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1.
Tangeretin and nobiletin are polymethoxyflavonoids that are contained in citrus fruits. Polymethoxyflavonoids are reported to have several biological functions including anti‐inflammatory, anti‐atherogenic, or anti‐diabetic effects. However, whether polymethoxyflavonoids directly affect glucose uptake in tissues is not well understood. In the current study, we investigated whether tangeretin and nobiletin affect glucose uptake in insulin target cells such as adipocytes. We observed that treatment with tangeretin or nobiletin significantly increased the uptake of [3H]‐deoxyglucose in differentiated 3T3‐F442A adipocytes in a concentration‐dependent manner. Data showed that phosphatidyl inositol 3 kinase, Akt1/2, and the protein kinase A pathways were involved in the increase in glucose uptake induced by polymethoxyflavonoids. These data suggest that the anti‐diabetic action of polymethoxyflavonoids is partly exerted via these signaling pathways in insulin target tissues. Copyright © 2012 John Wiley & Sons, Ltd.  相似文献   

2.
Coriander (Coriandrum sativum L.) is grown as a spice crop all over the world. The seeds have been used to treat indigestion, diabetes, rheumatism and pain in the joints. In the present study, an ethanol extract of the seeds was investigated for effects on insulin release from the pancreatic beta cells in streptozotocin‐induced diabetic rats. Blood samples were drawn from the retro‐orbital sinus before and 1.5, 3 and 5 h after administration of the seed extract. Serum glucose levels were determined by the glucose oxidase method. To determine the insulin releasing activity, after extract treatment the animals were anaesthetized by diethyl ether, the pancreas was excised, fixed in 10% formaldehyde and embedded in paraffin for sectioning. Pancreatic sections of 5 µm were processed for examination of insulin‐releasing activity using an immunocytochemistry kit. The results showed that administration of the ethanol extract (200 and 250 mg/kg, i.p.) exhibited a significant reduction in serum glucose. Administration of streptozotocin decreased the number of beta cells with insulin secretory activity in comparison with intact rats, but treatment with the coriander seed extract (200 mg/kg) increased significantly the activity of the beta cells in comparison with the diabetic control rats. The extract decreased serum glucose in streptozotocin‐induced diabetic rats and increased insulin release from the beta cells of the pancreas. Copyright © 2008 John Wiley & Sons, Ltd.  相似文献   

3.
目的探讨没食子儿茶素对脂肪细胞在高浓度葡萄糖条件下吸收葡萄糖的作用。方法应用3T3-L1前脂肪细胞分化模型,测定在脂肪细胞中没食子儿茶素对葡萄糖吸收的作用和对3T3-L1前脂肪细胞分化的影响。结果没食子儿茶素可促进脂肪细胞中高浓度葡萄糖(30 mmol/L)条件下由胰岛素刺激的葡萄糖吸收,加快3T3-L1前脂肪细胞的分化。结论没食子儿茶素可增加脂肪细胞葡萄糖吸收并促进3T3-L1前脂肪细胞分化,提示没食子儿茶素可有效改变血糖浓度和改善胰岛素抵抗。  相似文献   

4.
Ginsenosides, the active component of Panax ginseng, have been shown to evidence a variety of biological activities associated with hyperglycemia, obesity and type 2 diabetes mellitus. This study evaluated the effects of the ginsenosides, Rg3 and Re, on glucose uptake and the glucose transport system in mature 3T3‐L1 cells. The results demonstrated that the glucose uptake of ginsenosides Rg3 and Re at concentrations of 1–10 µM significantly increased by approximately ~10% and ~12%, respectively. Furthermore, the glucose transporter 4 (GLUT4) mRNA expression of ginsenosides Rg3 and Re at 10 µM was increased by approximately ~1.73 and 1.43 fold, respectively. It was further confirmed in a series of experiments that ginsenosides Rg3 and Re stimulated the mRNA expression of insulin receptor substrate (IRS‐1) and the expression of phosphatidylinositol 3‐kinase (PI3K)‐110α protein, which is involved in downstream events in the insulin signaling pathway. These findings demonstrate that ginsenosides Rg3 and Re may stimulate glucose uptake via the PI3K pathways involving IRS‐1. Further, our results suggest that both of these ginsenosides might prove useful as effective antidiabetic and antihyperglycemic agents. Copyright © 2010 John Wiley & Sons, Ltd.  相似文献   

