Aspirin suppresses hepatocellular carcinoma progression by inhibiting platelet activity

BACKGROUND Hepatocellular carcinoma(HCC)is the most common malignant liver disease in the world.Platelets(PLTs)are known to play a key role in the maintenance of liver homeostasis and the pathophysiological processes of a variety of liver diseases.Aspirin is the most classic antiplatelet agent.However,the molecular mechanism of platelet action and whether aspirin can affect HCC progression by inhibiting platelet activity need further study.AIM To explore the impact of the antiplatelet effect of aspirin on the development of HCC.METHODS Platelet-rich plasma,platelet plasma,pure platelet,and platelet lysate were prepared,and a coculture model of PLTs and HCC cells was established.CCK-8 analysis,apoptosis analysis,Transwell analysis,and real-time polymerase chain reaction(RT-PCR)were used to analyze the effects of PLTs on the growth,metastasis,and inflammatory microenvironment of HCC.RT-PCR and Western blot were used to detect the effects of platelet activation on tumor-related signaling pathways.Aspirin was used to block the activation and aggregation of PLTs both in vitro and in vivo,and the effect of PLTs on the progression of HCC RESULTS PLTs significantly promoted the growth,invasion,epithelial-mesenchymal transition,and formation of an inflammatory microenvironment in HCC cells.Activated PLTs promoted HCC progression by activating the mitogenactivated protein kinase/protein kinase B/signal transducer and activator of transcription three(MAPK/AKT/STAT3)signaling axis.Additionally,aspirin inhibited HCC progression in vitro and in vivo by inhibiting platelet activation.CONCLUSION PLTs play an important role in the pathogenesis of HCC,and aspirin can affect HCC progression by inhibiting platelet activity.These results suggest that antiplatelet therapy has promising application prospects in the treatment and combined treatment of HCC.

Therapeutic effect and psychological impact of aspirin plus edaravone on patients with cerebral infarction

BACKGROUND Cerebral infarction(CI)is characterized by a high prevalence,disability,and mortality.Timely or improper treatment greatly affects patient prognosis.AIM To explore the drug efficacy of aspirin plus edaravone and to explore their effect on quality of life(QOL),anxiety and depression in CI patients.METHODS We retrospectively analyzed the records of 124 CI patients treated between June 2019 and February 2021 who were assigned to an observation group(OG)(combination therapy of aspirin and edaravone,65 patients)or a control group(CG)(aspirin monotherapy,59 patients).The therapeutic effects,pre-and posttreatment National Institutes of Health Stroke Scale(NIHSS)scores,activities of daily living,degree of cognitive impairment,protein levels of glial fibrillary acidic protein(GFAP),neuron-specific enolase(NSE)and S-100B,occurrence of adverse reactions,and serum high-sensitivity C-reactive protein(hs-CRP),interleukin(IL)-6 and tumor necrosis factor(TNF)-αwere evaluated,detected and compared between the two groups.Finally,posttreatment QOL,anxiety,and depression were assessed by the Medical Outcomes Study 36-Item Short Form Health Survey Scale,Self-rating Depression Scale(SDS),and Self-rating Anxiety Scale(SAS),respectively.RESULTS Compared with the CG,the OG had markedly better therapeutic effects,greater improvements in activities of daily living,and better alleviation in cognitive dysfunction after treatment,as well as lower posttreatment NIHSS scores and serum NSE,GFAP,S-100B,hs-CRP,IL-6,and TNF-αlevels;the OG was similar to the CG in terms of adverse reactions but was better than the CG in terms of posttreatment QOL;and the OG also had lower SDS and SAS scores than the CG after treatment.CONCLUSION Aspirin plus edaravone had a good curative effect on CI.It can reverse cranial nerve damage in patients,improve neurological function and prognosis,and alleviate inflammation,anxiety,and depression;thus,it is considered safe and worthy of clinical application.

