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 che...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.展开更多
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 ...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.展开更多
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 pape...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.展开更多
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 edaravon...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.展开更多
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 ref...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。展开更多
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...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.展开更多
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 Janu...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.展开更多
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 Xin...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.展开更多
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 gast...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.展开更多
BACKGROUND Cirrhosis is a major risk factor for the development of hepatocellular carcinoma (HCC). Portal vein thrombosis is not uncommon after splenectomy in cirrhotic patients, and many such patients take oral antic...BACKGROUND Cirrhosis is a major risk factor for the development of hepatocellular carcinoma (HCC). Portal vein thrombosis is not uncommon after splenectomy in cirrhotic patients, and many such patients take oral anticoagulants including aspirin. However, the long-term impact of postoperative aspirin on cirrhotic patients after splenectomy remains unknown. AIM The main purpose of this study was to investigate the effect of postoperative long-term low-dose aspirin administration on the development of HCC and longterm survival of cirrhotic patients after splenectomy. METHODS The clinical data of 264 adult patients with viral hepatitis-related cirrhosis who underwent splenectomy at the First Affiliated Hospital of Xi’an Jiaotong University from January 2000 to December 2014 were analyzed retrospectively. Among these patients, 59 who started taking 100 mg/d aspirin within seven days were enrolled in the aspirin group. The incidence of HCC and overall survival were analyzed.RESULTS During follow-up, 41 (15.53%) patients developed HCC and 37 (14.02%) died due to end-stage liver diseases or other serious complications. Postoperative longterm low-dose aspirin therapy reduced the incidence of HCC from 19.02% to 3.40% after splenectomy (log-rank test, P=0.028). Univariate and multivariate analyses showed that not undertaking postoperative long-term low-dose aspirin therapy [odds ratio (OR)=6.211, 95% confidence interval (CI): 1.142-27.324, P=0.016] was the only independent risk factor for the development of HCC. Similarly, patients in the aspirin group survived longer than those in the control group (log-rank test, P=0.041). Univariate and multivariate analyses showed that the only factor that independently associated with improved overall survival was postoperative long-term low-dose aspirin therapy [OR = 0.218, 95%CI: 0.049- 0.960, P=0.044]. CONCLUSION In patients with viral hepatitis-related cirrhosis, long-term post-splenectomy administration of low-dose aspirin reduces the incidence of HCC and improves the long-term overall survival.展开更多
AIM:To compare the therapeutic effects of proton pump inhibitors(PPI) and histamine 2 receptor antagonists(H2RA) on gastroduodenal ulcers under continuous use of low-dose aspirin.METHODS:Sixty patients who had a gastr...AIM:To compare the therapeutic effects of proton pump inhibitors(PPI) and histamine 2 receptor antagonists(H2RA) on gastroduodenal ulcers under continuous use of low-dose aspirin.METHODS:Sixty patients who had a gastroduodenal ulcer on screening endoscopy but required continuous use of low-dose aspirin were randomly assigned to receive PPI(lansoprazole 30 mg,n = 30) or H2RA(famotidine 40 mg or if famotidine had been administered before assignment,ranitidine 300 mg,n = 30).The therapeutic effects were evaluated by endoscopy after 8-wk treatment.The presence or absence of Helicobacter pylori(H.pylori) was determined by urea breath test before treatment.Abdominal symptoms were compared with the gastrointestinal symptom rating scale(GSRS) questionnaire before and after treatment.RESULTS:Twenty-six patients in the PPI group and 26 patients in the H2RA group,excluding dropouts,were analyzed.There were no significant differences in median age,sex,underlying disease,smoking status,H.pylori infection,prevalence of ulcers before treatment,and lesion site between the two groups.The therapeutic effects were endoscopically evaluated as healed in 23 patients(88.5%) and not healed in 3 patients in the PPI group and as healed in 22 patients(84.6%) and not healed in 4 patients in the H2RA group.Abdominal symptoms before treatment were uncommon in both groups;the GSRS scores were not significantly reduced after treatment as compared with before treatment.CONCLUSION:The healing rate of gastroduodenal ulcers during continuous use of low-dose aspirin was greater than 80% in both the PPI group and the H2RA group,with no significant difference between the two groups.展开更多