5.
6.
The objectives of this paper is to investigate, demonstrate, and compare the mechanism of action of phytocannabinoids as antidiabetic and anti‐obesity agents in preadipocytes and adipocytes, relative to rosiglitazone and metformin. Briefly, cannabis extract, Δ9‐tetrahydrocannabinol and cannabidiol (in very low dosages) were shown to promote glucose uptake higher or to equivalent levels, reduce fat accumulation, and reverse the insulin‐resistant state of 3T3‐L1 cells more effectively, relative to rosiglitazone and metformin. The phytocannabinoids had a more pronounced effect in preadipocytes undifferentiated model rather than the differentiated model. They induced a protective effect at the mitochondrial level by preventing overactivity of the succinate dehydrogenase pathway (p < .01), unlike rosiglitazone, through activation of the glycerol‐3‐phosphate dehydrogenase shuttling system. An increase in oxygen consumption and an increased expression of beta to alpha adrenoceptors (p < .05) in treated cells were noted. These findings contribute toward understanding the mechanism of action of phytocannabinoids in fat cells and highlight the antidiabetic and anti‐obesity properties of various phytocannabinoids that could potentially support the treatment of obesity‐related insulin resistance.  相似文献   

7.
To examine the effects of Momordica charantia on glucose uptake and adiponectin secretion in adipose cells, 3T3-L1 adipocytes were treated with three concentrations (0.2, 0.3 and 0.4mg/ml) of water and ethanol extracts of Momordica charantia fruit and seeds alone and in combination with either 0.5nM or 50nM insulin. The treatment combination of 0.2mg/ml water extract and 0.5nM insulin was associated with significant (p<0.05) increases in glucose uptake (61%) and adiponectin secretion (75%) over control levels. The ethanol extract was not associated with an increase in glucose uptake; however, a dose-dependent decrease in basal glucose uptake and insulin-mediated glucose uptake was observed with the ethanol extract in combination with 50nM insulin. In the absence of insulin, no effects on glucose uptake were observed in adipocytes exposed to the water extracts whereas the highest concentration (0.4mg/ml) of the ethanol extract was associated with a significant (p<0.05) decrease in glucose uptake relative to controls. The present results indicate that water-soluble component(s) in Momordica charantia enhance the glucose uptake at sub-optimal concentrations of insulin in 3T3-L1 adipocytes, which is accompanied by and may be a result of increased adiponectin secretion from the 3T3-L1 adipocytes.  相似文献   

8.
ETHNOPHARMACOLOGICAL RELEVANCE: The molecular mechanism of a traditional hypoglycemic Chinese herbal formula. AIM OF THE STUDY: To explore the glucose uptake effect as well as the mechanism(s) of action of Bai-Hu-Tang (BHT), a traditional Chinese herbal formula, composed of anemarrhena, gypsum, licorice and rice. MATERIALS AND METHODS: Differentiated 3T3-L1 adipocytes were treated with vehicle, insulin or insulin plus different concentrations of BHT. The 2-deoxy-[(3)H] glucose uptake assay was performed to measure the amount of glucose uptake. To explore the mechanism(s) of glucose uptake of BHT, we used two insulin signaling transduction inhibitors, N-Acetyl-Leu-Leu-Norleu-al (ALLN), a calpain inhibitor, and LY 294002, a phosphatidylinositol (PI)3-kinase inhibitor, to test if the glucose uptake effect was mediated by the insulin signaling pathway. We then used Western blot analysis to re-confirm the result of the insulin signaling inhibition assay. Finally, reporter chimera assay of HuH-7 cells was used to measure the peroxisome proliferator-activated receptor gamma (PPARgamma) activation by BHT. RESULTS: BHT potentiated insulin-stimulated glucose uptake in 3T3-L1 adipocytes. The effect of BHT-stimulated glucose uptake was neither inhibited by ALLN nor by LY 294002. The protein expression of PI3 kinase pathway did not change after BHT stimulation. PPARgamma activation was elevated by 67.7+/-32% (p<0.05) in HuH-7 cells treated with 0.8 microg/ml of BHT. CONCLUSIONS: BHT stimulated glucose uptake in 3T3-L1 adipocytes. This effect was via PPARgamma activation rather than via the insulin signaling pathway.  相似文献   