Application of aspirin and low molecular weight heparin in major orthopedic surgery:Meta analysis of a randomized controlled trial

Objective:The perioperative period of major orthopedic surgery is associated with a high risk of thrombosis,but the best chemopreventive agent for thrombosis prophylaxis is still inconclusive.For this reason,this paper evaluated the efficacy and safety of aspirin versus low-molecular heparin using a Meta-analysis.Methods:Ten randomized controlled studies on the application of aspirin and low-molecular heparin for the prevention of deep vein thrombosis in orthopedic major surgery were retrieved by computer searches of PubMed,CochraneLibrary,WebofScience,China Knowledge Network,Wanfang,and Vipul databases according to inclusion and exclusion criteria,and the literature was managed using Endnote software,and the data were analyzed using Revman 5.3 software was used to perform Meta-analysis of the extracted data,focusing on the effects of these two drugs on pulmonary embolism,deep vein thrombosis,major bleeding events,minor bleeding events,wound complications,mortality and blood loss within 90 days after major orthopedic surgery.Results:(1)Ten randomized controlled trials of high quality were included,with a total of 12,974 patients,7,026 in the aspirin group and 5,948 in the low-molecular heparin group;(2)Meta-analysis showed that aspirin had a higher incidence of pulmonary embolism(OR=1.59,95%CI:1.02 to 2.49,P=0.04)and deep vein thrombosis(OR=1.60,95%CI:1.26 to 2.02,P=0.0001)than low molecular heparin;(3)The incidence of major bleeding events(OR=0.85,95%CI:0.47 to 1.55,P=0.60),minor bleeding events(OR=0.79,95%CI:0.55 to 1.12,P=0.18),adverse wound reactions(OR=0.79,95%CI:0.48 to 1.31,P=0.36),mortality within 90 days(OR=0.69,95%CI:0.20 to 2.31,P=0.55)and perioperative blood loss(MD=0.69,95%CI:0.20 to 2.31,P=0.55)in both drug groups,mortality within 90 days(OR=0.69,95%CI:0.20 to 2.31,P=0.55)and perioperative blood loss(MD=0.69,95%CI:0.20 to 2.31,P=0.55)were not statistically significant.Conclusion:Low-molecular heparin was superior to aspirin in the prevention of pulmonary embolism and lower extremity deep vein thrombosis after major orthopedic surgery,but the safety and adverse drug reactions of both groups were basically similar.Based on this,the authors recommend that low-molecular heparin should be preferred for the prevention of deep vein thrombosis in major orthopaedic surgery;however,the inclusion of randomized controlled trials remains limited,necessitating high-quality,large-sample,long-term follow-up clinical studies.

Distribution of gene polymorphisms associated with aspirin antiplatelet in the Han NSTEMI population

Objective:To analyze the genotype and allele distribution characteristics of GPⅢa PLA2(rs5918),PEAR1(rs12041331),and PTGS1(rs10306114)genes related to the antiplatelet pharmacological effects of aspirin,providing reference for individualized treatment of Chinese Han NSTEMI patients.Methods:A total of 107 Han patients with NSTEMI in Beijing Luhe Hospital affiliated to Capital Medical University from January 2016 to December 2022 were selected as the research subjects.The genotypes of GPⅢa PLA2(rs5918),PEAR1(rs12041331)and PTGS1(rs10306114)were detected by fluorescence staining in situ hybridization.The frequency distribution and allele distribution of genotype were analyzed.The results were analyzed whether there were statistical differences in the distribution of related alleles between the Han NSTEMI population and some populations in the 1000 Genomes database.Results:In the Han NSTEMI population,the genotype frequencies of GPⅢa PLA2(rs5918)locus were TT 97.20%,TC 2.80%and CC 0%,the allele frequencies were T 98.60%and C 1.40%.The genotype frequencies of PEAR1(rs12041331)locus were GG 42.06%,GA 44.86%and AA 13.08%,the allele frequencies were G 64.49%and A 35.51%.The genotypes at the PTGS1(rs10306114)locus were all AA(100%),no AG or GG genotype was found.Conclusion:In the NSTEMI population of Han nationality,the mutation at GPⅢa PLA2(rs5918)site related to aspirin antiplatelet pharmacology is rare,and there is no mutation at PTGS1(rs10306114)site.Wild homozygotes are dominant in these two gene loci,while mutations in PEAR1(rs12041331)are more common.Some of the findings in this study are similar to those in previous reports or other populations included in the relevant database;however,some results differ from previous reports or other populations。

