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Meaning in the Holy Quran: A Text Analysis of the "Surah Livestock" ("A1-An'am") Within the Framework of Grice's Theory of Implicature
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作者 Ali Ebrahimi Badejani Maryam Afshari Badejani Ahmad Reza Lotfi 《Sino-US English Teaching》 2013年第11期868-885,共18页
The Holy Quran (1982) is the Holy Book of the Moslems and the most understandable aspect of its eloquence. One of the most interesting aspects found in different languages is the use of implicatures or implied meani... The Holy Quran (1982) is the Holy Book of the Moslems and the most understandable aspect of its eloquence. One of the most interesting aspects found in different languages is the use of implicatures or implied meaning. How and why such implicatures are generated and are discussed in pragmatics? In this study, a list of conversations (direct and indirect) from "Surah Livestock" ("A1-An'am"), the sixth Chapter of the Holy Quran, and the implicatures implied in the conversations are analyzed through a pragmatic theory: CP (Cooperative Principle). The present study shows that in most cases, the non-observance of Grice's (1975) maxims is found in the maxim of Quantity and the least in Manner. Grice's CP and its contributory maxims have not been observed in the "Surah Livestock" in this study. All maxims of Grice have been flouted in This Surah (1982) and there is no difference among Gricean maxims as far as flouting in the Surah is concerned. 展开更多
关键词 "Surah Livestock" ("a1-an'am") ELOQUENCE IMPLICATURE CP (Cooperative Principle) maxims of Quality Quantity Relevance and Manner
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基于ACE2-Ang(1-7)-Mas轴研究参芪地黄汤对2型糖尿病模型大鼠认知功能的影响
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作者 齐雅芝 李君 +4 位作者 唐娅 曹睿 翟燕玲 徐强 韩玉生 《海南医学院学报》 CAS 北大核心 2024年第21期1625-1633,共9页
目的:观察参芪地黄汤对2型糖尿病(T2DM)认知障碍的改善作用,通过对ACE2-Ang-(1-7)-Mas轴的研究进一步探讨参芪地黄汤改善糖尿病认知功能障碍的可能机制。方法:24只雄性SD大鼠采用高脂高糖饲料喂养联合链脲佐菌素(STZ)腹腔注射构建T2DM... 目的:观察参芪地黄汤对2型糖尿病(T2DM)认知障碍的改善作用,通过对ACE2-Ang-(1-7)-Mas轴的研究进一步探讨参芪地黄汤改善糖尿病认知功能障碍的可能机制。方法:24只雄性SD大鼠采用高脂高糖饲料喂养联合链脲佐菌素(STZ)腹腔注射构建T2DM大鼠模型,随机分为模型组和参芪地黄汤低、中、高剂量组,每组6只,另设6只为空白对照组。给药组灌胃相应剂量药物(低中高剂量分别为10.8、21.6、32.4 g/kg)连续8周。Morris水迷宫实验观察大鼠行为学变化;HE染色观察大鼠海马组织的病理学改变;ELISA检测大鼠血清中胰岛素含量,海马中血管紧张素(1-7)[Ang(1-7)],白细胞介素1β(IL-1β),白细胞介素18(IL-18)和肿瘤坏死因子-α(TNF-α)的含量;免疫组化,Western blot检测海马中血管紧张素Ⅱ(AngⅡ)、血管紧张素转换酶2(ACE2)、Mas受体(MasR)、NOD样受体蛋白3(NLRP3)、半胱氨酸天冬酶-1(Caspase-1)蛋白。结果:与对照组比较,模型组空腹血糖水平升高;大鼠平均逃避潜伏时间显著延长,而穿越平台的次数则显著减少(P<0.01);海马组织结构疏松,炎细胞浸润明显,小胶质细胞显著增多。与模型组比较,各给药组空腹血糖水平均降低,胰岛素水平均升高;参芪地黄汤中、高剂量组大鼠潜伏期显著缩短,穿越平台次数显著增多(P<0.05);大鼠神经元结构较完整,炎细胞浸润、小胶质细胞显著减少。与对照组比较,模型组组织中Ang-(1-7)和IL-1β、IL-18和TNF-α等细胞因子水平显著上升(P<0.01),海马中ACE2、Mas表达显著下降(P<0.05),而AngⅡ、NLRP3、Caspase-1表达则显著上升(P<0.05);与模型组相比,经过给药后各组海马中AngⅡ、NLRP3、Caspase-1表达显著下降(P<0.05),ACE2、Mas则显著升高(P<0.05)。结论:参芪地黄汤可能通过调节ACE2-Ang-(1-7)-Mas轴抑制NLRP3炎性小体的激活,减少炎症级联反应从而改善T2DM模型大鼠认知功能障碍。 展开更多
关键词 2型糖尿病 认知功能障碍 参芪地黄汤 ACE2-ang-(1-7)-Mas
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采用B1-corrected variable-flip-angle(VFA)的定量动态增强MRI在乳腺良恶性病变的研究` 被引量:1
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作者 蒋辉 曲金荣 +3 位作者 宋颖 王立峰 刘翠翠 张宏凯 《中国CT和MRI杂志》 2024年第1期85-87,共3页