9.
Inonotus obliquus has been traditionally used for treatment of metabolic diseases; however, the mechanism remains to be elucidated. In this study, we found that the water‐soluble melanin complex extracted from I. obliquus improved insulin sensitivity and reduced adiposity in high fat (HF)‐fed obese mice. When the melanin complex was treated to 3T3‐L1 adipocytes, insulin‐stimulated glucose uptake was increased significantly, and its phosphoinositide 3‐kinase‐dependent action was proven with wortmannin treatment. Additionally, dose‐dependent increases in Akt phosphorylation and glucose transporter 4 translocation into the plasma membrane were observed in melanin complex‐treated cells. Adiponectin gene expression in 3T3‐L1 cells incubated with melanin complex increased which was corroborated by increased AMP‐activated protein kinase phosphorylation in HepG2 and C2C12 cells treated with conditioned media from the 3T3‐L1 culture. Melanin complex‐treated 3T3‐L1 cells showed no significant change in expression of several lipogenic genes, whereas enhanced expressions of fatty acid oxidative genes were observed. Similarly, the epididymal adipose tissue of melanin complex‐treated HF‐fed mice had higher expression of fatty acid oxidative genes without significant change in lipogenic gene expression. Together, these results suggest that the water‐soluble melanin complex of I. obliquus exerts antihyperglycemic and beneficial lipid‐metabolic effects, making it a candidate for promising antidiabetic agent. Copyright © 2014 John Wiley & Sons, Ltd.  相似文献   

10.
11.
Lonicera japonica Thunb. (Caprifoliaceae) is a traditional herbal medicine and has been used to treat diabetic symptoms. Notwithstanding its use, the scientific basis on anti‐diabetic properties of L. japonica is not yet established. This study is designed to investigate anti‐diabetic effects of L. japonica in type 2 diabetic rats. L. japonica was orally administered at the dose of 100 mg/kg in high‐fat diet‐fed and low‐dose streptozotocin‐induced rats. After the treatment of 4 weeks, L. japonica reduced high blood glucose level and homeostatic model assessment of insulin resistance in diabetic rats. In addition, body weight and food intake were restored by the L. japonica treatment. In the histopathologic examination, the amelioration of damaged β‐islet in pancreas was observed in L. japonica‐treated diabetic rats. The administration of L. japonica elevated peroxisome proliferator‐activated receptor gamma and insulin receptor subunit‐1 protein expressions. The results demonstrated that L. japonica had anti‐diabetic effects in type 2 diabetic rats via the peroxisome proliferator‐activated receptor gamma regulatory action of L. japonica as a potential mechanism. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   

12.

Ethnopharmacological relevance

Seeds of Centratherum anthelminticum (Asteraceae) have been popularly used in Ayurvedic medicine to treat diabetes and skin disorders. Folk medicine from Rayalaseema (Andhra Pradesh, India) reported wide spread usage in diabetes.

Aim of the study

To investigate the hypoglycemic properties and mechanism of the methanolic fraction of C. anthelminticum seeds (CAMFs) on mouse β-TC6 pancreatic cell line and streptozotocin (STZ)-induced diabetic rat models.

Materials and Methods

We investigated the crude methanolic fraction of C. anthelminticum seeds (CAMFs) on β-TC6 cell line and confirmed its effects on type 1 and type 2 diabetic rats to understand its mechanism in managing diabetes mellitus. CAMFs were initially tested on β-TC6 cells for cytotoxicity, 2-NBDG glucose uptake, insulin secretion and glucose transporter (GLUT-1, 2 and 4) protein expression. Furthermore, streptozotocin (STZ)-induced type 1 diabetic and STZ-nicotinamide-induced type 2 diabetic rats were intraperitoneally (i.p) injected or administered orally with CAMFs daily for 28 days. The effect of CAMFs on blood glucose and insulin levels was subsequently evaluated.

Results

In cell line studies, CAMFs showed non-cytotoxic effect on β-TC6 cell proliferation compared to untreated control cells at 50 μg/ml. CAMFs increased glucose uptake and insulin secretion dose-dependently by up-regulating GLUT-2 and GLUT-4 expression in these cells. Further in vivo studies on streptozotocin induced diabetic rat models revealed that CAMFs significantly reduced hyperglycemia by augmenting insulin secretion in type 2 diabetic rats. However, CAMFs displayed less significant effects on type 1 diabetic rats.