Aspirin interruption before neurosurgical interventions:A controversial problem

Aspirin is widely used for primary or secondary prevention of ischemic events.At the same time,chronic aspirin consumption can affect blood clot formation during surgical intervention and increase intraoperative blood loss.This is especially important for high-risk surgery,including neurosurgery.Current European Society of Cardiology guidelines recommend aspirin interruption for at least 7 d before neurosurgical intervention,but this suggestion is not supported by clinical evidence.This narrative review presents evidence that challenges the necessity for aspirin interruption in neurosurgical patients,describes options for aspirin effect monitoring and the clinical implication of these methods,and summarizes current clinical data on bleeding risk associated with chronic aspirin therapy in neurosurgical patients,including brain tumor surgery,cerebrovascular procedures,and spinal surgery.

Statin, aspirin and metformin use and risk of hepatocellular carcinoma related outcomes following liver transplantation: A retrospective study

BACKGROUND Liver transplantation(LT)is a potentially curative therapy for patients with hepatocellular carcinoma(HCC).HCC-recurrence following LT is associated with reduced survival.There is increasing interest in chemoprophylaxis to improve HCC-related outcomes post-LT.AIM To investigate whether there is any benefit for the use of drugs with proposed chemoprophylactic properties against HCC,and patient outcomes following LT.METHODS This was a retrospective study of adult patients who received Deceased Donor LT for HCC from 2005-2022,from a single Australian centre.Drug use was defined as statin,aspirin or metformin therapy for≥29 days,within 24 months post-LT.A cox proportional-hazards model with time-dependent covariates was used for survival analysis.Outcome measures were the composite-endpoint of HCC-recurrence and all-cause mortality,HCC-recurrence and HCC-related mortality.Sensitivity analysis was performed to account for immortality time bias and statin dosing.RESULTS Three hundred and five patients were included in this study,with 253(82.95%)males with a median age of 58.90 years.Aetiologies of liver disease were 150(49.18%)hepatitis C,73(23.93%)hepatitis B(HBV)and 33(10.82%)non-alcoholic fatty liver disease(NAFLD).56(18.36%)took statins,51(16.72%)aspirin and 50(16.39%)metformin.During a median follow-up time of 59.90 months,34(11.15%)developed HCC-recurrence,48(15.74%)died,17(5.57%)from HCC-related mortality.Statin,aspirin or metformin use was not associated with statistically significant differences in the composite endpoint of HCC-recurrence or all-cause mortality[hazard ratio(HR):1.16,95%CI:0.58-2.30;HR:1.21,95%CI:0.28-5.27;HR:0.61,95%CI:0.27-1.36],HCC-recurrence(HR:0.52,95%CI:0.20-1.35;HR:0.51,95%CI:0.14-1.93;HR 1.00,95%CI:0.37-2.72),or HCC-related mortality(HR:0.32,95%CI:0.033-3.09;HR:0.71,95%CI:0.14-3.73;HR:1.57,95%CI:0.61-4.04)respectively.Statin dosing was not associated with statist-ically significant differences in HCC-related outcomes.CONCLUSION Statin,metformin or aspirin use was not associated with improved HCC-related outcomes post-LT,in a largely historical cohort of Australian patients with a low proportion of NAFLD.Further prospective,multicentre studies are required to clarify any potential benefit of these drugs to improve HCC-related outcomes.