Objective:To study the effect of aspirin on healing process of osteoporotic fracture(OPF)in rats.Methods:A total of 50 female Wistar rata aged 3 months were randomly divided into observation group and control group,ca...Objective:To study the effect of aspirin on healing process of osteoporotic fracture(OPF)in rats.Methods:A total of 50 female Wistar rata aged 3 months were randomly divided into observation group and control group,castration method was adopted to establish the osteoporosis(OP)model.After artificial preparing fractures on the midpoint of left femur,fixing gram needle intramedullary.OPF modeling was complete.Aspirin lavage of 33 mg once a day was adoptde in observation group after modeling,same amount of normal saline was used in the control as placebo.From eash group,selected 5 rats at the 2nd.4th,8th and 12th week after modeling to measure the bone mineral density(BMD)and histogical examination of the fracture callus,radiology observation was conducted at the 8th and 12th week.Left femur biomechanical measurement was taken at the 12th week.Results:BMD values of observation group at each time point were significantly higher than that of the control group after modeling(P<0.05);Histological observation showed that at the 8th week,the endochondral ossification process of observation group was faster than that of observation group,with fuzzy fracture line in observation group and clear fracture line in observtion group;at the 12th week,fracture line disappeared in observation group,fracture line of the control group was fuzzy at the same time;three-point bending load of the left femur in observation group rats was significantly higher than that of control group after12 weeka(P<0.05).Conclusions:Asporin can accelerate the healing of new callus in OPF rats,increase bone density and biomechanics strength,and promote fracture of osteporotic rats.展开更多
AIM:To investigate the effect of aspirin on neuroendocrine tumor(NET)cell growth and signaling in vitro.METHODS:Human pancreatic BON1,bronchopulmonary NCI-H727 and midgut GOT1 neuroendocrine tumor cells were treated w...AIM:To investigate the effect of aspirin on neuroendocrine tumor(NET)cell growth and signaling in vitro.METHODS:Human pancreatic BON1,bronchopulmonary NCI-H727 and midgut GOT1 neuroendocrine tumor cells were treated with different concentrations of aspirin(from 0.001 to 5 mmol/L),and the resulting effects on metabolic activity/cell proliferation were measured using cell proliferation assays and SYBR-DNAlabeling after 72,144 and 216 h of incubation.The effects of aspirin on the expression and phosphorylation of several critical proteins that are involved in the most common intracellular growth factor signaling pathways(especially Akt protein kinase B)and mammalian target of rapamycin(mTOR)were determined by Western blot analyses.Propidium iodide staining and flow cytometry were used to evaluate changes in cell cycle distribution and apoptosis.Statistical analysis was performed using a 2-tailed Student’s t-test to evaluate the proliferation assays and cell cycle analyses.The results are expressed as the mean±SD of 3 or 4 independently performed experiments.Statistical significance was set at P<0.05.RESULTS:Treatment with aspirin suppressed the viability/proliferation of BON1,NCI-H727 and GOT1 cells in a time-and dose-dependent manner.Significant effects were observed at starting doses of 0.5-1 mmol/L and peaked at 5 mmol/L.For instance,after treatment with 1 mmol/L aspirin for 144 h,the viability of pancreatic BON1 cells decreased to 66%±13%(P<0.05),the viability of bronchopulmonary NCI-H727 cells decreased to 53%±8%(P<0.01)and the viability of midgut GOT1 cells decreased to 89%±6%(P<0.01).These effects were associated with a decreased entry into the S phase,the induction of the cyclin-dependent kinase inhibitor p21 and reduced expression of cyclindependent kinase 4 and cyclin D3.Aspirin suppressed mTOR downstream signaling,evidenced by the reduced phosphorylation of the mTOR substrates 4E binding protein 1,serine/threonine kinase P70S6K and S6 ribosomal protein and inhibited glycogen synthase kinase3 activity.We observed the(compensatory)activation of tuberous sclerosis 2,the serine/threonine specific protein kinase AKT and extracellular signal-regulated kinases.CONCLUSION:Aspirin demonstrates promising anticancer properties for NETs in vitro.Further preclinical and clinical studies are needed.展开更多