Conclusions

CAMFs demonstrated anti-diabetic potential on β-TC6 cells and type 2 diabetic rat model, plausibly through enhancing glucose uptake and insulin secretion.  相似文献   

13.
Mulberry (Morus alba L.) leaf tea is promoted for its health benefits and the control of diabetes in Asian nations. The blood glucose lowering activity of mulberry leaf extract (MA) has been proven; however, the molecular basis underlying this effect remains unclear. The aim of the present work is to elucidate its mechanism of the antihyperglycemic action, by examining the effect of MA on glucose uptake and the translocation of glucose transporter 4 protein (GLUT4) to the plasma membrane of adipocytes isolated from diabetic rats. The incubation of adipocytes with 5-45 μg/ml MA resulted in 31-54% increase of glucose uptake in a dose-dependent manner. This glucose uptake enhancing effect was inhibited by the phosphoinositol 3-kinase (PI3-K) inhibitor, wortmannin (100 nM). The GLUT4 protein on the plasma membrane fraction of adipocytes was markedly increased after treatment with 15 μg/ml MA extract. Interestingly, gallic acid, one of the phenolic compounds found in MA extract, increased glucose uptake and enhanced the translocation of GLUT4 at concentrations comparable to the amount of gallic acid in the effective concentration ranges of MA. Thus, it is likely that gallic acid contributes, at least in part, to its antihyperglycemic activity. The present results suggest that the antihyperglycemic action of MA is mediated by increasing glucose uptake via the activation of PI3-K signaling pathway and translocation of GLUT4 to the plasma membrane. These findings are the first molecular evidence supporting the mulberry tea as herbal medicine for diabetic patients.  相似文献   

14.
Umbelliferone (UMB) is a natural product that has several pharmacological effects including antihyperglycemic activity in diabetic rats. Thus, the objective of this study was to investigate the effect of UMB on insulin resistance and on the regulation of glucose and lipid metabolism in type 2 diabetic rats. Type 2 diabetes was induced in rats by feeding a high‐fat diet (45 kcal% fat) and a single dose of streptozotocin injection. After 8 weeks of treatment, UMB significantly reduced the elevated blood glucose levels and insulin resistance and increased the liver glycogen and serum adiponectin. Moreover, the serum lipid and the storages of triglyceride and non‐esterified fatty acid in liver tissue were reduced. From histological examination, the lipid droplets in liver tissue were clearly decreased, and the fat cell size in the fat tissue was smaller in diabetic rats treated with UMB. Interestingly, UMB increased fat cell adiponectin, plasma membrane glucose transporter 4 (GLUT4) and peroxisome proliferator‐activated receptor gamma (PPARγ), and liver PPARα protein expressions. Our findings demonstrate that UMB improves glucose and lipid metabolism in type 2 diabetes by stimulating the insulin secretion and the related mechanisms via stimulating expression of adiponectin, GLUT4, PPARγ, and PPARα‐protein expressions. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   

15.
Chlorella is a type of unicellular fresh water algae. In an attempt to develop new agents for handling insulin resistance, Chlorella was employed to screen the effect on insulin resistance in rats induced by fructose‐rich chow. A single oral administration of Chlorella for 90 min decreased the plasma glucose in a dose‐dependent manner in rats receiving 4‐week fructose‐rich chow. In addition, chronic treatment with Chlorella for 15 days also lowered plasma glucose in the same manner. Then, the insulin action on glucose disposal rate was measured using the glucose‐insulin index, values of the areas under the curves of glucose and insulin during the intraperitoneal glucose tolerance test (IPGTT). Oral administration (three times daily for 5 days) of Chlorella to rats receiving 4 weeks of fructose‐rich chow abolished the elevated value of the glucose‐insulin index, indicating that Chlorella has an ability to improve insulin resistance. An increase of insulin sensitivity by Chlorella was further evaluated using the plasma glucose lowering action of exogenous insulin in streptozotocin‐induced diabetic rats (STZ‐diabetic rats). Oral administration of Chlorella three times daily to STZ‐diabetic rats increased the response to exogenous insulin 15 days later. The obtained results suggest that oral administration of Chlorella has the ability to improve insulin sensitivity, which may be used as an adjuvant therapy for patients with insulin resistance. Copyright © 2011 John Wiley & Sons, Ltd.  相似文献   