Analysis of the Therapeutic Effect of Clopidogrel Bisulfate Tablets + Aspirin Enteric-Coated Tablets on Acute Myocardial Infarction

Objective:To investigate and analyze the clinical effect of clopidogrel bisulfate tablets combined with aspirin enteric-coated tablets on acute myocardial infarction(AMI)patients.Methods:The study period was from January 2020 to December 2023,the sample source was 82 AMI patients admitted to our hospital,grouped into an observation group(n=41)and a control group(n=41)by the numerical table method.The patients in the control group were treated with aspirin enteric-coated tablets,and the patients in the observation group were treated with aspirin enteric-coated tablets combined with clopidogrel bisulfate.The clinical efficacy,coagulation indexes,and the incidence of cardiovascular adverse events between the two groups were compared.Results:The clinical efficacy of the observation group was higher than that of the control group(P<0.05);the platelet aggregation rate(PAR)of the observation group was lower than that of the con-trol group after treatment(P<0.05),and there was no significant difference in the prothrombin time(PT)and activated partial thromboplastin time(APTT)between the two groups(P>0.05).The incidence of cardiovascular adverse events in the observation group was lower than that of the control group(P<0.05).Conclusion:The treatment effect of clopidogrel bisulfate tablets combined with aspirin enteric-coated tablets on AMI patients is remarkable.It reduces the PAR and the incidence of cardiovascular adverse events,so this treatment method should be popularized.

Analysis of the Effectiveness of Clopidogrel Combined with Aspirin in the Treatment of Coronary Heart Disease in Community-Dwelling Elderly

Objective:To analyze the combined therapeutic effect of clopidogrel(CLO)and aspirin(ASP)on coronary heart disease(CHD)in community-dwelling elderly.Methods:Thirty elderly patients with CHD who were admitted to the Xinxin Community Health Service Station,Pangzhuang Street,Quanshan District,Xuzhou City,from November 2020 to November 2022 were selected and randomly grouped into an observation group and a control group,with 15 cases in each group.The observation group was given the combination of CLO and ASP and the reference group was given only ASP.The total effective rate and other treatment indicators between the two groups were compared.Results:The total effective rate of the observation group(93.33%)was higher than that of the reference group(60.00%)(P<0.05).The adverse drug reaction rate(13.33%)and long-term cardiovascular adverse event rate(6.67%)of the observation group were lower than those of the reference group at 46.67%and 40.00%respectively,(P<0.05).Before treatment,the two groups had no difference in the quality-of-life scores(P>0.05).After treatment,the quality-of-life scores of the observation group were higher than those of the reference group(P<0.05).Conclusion:CLO combined with ASP improved the therapeutic effect of community-dwelling elderly patients with CHD,reduced adverse reactions during medication,prevented adverse cardiovascular events,and comprehensively improved the patient’s quality of life.

新型无机/有机复合发光材料Eu(aspirin)_3phen-MCM-41的光学性能

在室温下,将MCM-41和热处理后的发光客体Eu(aspirin)3phen进行组装,通过XRD、N2-吸脱附和PL等表征技术对组装体进行了研究,考察其光致发光性能。结果表明:Eu(aspirin)3phen进入MCM-41孔道后,充当了'二次模板剂',使MCM-41的骨架有序性增加。经热处理后Eu(aspirin)3phen与MCM-41组装后,组装体的发光强度与相应Eu(aspi-rin)3phen粉末相当。未焙烧的MCM-41表面和稀土有机配合物成键后,Eu(aspirin)3phen分子出现反演中心,5D0→7F2跃迁明显减弱,而焙烧后MCM-41表面对Eu3+的5D0→7F2电偶极跃迁强度没有影响。

Simultaneous Determination of Tetramethylpyrazine and Aspirin in a New Compound Formulation by Liquid Chromatography