AIM: To study the antineoplastic efficacy of 10% aspirin intralesional injection on VX2 hepatic tumors in a rabbit model. METHODS: Thirty-two male rabbits (age: 6-9 wk; body weight: 1700-2500 g) were inoculated with V...AIM: To study the antineoplastic efficacy of 10% aspirin intralesional injection on VX2 hepatic tumors in a rabbit model. METHODS: Thirty-two male rabbits (age: 6-9 wk; body weight: 1700-2500 g) were inoculated with VX2 hepatic tumor cells (104 cells/rabbit) via supraumbilical median laparotomy. On day 4 post-implantation, when the tumors were about 1 cm in diameter, the rabbits were randomly divided into the following groups (n = 8 each group) to assess early (24 h) and late (7 d) antineoplastic effects of intratumoral injection of 10% bicarbonate aspirin solution (experimental groups) in comparison to intratumoral injection of physiological saline solution (control groups): group 1, 24 h control; group 2, 24 h experimental; group 3, 7 d control; group 4, 7 d experimental. The serum biochemistry profile (measurements of glycemia, alkaline phosphatase, gamma-glutamyl transferase, aspartateaminotransferase, and alanine aminotransferase) and body weight measurements were obtained for all animals at the following time points: D0, before tumor implant; D4, day of treatment; D5, day of sacrifice for groups 1 and 2; D11, day of sacrifice for groups 3 and 4. Gross assessments of the abdominal and thoracic cavities were carried out upon sacrifice. The resected liver tissues, including hepatic tumors, were qualitatively (general morphology, signs of necrosis) and quantitatively (tumor area) assessed by histopathological analysis. RESULTS: Gross examination showed no alterations, besides the left hepatic lobe tumors, had occurred in the thoracic and abdominal cavities of any animal at any time point evaluated. However, the features of the tumor foci were distinctive between the groups. Compared to the control groups, which showed normal unabated tumor progression, the aspirin-treated groups showed imprecise but limited tumor boundaries and a general red-white coloration (indicating hemorrhaging) at 24 h post-treatment, and development of yellow-white areas of a cicatricial aspect at 7 d after treatment. At all time points evaluated, all except one biochemical parameters tested within the reference range (P > 0.05); a significant increase was detected in the alkaline phosphatase level of the control group 3 on D11 (P < 0.05). At 24 h post-treatment, the aspirintreated groups showed extensive coagulation necrosis accompanied by a remarkable absence of viable tumor foci; at 7 d after treatment, the tumors had completely disappeared in these animals and fibrous necrotic nod- ules had developed. In contrast, throughout the study course, the tumors of the control groups remained unchanged, showing tumor nodules without necrosis at the time point corresponding to 24 h post-treatment and increased amounts of tumor nodules at the time point corresponding to 7 d post-treatment. Quantitative analysis of the remaining tumor area revealed that the aspirin-treated groups had significantly smaller tumor foci at 24 h post-treatment (8.5% ± 0.7%) andat 7 d after treatment (11.0% ± 4.2%), compared to those in the control groups (24 h: 98.5% ± 1.5% and 7 d: 94.0% ± 2.7%; both,P < 0.005). CONCLUSION: Intralesional injection of a 10% aspirin solution causes destruction of VX2 hepatic tumors in rabbits without evidence of relapse at 7 d after treat- ment administration.展开更多
Comparative DFT computations were studied between Paracetamol (PA) and its analogues such as p-nitroace- tanilide (PA-NO2), p-bromoacetanilide (PA-Br) and N-acetylanthranilic acid (NAA) which can be considered also as...Comparative DFT computations were studied between Paracetamol (PA) and its analogues such as p-nitroace- tanilide (PA-NO2), p-bromoacetanilide (PA-Br) and N-acetylanthranilic acid (NAA) which can be considered also as analogue of Aspirin (ASP). As well, Thio-Aspirin, Acetyl-Thio-Salicylic acid, (TASP) is another analogue of ASP. From DFT studies, it has been concluded that PA and its analogues have the predominant trans-conformers with respect to directions of the carbonyl group in the acetyl moiety and the amino-hydrogen atom but the predominant conformer of NAA molecule is the cis-form. Phenacetin (PH) molecule which has ethoxy group in the Para-position instead of the hydroxyl group in the Para-position in PA molecule is another analogue of PA. The electron transfer energy between the drugs and the nucleic acid bases can be illustrated as cancer energy barrier. The cancer energy barriers were calculated from the DFT parameters for all the studied molecules showing the carcinogenic effect. The metabolized product N-acetylimidoquinone, m-PA, is produced in the liver from PA and PH. m-PA has higher electron affinity more than those of the nucleic acid bases indicating to the strong electronic withdrawing power from the nucleus in the human being liver cell, hence m-PA is responsible for the carcinogenic behavior of the liver cell since it has low energy barrier with guanine, 0.3 eV. Therefore the electron transfer between m-PA and guanine takes place spontaneously in the liver. From CI calculations it has been concluded that the singlet transition energies for the trans and cis conformers of PA are the same. The comparative spectral studies have been scanned for some analogues in the visible and UV regions using solvents of different polarities. The complex between PA and Zn2+ was studied by DFT method.展开更多
基金This study was approved by the Austin Health Human Ethics Research Committee(No.HREC/87459/Austin-2022).