目的探讨采用B1-corrected VFA技术的定量动态增强(Dynamic Contrast Enhancement,DCE)MRI在乳腺良恶性鉴别诊断中的价值。方法前瞻性研究本院63例乳腺疾病患者,行3.0 T DCE-MR检查,结合B1-corrected VFA技术获得T1值,在此基础上计算出D... 目的探讨采用B1-corrected VFA技术的定量动态增强(Dynamic Contrast Enhancement,DCE)MRI在乳腺良恶性鉴别诊断中的价值。方法前瞻性研究本院63例乳腺疾病患者,行3.0 T DCE-MR检查,结合B1-corrected VFA技术获得T1值,在此基础上计算出DCE-MRI定量参数:容量转移常数(Ktrans)、速率常数(Kep)和血管外细胞外间隙容积比(Ve),对乳腺恶性、良性及正常腺体组获得的定量参数行Kruskal-Wallis检验;最后绘制ROC(receiver operating characteristic curve,ROC)曲线。结果恶性肿瘤组Ktrans、Kep、Ve中位数(最小值最大值)分别为0.010(0.0010.118)min-1、0.145(0.0020.863)min-1、0.058(0.0020.611);良性病变组Ktrans、Kep、Ve中位数为0.238(0.0090.740)min-1、0.365(0.0201.012)min-1、0.517(01810.923);正常腺体组Ktrans、Kep、Ve中位数为0.812(0.1212.352)min-1、1.147(0.3282.363)min-1、0.712(0.4041.183)。Kruskal-Wallis检验显示三组间Ktrans、Kep、Ve P<0.05,均有统计学意义;良恶性组间、恶性与正常组间的Ktrans、Kep、Ve差异有统计学意义,而良性和正常组之间的Ve值无统计学意义。三者AUC分别为0.875、0.957、0.707,三者判断乳腺良恶性变的Ktrans、Kep、Ve敏感度分别为93.8%、97.9%、45.8%;特异度分别为66.7%、86.73%、86.7%。结论结合B1-corrected VFA序列测量的3.0T DCE-MRI参数Ktrans、Kep、Ve可以反映乳腺良恶性病变的血流灌注特征,可用于乳腺病变良恶性的鉴别诊断。 展开更多
关键词 乳腺 B1-corrected VFA 动态增强磁共振成像
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ACE2-Ang(1-7)-MasR轴对心血管系统保护作用的研究进展
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作者 郑梦迪 王治 《中国心血管病研究》 CAS 2024年第6期517-521,共5页
肾素-血管紧张素系统(RAS)是人体重要的体液调节系统之一,在维持机体血压稳定和水电解质平衡中发挥了重要作用。近年来,发现了RAS系统的新支路,ACE2和Ang(1-7)等是心血管系统的关键保护因子,ACE2-Ang(1-7)-MasR轴成为了心血管疾病领域... 肾素-血管紧张素系统(RAS)是人体重要的体液调节系统之一,在维持机体血压稳定和水电解质平衡中发挥了重要作用。近年来,发现了RAS系统的新支路,ACE2和Ang(1-7)等是心血管系统的关键保护因子,ACE2-Ang(1-7)-MasR轴成为了心血管疾病领域的研究热点。非经典的RAS系统ACE2-Ang(1-7)-MasR轴能够拮抗经典的ACE-AngⅡ-AT1R轴,二者共同维系机体的平衡,该轴在高血压、冠心病、心律失常和心力衰竭等心血管疾病治疗中可能成为新的治疗靶点。 展开更多
关键词 肾素-血管紧张素系统 血管紧张素转换酶2 血管紧张素(1-7) 血管紧张素(1-9) AT2受体 心肾综合征 MAS受体
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Bifurcations, Analytical and Non-Analytical Traveling Wave Solutions of (2 + 1)-Dimensional Nonlinear Dispersive Boussinesq Equation
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作者 Dahe Feng Jibin Li Airen Zhou 《Applied Mathematics》 2024年第8期543-567,共25页
For the (2 + 1)-dimensional nonlinear dispersive Boussinesq equation, by using the bifurcation theory of planar dynamical systems to study its corresponding traveling wave system, the bifurcations and phase portraits ... For the (2 + 1)-dimensional nonlinear dispersive Boussinesq equation, by using the bifurcation theory of planar dynamical systems to study its corresponding traveling wave system, the bifurcations and phase portraits of the regular system are obtained. Under different parametric conditions, various sufficient conditions to guarantee the existence of analytical and non-analytical solutions of the singular system are given by using singular traveling wave theory. For certain special cases, some explicit and exact parametric representations of traveling wave solutions are derived such as analytical periodic waves and non-analytical periodic cusp waves. Further, two-dimensional wave plots of analytical periodic solutions and non-analytical periodic cusp wave solutions are drawn to visualize the dynamics of the equation. 展开更多
关键词 (2 + 1)-Dimensional Nonlinear Dispersive Boussinesq Equation BIFURCATIONS Phase Portrait Analytical Periodic Wave Solution Periodic Cusp Wave Solution
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Evaluation of teplizumab's efficacy and safety in treatment of type 1 diabetes mellitus:A systematic review and meta-analysis
