Causal relationship between feelings and cognitive decline:An univariable and multivariable Mendelian randomization study

BACKGROUND While the impact of depression on cognition is well-documented,the relationship between feelings and cognition has received limited attention.AIM To explore the potential association between feelings and cognition with a twosample Mendelian randomization(MR)analysis.METHODS Our analysis utilized genome-wide association data on various feelings(fed-up feelings,n=453071;worrier/anxious feelings,n=450765;guilty feelings,n=45-0704;nervous feelings,n=450700;sensitivity/hurt feelings,n=449419;miserableness,n=454982;loneliness/isolation,n=455364;happiness,n=152348)in the European population and their impact on cognitive functions(intelligence,n=269867).Conducting a univariable MR(UVMR)analysis to assess the relationship between feelings and cognition.In this analysis,we applied the inverse variance weighting(IVW),weighted median,and MR Egger methods.Additionally,we performed sensitivity analysis(leave-one-out analysis),assessed heterogeneity(using MR-PRESSO and Cochran’s Q test),and conducted multiple validity test(employing MR-Egger regression).Subsequently,a multivariable MR(MVMR)analysis was employed to examine the impact of feelings on cognition.IVW served as the primary method in the multivariable analysis,complemented by median-based and MR-Egger methods.RESULTS In this study,UVMR indicated that sensitivity/hurt feelings may have a negative causal effect on cognition(OR=0.63,95%CI:0.43-0.92,P=0.017).After adjustment of other feelings using MVMR,a direct adverse causal effect on cognition was observed(OR_(MVMR)=0.39,95%CI:0.17-0.90,P_(MVMR)=0.027).While a potential increased risk of cognitive decline was observed for fed-up feelings in the UVMR analysis(ORUVMR=0.64,95%CI:0.42-0.97,PUVMR=0.037),this effect disappeared after adjusting for other feelings(OR_(MVMR)=1.42,95%CI:0.43-4.74,P_(MVMR)=0.569).These findings were generally consistent across MV-IVW,median-based,and MR-Egger analyses.MR-Egger regression revealed pleiotropy in the impact of worrier/anxious feelings on cognition,presenting a challenge in identifying the effect.Notably,this study did not demonstrate any significant impact of guilty feelings,nervous feelings,miserableness,or loneliness/isolation on cognition.Due to a limited number of instrumental variables for happiness,this study was unable to analyze the relationship between happiness and cognition.CONCLUSION This MR study finds that sensitivity/hurt feelings are associated with cognitive decline,while the link between worrier/anxious feelings and cognition remains inconclusive.Insufficient evidence supports direct associations between happiness,guilty feelings,nervous feelings,miserableness,loneliness/isolation,and cognition.

Analysis of the intestinal flora in patientswith primary liver cancer

Objective To investigate the differences in intestinal flora of patients with primary liver cancer and ofhealthy individuals and to investigate the effect of the differential flora on the development of liver cancer.Methods Overall, 67 patients with primary liver cancer who received systematic and complete treatmentbetween January 2019 and December 2020 at the Sixth People’s Hospital of Qingdao and had completeclinical data were enrolled in this study, and 26 individuals who were healthy on physical examination inthe same period were used as healthy controls. Macro genome and 16s ribosome Deoxyribo Nucleic Acid(rDNA) high-throughput sequencing were performed on the stool flora of the enrolled patients and controls,and the differences in the intestinal flora were analyzed using the LEfSe bioinformatics software.Results Compared with the control samples, all the tested patient samples showed statistically significantdifferences in the number of colonies of 5 bacterial phyla, 5 orders, 8 families, 11 genera, and 14 species(P < 0.05).Conclusion Compared with healthy people, patients with primary liver cancer have significant differencesin the intestinal flora composition. The alteration of the intestinal flora may be correlated with the occurrenceof primary liver cancer, and the intestinal flora may become a novel target for the prevention and treatmentof primary liver cancer.