文摘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.
文摘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.
基金Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2019D01C244)Special Research Project for Health and Young Medical Science and Technology Talents in Xinjiang Uygur Autonomous Region(No.WJWY-202142)。
文摘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.
文摘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.
基金Capital Clinical Characteristic Application Research Project(No.Z181100001718144)Beijing Tongzhou District Science and Technology Plan Project(No.KJ2017CX036-06)In-hospital Project of Shanghai Jinshan District Integrated Traditional Chinese and Western Medicine Hospital(No.2022-1)。
文摘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。
文摘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.
文摘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.
文摘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.
文摘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.
基金Supported by the Ministry of Education Innovation Team Development Program of China,No.IRT16R57
文摘BACKGROUND Cirrhosis is a major risk factor for the development of hepatocellular carcinoma (HCC). Portal vein thrombosis is not uncommon after splenectomy in cirrhotic patients, and many such patients take oral anticoagulants including aspirin. However, the long-term impact of postoperative aspirin on cirrhotic patients after splenectomy remains unknown. AIM The main purpose of this study was to investigate the effect of postoperative long-term low-dose aspirin administration on the development of HCC and longterm survival of cirrhotic patients after splenectomy. METHODS The clinical data of 264 adult patients with viral hepatitis-related cirrhosis who underwent splenectomy at the First Affiliated Hospital of Xi’an Jiaotong University from January 2000 to December 2014 were analyzed retrospectively. Among these patients, 59 who started taking 100 mg/d aspirin within seven days were enrolled in the aspirin group. The incidence of HCC and overall survival were analyzed.RESULTS During follow-up, 41 (15.53%) patients developed HCC and 37 (14.02%) died due to end-stage liver diseases or other serious complications. Postoperative longterm low-dose aspirin therapy reduced the incidence of HCC from 19.02% to 3.40% after splenectomy (log-rank test, P=0.028). Univariate and multivariate analyses showed that not undertaking postoperative long-term low-dose aspirin therapy [odds ratio (OR)=6.211, 95% confidence interval (CI): 1.142-27.324, P=0.016] was the only independent risk factor for the development of HCC. Similarly, patients in the aspirin group survived longer than those in the control group (log-rank test, P=0.041). Univariate and multivariate analyses showed that the only factor that independently associated with improved overall survival was postoperative long-term low-dose aspirin therapy [OR = 0.218, 95%CI: 0.049- 0.960, P=0.044]. CONCLUSION In patients with viral hepatitis-related cirrhosis, long-term post-splenectomy administration of low-dose aspirin reduces the incidence of HCC and improves the long-term overall survival.
文摘AIM:To compare the therapeutic effects of proton pump inhibitors(PPI) and histamine 2 receptor antagonists(H2RA) on gastroduodenal ulcers under continuous use of low-dose aspirin.METHODS:Sixty patients who had a gastroduodenal ulcer on screening endoscopy but required continuous use of low-dose aspirin were randomly assigned to receive PPI(lansoprazole 30 mg,n = 30) or H2RA(famotidine 40 mg or if famotidine had been administered before assignment,ranitidine 300 mg,n = 30).The therapeutic effects were evaluated by endoscopy after 8-wk treatment.The presence or absence of Helicobacter pylori(H.pylori) was determined by urea breath test before treatment.Abdominal symptoms were compared with the gastrointestinal symptom rating scale(GSRS) questionnaire before and after treatment.RESULTS:Twenty-six patients in the PPI group and 26 patients in the H2RA group,excluding dropouts,were analyzed.There were no significant differences in median age,sex,underlying disease,smoking status,H.pylori infection,prevalence of ulcers before treatment,and lesion site between the two groups.The therapeutic effects were endoscopically evaluated as healed in 23 patients(88.5%) and not healed in 3 patients in the PPI group and as healed in 22 patients(84.6%) and not healed in 4 patients in the H2RA group.Abdominal symptoms before treatment were uncommon in both groups;the GSRS scores were not significantly reduced after treatment as compared with before treatment.CONCLUSION:The healing rate of gastroduodenal ulcers during continuous use of low-dose aspirin was greater than 80% in both the PPI group and the H2RA group,with no significant difference between the two groups.
