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1.
目的 观察百草枯(paraquat,PQ)和代森锰(maneb,MB)联合染毒对大鼠运动行为和黑质纹状体系统神经元形态及电活动的影响,以探讨这两种农药与帕金森病(Parkinson's disease,PD)发病的关系.方法 37只大鼠随机分为对照组(11只)、PQ组(PQ 10mg/kg,13只)、PQ(10mg/kg)和MB(30 mg/kg)联合染毒组(PQ+MB组13只),每周2次腹腔注射,染毒6周,观察动物在斜板试验、网格试验和开阔试验中运动行为的变化情况;HE染色观察黑质神经元形态;利用细胞外电生理学方法记录纹状体神经元自发电活动.结果 与对照组或同组染毒前比较,PQ组及PQ+MB组大鼠从斜板上下滑次数增加,在网格上移动潜伏期延长,在开阔试验中自发运动减少,差异均有统计学意义(P<0.05或P<0.01).染毒后PQ组及PQ+MB组大鼠黑质致密部神经元出现受损形态改变,PQ组及PQ+MB组细胞密度分别为(82.17±12.91)和(41.15±6.44)个/mm2,与对照组[(143.10±20.85)个/mm2]比较,差异有统计学意义(P<0.01).PQ组纹状体神经元的平均放电频率为(5.97±7.30)Hz,PQ+MB组为(6.95±9.87)Hz,较对照组[(1.78±5.05)Hz]明显提高,差异均有统计学意义(P<0.01);PQ+MB组神经元混合簇状放电比例(22.3%)较对照组(9.8%)和PQ组(5.6%)明显增加,差异有统计学意义(P<0.05,P<0.01).结论 MB能加重PQ对大鼠黑质纹状体系统的损伤效应,表明这两种农药的协同毒性作用与PD发病相关联.
Abstract:
Objective To investigate the effects of exposure of paraquat and maneb on the behavior,the morphology and electrical activity of the Substantianigra and striatum, and to discuss the relationship between this two pesticides and Parkinson's disease. Methods 37 rats were divided randomly into 3 groups:control group(n=11 ), paraquat ( 10 mg/kg) group (n=13) and combinative group of paraquat ( 10 mg/kg) and maneb(30 mg/kg)(n= 13 ), and were exposed twice a week for 6 weeks by intraperitoneal injection. The behavior of animals in the declined-plane, the vertical-grid and the open-field test were observed. The morphology of substantia nigral neurons were investigated by HE pathology. The spontaneous discharge of striatum neurons were recorded after exposure. Results Compared to the control group and the pre-exposure group, both the numbers of animals sliding down from the declined-plane and the latency of rats' moving on the vertical-grid significantly increased, and the animals' autonomic movement decreased significantly (P<0.05,P<0.001). After the combinative exposure, the neurons of the Substantial nigra pars compacta (SN Pc ) were progressively impaired, the cell density of the paraquat group [(82.17±12.91 ) n/mm2] and the combined group [(41.15±6.44 )n/mm2] were lower than that in control group( 143.10±20.85 n/mm2) (P<0.01). In the paraquat group(5.97±7.30 Hz) and the combined group [(6.95±9.87 ) Hz], the average discharge rates of the striatum neurons were increased significantly compared to the control group [( 1.78±5.05 ) Hz] (P<0.01).The bursting discharge was increased significantly in the combined group(22.3% ) compared to the control group(9.8% ) and the paraquat group (5.6%) (P<0.05,P<0.01). Conclusion The co-exposure of paraquat and maneb could induce similar symptoms to Parkinsonism syndrome of rats such as rigidity, moving reduction and etc, and the combined exposure had a certain enhanced effect compared to alone paraquat exposure. The combinative exposure of paraquat and maneb could cause neural loss in SNPc and it is involved with the enhanced electrophysiological activity in striatum. The synergy toxicity of paraquat and maneb in nigrostriatal system is related to Parkinson's disease.  相似文献   