Milk fat globule epithelial growth factorⅧ(MFG-E8)sustains survival of cancer cells by prompting tumor angiogenesis and suppressing host immunities

Milk fat globule epithelial growth factor VIII(MFG-E8) is a novel adhesion protein mainly produced by macrophages and dendritic cells; it is expressed in most of the human tissues and functions to prompt cancer progression and survival. MFG-E8 contains a signal sequence for secretion, two epidermal growth factor(EGF)-like domains at the NH2 terminus and two discoidin domains with blood-clotting factor V/factor Ⅷ(C1 and C2) at the COOH terminus. The second EGF domain contains an arginine-glycine-aspartic(RGD) integrin-binding motif that engages α_vβ_5 integrins to facilitate cell adhesion and induce integrinmediated signal transduction. Integrin α_vβ_3 associates with VEGF receptor 2, engagement of integrins can promote angiogenesis, which plays key roles in growth, proliferation, and survival of cancer cells. VEGF stimulates the expression of α_vβ_3 and α_vβ_5 integrins on angiogenic vasculature, thereby potentiating effects of VEGF receptor engagement. Mice expressing a mutant form of α_vβ_3 integrin are unable to undergo tyrosine phosphorylation, confirming the important role that this integrin plays in pathological angiogenesis and providing important mechanistic insights. The C-terminus discoidin-like domains promote binding to membrane phospholipids, functioning close to VEGF like angiogenesis. MFG-E8 is an opsonin for apoptotic cells, and it acts as a bridging protein between apoptotic cells and phagocytes. It also influences cell immunities by altering CD4^+ and/or CD8^+ cells. Antibody or small peptide works with MFG-E8 at different functional sites or interacts with EGF-like domains and/or discoidin-like domains may play an important role in anti-angiogenesis or immune restoration. Altering the structures and/or functions of MFG-E8 and/or its domains is promising for development of novel anti-cancer strategies.

Prevalence of and risk factors for postprandial hypotension in older Chinese men

ObjectiveTo 估计流行并且冒险因素因为在旧、很旧的中国 men.MethodsThe 学习之中的饭后的低血压(PPH ) 65 包括了 349 个中国人并且更旧，组织了进二个年龄范畴：组 1 (旧) 65 ～ 80 年包括了 163 个人；组 2 (很旧) 超过 80 年包括了 186 个人。在饭以后的血压变化被估计由监视的回廊血压的每 15 min。在饭摄取以后并且在相对血压变化处于基线条件站起来和变化以后的症状连续地被观察。另外的基线数据包括了身体团索引，病历，和 PPH 的药 use.ResultsThe 流行总的来说是 59.3% 并且比组织 1 在组 2 是显著地更高的(63.4% 对 54.6% ， P &#x0003c；0.05 ) 。在组 2，在早餐(33.8%) 和午餐(32.1%) 以后的 PPH 的流行在晚饭(20.9%) 以后比那高， P &#x0003c；0.05。高血压和年龄是为 PPH 的重要风险因素(或 = 2.188， 95% CI：1.134 &#x02212； 4.223， P = 0.02；或 = 1.86， 95% CI：1.112 &#x02212； 3.11， P = 0.018，分别地) 。相反， acarbose 使用对 PPH 是保护的(或 = 0.4， 95% CI：0.189 &#x02212； 0.847， P = 0.017 ) 。在血压的减少在 PPH 期间是 20 &#x02212； 40 mmHg 和最大值是 90 mmHg。 PPH 通常发生在 30 &#x02212 ；在饭以后的 60 min 并且持续了 30 &#x02212 ； 120 min.ConclusionsThese 调查结果证明在超过 80 年的人的 PPH 的流行比在 65～80 年的人的那些显著地高，并且血压衰落为超过 80 年的人也是更高的。另外，高血压和年龄是为在老人的 PPH 的主要风险因素，它建议那阻止并且对待的 PPH 是值得的。

High prevalence of aspirin resistance in elderly patients with cardiovascular disease and metabolic syndrome

BackgroundMetabolic 症候群被知道是一个 prothrombotic 状态。我们拿了这研究检验阿司匹林抵抗可以与新陈代谢的症候群被联系的一个假设，并且与心血管的疾病(CVD ) 在病人估计阿司匹林抵抗的另外的潜在的决定因素有 CVD 的 469 个老病人全部的 .MethodsA 被招募。有新陈代谢的症候群的 172 个病人并且没有新陈代谢的症候群(控制组) ， 297 收到了每日的阿司匹林治疗(&#x02265；75 mg ) 超过一个月。血小板聚集被轻传播 aggregometry (LTA ) 测量。阿司匹林抵抗被定义为 &#x02265；20% arachidonic 酸(AA )- 并且 &#x02265；70% 腺苷 diphosphate (自动数据处理) 根据 LTA 导致了聚集。阿司匹林半应答者被定义为遇见一个(然而并非) 这些 criteria.ResultsBy LTA， 469 中的 38 个(8.1%) 病人们是阿司匹林抵抗。阿司匹林抵抗的流行与控制组相比在新陈代谢的症候群组是更高的[11.6 % 对 6.6% ，机会比率(或)= 2.039；95% 信心间隔(CI ) ：1.047-3.973 ] 。在 multivariate 逻辑回归分析，新陈代谢的症候群(或 = 4.951， 95% CI：1.440-17.019， P = 0.011 ) 是为有 CVD 和新陈代谢的症候群的病人的重要数字是的阿司匹林 resistance.ConclusionsA 的一个重要风险因素对阿司匹林治疗抵抗。这可能进一步在这些病人增加心血管的病态和死亡的风险。