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作者 Xiao-Lan Ma Dan Ge Xue-Jian Hu 《World Journal of Diabetes》 SCIE 2024年第7期1615-1626,共12页
BACKGROUND Islets of Langerhans beta cells diminish in autoimmune type 1 diabetes mellitus(T1DM).Teplizumab,a humanized anti-CD3 monoclonal antibody,may help T1DM.Its long-term implications on clinical T1DM developmen... BACKGROUND Islets of Langerhans beta cells diminish in autoimmune type 1 diabetes mellitus(T1DM).Teplizumab,a humanized anti-CD3 monoclonal antibody,may help T1DM.Its long-term implications on clinical T1DM development,safety,and efficacy are unknown.AIM To assess the effectiveness and safety of teplizumab as a therapeutic intervention for individuals with T1DM.METHODS A systematic search was conducted using four electronic databases(PubMed,Embase,Scopus,and Cochrane Library)to select publications published in peerreviewed journals written in English.The odds ratio(OR)and risk ratio(RR)were calculated,along with their 95%CI.We assessed heterogeneity using Cochrane Q and I2 statistics and the appropriate P value.RESULTS There were 8 randomized controlled trials(RCTs)in the current meta-analysis with a total of 1908 T1DM patients from diverse age cohorts,with 1361 patients receiving Teplizumab and 547 patients receiving a placebo.Teplizumab was found to have a substantial link with a decrease in insulin consumption,with an OR of 4.13(95%CI:1.72 to 9.90).Teplizumab is associated with an improved Cpeptide response(OR 2.49;95%CI:1.62 to 3.81)and a significant change in Glycated haemoglobin A1c(HbA1c)levels in people with type 1 diabetes[OR 1.75(95%CI:1.03 to 2.98)],and it has a RR of 0.71(95%CI:0.53 to 0.95).CONCLUSION In type 1 diabetics,teplizumab decreased insulin consumption,improved C-peptide response,and significantly changed HbA1c levels with negligible side effects.Teplizumab appears to improve glycaemic control and diabetes management with good safety and efficacy. 展开更多
关键词 Type-1 diabetes mellitus Teplizumab Anti-CD3 monoclonal antibody INSULIN Glycated haemoglobin a1c Cpeptide
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The Association between GLP-1 Receptor-Based Agonists and the Incidence of Asthma in Patients with Type 2 Diabetes and/or Obesity:A Meta-Analysis
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作者 Mengqing Zhang Chu Lin +7 位作者 Xiaoling Cai Ruoyang Jiao Shuzhen Bai Zonglin Li Suiyuan Hu Fang Lyu Wenjia Yang Linong Ji 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2024年第6期607-616,共10页
Objective Recent studies have indicated potential anti-inflammatory effects of glucagon-like peptide-1 receptor agonists(GLP-1RAs)on asthma,which is often comorbid with type 2 diabetes mellitus(T2DM)and obesity.Theref... Objective Recent studies have indicated potential anti-inflammatory effects of glucagon-like peptide-1 receptor agonists(GLP-1RAs)on asthma,which is often comorbid with type 2 diabetes mellitus(T2DM)and obesity.Therefore,we conducted a meta-analysis to assess the association between the administration of glucagon-like peptide-1(GLP-1)receptor-based agonists and the incidence of asthma in patients with T2DM and/or obesity.Methods PubMed,Web of Science,Embase,the Cochrane Central Register of Controlled Trials,and Clinicaltrial.gov were systematically searched from inception to July 2023.Randomized controlled trials(RCTs)of GLP-1 receptor-based