Aim To establish a reversed-phase liquid chromatographic (LC) method forsimultaneous determination of tetramethylpyrazine (TMP) and aspirin in a new compound formulation.Methods Chromatographic separation of the two drugs was achieved on a Diamonsil C_(18) column, usinga binary mixture of methanol-1.5% acetic acid (35:65, V/V, pH = 3.1) as mobile phase at a flow rateof 1.0 mL·min^(-1). Results Separation was completed in less than 12 min. Benzoic acid was used asthe internal standard. Recoveries at levels corresponding to 80 % to 120 % of the label claim ofthe formulation ranged from 99.6 to 100.3 % for aspirin and from 99.9 to 101.3% for TMP. The linearrange was 12.6 - 150.9 μg·mL^(-1)(r= 0.9997, n = 5) for aspirin and 25.0- 300.0 μg·mL^(-1) (r =0.9999, n = 5) for TMP. Conclusion The method developed can be used for the simultaneousdetermination of TMP and aspirin in pharmaceutical preparations.

VerifyNow-Aspirin评估阿司匹林抗血小板效应及其影响因素分析

目的联合VerifyNow-Aspirin与尿11-脱氢-血栓烷B2测定,评估阿司匹林抗血小板效应及其影响因素。方法选择规律服用阿司匹林至少两周的冠心病患者264例,年龄33～86(65.31±10.23)岁,其中男147例(55.7%),女117例(44.3%)。阿司匹林标准剂量组(100mg/d)241例,低剂量组(25～75mg/d)23例。采用VerifyNow-aspirin系统测定服用阿司匹林后血小板残余活性(用ARU表示),酶联免疫吸附法检测尿11-脱氢-血栓烷B2(11-DH-TXB2)浓度,并记录入选人群的基线资料及心血管疾病危险因素。结果以ARU≥550为切割值定义阿司匹林低反应性(ALR)人群,标准剂量组人群中ALR发生率为8.6%(23例)。ALR人群尿11-DH-TXB2显著高于正常反应组,差异有统计学意义(2.85±0.73pg/ml vs 2.51±0.49pg/ml,P<0.05),但二者之间相关性较差(r=0.18,P=0.04)。女性、高血压及糖尿病均为ARU升高的预测因素(均P<0.05),但其组间尿11-DH-TXB2水平差异无统计学意义(均P>0.05)。与阿司匹林标准剂量组比较,低剂量组人群残余血小板活性显著增强,同时伴有尿11-DH-TXB2升高(均P<0.05)。结论阿司匹林抗血小板效应存在个体差异,且具有一定量效关系,而VerifyNow和尿11-DH-TXB2对评估阿司匹林抗血小板效应及其发生机制具有一定互补性。

小剂量Aspirin对动脉粥样硬化兔主动脉斑块炎症反应和COX-2表达的影响

目的探讨小剂量阿司匹林对兔动脉粥样硬化主动脉斑块炎性过程和COX-2表达的影响。方法24只雄性新西兰兔随机分为对照组(喂食普通兔料)、高脂模型组(喂食高脂饲料)、阿司匹林组(喂食高脂饲料并给与小剂量阿司匹林干预),饲养12周后处死动物,取主动脉进行病理学检查,测定斑块面积,采用免疫组化方法观察各组巨噬细胞的表达情况,Western-bolt分析COX-2的表达。结果病理学大体观察发现,对照组、高脂模型组和阿司匹林组主动脉壁脂质斑块面积占整条主动脉内壁面积的百分比分别为0%、(59.62±10.74)%、(48.33±7.85)%,各组间两两比较均有显著性差异(P<0.05)。阿司匹林组斑块区巨噬细胞含量、COX-2表达明显低于高脂模型组。结论小剂量阿司匹林干预可以通过抑制病灶区的炎症反应、COX-2的表达来有效减轻高脂饮食所致的新西兰兔动脉粥样硬化的严重程度。

Tb（aspirin）3phen和MCM-41组装体的光谱研究

将MCM-41和客体Tb（aspirin）3phen进行组装，采用XRD、IR和PL进行了表征，探讨了主体McM-41和客体Tb（aspirin）1phen间的相互影响。MCM-41焙烧后再进行组装，Tb（aspirin）3phen可增加MCM-41的骨架有序性，充当“二次模板剂”的作用。IR谱图中，Tb（aspirin）3phen-MCM-41组装体在波数1384cm^-1处明显保留了Tb-N键的振动吸收。405nm发射峰强度，L和544nm发射峰强度，ILn的比值I，与McM-41不同的表面环境有关，且McM-41的不同表面环境对配体phen三重态和单重态能级的影响顺序为：MCM-41B外表面〉MCM-41A外表面〉McM-41A内表面。