2.
Cardiovascular (CV) system dysfunction can result in the development of cardiovascular diseases (CVDs), a key cause of death around the world. For many people, the most common treatment choices are still based on various plants used in traditional and folk medicine. Interestingly, many of these plants demonstrate various biological activities and pro-health properties; as such, there has been growing scientific interest in their use as medicines, including treatments for CVDs. Due to their varied biological properties, including anti-inflammatory and anticancer potential, the members of the Asteraceae and Cucurbitaceae have long been used in traditional medicine. These properties are believed to derive from the chemical composition of the plants, which includes various flavonoids, phenolic acids, and terpenes. Although many of their pro-health properties have been well described, their effect on the cardiovascular system and CVDs remains unclear. The present work reviews the current literature about the effects of preparations of vegetables of the Asteraceae and Cucurbitaceae families on the cardiovascular system and CVDs. Various species from the two families demonstrate antioxidant and antiplatelet activities in vitro and in vivo, which play key roles in the prophylaxis and treatment of CVDs. Additionally, some species have been evaluated for their anticoagulant activity. This review also describes the biological properties of these vegetables and discusses their anti-hyperlipidemic action, and their potential for obesity prevention and body weight control.  相似文献   

3.
Polycystic ovary syndrome (PCOS) affects several reproductive and endocrine features in females and has a poorly understood etiology. Treatment strategies for PCOS are limited and are based primarily on diet and nutrient supplementation. Recent studies have recommended some nutrients such as vitamins, minerals and vitamin-like nutrients for the therapy for PCOS. Therefore, it is claimed that the cause of PCOS could be vitamin or mineral deficiency. This review provides a narrative on the effect of nutritional supplementation on oxidative stress induced in PCOS. Oxidative stress plays a formative role in PCOS pathophysiology. This article reviews oxidative stress, its markers, nutritional supplementation and clinical studies. We also aim to show the effect of nutritional supplementation on genes affecting hormonal and glucose-mediated pathways.  相似文献   

4.
Elevated levels of oxidative stress could cause and aggravate Alzheimer’s disease (AD). Selenium (Se) is a trace element with antioxidant and anti-inflammatory activity with neuroprotective effects. To evaluate the effects of Se supplementation in patients with AD or mild cognitive impairment (MCI) through a systematic review and meta-analysis, data were searched and collected from four electronic databases, including clinical trial studies published until December 2020, following the PRISMA guidelines. Statistical analysis was performed by RevMan, and the risk of bias was assessed using the Rob 2 tool. A total of 1350 scientific papers were collected, and following evaluation 11 papers were included in the systematic review and 6 of these were used in the meta-analysis. Studies that evaluated only Se supplementation observed an improvement in Se levels, glutathione peroxidase (GPX) activity, and in some cognitive tests in MCI patients; similarly, improvement in Se levels and mini-mental score was also observed in AD patients. Regarding supplementation of Se plus other nutrients, improvement in cognitive tests was observed in both AD and MCI patients. Therefore, Se supplementation is a good alternative for patients with AD and MCI for improving Se levels and GPX activity. More detailed studies are required to further evaluate the effects of Se on the cognitive deficit and oxidative stress associated with AD and MCI.  相似文献   

5.
目的观察S100A4蛋白在力竭运动损伤心肌组织中的表达变化,探讨S100A4蛋白对力竭运动损伤心肌组织的作用。方法 W istar大鼠12只,随机分为对照组和力竭运动组,大鼠进行力竭训练10d后,取血及心肌组织,用光镜和电镜对心肌进行组织学观察;采用蛋白免疫印迹(western-b lot)法和免疫组织化学法检测心肌蛋白表达。结果力竭运动组大鼠心肌组织苏木精-伊红(HE)染色可见大鼠心肌和血管内皮细胞空泡变性和心肌间质水肿等;电镜可见血管内皮细胞发生典型细胞凋亡特征;W estern-b lot结果表明,对照组心肌中S100A4蛋白弱表达,而力竭运动组S100A4蛋白表达量升高;免疫组化结果显示,与对照组比较,力竭运动组心肌中S100A4蛋白表达升高1.68倍,且在心肌和血管内皮细胞中均有表达。结论力竭运动造成大鼠心肌损伤,S100A4蛋白在损伤心肌中表达升高。  相似文献   