Sorafenib in Liver Function Impaired Advanced Hepatocellular Carcinoma

Objective To explore the efficacy and safty of sorafenib in Child-Pugh class B to class C hepatocellular carcinoma(HCC).Methods In this three-center open-label study from November 2011 to May 2013,we randomly assigned 189 patients with advanced Child-Pugh class B or C HCC patients into two groups,one group with 95 patient to receive sorafenib(400 mg a time,twice a day) and the other group with 94 patients to receive best supportive care.The primary end points were progression-free survival and overall survival.Results The median progression-free survival was 2.2 months and 1.9 months in the sorafenib group and best supportive care group respectively(Hazard ratio in the sorafenib group,0.55;95% confidence interval,0.40-0.75;P=0.002).The median overall survival was 4.0 months and 3.5 months in the sorafenib group and best supportive care group respectively(Hazard ratio in the sorafenib group,0.48;95% confidence interval,0.35-0.68;P<0.001).The main adverse effect of sorafenib was rash and acne of the skin(in 51.7% patients).The incidences of severe rash,diarrhea,and dry skin were 5.6%,5.6%,and 2.2% in the sorafenib group.One patient reached partial response in the sorafenib group.Conclusions Sorafenib is safe in patients with liver function impaired advanced HCC.It is effective in terms of progression-free survival and overall survival compared with best supportive care.Liver functions are the important predictive factors.

Clinical Observation of Bevacizumab Combined with S-1 in the Treatment of Pretreated Advanced Esophageal Carcinoma

Objective To investigate the clinical effects and safety of bevacizumab combined with S-1 as the second-line treatment of recurrent and/or metastatic esophageal cancer after chemoradiation. Methods Patients with recurrent or metastatic esophageal cancer after chemoradiation were treated with bevacizumab and S-1. Bevacizumab was used by intravenous infusion, 7.5mg/kg body weight on day 1; S-1 was used by oral at 80mg/m^2·d on day 1-14, 21 days as a cycle of treatment and repeated until either progressive disease or intolerable toxicity occurred. Chest CT were performed and RECIST 1.1 was used for response evaluation. Kaplan-Meier method was used for survival analysis. Side effects were recorded and analyzed. Results Totally 78 patients were enrolled in the study, including 67 squamous cell carcinoma and 11 adenocarcinoma histologically. The overall response(CR+PR) rate was 22.4%(17/76) and disease control(CR+PR+SD) rate was 61.8%(47/76) respectively. The median follow-up time was 20 months(range from 9 to 44 months). The median progression-free survival(PFS) was 4.9 months(95% CI 4.4-5.5) and the median overall survival(OS) was 8.1 months(95% CI 7.6-9.2). The median PFS and OS of patients with metastasis diseases were 6.2 months(95% CI 3.3 to 6.3) and 8.5 months(95% CI 5.8 to 11.2), where PFS was longer than that of patients with local regional recurrence(median 5.0 months, 95% CI 3.0 to 5.5, P=0.017) and OS was longer than that of patients with regional disease and metastasis(median 8.0 months, 95% CI 4.6 to 9.5, P=0.010). The common adverse effects were mild to moderate neutropenia(84.2%), grade Ⅰ -Ⅱ hand and foot syndrome(51.3%), grade Ⅰ -Ⅱ nausea(48.7%), mild epistaxis(30.1%) and mild vomiting(14.5%). Esophageal bleeding occurred in 7.9% of patients. One patient(1.3%) died from massive bleeding which was caused by esophageal perforation. Conclusion Bevacizumab combined with S-1 was effective and safe for esophageal cancer patients who had recurrent or metastatic diseases after chemoradiation.