As_2O_3与Aspirin联合应用对人胃癌SGC-7901细胞凋亡的影响

目的:观察As2O3与Aspirin联合应用对人胃癌SGC-7901细胞凋亡的影响并探讨其可能机制.方法:As2O3和Aspirin处理SGC-7901细胞,实验分为:阴性对照组、2mmol/L Aspirin组、1mmol/L Aspirin组、4μmol/L As2O3组、2μmol/L As2O3组和2μmol/L As2O3组+1mmol/L Aspirin组,流式细胞术检测As2O3和Aspirin单独及联合应用对SGC-7901细胞凋亡的作用,免疫细胞化学法检测Bcl-2和Bax蛋白的表达.结果:2μmol/L As2O3+1mmol/L Aspirin联合应用组与4μmol/L As2O3组、2mmol/L Aspirin组SGC-7901细胞在细胞周期G1期前均出现明显的亚二倍体凋亡峰,差异无明显统计学意义,与阴性对照组细胞、2μmol/L As2O3及1mmol/L Aspirin单药组相比,差异均有统计学意义(均P<0.05).As2O3与Aspirin联合应用组使Bcl-2表达下降,Bax表达增高,与阴性对照组、2μmol/L As2O3及1mmol/L Aspirin单药组相比,差异均具统计学意义(50.21%±5.94%vs91.65%±11.51%,88.66%±10.53%89.27%±9.84%;40.72%±9.54%vs21.03%±4.32%,23.07%±6.23%,22.67%±3.16%,均P<0.05).结论:As2O3和Aspirin可能通过改变Bcl-2和Bax表达诱导SGC-7901细胞凋亡,两者联合应用具有协同作用.

载体MCM-41对Tb(aspirin)_3phen发光性能的影响

在室温下,乙二胺环境中合成了高度有序的介孔材料MCM-41,并将经热处理的发光客体Tb(aspi-rin)3phen组装进其孔道,通过激发发射光谱对其光致发光性能进行了研究。结果表明,Tb(aspirin)3phen240～375 nm区间的宽激发峰归属于配体aspirin羰基n→π*跃迁、苯环π→π*跃迁,和phen的杂菲基团吸收,Tb3+的特征发射是由于Antenna效应引起的。相对于纯Tb(aspirin)3phen,Tb(aspirin)3phen-MCM-41B和Tb(aspirin)3phen/MCM-41A的激发谱带出现了明显的分裂,而Tb(aspirin)3phen-MCM-41A只在353nm处剩下了相对较窄的单峰。Tb(aspirin)3phen-MCM-41B,Tb(aspirin)3phen/MCM-41A和Tb(aspirin)3phen-MCM-41A的短波段激发峰依次减弱消失,长波段激发峰逐渐增强,而405 nm发射峰强度IL和544 nm发射峰强度ILn的比值I(I=IL/ILn)依次减小。MCM-41骨架与Tb(aspirin)3phen成键后,不同程度降低了配体aspirin和phen单重态S1和三重态T1能级,且对phen的影响大于aspirin。不同的MCM-41表面晶格场对配体能级的影响顺序为:MCM-41B外表面>MCM-41A外表面>MCM-41A内表面。I值可定性表示MCM-41表面晶格场对配体能级影响程度和MCM-41表面Tb(aspirin)3phen的含量。