6.
Abstract

We investigated the ability of eicosapentaenoic acid (EPA) to prevent high-fat diet (HFD)-induced obesity and non-alcoholic fatty liver disease (NAFLD). Male C57BL/6J mice were fed standard chow (5.3% fat content), an HFD (32.0% fat content) or an HFD?+?EPA (1?g/kg/day EPA for the last 6 weeks) for 12 weeks. Serum total cholesterol, hepatic triglyceride and total cholesterol levels were significantly increased in the HFD group, in comparison with those of normal mice (p?<?0.01). In contrast, hepatic triglyceride and total cholesterol levels were significantly decreased in the HFD?+?EPA group, in comparison with those of the HFD group (p?<?0.05). In addition, EPA decreased the body weight of obese mice and improved hepatic function. Hepatic superoxide dismutase activity and glutathione levels were significantly decreased in obese mice, but increased with EPA administration. Our data suggest that EPA supplementation has a beneficial effect on NAFLD progression.  相似文献   

7.
Reductions in measures of dendritic morphology in the agranular insular cortex have been identified as consequences of prenatal exposure to moderate levels of ethanol in the rat. Motivated by the strong connectivity between this region of frontal cortex and the striatum and a growing body of data linking specific components of the mesocortical/limbic system to effects of ethanol and ethanol self-administration, the current study investigated the effects of moderate fetal ethanol exposure on the dendritic morphology of medium spiny neurons (MSNs) in several regions of the striatum. Throughout gestation, pregnant rat dams either consumed a saccharin solution (control) or achieved average daily blood ethanol concentrations of 84 mg% via voluntary consumption of a 5% ethanol solution. The brains of adult male offspring were extracted and processed for Golgi-Cox staining. MSNs from the dorsomedial striatum, dorsolateral striatum and the nucleus accumbens core and shell were sampled for analysis. Relative to saccharin controls, robust reductions in dendritic length and branching, but not spine density, were observed in the shell of the nucleus accumbens in fetal-ethanol-exposed rats. No significant prenatal ethanol effects were found in the other regions of the striatum. These findings suggest that exposure to moderate levels of ethanol in utero can have profound effects on brain regions related to reward processing and provide possible clues relevant to understanding increased self-administration of drugs of abuse in animals exposed to ethanol during brain development.  相似文献   

8.
Iron is an indispensable nutrient for life. A lack of it leads to iron deficiency anaemia (IDA), which currently affects about 1.2 billion people worldwide. The primary means of IDA treatment is oral or parenteral iron supplementation. This can be burdened with numerous side effects such as oxidative stress, systemic and local-intestinal inflammation, dysbiosis, carcinogenic processes and gastrointestinal adverse events. Therefore, this review aimed to provide insight into the physiological mechanisms of iron management and investigate the state of knowledge of the relationship between iron supplementation, inflammatory status and changes in gut microbiota milieu in diseases typically complicated with IDA and considered as having an inflammatory background such as in inflammatory bowel disease, colorectal cancer or obesity. Understanding the precise mechanisms critical to iron metabolism and the awareness of serious adverse effects associated with iron supplementation may lead to the provision of better IDA treatment. Well-planned research, specific to each patient category and disease, is needed to find measures and methods to optimise iron treatment and reduce adverse effects.  相似文献   

9.
目的探讨茵栀黄联合二甲双胍治疗非酒精性脂肪肝病(NAFLD)的临床疗效及对患者血糖、血脂和氧化应激水平的影响。方法对我院2015年1月至2017年6月收治的96例NAFLD患者的临床资料进行回顾性分析,根据治疗方式不同将其分为研究组、对照组(各48例),对照组在常规治疗的基础上采用单纯二甲双胍治疗,研究组在常规治疗的基础上采用茵栀黄注射液联合二甲双胍治疗。比较两组治疗疗效及治疗前后丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、血清甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、空腹血糖(FPG)、餐后2 h血糖(2hPG)、超氧化物歧化酶(SOD)、丙二醛(MDA)及Irisin指标水平。结果研究组治疗总有效率(89.58%)明显高于对照组(70.83%),P<0.05;两组患者治疗前ALT、AST、FPG、2hPG、Irisin、TG、TC、HDL-C、LDL-C、SOD、MDA水平比较均无差异(P>0.05);治疗后两组患者ALT、AST、FPG、2hPG、Irisin、TG、TC、LDL-C、MDA水平均较治疗前下降,且研究组较对照组下降更明显(P<0.05);HDL-C、SOD均较治疗前上升,且研究组较对照组上升更明显(P<0.05)。结论茵栀黄联合二甲双胍治疗NAFLD临床疗效显著,还可有效地改善患者肝功能及血糖、血脂代谢,并具有一定的抗氧化应激作用。  相似文献   

