); The postoperative drainage volume [(645.79±205.25)ml vs (886.67±360.96)ml, P=0.006], erythrocyte infusion volume [(3.24±2.53)U vs (4.77±1.97)U, P=0.016], platelet infusion volume [0.00(0.00, 0.00)U vs 1.00(0.125, 2.00)U, P=0.002] and thromboelastogram coagulation reaction time [(7.38±1.74)min vs (9.09±3.57)min, P=0.047] in group A2 were significantly better than those in group B2 (all P<0.05); There were no significant difference in the above indexes between A1 and B1 group (all P>0.05). Conclusions:APS can improve the coagulation function of patients undergoing cardiopulmonary bypass and reduce the amount of bleeding and blood products. Its protective effect is more prominent in high-risk cardiovascular surgery with long cardiopulmonary bypass and complex operation.
4.Costunolide covalently targets NACHT domain of NLRP3 to inhibit inflammasome activation and alleviate NLRP3-driven inflammatory diseases.
Haowen XU ; Jiahao CHEN ; Pan CHEN ; Weifeng LI ; Jingjing SHAO ; Shanshan HONG ; Yi WANG ; Lingfeng CHEN ; Wu LUO ; Guang LIANG
Acta Pharmaceutica Sinica B 2023;13(2):678-693
The NLRP3 inflammasome's core and most specific protein, NLRP3, has a variety of functions in inflammation-driven diseases. Costunolide (COS) is the major active ingredient of the traditional Chinese medicinal herb Saussurea lappa and has anti-inflammatory activity, but the principal mechanism and molecular target of COS remain unclear. Here, we show that COS covalently binds to cysteine 598 in NACHT domain of NLRP3, altering the ATPase activity and assembly of NLRP3 inflammasome. We declare COS's great anti-inflammasome efficacy in macrophages and disease models of gouty arthritis and ulcerative colitis via inhibiting NLRP3 inflammasome activation. We also reveal that the α-methylene-γ-butyrolactone motif in sesquiterpene lactone is the certain active group in inhibiting NLRP3 activation. Taken together, NLRP3 is identified as a direct target of COS for its anti-inflammasome activity. COS, especially the α-methylene-γ-butyrolactone motif in COS structure, might be used to design and produce novel NLRP3 inhibitors as a lead compound.