Influence of dynamic tissue properties on temperature elevation and lesions during HIFU scanning therapy:Numerical simulation

When large tumors are treated,ablation of the entire volume of tumors requires multiple treatment spots formed by high intensity-focused ultrasound(HIFU)scanning therapy.The heating effect of HIFU on biological tissue is mainly reflected in temperature elevation and tissue lesions.Tissue property parameters vary with temperature and,in turn,the distribution of temperature as well as the heating effects change accordingly.In this study,an HIFU scanning therapy model considering dynamic tissue properties is provided.The acoustic fields and temperature fields are solved combining the Helmholtz wave equation with Pennes bio-heat transfer equation based on the finite element method(FEM)to investigate the effects of various tissue properties(i.e.,the attenuation coefficient,acoustic velocity,thermal conductivity,specific heat capacity,density,and blood perfusion rate)on heating performance.Comparisons of the temperature distribution and thermal lesions under static and dynamic properties are made based on the data of tissue property parameters varying with temperature.The results show that the dynamic changes of thermal conductivity,specific heat capacity,and acoustic velocity may account for the decrease of temperature elevation in HIFU treatment,while the dynamic changes of attenuation coefficient,density,and blood perfusion rate aggravate the increase of temperature on treatment spots.Compared with other properties,the dynamic change of attenuation coefficient has a greater impact on tissue temperature elevation.During HIFU scanning therapy,the temperature elevation and tissue lesions of the first treatment spot are smaller than those of the subsequent treatment spots,but the temperature on the last treatment spot drops faster during the cooling period.The ellipsoidal tissue lesion is not symmetrical;specifically,the part facing toward the previous treatment spot tends to be larger.Under the condition of the same doses,the temperature elevation and the size of tissue lesions under dynamic properties present significant growth in comparison to static properties.Besides,the tissue lesion begins to form earlier with a more unsymmetrical shape and is connected to the tissue lesion around the previous treatment spot.As a result,lesions around all the treatment spots are connected with each other to form a closed lesion region.The findings in this study reveal the influence of dynamic tissue properties on temperature elevation and lesions during HIFU scanning therapy,providing useful support for the optimization of treatment programs to guarantee higher efficacy and safety.

Is combined lipid-regulating therapy safe and feasible for the very old patients with mixed dyslipidemia?

OBJECTIVES: To detect the efficacy and safety of combined lipid-regulating therapies in the very old patients with mixed dyslipidemia and determine an appropriate therapy for them。 METHODS: Four hundred and fifty patients aged over 75 with mixed dyslipidemia were divided into five groups according to different combination therapies。 Lipid levels and drug related adverse events were tested during the study。 RESULTS: Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were reduced in every group compared to baseline: statin + ezetimibe: -30.0% and -55.5%; statin + policosanol: -31.1% and -51.2%; statin + fibrates: -23.7% and -44.6%; statin + niacin: -25.2% and -43.0%; and niacin + fibrates: -11。3% and -23.5%。 The target achievement rates of LDL-C all exceeded 50%, except in niacin + fibrates (42.0%); statin + ezetimibe: 57.0%; statin + policosanol: 56.0%; statin + niacin: 52.0%; and statin + fibrates: 50.0%。 However, overall, the niacin + fibrates group was the most effective in decreasing triglyceride (TG) and increasing high-density lipoprotein cholesterol (HDL-C) as follows: niacin + fibrates: -39.3% and 28.6%; statin + fibrates: -29.3% and 18.4%; statin + niacin: -18.5% and 16.7%; statin + ezetimibe: -17.1% and 7.1%; and statin + policosanol: -15.6% and 9.5%。 The achievement rates of TG and HDL-C levels in niacin + fibrates (58.0% and 39.0%) were better than the other four groups: statin + niacin (34.0% and 34.0%), statin + fibrates (43.0% and 28.0%), statin + policosanol (30.0% and 24.0%) and statin + ezetimibe (28.0% and 25.0%)。 Patients in all five groups experiencing drug adverse events were only 2% and no severe adverse events occurred。 CONCLUSIONS: Statin + ezetimibe was the most effective group in lowering TC and LDL-C levels, while niacin + fibrates was the most effective in decreasing TG and increasing HDL-C levels。 The commonly used combined lipid-regulating therapies with common dosages in this study were all quite safe and feasible for the very old patients with mixed hyperlipidemia。

Metachronous pulmonary and pancreatic metastases arising from sigmoid colon cancer:A case report