agonists(GLP-1RA,GLP-1 based dual and triple receptor agonist)with reports of asthma events were included.Outcomes were computed as risk ratios(RR)using a fixedeffects model.Results Overall,39 RCTs with a total of 85,755 participants were included.Compared to non-GLP-1 receptor-based agonist users,a trend of reduced risk of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments,although the difference was not statistically significant[RR=0.91,95%confidence interval(CI):0.68 to 1.24].Further Subgroup analyses indicated that the use of light-molecular-weight GLP-1RAs might be associated with a reduced the risk of asthma when compared with non-users(RR=0.65,95%CI:0.43 to 0.99,P=0.043).We also performed sensitivity analyses for participant characteristics,study design,drug structure,duration of action,and drug subtypes.However,no significant associations were observed.Conclusion Compared with non-users,a modest reduction in the incidence of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments.Further investigations are warranted to assess the association between GLP-1 receptor-based agonists and the risk of asthma. 展开更多
关键词 Glucagon-like peptide-1 receptor agonists Twincretins ASTHMA Type 2 diabetes mellitus OBESITY
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Association between 5-HTR1A gene C-1019G polymorphism and antidepressant response in patients with major depressive disorder:A meta-analysis
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作者 Huai-Neng Wu Shuang-Yue Zhu +2 位作者 Li-Na Zhang Bian-Hong Shen Lian-Lian Xu 《World Journal of Psychiatry》 SCIE 2024年第10期1573-1582,共10页
BACKGROUND Major depressive disorder(MDD)is a substantial global health concern,and its treatment is complicated by the variability in individual response to antide-pressants.AIM To consolidate research and clarify th... BACKGROUND Major depressive disorder(MDD)is a substantial global health concern,and its treatment is complicated by the variability in individual response to antide-pressants.AIM To consolidate research and clarify the impact of genetic variation on MDD treatment outcomes.METHODS Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,a systematic search across PubMed,EMBASE,Web of Science,and the Cochrane Library was conducted without date restrictions,utilizing key terms related to MDD,serotonin 1A receptor polymorphism(5-HTR1A),C-1019G polymorphism,and antidepressant response.Studies meeting inclusion criteria were thoroughly screened,and quality assessed using the Newcastle-Ottawa Scale.Statistical analyses,includingχ2 and I²values,were used to evaluate heterogeneity and fixed-effect or random-effect models were applied accordingly.RESULTS The initial search yielded 1216 articles,with 11 studies meeting criteria for inclusion.Analysis of various genetic models showed no significant association between the 5-HTR1A C-1019G polymorphism and antidepressant efficacy.The heterogeneity was low to moderate,and no publication bias was detected through funnel plot symmetry and Egger's and Begg's tests.CONCLUSION This meta-analysis does not support a significant association between the 5-HTR1A C-1019G polymorphism and the efficacy of antidepressant treatment in MDD.The findings call for further research with larger cohorts to substantiate these results and enhance the understanding of antidepressant pharmacogenetics. 展开更多