基金supported by Guangdong Science and Technology Projects,grant No.2010b031600288
文摘Objective:To study the effect of aspirin on healing process of osteoporotic fracture(OPF)in rats.Methods:A total of 50 female Wistar rata aged 3 months were randomly divided into observation group and control group,castration method was adopted to establish the osteoporosis(OP)model.After artificial preparing fractures on the midpoint of left femur,fixing gram needle intramedullary.OPF modeling was complete.Aspirin lavage of 33 mg once a day was adoptde in observation group after modeling,same amount of normal saline was used in the control as placebo.From eash group,selected 5 rats at the 2nd.4th,8th and 12th week after modeling to measure the bone mineral density(BMD)and histogical examination of the fracture callus,radiology observation was conducted at the 8th and 12th week.Left femur biomechanical measurement was taken at the 12th week.Results:BMD values of observation group at each time point were significantly higher than that of the control group after modeling(P<0.05);Histological observation showed that at the 8th week,the endochondral ossification process of observation group was faster than that of observation group,with fuzzy fracture line in observation group and clear fracture line in observtion group;at the 12th week,fracture line disappeared in observation group,fracture line of the control group was fuzzy at the same time;three-point bending load of the left femur in observation group rats was significantly higher than that of control group after12 weeka(P<0.05).Conclusions:Asporin can accelerate the healing of new callus in OPF rats,increase bone density and biomechanics strength,and promote fracture of osteporotic rats.
文摘AIM:To investigate the effect of aspirin on neuroendocrine tumor(NET)cell growth and signaling in vitro.METHODS:Human pancreatic BON1,bronchopulmonary NCI-H727 and midgut GOT1 neuroendocrine tumor cells were treated with different concentrations of aspirin(from 0.001 to 5 mmol/L),and the resulting effects on metabolic activity/cell proliferation were measured using cell proliferation assays and SYBR-DNAlabeling after 72,144 and 216 h of incubation.The effects of aspirin on the expression and phosphorylation of several critical proteins that are involved in the most common intracellular growth factor signaling pathways(especially Akt protein kinase B)and mammalian target of rapamycin(mTOR)were determined by Western blot analyses.Propidium iodide staining and flow cytometry were used to evaluate changes in cell cycle distribution and apoptosis.Statistical analysis was performed using a 2-tailed Student’s t-test to evaluate the proliferation assays and cell cycle analyses.The results are expressed as the mean±SD of 3 or 4 independently performed experiments.Statistical significance was set at P<0.05.RESULTS:Treatment with aspirin suppressed the viability/proliferation of BON1,NCI-H727 and GOT1 cells in a time-and dose-dependent manner.Significant effects were observed at starting doses of 0.5-1 mmol/L and peaked at 5 mmol/L.For instance,after treatment with 1 mmol/L aspirin for 144 h,the viability of pancreatic BON1 cells decreased to 66%±13%(P<0.05),the viability of bronchopulmonary NCI-H727 cells decreased to 53%±8%(P<0.01)and the viability of midgut GOT1 cells decreased to 89%±6%(P<0.01).These effects were associated with a decreased entry into the S phase,the induction of the cyclin-dependent kinase inhibitor p21 and reduced expression of cyclindependent kinase 4 and cyclin D3.Aspirin suppressed mTOR downstream signaling,evidenced by the reduced phosphorylation of the mTOR substrates 4E binding protein 1,serine/threonine kinase P70S6K and S6 ribosomal protein and inhibited glycogen synthase kinase3 activity.We observed the(compensatory)activation of tuberous sclerosis 2,the serine/threonine specific protein kinase AKT and extracellular signal-regulated kinases.CONCLUSION:Aspirin demonstrates promising anticancer properties for NETs in vitro.Further preclinical and clinical studies are needed.