BACKGROUND Metachronous pulmonary and pancreatic metastases from colorectal cancer are rare.The diagnosis of pancreatic metastases is difficult and predominantly relies on computed tomography,pathology and immunohistochemistry.Here,we describe the use of next-generation sequencing(NGS)for determination of the origin of metastasis and prognostic prediction of colorectal cancer.CASE SUMMARY A 59-year-old man was diagnosed with sigmoid adenocarcinoma stage IIA(T3N0M0)and underwent surgery in April 2014,followed by XELOX adjuvant chemotherapy.The patient developed pulmonary metastasis in the right upper lung and underwent surgery in May 2016 without further adjuvant chemotherapy.In May 2018,pancreatic metastasis was found and he underwent pancreaticoduodenectomy.After surgery,he was treated with adjuvant S-1 chemotherapy from June 2018 to March 2019.Histopathological review of the specimens from all three lesions indicated consistent patterns characteristic of colon cancer.Concordant gene mutation profiles were observed across the three lesions that included oncogenic driver mutations most frequently seen in colon cancer(e.g.,APC,TP53,KRAS and FBXW7).Blood circulating tumor(ct)DNA before adjuvant chemotherapy was undetectable with NGS,suggesting a favorable response to chemotherapy.The patient was alive and well at the latest follow-up visit,achieving a disease-free survival of 17 mo.CONCLUSION The genetic profiles of primary tumor,metastases and ctDNA may have clinical value in auxiliary diagnosis,prognosis and therapeutic decision-making.

Clinical significance of S100A7 protein in predicting recurrence of breast cancer in patients undergoing breast-conserving surgery with radiotherapy

Objective To investigate the relationship between the expression of S100A7 protein and prediction of recurrence and prognosis of breast cancer in patients undergoing breast-conserving surgery combined with radiotherapy.Methods 349 samples of carcinoma tissue wax blocks were selected from January 2011 to January 2014 in Qingdao Central Hospital.All the patients had undergone breast-conserving surgery.We analyzed S100A7 expression in tumor tissue by immunohistochemical staining.Using univariate and multivariate analyses,we evaluated the relationship between S100A7 and clinical results,to explore independent risk factors for local regional recurrence(LRR).Results The positive expression of S100A7 in the recurrence group(66.7%)was significantly higher than in the non-recurrence group(38.4%),P=0.025.A log-rank test showed that high S100A7 expression was significantly correlated with 5-year regional recurrence free survival rate(RFS)(94.9%vs 89.5%,P=0.0408),distant metastasis free survival rate(DFS)(95.4%vs 83.5%,P<0.001),and overall survival rate(OS)(99.0%vs 92.5%,P=0.0011).Histological grade,vessel carcinoma embolus,lymph node metastasis,S100A7 expression,and tumor size were factors that influenced RFS.Multivariate analysis of the Cox proportional hazard model showed that high S100A7 expression was an independent risk factor that affected breast cancer RFS(HR=6.864,95%CI:1.575-29.915,P=0.01).Thus,we concluded that high S100A7 expression is associated with increased risk of LRR and distant metastasis of breast cancer after breast-conserving surgery and postoperative radiotherapy.S100A7 can be used as a molecular marker to screen for patients with high recurrence risk after breast-conserving surgery.

Correlation analysis of breast fibroadenoma and the intestinal flora based on 16S rRNA sequencing

Objective To analyze the characteristics of the intestinal microflora in patients with breast fibroadenoma using 16S ribosomal RNA(rRNA)high-throughput sequencing.Methods Fecal samples from 20 patients with breast fibroadenoma and 36 healthy subjects were randomly collected and analyzed using high-throughput sequencing technology for 16S rRNA V4 region sequencing,and the alpha diversity(Chao index,Shannon index)was calculated using Mothur(v.1.39.5)software.Beta diversity was analyzed using QIIME(v1.80).SPSS software(version 23.0)and the t-test of two independent samples were used to analyze differences in the abundance of bacteria between the two groups.Results Compared with that in the healthy control group,theαdiversity of the intestinal microflora in breast fibroadenoma patients increased,but the difference was not statistically significant(P>0.05).At the phylum level,significant differences were observed between the two groups.The abundance of Firmicutes was higher in the breast fibroadenoma group(P<0.05),whereas the abundance of Synergistetes was higher in the healthy control group(P<0.005).A total of five bacterial genera showed significant differences between the two groups:the breast fibroadenoma group showed higher levels of Bautia(P<0.005),Coprococcus(P<0.005),Roseburia(P<0.05),and Ruminococcus(P<0.005),whereas Sutterella was more abundant in the healthy control group than in the breast fibroadenoma group(P<0.05).Conclusion The diversity and abundance of the intestinal flora in patients with breast fibroadenoma are significantly different from those in healthy subjects,suggesting that an imbalance in the intestinal flora is correlated with the occurrence of breast fibroadenoma.