16.
The global epidemic of type 2 diabetes demands the rapid evaluation of new and accessible interventions. This study investigated whether Aegle marmelos fruit aqueous extract (AMF; 250, 500 and 1000 mg/kg) improves insulin resistance, dyslipidemia and β‐cell dysfunction in high fat diet fed‐streptozotocin (HFD‐STZ)‐induced diabetic rats by modulating peroxisome proliferator‐activated receptor‐γ (PPARγ) expression. The serum levels of glucose, insulin, homeostasis model assessment of insulin resistance (HOMA‐IR), homeostasis model assessment of β‐cell function (HOMA‐B), lipid profile, TNF‐α and IL‐6 were evaluated. Further, the TBARS level and SOD activity in pancreatic tissue and PPARγ protein expression in liver were assessed. In addition, histopathological and ultrastructural studies were performed to validate the effect of AMF on β‐cells. The HFD‐STZ treated rats showed a significant increase in the serum levels of glucose, insulin, HOMA‐IR, TNF‐α, IL‐6, dyslipidemia with a concomitant decrease in HOMA‐B and PPARγ expression. Treatment with AMF for 21 days in diabetic rats positively modulated the altered parameters in a dose‐dependent manner. Furthermore, AMF prevented inflammatory changes and β‐cell damage along with a reduction in mitochondrial and endoplasmic reticulum swelling. These findings suggest that the protective effect of AMF in type 2 diabetic rats is due to the preservation of β‐cell function and insulin‐sensitivity through increased PPARγ expression. Copyright © 2011 John Wiley & Sons, Ltd.  相似文献   

17.

Ethnopharmacology relevance

Adipocytes are major tissues involved in glucose uptake second to skeletal muscle and act as the main adipocytokines mediator that regulates glucose uptake mechanism and cellular differentiation. The objective of this study were to examine the effect of the SDF7, which is a fraction consists of four flavonoid compounds (quercetin: p-coumaric acid: luteolin: apigenin=8: 26: 1: 3) from Scoparia dulcis Linn., on stimulating the downstream components of insulin signalling and the adipocytokines expression on different cellular fractions of 3T3-F442a adipocytes.

Material and methods

Morphology and lipid accumulation of differentiated 3T3-F442a adipocytes by 100 nM insulin treated with different concentrations of SDF7 and rosiglitazone were examined followed by the evaluation of glucose uptake activity expressions of insulin signalling downstream components (IRS-1, PI3-kinase, PKB, PKC, TC10 and GLUT4) from four cellular fractions (plasma membrane, cytosol, high density microsome and low density microsome). Next, the expression level of adipocytokines (TNF-α, adiponectin and leptin) and immunoblotting of treated 3T3-F442 adipocytes was determined at 30 min and 480 min. Glucose transporter 4 (GLUT4) translocation of 3T3-F442a adipocytes membrane was also determined. Lastly, mRNA expression of adiponectin and PPAR-γ of 3T3-F442a adipocytes were induced and compared with basal concentration.

Results

It was found that SDF7 was able to induce adipocytes differentiation with great extends of morphological changes, lipid synthesis and lipid stimulation in vitro. SDF7 stimulation of glucose transport on 3T3-F442a adipocytes are found to be dose independent, time-dependent and plasma membrane GLUT4 expression-dependent. Moreover, SDF7 are observed to be able to suppress TNF-α and leptin expressions that were mediated by 3T3-F442a adipocytes, while stimulated adiponectin secretion on the cells. There was a significant expression (p<0.01) of protein kinase C and small G protein TC10 on 3T3-F442a adipocytes upon treatment with SDF7 as compared to the control. SDF7 was also found to be effective in stimulating adiponectin and PPAR-γ mRNA upregulation at 50 µg/ml.