Clinical importance of aspirin and clopidogrel resistance

Aspirin and clopidogrel are important components of medical therapy for patients with acute coronary syndromes, for those who received coronary artery stents and in the secondary prevention of ischaemic stroke. Despite their use, a significant number of patients experience recurrent adverse ischaemic events. Interindividual variability of platelet aggregation in response to these antiplatelet agents may be an explanation for some of these recurrent events, and small trials have linked "aspirin and/or clopidogrel resistance", as measured by platelet function tests, to adverse events. We systematically reviewed all available evidence on the prevalence of aspirin/clopidogrel resistance, their possible risk factors and their association with clinical outcomes. We also identified articles showing possible treatments. After analyzing the data on different laboratory methods, we found that aspirin/clopidogrel resistance seems to be associated with poor clinical outcomes and there is currently no standardized or widely accepted definition of clopidogrel resistance. Therefore, we conclude that specific treatment recommendations are not established for patients who exhibit high platelet reactivity during aspirin/clopidogrel therapy or who have poor platelet inhibition by clopidogrel.

Clinical features of gastroduodenal injury associated with long-term low-dose aspirin therapy

Low-dose aspirin(LDA) is clinically used for the prevention of cardiovascular and cerebrovascular events with the advent of an aging society.On the other hand,a very low dose of aspirin(10 mg daily) decreases the gastric mucosal prostaglandin levels and causes significant gastric mucosal damage.The incidence of LDAinduced gastrointestinal mucosal injury and bleeding has increased.It has been noticed that the incidence of LDA-induced gastrointestinal hemorrhage has increased more than that of non-aspirin non-steroidal anti-inflammatory drug(NSAID)-induced lesions.The pathogenesis related to inhibition of cyclooxygenase(COX)-1 includes reduced mucosal flow,reduced mucus and bicarbonate secretion,and impaired platelet aggregation.The pathogenesis related to inhibition of COX-2 involves reduced angiogenesis and increased leukocyte adherence.The pathogenic mechanisms related to direct epithelial damage are acid back diffusion and impaired platelet aggregation.The factors associated with an increased risk of upper gastrointestinal(GI) complications in subjects taking LDA are aspirin dose,history of ulcer or upper GI bleeding,age > 70 years,concomitant use of non-aspirin NSAIDs including COX-2-selective NSAIDs,and Helicobacter pylori(H.pylori) infection.Moreover,no significant differences have been found between ulcer and non-ulcer groups in the frequency and severity of symptoms such as nausea,acid regurgitation,heartburn,and bloating.It has been shown that the ratios of ulcers located in the body,fundus and cardia are significantly higher in bleeding patients than the ratio of gastroduodenal ulcers in patients taking LDA.Proton pump inhibitors reduce the risk of developing gastric and duodenal ulcers.In contrast to NSAIDinduced gastrointestinal ulcers,a well-tolerated histamine H2-receptor antagonist is reportedly effective in prevention of LDA-induced gastrointestinal ulcers.The eradication of H.pylori is equivalent to treatment with omeprazole in preventing recurrent bleeding.Continuous aspirin therapy for patients with gastrointestinal bleeding may increase the risk of recurrent bleeding but potentially reduces the mortality rates,as stopping aspirin therapy is associated with higher mortality rates.It is very important to prevent LDA-induced gastroduodenal ulcer complications including bleeding,and every effort should be exercised to prevent the bleeding complications.

Platelet thromboxane(11-dehydro-Thromboxane B_2) and aspirin response in patients with diabetes and coronary artery disease

Aspirin(ASA) irreversibly inhibits platelet cyclooxygenase-1(COX-1) leading to decreased thromboxane-mediated platelet activation. The effect of ASA ingestion on thromboxane generation was evaluated in patients with diabetes(DM) and cardiovascular disease. Thromboxane inhibition was assessed by measuring the urinary excretion of 11-dehydro-thromboxane B2(11dhTxB2), a stable metabolite of thromboxane A2. The mean baseline urinary 11dhTxB2 of DM was 69.6% higher than healthy controls(P = 0.024): female subjects(DM and controls) had 50.9% higher baseline 11dhTxB2 than males(P = 0.0004), while age or disease duration had no influence. Daily ASA ingestion inhibited urinary 11dhTxB2 in both DM(71.7%) and controls(75.1%, P < 0.0001). Using a pre-established cut-off of 1500 pg/mg of urinary 11dhTxB2, there were twice as many ASA poor responders(ASA "resistant") in DM than in controls(14.8% and 8.4%, respectively). The rate of ASA poor responders in two populations of acute coronary syndrome(ACS) patients was 28.6 and 28.7%, in spite of a significant(81.6%) inhibition of urinary 11dhTxB2(P < 0.0001). Both baseline 11dhTxB2 levels and rate of poor ASA responders were significantly higher in DM and ACS compared to controls. Underlying systemic oxidative inflammation may maintain platelet function in atherosclerotic cardiovascular disease irrespective of COX-1 pathway inhibition and/or increase systemic generation of thromboxane from non-platelet sources.