关键词 Major depressive disorder Antidepressant efficacy 5-HTR1A gene C-1019G polymorphism META-anALYSIS
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Procyanidin A_1 and its digestive products alleviate acrylamide-induced IPEC-J2 cell damage through regulating Keap1/Nrf2 pathway
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作者 Fangfang Yan Qun Lu +1 位作者 Chengming Wang Rui Liu 《Food Science and Human Wellness》 SCIE CSCD 2024年第3期1475-1484,共10页
Our previous study has revealed that procyanidin A_(1)(A_(1))and its simulated digestive product(D-A,)can alleviate acrylamide(ACR)-induced intestine cell damage.However,the underlying mechanism remains unknown.In thi... Our previous study has revealed that procyanidin A_(1)(A_(1))and its simulated digestive product(D-A,)can alleviate acrylamide(ACR)-induced intestine cell damage.However,the underlying mechanism remains unknown.In this study,we elucidated the molecular mechanism for and D-A_(1) to alleviate ACR-stimulated IPEC-J2 cell damage.ACR slightly activated nuclear factor erythroid 2-related factor 2(Nrf2)signaling and its target genes,but this activation could not reduce intestine cell damage.A_(1) and D-A_(1) could alleviate ACR-induced cell damage,but the effect was abrogated in cells transiently transfected with Nrf2 small interfering RNA(siRNA).Further investigation confirmed that A_(1) and D-A_(1) interacted with Ketch-like ECH-associated protein 1(Keapl),which boosted the stabilization of Nrf2,subsequently promoted the translocation of Nrf2 into the nucleus,and further increased the expression of antioxidant proteins,thereby inhibiting glutathione(GSH)consumption,maintaining redox balance and eventually alleviating ACR-induced cell damage.Importantly,there was no difference between A_(1) and D-A_(1) treated groups,indicating that A_(1) can tolerate gastrointestinal digestion and may be a potential compound to limit the toxicity of ACR. 展开更多
关键词 Procyanidin A_1 Digestive products Acrylamide Nuclear factor erythroid 2-related factor 2(Nrf2) Intestinal cell damage
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Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor-and Cygb-associated signaling pathways
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作者 Biao Xiao Chaoyang Chu +6 位作者 Zhicheng Lin Tianyuan Fang Yuyu Zhou Chuxia Zhang Jianghui Shan Shiyu Chen Liping Li 《Neural Regeneration Research》 SCIE CAS 2025年第9期2706-2726,共21页
A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigati... A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease. 展开更多
关键词 acousto-optic stimulation adult neurogenesis Alzheimer's disease amyloid precursor protein/presenilin 1 mice amyloid-beta deposition brain cell apoptosis cognitive impairment depression-like behavior involuntary treadmill exercise olfactory stimulation serum metabolites
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Prolonged intermittent theta burst stimulation restores the balance between A_(2A)R-and A_(1)R-mediated adenosine signaling in the 6-hydroxidopamine model of Parkinson's disease
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作者 Milica Zeljkovic Jovanovic Jelena Stanojevic +4 位作者 Ivana Stevanovic Milica Ninkovic Tihomir V.Ilic Nadezda Nedeljkovic Milorad Dragic 《Neural Regeneration Research》 SCIE CAS 2025年第7期2053-2067,共15页