10.
Dementia, and especially Alzheimer’s disease (AD), puts significant burden on global healthcare expenditure through its increasing prevalence. Research has convincingly demonstrated the implication of oxidative stress in the pathogenesis of dementia as well as of the conditions which increase the risk of developing dementia. However, drugs which target single pathways have so far failed in providing significant neuroprotection. Natural antioxidants, due to their effects in multiple pathways through which oxidative stress leads to neurodegeneration and triggers neuroinflammation, could prove valuable weapons in our fight against dementia. Although efficient in vitro and in animal models of AD, natural antioxidants in human trials have many drawbacks related to the limited bioavailability, unknown optimal dose, or proper timing of the treatment. Nonetheless, trials evaluating several of these natural compounds are ongoing, as are attempts to modify these compounds to achieve improved bioavailability.  相似文献   

11.
目的 探讨深海鱼油对大气细颗粒物(PM2.5)引起的心血管系统中的炎性损伤和氧化应激损伤影响。方法 将SD雄性大鼠随机分为鱼油低、中、高剂量组, 鱼油对照组, 溶剂对照组(玉米油)和PM2.5染毒组;鱼油组大鼠先进行深海鱼油灌胃28 d, 再进行PM2.5气管滴注染毒隔天1次, 共3次, PM2.5染毒期间同时进行鱼油灌胃, PM2.5染毒组先正常饲养28 d, 再进行PM2.5染毒;取血清检测白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α) 、超敏C反应蛋白(hs-CRP)、丙二醛(MDA)、总超氧化物歧化酶(T-SOD)、谷胱甘肽(GSH)和谷胱甘肽过氧化物酶(GSH-Px)。结果 与溶剂对照组比较, PM2.5染毒组大鼠血清中IL-6 、TNF-α、hs-CRP、MDA含量[分别为(24.94±2.06)、(821.45±14.26)ng/mL、(3.10±0.28)mg/L、(15.88±1.41)nmol/mL]升高, GSH、GSH-Px、T-SOD活性[(4.62±0.37)μmol/L、(289.28±30.65)活力单位、(239.26±4.97)U/mL]降低(均P<0.05);与PM2.5染毒组比较, 鱼油高剂量组大鼠血清中IL-6 、TNF-α、hs-CRP、MDA含量[分别为(16.67±0.23)、(73.01±3.80)ng/mL、(1.36±0.22)mg/L、(11.82±0.79)nmol/mL]下降, GSH、GSH-Px、T-SOD活性[(24.05±3.83)μmol/L、(531.33±40.39)活力单位、(273.36±3.92)U/mL]升高, 呈剂量效应关系(均P<0.05)。结论 深海鱼油对大气PM2.5所致心血管系统炎性反应和氧化应激损伤具有明显拮抗作用。  相似文献   

12.
Cardiovascular disease (CVD) prevalence, pathogenesis, and manifestation is differentially influenced by biological sex. Berry polyphenols target several signaling pathways pertinent to CVD development, including inflammation, oxidative stress, and cardiac and vascular remodeling, and there are innate differences in these pathways that also vary by sex. There is limited research systematically investigating sex differences in berry polyphenol effects on these pathways, but there are fundamental findings at this time that suggest a sex-specific effect. This review will detail mechanisms within these pathological pathways, how they differ by sex, and how they may be individually targeted by berry polyphenols in a sex-specific manner. Because of the substantial polyphenolic profile of berries, berry consumption represents a promising interventional tool in the treatment and prevention of CVD in both sexes, but the mechanisms in which they function within each sex may vary.  相似文献   