文摘AIM: To study the antineoplastic efficacy of 10% aspirin intralesional injection on VX2 hepatic tumors in a rabbit model. METHODS: Thirty-two male rabbits (age: 6-9 wk; body weight: 1700-2500 g) were inoculated with VX2 hepatic tumor cells (104 cells/rabbit) via supraumbilical median laparotomy. On day 4 post-implantation, when the tumors were about 1 cm in diameter, the rabbits were randomly divided into the following groups (n = 8 each group) to assess early (24 h) and late (7 d) antineoplastic effects of intratumoral injection of 10% bicarbonate aspirin solution (experimental groups) in comparison to intratumoral injection of physiological saline solution (control groups): group 1, 24 h control; group 2, 24 h experimental; group 3, 7 d control; group 4, 7 d experimental. The serum biochemistry profile (measurements of glycemia, alkaline phosphatase, gamma-glutamyl transferase, aspartateaminotransferase, and alanine aminotransferase) and body weight measurements were obtained for all animals at the following time points: D0, before tumor implant; D4, day of treatment; D5, day of sacrifice for groups 1 and 2; D11, day of sacrifice for groups 3 and 4. Gross assessments of the abdominal and thoracic cavities were carried out upon sacrifice. The resected liver tissues, including hepatic tumors, were qualitatively (general morphology, signs of necrosis) and quantitatively (tumor area) assessed by histopathological analysis. RESULTS: Gross examination showed no alterations, besides the left hepatic lobe tumors, had occurred in the thoracic and abdominal cavities of any animal at any time point evaluated. However, the features of the tumor foci were distinctive between the groups. Compared to the control groups, which showed normal unabated tumor progression, the aspirin-treated groups showed imprecise but limited tumor boundaries and a general red-white coloration (indicating hemorrhaging) at 24 h post-treatment, and development of yellow-white areas of a cicatricial aspect at 7 d after treatment. At all time points evaluated, all except one biochemical parameters tested within the reference range (P > 0.05); a significant increase was detected in the alkaline phosphatase level of the control group 3 on D11 (P < 0.05). At 24 h post-treatment, the aspirintreated groups showed extensive coagulation necrosis accompanied by a remarkable absence of viable tumor foci; at 7 d after treatment, the tumors had completely disappeared in these animals and fibrous necrotic nod- ules had developed. In contrast, throughout the study course, the tumors of the control groups remained unchanged, showing tumor nodules without necrosis at the time point corresponding to 24 h post-treatment and increased amounts of tumor nodules at the time point corresponding to 7 d post-treatment. Quantitative analysis of the remaining tumor area revealed that the aspirin-treated groups had significantly smaller tumor foci at 24 h post-treatment (8.5% ± 0.7%) andat 7 d after treatment (11.0% ± 4.2%), compared to those in the control groups (24 h: 98.5% ± 1.5% and 7 d: 94.0% ± 2.7%; both,P < 0.005). CONCLUSION: Intralesional injection of a 10% aspirin solution causes destruction of VX2 hepatic tumors in rabbits without evidence of relapse at 7 d after treat- ment administration.
文摘Comparative DFT computations were studied between Paracetamol (PA) and its analogues such as p-nitroace- tanilide (PA-NO2), p-bromoacetanilide (PA-Br) and N-acetylanthranilic acid (NAA) which can be considered also as analogue of Aspirin (ASP). As well, Thio-Aspirin, Acetyl-Thio-Salicylic acid, (TASP) is another analogue of ASP. From DFT studies, it has been concluded that PA and its analogues have the predominant trans-conformers with respect to directions of the carbonyl group in the acetyl moiety and the amino-hydrogen atom but the predominant conformer of NAA molecule is the cis-form. Phenacetin (PH) molecule which has ethoxy group in the Para-position instead of the hydroxyl group in the Para-position in PA molecule is another analogue of PA. The electron transfer energy between the drugs and the nucleic acid bases can be illustrated as cancer energy barrier. The cancer energy barriers were calculated from the DFT parameters for all the studied molecules showing the carcinogenic effect. The metabolized product N-acetylimidoquinone, m-PA, is produced in the liver from PA and PH. m-PA has higher electron affinity more than those of the nucleic acid bases indicating to the strong electronic withdrawing power from the nucleus in the human being liver cell, hence m-PA is responsible for the carcinogenic behavior of the liver cell since it has low energy barrier with guanine, 0.3 eV. Therefore the electron transfer between m-PA and guanine takes place spontaneously in the liver. From CI calculations it has been concluded that the singlet transition energies for the trans and cis conformers of PA are the same. The comparative spectral studies have been scanned for some analogues in the visible and UV regions using solvents of different polarities. The complex between PA and Zn2+ was studied by DFT method.