An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease prog... An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control. 展开更多
关键词 A_(1)R A_(2A)R adenosine receptors ADENOSINE ecto-5′-nucleotidase intermittent theta burst stimulation non-invasive brain stimulation Parkinson's disease purinergic signalling
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GLP-1受体激动剂对心血管作用的研究进展 被引量:2
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作者 柯志强 马倩倩 +3 位作者 李丹 赵辛元 刘超 苏正定 《中国药理学通报》 CAS CSCD 北大核心 2024年第3期426-430,共5页
胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)由肠道内分泌细胞产生。GLP-1受体激动剂(GLP-1 receptor agonists,GLP-1RAs)促进葡萄糖相关的胰岛素分泌和抑制胰高血糖素分泌。GLP-1RAs还能抑制胃排空、食物摄入和限制体质量增加。... 胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)由肠道内分泌细胞产生。GLP-1受体激动剂(GLP-1 receptor agonists,GLP-1RAs)促进葡萄糖相关的胰岛素分泌和抑制胰高血糖素分泌。GLP-1RAs还能抑制胃排空、食物摄入和限制体质量增加。在过去的十年中,GLP-1RAs对心血管系统影响的研究已经取得重大进展。口服小分子GLP-1RAs具有潜在优势,可以提高该类药物的应用。该文综述了GLP-1RAs在心血管疾病治疗中的多种作用,为GLP-1RAs的心血管获益提供新见解。 展开更多
关键词 2型糖尿病 GLP-1 心血管疾病 GLP-1受体激动剂 口服GLP-1受体激动剂 小分子GLP-1受体激动剂
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山姜素调节VEGF/SphK1/S1P信号通路对膝骨关节炎大鼠血管生成的影响 被引量:2
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作者 罗锟 王智 王柯 《天津医药》 CAS 2024年第5期480-485,共6页
目的探讨山姜素(APT)调节血管内皮生长因子/鞘氨醇激酶1/1磷酸鞘氨醇(VEGF/SphK1/S1P)信号通路对膝骨关节炎(KOA)大鼠血管生成的影响。方法采用改良的Videman法构建KOA大鼠模型,将90只大鼠分为对照组(Control组)、模型组(Model组)、山... 目的探讨山姜素(APT)调节血管内皮生长因子/鞘氨醇激酶1/1磷酸鞘氨醇(VEGF/SphK1/S1P)信号通路对膝骨关节炎(KOA)大鼠血管生成的影响。方法采用改良的Videman法构建KOA大鼠模型,将90只大鼠分为对照组(Control组)、模型组(Model组)、山姜素低剂量组(L-APT组)、山姜素高剂量组(H-APT组)、山姜素高剂量组+慢病毒阴性对照组(APT+NC组)、山姜素高剂量组+过表达SphK1慢病毒组(APT+SphK1组),每组15只。HE染色观察大鼠软骨组织病理变化;酶联免疫吸附试验测定软骨组织白细胞介素(IL)-1β、肿瘤坏死因子α(TNF-α)、IL-6、基质金属蛋白酶-13(MMP-13)水平;TUNEL检测软骨组织细胞凋亡情况;免疫组化检测血管内皮生长因子(VEGF)、CD31蛋白表达情况;Western blot检测血管内皮生长因子受体2(VEGFR2)、磷酸化VEGFR2(p-VEGFR2)、SphK1、S1P蛋白水平。结果与Control组比较,Model组大鼠出现病理损伤,细胞凋亡率、IL-1β、TNF-α、IL-6、MMP-13、VEGF阳性表达、CD31阳性表达和p-VEGFR2、SphK1、S1P蛋白表达水平增加(P<0.05);与Model组比较,L-APT组、H-APT组病理损伤明显减轻,细胞凋亡率、IL-1β、TNF-α、IL-6、MMP-13、VEGF阳性表达、CD31阳性表达和pVEGFR2、SphK1、S1P蛋白表达水平降低(P<0.05);与APT+NC组比较,APT+SphK1组软骨组织病理损伤加重,细胞凋亡率、IL-1β、TNF-α、IL-6、MMP-13、VEGF阳性表达、CD31阳性表达和p-VEGFR2、SphK1、S1P蛋白表达水平增加(P<0.05)。结论APT通过抑制VEGF/SphK1/S1P信号通路抑制KOA大鼠血管生成。 展开更多
关键词 骨关节炎 新生血管化 病理性 血管内皮生长因子类 山姜素 鞘氨醇激酶1 1磷酸鞘氨醇
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1-甲基环丙烯结合水杨酸处理维持百香果甲基环丙烯结合水杨酸处理维持百香果果实贮藏品质 被引量:2
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作者 杨秀群 谢国芳 +1 位作者 袁孟孟 娄杰 《食品研究与开发》 CAS 2024年第10期52-58,共7页
为延长百香果的贮藏期并保持贮藏过程中的品质,对比研究2 mmol/L水杨酸(salicylic acid,SA)、1 mmol/L 1-甲基环丙烯(1-methylcyclopropene,1-MCP)、1-MCP结合SA处理对紫色百香果果实采后贮藏期间品质、活性氧、抗氧化酶指标的影响。百... 为延长百香果的贮藏期并保持贮藏过程中的品质,对比研究2 mmol/L水杨酸(salicylic acid,SA)、1 mmol/L 1-甲基环丙烯(1-methylcyclopropene,1-MCP)、1-MCP结合SA处理对紫色百香果果实采后贮藏期间品质、活性氧、抗氧化酶指标的影响。百香果果实经SA、1-MCP和1-MCP结合SA处理后,一定程度抑制乙烯的释放和脂氧合酶(li-poxygenase,LOX)活性,促进几丁质酶(chitinase,CHI)和β-1,3-葡聚糖酶(β-1,3-glucanase,GLU)的活性,增强抗氧化和抗病性作用,降低腐烂率。但因SA可以增强呼吸,故导致凹陷和失重,加快总酸流失;1-MCP抑制呼吸作用,增强超氧化物歧化酶(superoxide dismutase,SOD)活性,有利于控制失重和凹陷,但其对过氧化物酶(peroxidase,POD)活性的影响不利于控制衰老。1-MCP结合SA对POD活性,CHI活性以及GLU活性的正向影响强于单独使用1-MCP或SA处理。因此,1-MCP结合SA通过提高百香果果实的抗氧化能力和抗病能力,降低百香果果实的凹陷、失重和腐烂率,且可有效避免单独使用1-MCP或SA处理的不良作用,协同维持百香果果实采后贮藏品质。 展开更多
关键词 百香果 1-甲基环丙烯(1-MCP) 水杨酸(SA) 维持 贮藏
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青藤碱可有效抑制白细胞介素1β介导的髓核细胞凋亡 被引量:4