13.
Carotenoids constitute a ubiquitous group of isoprenoid pigments. They are very efficient physical quenchers of singlet oxygen and scavengers of other reactive oxygen species. Carotenoids can also act as chemical quenchers undergoing irreversible oxygenation. The molecular mechanisms underlying these reactions are still not fully understood, especially in the context of the anti- and pro-oxidant activity of carotenoids, which, although not synthesized by humans and animals, are also present in their blood and tissues, contributing to a number of biochemical processes. The antioxidant potential of carotenoids is of particular significance to human health, due to the fact that losing antioxidant-reactive oxygen species balance results in “oxidative stress”, a critical factor of the pathogenic processes of various chronic disorders. Data coming from epidemiological studies and clinical trials strongly support the observation that adequate carotenoid supplementation may significantly reduce the risk of several disorders mediated by reactive oxygen species. Here, we would like to highlight the beneficial (protective) effects of dietary carotenoid intake in exemplary widespread modern civilization diseases, i.e., cancer, cardiovascular or photosensitivity disorders, in the context of carotenoids’ unique antioxidative properties.  相似文献   

14.
The increased incidence of obesity, diabetes mellitus, aging, and associated comorbidities indicates the interplay between genetic and environmental influences. Several dietary components have been identified to play a role in the pathogenesis of the so-called “modern diseases”, and their complications including advanced glycation end products (AGEs), which are generated during the food preparation and processing. Diet-derived advanced glycation end products (dAGEs) can be absorbed in the gastrointestinal system and contribute to the total body AGEs’ homeostasis, partially excreted in the urine, while a significant amount accumulates to various tissues. Various in vitro, in vivo, and clinical studies support that dAGEs play an important role in health and disease, in a similar way to those endogenously formed. Animal studies using wild type, as well as experimental, animal models have shown that dAGEs contribute significantly to the pathogenesis of various diseases and their complications, and are involved in the changes related to the aging process. In addition, they support that dAGEs’ restriction reduces insulin resistance, oxidative stress, and inflammation; restores immune alterations; and prevents or delays the progression of aging, obesity, diabetes mellitus, and their complications. These data can be extrapolated in humans and strongly support that dAGEs’ restriction should be considered as an alternative therapeutic intervention.  相似文献   

15.
Non-alcoholic fatty liver disease (NAFLD) is currently estimated as the most prevalent chronic liver disease in all age groups. An increasing body of evidence obtained in experimental and clinical data indicates that oxidative stress is the most important pathogenic factor in the development of NAFLD. The study aimed to investigate the impact of α-lipoic acid (LA), widely used as an antioxidant, on the effects of a hypercaloric choline-deficient diet. Male Wistar rats were divided into three groups: control diet (C); hypercaloric choline-deficient diet (HCCD), and hypercaloric choline-deficient diet with α-lipoic acid (HCCD+LA). Supplementation of HCCD with LA for eight weeks led to a decrease in visceral adipose tissue/body weight ratio, the activity of liver glutathione peroxidase and paraoxonase-1, plasma, and liver total antioxidant activity, as well as an increase in liver/body weight ratio, liver total lipid and triglyceride content, and liver transaminase activities compared to the HCCD group without LA. In conclusion, our study shows that α-lipoic acid detains obesity development but exacerbates the severity of diet-induced oxidative stress and lipid accumulation in the liver of male Wistar rats fed a hypercaloric choline-deficient diet.  相似文献   

16.
This study examined the effect of Carthamus tinctorius (CT) extract plus captopril treatment on blood pressure, vascular function, nitric oxide (NO) bioavailability, oxidative stress and renin-angiotensin system (RAS) in Nω-Nitro-l-arginine methyl ester (l-NAME)-induced hypertension. Rats were treated with l-NAME (40 mg/kg/day) for five weeks and given CT extract (75 or 150 or 300 or 500 mg/kg/day): captopril (5 mg/kg/day) or CT extract (300 mg/kg/day) plus captopril (5 mg/kg/day) for two consecutive weeks. CT extract reduced blood pressure dose-dependently, and the most effective dose was 300 mg/kg/day. l-NAME-induced hypertensive rats showed abnormalities including high blood pressure, high vascular resistance, impairment of acetylcholine-induced vasorelaxation in isolated aortic rings and mesenteric vascular beds, increased vascular superoxide production and plasma malondialdehyde levels, downregulation of eNOS, low level of plasma nitric oxide metabolites, upregulation of angiotensin II type 1 receptor and increased plasma angiotensin II. These abnormalities were alleviated by treatment with either CT extract or captopril. Combination treatment of CT extract and captopril normalized all the abnormalities found in hypertensive rats except endothelial dysfunction. These data indicate that there are synergistic antihypertensive effects of CT extract and captopril. These effects are likely mediated by their anti-oxidative properties and their inhibition of RAS.  相似文献   