Meta-analysis of aspirin-heparin therapy for un-explained recurrent miscarriage

Objective This study was designed to evaluate the efficacy and safety of aspirin-heparin treatment for un-explained recurrent spontaneous abortion(URSA). Methods Literatures reporting the studies on the aspirin-heparin treatment of un-explained recurrent miscarriage with randomized controlled trials(RCTs) were collected from the major publication databases. The live birth rate was used as primary indicator, preterm delivery, preeclampsia, intrauterine growth restriction, and adverse reactions(thrombocytopenia) were used as the secondary indicators. The quality of the included studies was evaluated using RCT bias risk assessment tool in the Cochrane Handbook(v5.1.0). Meta-analysis was conducted using RevM an(v5.3) software. Subgroup analyses were conducted with an appropriately combined model according to the type of the treatments if heterogeneity among the selected studies was detected. Results Six publications of RCTs were included in this study. There were a total of 907 pregnant women with diagnosis of URSA, 367 of them were pooled in the study group with aspirin-heparin therapy and 540 women in the control group with placebo, aspirin or progesterone therapy. Meta-analysis showed that the live birth rate in the study group was significantly different from that in the control group [RR = 1.18, 95% CI(1.00-1.39), P=0.04]. Considering the clinical heterogeneity among the six studies, subgroup analysis were performed. Live birth rates in the aspirin-heparin treated groups and placebo groups were compared and no significant difference was found. There were no significant differences found between the two groups in the incidence of preterm delivery [RR=1.22, 95% CI(0.54-2.76), P=0.64], preeclampsia [RR=0.52, 95% CI(0.25-1.07), P=0.08], intrauterine growth restriction [RR=1.19, 95% CI(0.56-2.52), P=0.45] and thrombocytopenia [RR=1.17, 95% CI(0.09-14.42), P=0.90]. Conclusion This meta-analysis did not provide evidence that aspirin-heparin therapy had beneficial effect on un-explained recurrent miscarriage in terms of live birth rate, but it was relatively safe for it did not increase incidence of adverse pregnancy and adverse events. More well-designed and stratified double-blind RCT, individual-based meta-analysis regarding aspirin-heparin therapy are needed in future.

Aspirin suppresses growth of human gastric carcinoma cell by inhibiting survivin expression

Regular use of aspirin （ASA） could reduce the risk of gastric cancer although the precise mechanism remains unclear. Down-regulation of survivin may be one of the cyclooxygenase-independent mechanisms whereby ASA induces apoptosis of gastric cancer cell. In this study, we investigated the effect of ASA on the growth, apoptosis and survivin expression of gastric cancer cell line SGC7901. The survival of cells treated with 3.0 and 10.0 mmol/L ASA for 24 h was decreased by 44.6% and 88.5%, respectively. ASA at 3.0 mmol/L inhibited the viability of SGC7901 cells in a time-dependent manner. Apoptosis analysis showed similar results with MTT assay. ASA at 3.0 and 10.0 mmol/L decreased the mRNA transcript levels of survivin and reduced survivin protein levels in SGC7901 cells also in a time-dependent manner. Our findings indicated that ASA inhibited the proliferation of SGC7901 by suppressing survivin at both the transcriptional and translational level.