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作者 王倩 卢子昂 +3 位作者 李利和 吕超亮 王盟 张存鑫 《中国组织工程研究》 CAS 北大核心 2024年第2期224-230,共7页
背景:椎间盘退变是导致脊柱退行性疾病的基础,然而目前尚无有效的治疗药物。目的:探讨青藤碱是否可以抑制白细胞介素1β诱导的髓核细胞凋亡及其分子机制。方法:采用胰酶联合Ⅱ型胶原酶消化法体外培养大鼠髓核细胞,并绘制细胞生长曲线,采... 背景:椎间盘退变是导致脊柱退行性疾病的基础,然而目前尚无有效的治疗药物。目的:探讨青藤碱是否可以抑制白细胞介素1β诱导的髓核细胞凋亡及其分子机制。方法:采用胰酶联合Ⅱ型胶原酶消化法体外培养大鼠髓核细胞,并绘制细胞生长曲线,采用CCK-8法筛选合适的青藤碱药物浓度。将髓核细胞分为对照组、青藤碱组、白细胞介素1β组、青藤碱+白细胞介素1β组、锌原卟啉(血红素氧合酶1抑制剂)组、锌原卟啉+青藤碱组、锌原卟啉+白细胞介素1β组、青藤碱+锌原卟啉+白细胞介素1β组。分别检测各组髓核细胞增殖活性、活性氧含量、凋亡率及血红素氧合酶1的表达情况。结果与结论:①体外培养的大鼠髓核细胞呈现多角形、三角形、短楔形等形态,其呈现“S”型曲线生长,接种第1-3天生长缓慢,第4-6天生长迅速,第七八天生长速度缓慢,进入“平台期”,细胞数量不再增加;②当青藤碱的浓度≤80μmol/L时,髓核细胞的增殖活性不会受到显著影响(P>0.05);③白细胞介素1β可以显著降低髓核细胞的增殖活性,增加活性氧含量,导致细胞凋亡(P<0.01);④当采用青藤碱干预后,不仅可以促进血红素氧合酶1的表达(P<0.05),而且可以抑制白细胞介素1β诱导的髓核细胞增殖活性降低、活性氧含量和凋亡率增加(P<0.05),其作用可被锌原卟啉逆转(P<0.01)。 展开更多
关键词 青藤碱 白细胞介素1Β 血红素氧合酶1 髓核细胞 细胞增殖 细胞凋亡 活性氧 椎间盘 椎间盘退变
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糖尿病视网膜病变患者SDF-1、HO-1及MDA水平变化及与IL-6、TNF-α、CRP的相关性 被引量:1
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作者 赵玉杰 王敏 +3 位作者 刘钰凤 刘学晶 钟胜楠 李莹 《分子诊断与治疗杂志》 2024年第3期539-542,552,共5页
目的 分析糖尿病视网膜病变(DR)患者基质细胞衍生因子(SDF-1)、血红素加氧酶-1(HO-1)及丙二醛(MDA)水平变化及与白介素-6(IL-6)、肿瘤坏死因子(TNF-α)、C反应蛋白(CRP)的相关性。方法 选取2020年5月至2023年1月解放军总医院收治的131... 目的 分析糖尿病视网膜病变(DR)患者基质细胞衍生因子(SDF-1)、血红素加氧酶-1(HO-1)及丙二醛(MDA)水平变化及与白介素-6(IL-6)、肿瘤坏死因子(TNF-α)、C反应蛋白(CRP)的相关性。方法 选取2020年5月至2023年1月解放军总医院收治的131例DR患者为DR组,另选取同期在本院住院的2型糖尿病患者100例为非DR组。比较两组SDF-1、HO-1、MDA水平;比较两组IL-6、TNF-α、CRP水平;比较不同分期DR患者SDF-1、HO-1、MDA水平;采用Logistic回归分析影响DR发生的相关因素,分析DR组患者SDF-1、HO-1、MDA水平与IL-6、TNF-α、CRP的相关性。结果 DR组SDF-1、HO-1水平比非DR组低,MDA水平比非DR组高,差异有统计学意义(P<0.05);DR组IL-6、TNF-α、CRP水平均比非DR组高,差异有统计学意义(P<0.05);SDF-1、HO-1水平:Ⅰ~Ⅱ期>Ⅲ~Ⅳ期>Ⅴ~Ⅵ期,MDA水平:Ⅰ~Ⅱ期<Ⅲ~Ⅳ期<Ⅴ~Ⅵ期,差异有统计学意义(P<0.05);经Logistic多因素分析显示,性别为女、BMI≥24 km/m2、合并患有高血压、高血脂、IL-6>1.17 mg/mL、TNF-α>30 ng/L、CRP>10 ng/mL、SDF-1>2 ng/mL、HO-1<125 ng/mL、MDA>4.06μmol/mL均是影响DR发生的独立危险因素(P<0.05);血清炎性因子IL-6、TNF-α、CRP与SDF-1、HO-1呈负相关,与MDA呈正相关,且均为中度相关(P<0.05)。结论 SDF-1、HO-1、MDA、IL-6、CRP、TNF-α水平与DR的发生、发展有一定关系,通过检测上述指标水平可为进一步探讨DR的发病机制和治疗方法提供新的思路。 展开更多
关键词 糖尿病视网膜病变 SDF-1 HO-1 MDA IL-6 CRP TNF-α
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铁抑素-1对糖尿病中晚期小鼠肝肾组织的保护作用 被引量:1
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作者 王欢 朱铭星 +3 位作者 吴止境 陈伟文 郑燕芳 黄鸣清 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 2024年第6期848-856,共9页
糖尿病是一种发病率高且并发症多的代谢性疾病,其中2型糖尿病(type 2 diabetes mellitus,T2DM)占比较大。目前研究表明,T2DM伴随着肝、肾等脏器损伤引起并发症,严重危害人体健康。铁死亡通过芬顿反应产生大量活性氧(reactive oxygen spe... 糖尿病是一种发病率高且并发症多的代谢性疾病,其中2型糖尿病(type 2 diabetes mellitus,T2DM)占比较大。目前研究表明,T2DM伴随着肝、肾等脏器损伤引起并发症,严重危害人体健康。铁死亡通过芬顿反应产生大量活性氧(reactive oxygen species,ROS),ROS累积会激活缺氧诱导因子-1α(hypoxia inducible factor-1,HIF-1α),从而引发血管内皮生长因子(vascular endothelial growth factor,VEGF)水平升高,铁死亡抑制剂——铁抑素-1(ferrostatin-1,Fer-1)具有强抗氧化能力,所以基于缺氧诱导因子-1α/血管内皮生长因子(HIF-1α/VEGF)信号通路,探讨Fer-1对糖尿病中晚期小鼠肝、肾组织的保护作用。实验以21~22周龄db/db小鼠作为糖尿病中晚期模型,铁死亡抑制剂Fer-1为干预药物。db/m小鼠为空白对照组,连续4周测量体重、血糖,实验中还对各组小鼠进食量、饮水量进行记录;测定血清中丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)水平,测定肝肾组织中ROS、谷胱甘肽(glutathione,GSH)活性以及尿蛋白含量,并用苏木素-伊红(hematoxylin-eosin,HE)染色处理肝、肾组织切片,光镜观察病理学形态,再通过Western印迹法分别检测肝、肾组织中HIF-1α、VEGF和谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)蛋白质水平。在db/db组小鼠中发现,Fer-1(1 mg·kg^(-1),ig)可明显减少进食量和饮水量,降低小鼠血清中的ALT、AST水平、肝肾组织中ROS生成量以及尿蛋白水平,显著升高GSH活性,显著改善了肝、肾的病理组织状况,并且明显抑制肝肾组织中HIF-1α和VEGF蛋白质指标、提高GPX4蛋白水平。Fer-1虽不能改变糖尿病小鼠的体重和降低血糖,但能对糖尿病中晚期小鼠的肝、肾组织发挥保护作用,其作用机制可能与HIF-1α/VEGF和GPX4有关。 展开更多
