1.Effect of primary percutaneous transluminal coronary angioplasty and stent implantation on left ventricular remodeling and function in patients with acute myocardial infarction:compared with thrombolytic therapy
Wenlin REN ; Dayi HU ; Yuanhua ZHAO
Chinese Journal of Interventional Cardiology 1993;0(02):-
Objective To observe prospectively the changes of left ventricular size and function, and to evaluate the impact of primary percutaneous transluminal coronary angioplasty (p-PTCA) and stent implantation and thrombolytic therapy on left ventricular remodeling and function. Methods The patients with a first acute myocardial infarct and without contraindications to thrombolytic therapy were randomly assingned to p-PTCA group or urokinase (1?500?000 IU) therapy group within 12 hrs from the onset of symptoms or within 12~24 hrs if the evidence of myocardial ischemia in infarc zones was available. Two-demensional echocardaography were applied in the 2 nd , 12 th , and 24 th week after infarction, and major cardiac events were recorded. Results Sixty-five patients were enrolled (male 55, female 10, age 58.95?8.94 y). The patency of infarct related artery of 32 patients assigned to p-PTCA was 100%, while that of thrombolytic therapy group (33 patients) was 75.76%. The differences of end-systolic volume index (ESVI), end-diastolic volume index (EDVI), left ventricular ejection fraction (LVEF), and regional wall motion score index (RWMI) were significant statistically between p-PTCA group and thrombolytic therapy group ( P
2.Influence of valsartan-eluting stent implantation into rabbit abdominal aorta on collagen deposition and AT2 receptor expression
Guihua LI ; Lei WANG ; Sanqing JIA ; Lin ZHAO ; Daokuo YAO ; Rangjing DING ; Wenlin REN
Chinese Journal of Tissue Engineering Research 2008;12(9):1761-1765
BACKGROUND:Clinical trials have shown that oral administration of valsartan can decrease in-stent restenosis after stent implantation.But whether valsartan used locally also has the sanle effect and the possible mechanism should be validated.OBJECTIVE:To observe the effect of valsartan-eluting stents on collagen deposition in neointima and AT2 receptor expression after implanting valsartan-eluting stents into rabbit abdominal orta.DESIGN:Randomized and controlled animal experiment.SETTING:Beijing Friendship Hospital.MATERIALS:The experiment was performed at the Laboratory of Beijing Friendship Hospital between October 2004 and March 2006.Fifteen New Zealand white rabbits,irrespective of gender,weighing 2.75-3.25 kg were selected(Animal Laboratory of Beijing Friendship Hospital).The rabbits were adaptively fed for one week.All the operations of rabbits during the experiment were accorded with animal ethical standards.Valsartan powder was presented as a gift by Novartis.China;Reagent of MASSON was provided by Department of Pathology of Beijing Friendship Hospital;1%picrosirius solution was provided by the Department of Pathology of China-Japan Friendship Hospital:Mice-anti-rabbit monoclonal AT2 antibody was product of Santa Cruz Biotechnology (USA);Envision reagent was purphased from Dako;primers were synthesized by SBS Genetech(SBS).METHODS:①The animals were randomized into bare-metal stent group,carrier-eluting stent group and valsartan-eluting stent group with 5 animals in each group.All rabbits were implanted with corresponding types of above-mentioned stents into abdominal aortas down below renal artery.②Quantitative angiography before,immediately after and 3 months after stent implantation were performed to compare vascular diameters of the aortas.③Three months Iater,the rabbits were executed after anaesthesia.The vessels with stents were processed with HE staining.Indices of the vascular neointimal formation,I.e. iBrier and external elastic membrane luminal area,the maximal intimal thickness,neointimal area and stenosis area percent were measured.④The collagen deposition in neointima was observed through MASSON staining,and the type of collagen was identified through picrosirius stain.⑤The expressions of AT2R mRNA and proteins were also compared by RT-PCR and immunohistochemistry among three groups.MAIN OUTCOME MEASURES:①The diameters of aorta with stent at different time;②Inner and extemal elastic membrane luminal area,the maximal intimal thickness,neointimal area and stenosis area percent;③Collagen deposition and type of collagen of the aorta with stent;④AT2R mRNA and protein expressions.RESULTS:Of 15 rabbits selected in the experiment,1 rabbit of the bare-metal stent group died during stent implanting,and 1 of the carrier-eluting stent group died during breeding after stenting.Finally,13 rabbits were included in final analysis.①There were no significant differences in the mean aortic diameters between any two of the three groups before,immediately after and 3 months after stent implantation(P>0.05).②A larger 1uminal area and a less neointimal hyperplasia in valsartan eluting-stents group were found compared with the other two groups(P<0.01).③MASSON staining showed that collagen deposition was rich in neointima of bare-metal stent group and carrier-eluting stent group while rare in neointima of valsartan eluting stent group.Pierosirius staining suggested that the deposited collagen was type Ⅲ collagen predominantly accompanied by type Ⅰ collagen around stents struts;the type Ⅲcollagen deposition was obviously decreased in valsartan eluting stent group.④AT2R protein only expressed in adventitia of bare-metal stet group and arrier-eluting stent group while expressed in all layers of valsartan eluting-stents group.The AT2R mRNA/a-Actin mRNA of valsartan eluting stent group was significantly higher than that in the other two groups(P<0.01).CONCLUSION:Valsartan eluting-stents inhibits neointimal hyperplasia after stenting by decreasing collagen deposition.especially collagen Ⅲ.The mechanism may be related with the upregulation of AT2R mRNA and protein expressions by valsartan-eluting stent.