Conclusion

SDF7 exhibited good lipogenesis, adiponectinesis and glucose uptake stimulatory properties on 3T3-F442a adipocytes.  相似文献   

18.
目的:观察银杏叶提取物(GbE)对糖尿病大鼠模型膈肌葡萄糖摄取率和葡萄糖转运体4(GLUT4)mRNA表达水平的影响.方法:40只雄性SD大鼠随机分为正常对照组10只,造模组30只.应用高糖高脂饮食加小剂量链脲佐菌素诱发糖尿病大鼠模型.随机选取造模成功大鼠20只均分成2组:糖尿病组、GbE治疗组.GbE治疗组按8 mg·kg~(-1)·d~(-1)剂量腹腔注射GbE,持续8周.检测各组大鼠空腹血糖和胰岛素水平,膈肌组织葡萄糖摄取率和CLUT4 mRNA水平,并观察其超微结构的变化.结果:与正常对照组比较,糖尿病组大鼠空腹血糖和胰岛素升高(P<0.01);膈肌葡萄糖摄取率和GLUT4 mR-NA水平下降(P<0.05,P<0.01);电镜下主要表现为膈肌线粒体扩张,嵴变短,空泡化.GbE治疗组L述变化明显减轻.结论:GbE可部分纠正糖尿病大鼠模型高血糖、高胰岛素状态,并减轻膈肌损伤,其作用与增强膈肌GLUT4基因表达,促进膈肌对葡萄糖的摄取和利用有关.  相似文献   

19.

Ethnopharmacological relevance

Ibervillea sonorae (S. Watson) Greene (Cucurbitaceae), a plant used for the empirical treatment of type 2 diabetes in México, exerts antidiabetic effects on animal models but its mechanism of action remains unknown. The aim of this study is to investigate the antidiabetic mechanism of an Ibervillea sonorae aqueous extract (ISE).

Materials and methods

Non-toxic ISE concentrations were assayed on the glucose uptake by insulin-sensitive and insulin-resistant murine and human cultured adipocytes, both in the absence or the presence of insulin signaling pathway inhibitors, and on murine and human adipogenesis. Chemical composition of ISE was examined by spectrophotometric and HPLC techniques.

Results

ISE stimulated the 2-NBDGlucose uptake by mature adipocytes in a concentration-dependent manner. ISE 50 µg/ml induced the 2-NBDG uptake in insulin-sensitive 3T3-F442A, 3T3-L1 and human adipocytes by 100%, 63% and 33%, compared to insulin control. Inhibitors for the insulin receptor, PI3K, AKT and GLUT4 blocked the 2-NBDG uptake in murine cells, but human adipocytes were insensitive to the PI3K inhibitor Wortmannin. ISE 50 µg/ml also stimulated the 2-NBDG uptake in insulin-resistant adipocytes by 117% (3T3-F442A), 83% (3T3-L1) and 48% (human). ISE induced 3T3-F442A adipogenesis but lacked proadipogenic effects on 3T3-L1 and human preadipocytes. Chemical analyses showed the presence of phenolics in ISE, mainly an appreciable concentration of gallic acid.

Conclusion

Ibervillea sonorae exerts its antidiabetic properties by means of hydrosoluble compounds stimulating the glucose uptake in human preadipocytes by a PI3K-independant pathway and without proadipogenic effects.  相似文献   

20.
葛根对地塞米松诱导的胰岛素抵抗的影响   总被引:17,自引:0,他引:17  
目的 :探讨葛根提取物对地塞米松造成的胰岛素抵抗的影响及其作用机理。方法 :采用地塞米松诱导 3T3-L1脂肪细胞胰岛素抵抗 ,检测药物对细胞培养基中葡萄糖浓度的影响 ;采用肌肉注射地塞米松 ( 1mg·kg-1,隔日 1次 )的方法建立胰岛素抵抗动物模型 ,测定空腹血糖 (FBG)、血清胰岛素 (FINS) ,并计算胰岛素抵抗指数 (IRI)与胰岛素敏感指数 (ISI)。结果 :葛根提取物能够明显降低胰岛素抵抗 3T3-L1脂肪细胞培养基中的葡萄糖水平 ,增强细胞对胰岛素的敏感性 ;葛根提取物显著降低胰岛素抵抗大鼠空腹血清胰岛素水平及胰岛素抵抗指数 ,有效改善了大鼠的胰岛素抵抗状态。结论 :葛根对地塞米松造成的胰岛素抵抗具有明显的改善作用。  相似文献   

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