关键词 铁抑素-1 糖尿病肝肾损伤 铁死亡 DB/DB小鼠 HIF-1α/VEGF
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PTED治疗对腰椎间盘突出症IL-6、HMGB-1、IL-17水平的影响 被引量:4
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作者 刘智伟 白晓亮 +3 位作者 孔亚荣 裴勃 蒋美超 连勇 《分子诊断与治疗杂志》 2024年第1期149-152,157,共5页
目的探讨经皮椎间孔镜下椎间盘切除术(PTED)治疗对腰椎间盘突出症白介素-6(IL-6)、白介素-17(IL-17)和高迁移率族蛋白-1(HMGB-1)水平的影响。方法选取2019年4月至2022年8月保定市第一中心医院收治的122例腰椎间盘突出症患者为研究对象,... 目的探讨经皮椎间孔镜下椎间盘切除术(PTED)治疗对腰椎间盘突出症白介素-6(IL-6)、白介素-17(IL-17)和高迁移率族蛋白-1(HMGB-1)水平的影响。方法选取2019年4月至2022年8月保定市第一中心医院收治的122例腰椎间盘突出症患者为研究对象,根据不同治疗方案分为TLIF组[n=58,经椎间孔腰椎融合术(TLIF)治疗]和PTED组(n=64,PTED治疗),比较两组IL-6、HMGB-1、IL-17水平、分析PTED组不同临床特征与病理特征的IL-6、HMGB-1、IL-17水平、采用多元Logistic回归分析影响PTED组IL-6、HMGB-1、IL-17水平的危险因素,比较两组临床疗效及并发症情况。结果PTED组总有效率(98.44%)高于TLIF组(87.93%),差异有统计学意义(P<0.05);PTED组IL-6、IL-17、HMGB-1水平均低于TLIF组,差异有统计学意义(P<0.05);PTED组不同年龄、有无糖尿病、手术时间长短、是否吸烟、是否营养不良和是否免疫功能低下之间IL-6、IL-17、HMGB-1水平比较,差异有统计学意义(P<0.05);不同性别、不同BMI、术中出血量多少、有无使用内固定之间IL-6、IL-17、HMGB-1水平比较,差异无统计学意义(P>0.05);多元Logistic回归分析显示,年龄>60岁、手术时间>3h、营养不良、糖尿病、免疫功能低下、吸烟为影响PTED组IL-6、IL-17、HMGB-1水平的危险因素(P<0.05);PTED组并发症总发生率低于TLIF组,差异有统计学意义(P<0.05)。结论PTED治疗能明显降低腰椎间盘突出症患者IL-6、HMGB-1和IL-17水平,且手术疗效确切;而年龄、手术时间、营养不良、糖尿病、免疫功能低下、吸烟等是影响PTED治疗对腰椎间盘突出症IL-6、HMGB-1、IL-17水平的危险因素。 展开更多
关键词 PTED 腰椎间盘突出症 IL-6 HMGB-1 IL-17
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口服葡萄糖耐量试验1h血糖对糖尿病前期的诊断和鉴别价值 被引量:2
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作者 韩福禄 姚兴伟 +6 位作者 栗晓彬 李洪敏 张梅 武玉鑫 宋天佳 杨琦 刘尚建 《郑州大学学报(医学版)》 CAS 北大核心 2024年第2期201-205,共5页
目的:探讨口服葡萄糖耐量试验(OGTT)1 h血糖对糖尿病前期的诊断和鉴别价值。方法:收集2019年6月至2022年6月于北京中医药大学东直门医院门诊及住院行OGTT的受试者1 206例,其中血糖正常412例,糖尿病前期358例,糖尿病436例。比较3组OGTT... 目的:探讨口服葡萄糖耐量试验(OGTT)1 h血糖对糖尿病前期的诊断和鉴别价值。方法:收集2019年6月至2022年6月于北京中医药大学东直门医院门诊及住院行OGTT的受试者1 206例,其中血糖正常412例,糖尿病前期358例,糖尿病436例。比较3组OGTT不同时点血糖与空腹血糖(FPG)、空腹胰岛素(FINS)、稳态模型胰岛素抵抗指数(HOMA-IR)、胰岛β细胞分泌功能指数(HOMA-β)水平;采用ROC曲线分析OGTT 1 h血糖对糖尿病前期的诊断和鉴别价值。结果:3组OGTT各时点血糖均为糖尿病组>糖尿病前期组>血糖正常组(P<0.05)。FPG、HOMA-IR糖尿病组>糖尿病前期组>血糖正常组,FINS、HOMA-β糖尿病组<糖尿病前期组<血糖正常组(P<0.05)。ROC曲线分析结果显示,OGTT 1 h血糖诊断糖尿病前期的AUC(95%CI)为0.758(0.724~0.792),以敏感度最大选取最佳切点值,该值为9.35 mmol/L,此时敏感度为0.701,特异度为0.709;OGTT 1 h血糖对糖尿病和糖尿病前期鉴别的AUC(95%CI)为0.956(0.942~0.969),以敏感度最大选取最佳切点值,该值为12.55 mmol/L,此时敏感度为0.901,特异度为0.908。结论:OGTT 1 h血糖对糖尿病前期具有一定的诊断和鉴别价值。 展开更多
关键词 糖尿病 糖尿病前期 口服葡萄糖耐量试验1 h血糖
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肺腺癌患者胸水肿瘤细胞PD-L1/TTF-1表达及应用分析 被引量:1
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作者 刘菲菲 姚健楠 +4 位作者 谷雨妹 赵宏颖 曹勍 金木兰 李雪 《标记免疫分析与临床》 CAS 2024年第3期405-409,420,共6页
目的探讨肺腺癌患者胸水肿瘤细胞程序性细胞死亡配体1(PD-L1)/甲状腺转录因子1(TTF-1)、PD-L1免疫组化染色的表达及与组织标本PD-L1表达一致性及其应用研究。方法选取2021年1月至2023年4月间首都医科大学附属北京朝阳医院收治的符合入... 目的探讨肺腺癌患者胸水肿瘤细胞程序性细胞死亡配体1(PD-L1)/甲状腺转录因子1(TTF-1)、PD-L1免疫组化染色的表达及与组织标本PD-L1表达一致性及其应用研究。方法选取2021年1月至2023年4月间首都医科大学附属北京朝阳医院收治的符合入组条件的50例肺腺癌患者为研究对象,比较同一病例组织标本中肿瘤细胞的PD-L1表达和胸水细胞蜡块中肿瘤细胞的PD-L1、PD-L1/TTF-1表达情况,评估它们之间表达的一致性。结果50例肺腺癌组织标本PD-L1的表达与患者性别、年龄、标本类型、病灶性质、标本来源和EGFR突变对比差异无统计学意义(P>0.05);胸水细胞蜡块中肿瘤细胞PD-L1/TTF-1免疫组化双染的表达与组织标本PD-L1表达的一致性较好(κ=0.846,P<0.05),明显高于PD-L1免疫组化单染(κ=0.754,P<0.05),与手术或活检切除标本一致性较好(κ=0.90,P<0.05),高于胸腔镜或穿刺小标本(κ=0.82,P<0.05),与原发病灶标本的一致性适中(κ=0.689,P<0.05),与转移病灶标本的一致性较好(κ=0.779,P<0.05)。结论胸水细胞学标本采用PD-L1/TTF-1免疫组化双染与组织标本PD-L1表达一致性较高,细胞蜡块PD-L1/TTF-1双染可在组织不易获取时作为一种有益补充,供临床制定免疫治疗方案参考。 展开更多
关键词 肺肿瘤 腺癌 胸水细胞学 PD-L1 TTF-1
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