Human umbilical cord mesenchymal stem cells for psoriasis:a phase 1/2a,single-arm study

Psoriasis is a common,chronic immune-mediated systemic disease that had no effective and durable treatment.Mesenchymal stem cells(MSCs)have immunomodulatory properties.Therefore,we performed a phase 1/2a,single-arm clinical trial to evaluate the safety and efficacy of human umbilical cord-derived MSCs(UMSCs)in the treatment of psoriasis and to preliminarily explore the possible mechanisms.Seventeen patients with psoriasis were enrolled and received UMsC infusions.Adverse events,laboratory parameters,PASl,and PGA were analyzed.We did not observe obvious side effects during the treatment and 6-month follow-up.A total of 47.1%(8/17)of the psoriasis patients had at least 40%improvement in the PASl score,and 17.6%(3/17)had no sign of disease or minimal disease based on the PGA score.And the efficiency was 25%(2/8)for males and 66.7%(6/9)for females.After UMSC transplantation(UMSCT),the frequencies of Tregs and CD4^(+)memory T cells were significantly increased,and the frequencies of T helper(Th)17 and CD4^(+)naive T cells were significantly decreased in peripheral blood(PB)of psoriasis patients.And all responders showed significant increases in Tregs and CD4^(+)memory T cells,and significant decreases in Th17 cells and serum IL-17 level after UMsCT.And baseline level of Tregs in responders were significantly lower than those in nonresponders.In conclusion,allogeneic UMSCT is safe and partially effective in psoriasis patients,and level of Tregs may be used as a potent biomarker to predict the clinical efficacy of UMSCT.Trial registration Clinical Trials NCT03765957.

AZD9291-induced Acute Interstitial Lung Disease

To the Editor： A 32-year-old Chinese male patient with 1 week cough and dyspnea on exertion was presented to hospital. He was a metastatic lung adenocarcinoma patient with 3 years treatment history. In October 2012, the patient complained cough, short of breath, and thoracic computerized axial tomography scan （CAT-scan） revealed left lung hilum mass with the right lung multismall patches or opacities. Core needle biopsy on supraclavicular lymph nodes was performed and diagnosis of Stage IV （T3N3MIa） lung adenocarcinoma was made by radiologist, pathologist, and oncologist.

Effects of Simvastatin on Endoplasmic Reticulum Stress-Mediated Apoptosis in Atherosclerotic Calcification

Objective:The effectiveness of statins in reducing atherosclerotic calcification remains controversial.The aim of this study was to confirm that simvastatin reduces atherosclerotic calcification and stabilizes plaque by restricting endoplasmic reticulum stress(ERS)-mediated apoptosis.Methods:Twenty-four 8-week-old male apolipoprotein E(ApoE)-/-mice(C57BL/6J genetic background)were selected and randomly divided into model(n=12)and simvastatin(n=12)groups.Twelve male C57BL/6J mice were selected as control group(n=12).The mice were adaptively fed for 2 weeks and were put on a high-fat diet thereafter.After 9 weeks,they were treated with simvastatin(20 mg/kg)or phosphate-buffered saline daily for 8 weeks.Aortic sinus samples were obtained from ApoE-/-and C57BL/6J mice for hematoxylin and eosin,von Kossa,alizarin Red S,terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling,and immunohistochemical staining after in vivo treatment with simvastatin.In addition,mouse vascular smooth muscle cells were analyzed after exposure to simvastatin in vitro.Results:Administration of simvastatin in vivo drastically attenuated the atherosclerosis,calcification,and apoptosis,and decreased the serum levels of triglycerides,total cholesterol,low-density lipoprotein cholesterol,and high-density lipoprotein cholesterol.The expression levels of glucose-regulated protein,78 kDa(GRP78),C/EBP homologous protein(CHOP),and caspase 12(CASP12)in the aortic sinus decreased in the simvastatin group compared with the model group.In vitro,simvastatin or simvastatin plus ERS inhibitor(taurine)attenuated calcification and apoptosis,and reduced the expression of ERS-related proteins GRP78,CHOP,and CASP12.Conclusion:Treatment with simvastatin suppressed atherosclerotic calcification.This effect may be mediated through the inhibition of ERS-related apoptosis.