17.
《Vaccine》2022,40(33):4700-4708
The addition of pneumococcal conjugate vaccines (PCVs) to the United States (US) national immunization program led to significant reductions in incidence, mortality, and associated sequelae caused by pneumococcal disease (PD) in children and adults through direct and indirect protection. However, there remains clinical and economic burden due to PD caused by serotypes not included in the current 13-valent PCV (PCV13) formulation. To address this unmet need, 15-valent PCV (PCV15) and 20-valent PCV (PCV20), containing additional serotypes to PCV13, were recently approved in the US for adults and are anticipated for pediatrics in the near future. The study objective was to estimate the annual number of cases, deaths, and economic burden of PD due to serotypes included in PCV13, PCV15, and PCV20 for both US pediatric and adult populations. An Excel-based model was developed to calculate clinical and economic outcomes using published age-group specific serotype coverage; incidence of invasive PD, community-acquired pneumonia, and acute otitis media; case fatality rates; and disease-related costs. The results showed that across all age groups, the estimated annual PD cases and associated deaths covered by PCV13 serotypes were 914,199 and 4320, respectively. Compared with PCV13 serotypes, the additional 2 and 7 serotypes covered by PCV15 and PCV20 were attributed with 550,475 and 991,220 annual PD cases, as well as 1425 and 3226 annual deaths, respectively. This clinical burden translates into considerable economic costs ranging from $903 to $1,928 million USD that could be potentially addressed by PCV15 and PCV20. The additional serotypes included in PCV20 contribute substantially to the clinical and economic PD burden in the US pediatric and adult populations. Despite the success of the PCV13 pediatric national immunization program and increased adult uptake of PCV13 and 23-valent polysaccharide vaccine, broader PCV serotype coverage is needed across all ages to further reduce pneumococcal disease burden.  相似文献   

18.
《Vaccine》2022,40(18):2635-2646
Objective(s)In the context of age- and risk-based pneumococcal vaccine recommendations in Canada, this study presents updated data from active surveillance of pneumococcal community acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD) in hospitalized adults from 2010 to 2017.MethodsS. pneumoniae was detected using culture (blood and sputum), and urine antigen detection (UAD). Serotyping was performed with Quellung, PCR, or using the PCV13- and PPV23 (non-PCV13)-specific UADs. Laboratory results, demographic, and outcome data were categorized by age (16–49, 50–64, and 65 + ) and by disease [non-bacteremic pCAP, bacteremic pCAP, and IPD(non-CAP)].Results11,129 CAP cases and 216 cases of IPD (non-CAP) were identified. Laboratory testing for S. pneumoniae was performed in 8912 CAP cases, identifying 1264 (14.2%) as pCAP. Of pCAP cases, 811 (64.1%) were non-bacteremic and 455 (35.9%) were bacteremic. Adults 65 + years represented 54.5% of non-bacteremic pCAP, 41.4% of bacteremic pCAP, and 48.6% of IPD cases. Adults 50–64 years contributed 30.3%, 33.1%, and 29.9%, respectively. In pCAP, PCV13 serotypes declined between 2010 and 2014 due to declines in serotypes 7F and 19A, then plateaued from 2015 to 2017 with persistence of serotype 3. In later study years, non-bacteremic pCAP was predominant, and PPV23 (non-PCV13) serotypes increased from 2015 to 2017, with serotypes 22F, 11A, and 9 N being most frequently identified. Compared to non-pCAP, pCAP cases were more likely to be admitted to intensive care units and require mechanical ventilation. These outcomes and mortality were more common in bacteremic pCAP and IPD, versus non-bacteremic pCAP.Conclusion(s)Along with IPD, pCAP surveillance (bacteremic and non-bacteremic) is important as their trends may differ over time. With insufficient herd protection from PCV13 childhood immunization, or use of PPV23 in adults, this study supports direct adult immunization with PCV13 or higher valency conjugate vaccines to reduce the residual burden of pCAP and IPD.  相似文献   

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