3.The effect of different dosage of aspirin on inflammatory biomarkers and prognosis in acute coronary syndrome
Wenlin REN ; Lifen SONG ; Yuqing LIANG ; Ruijie LI ; Zhinong YIN ; Yuyun XU ; Dayi HU
Chinese Journal of Internal Medicine 2009;48(12):1008-1011
Objective To observe and assess the effect of different dosages of aspirin on inflammatory biomarkers, hemorheology (platelet aggregation rate) and clinical prognosis in patients with acute coronary syndrome ( ACS). Methods ACS patients were randomly assigned to receive different dosages of aspirin treatment orally. Patients in group A,B and C took 100 mg, 500 mg and 1000 mg of aspirin per day respectively. They were treated and followed-up for 1 year. High-sensitivity C-reactive protein ( hsCRP) , IL-6, tumor necrosis TNFot and platelet aggregation rate were examined and major adverse cardiac events( MACE) were recorded. Results A total of 312 patients with ACS were enrolled in the study. The baseline characteristics of the three groups were not different with respect to age, gender, cardiovascular risk profile, level of inflammatory biomarkers and concomitant treatment before and after randomization. The levels of baseline serum hsCRP, IL-6 and TNFa were higher in subjects of the study as compared with normal reference value (P<0. 05, <0. 05, <0. 01) and they decreased significantly after therapy with 3 different doses of aspirin (detected at 30 days, 6 months and 12 months, P <0. 001 ) , but there were no significant differences among the three groups( P >0. 05) . Rehospitalization , MACE and the change of platelet aggregation ratio were not significantly different among the three groups. The incidence of gastrointestinal complaints was significantly higher in groups B and C than in group A ( P < 0. 05 ). Conclusions The levels of serum inflammatory biomarker increase in patients with ACS. Aspirin therapy may decrease the level of inflammatory markers significantly, but increasing the dosage of aspirin from 100 mg to 1000 mg daily does not decrease the level of inflammatory markers and the clinical MACEs further. However, the incidence of gastrointestinal complaints increase significantly with the increase of aspirin dosage.
4.Compliance of secondary prevention in patients with coronary artery disease post coronary revascularization
Wenlin REN ; Lihui ZHOU ; Yang WU ; Fengying ZHANG ; Zongjing FAN ; Kourong ZHAO ; Yanhui WANG ; Li LI ; Guihua LI ; Lin PI ; Mingming ZHANG ; Dayi HU ; Yuyun XU
Chinese Journal of General Practitioners 2012;11(4):268-272
Objective To investigate the compliance status of secondary prevention in patients with coronary artery disease (CAD) following revascularization.MethodsA total of 512 patients with CAD who received procedures for coronary revascularization were enrolled in the study from January 2009 to October 2010,including 472 cases of percutaneous coronary intervention stenting,25 cases of coronary artery bypass grafting and 15 cases of stenting plus bypass.The demographic information,prophylactic drug therapies, lifestylechangesandmodifiableriskfactorsweresurveyedwithquestionnaires,anthroposomatologicalmeasurementsandlaboratorytestsinpatients3monthsaftercoronary revascularization.ResultsThe proportion of patients on statins,aspirin,β-blockers,angiotensin-converting enzymeinhibitors/angiotensinreceptorblockers(ACEIs/ARBs)andinfluenzavaccinationwere 81.4% (417/512),93.9% ( 481/512 ),82.0% ( 420/512 ),76.2% ( 390/512 ) and 3.7% ( 19/512 ) respectively.Based on the criteria recommended by the American Heart Association/American College of Cardiology (AHA/ACC)Guidelines for Secondary Prevention for Patients with Coronary and Other Atherosclerotic Vascular Disease: 2006 Update, the percentages of achieving therapeutic targets of modifiable risk factor management were as follows:glycosylated hemoglobin (90.2%,462/512 ),total cholesterol ( 68.6%,351/512 ),triglycerides ( 58.8%,301/512 ),high-density lipoprotein cholesterol ( 91.6%,469/512 ),low-density lipoprotein cholesterol ( 44.5 %,228/512 ),systolic pressure ( 75.2 %,385/512 ) and diastolic pressure (90.4%,463/512 ) respectively.And the proportions of improved lifestyle were as follows:smoking cessation/non-smoking 81.4% (417/512),diet control 78.5% ( 402/512 ),achieving weight targets 61.7% (316/512)and regular exercise 58.2% (298/512).ConclusionsThere is a relatively high percentage of standardized antiplatelet therapy and continuous statins medication in patients with coronary artery disease following revascularization. However,many significant modifiable risk factors have not been controlled optimally and lifestyle of patients needs further improvement. There is still a considerable scope for further improvement of secondary prevention in this group of patients.
5.Anticarin-β shows a promising anti-osteosarcoma effect by specifically inhibiting CCT4 to impair proteostasis.
Gan WANG ; Min ZHANG ; Ping MENG ; Chengbo LONG ; Xiaodong LUO ; Xingwei YANG ; Yunfei WANG ; Zhiye ZHANG ; James MWANGI ; Peter Muiruri KAMAU ; Zhi DAI ; Zunfu KE ; Yi ZHANG ; Wenlin CHEN ; Xudong ZHAO ; Fei GE ; Qiumin LV ; Mingqiang RONG ; Dongsheng LI ; Yang JIN ; Xia SHENG ; Ren LAI
Acta Pharmaceutica Sinica B 2022;12(5):2268-2279
Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.