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IMMUNOCHEMICAL IDENTIFICATION AND LOCALIZATION OF CYTOCHROME P-450HSjISOZYME, AN ENZYME RELATED TO NITROSAMINE METABOLISM, IN HUMAN GASTRIC MUCOSA AND GASTRIC CARCINOMA
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作者 方策 沈云英 +1 位作者 吴德丰 潘秀森 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 1989年第2期19-23,共5页
Monoclonal antibody (MAb) to rat liver cyto-chrome P-450j isozyme, an activating enzyme specific to nitrosamine metabolism, was used coupled with immunoblotting, densitometer scanning of SDS-PAGE gels and immunohistoc... Monoclonal antibody (MAb) to rat liver cyto-chrome P-450j isozyme, an activating enzyme specific to nitrosamine metabolism, was used coupled with immunoblotting, densitometer scanning of SDS-PAGE gels and immunohistochemical technique. The trace P-450HSj isozyme (Mr. 51.5 Kd) was found in human gastric mucosa. It was similar to P-450j in molecular weight, catalytic and immunochemical properties. The concentrations of P-450HSj in mucosa of lesser curvature were higher than those in greater curvature. This might be one of the important reasons that lesser curvature is the commonest area for gastric carcinoma. But there was possibly less P-450HSj in gastric mucosa with cancer. Im-munohistochemically, P-450HSj was discovered in the cytoplasm of some glandular epithelial cells, especially in the glands with hyperplastic and intestinal metaplastic changes adjacent to carcinoma. It was also found in some normal glands and in tumor cells of high-differentiated adenocarcinoma, but not in those of low-differentiated ones. Following subjects are discussed: (1) the method of detecting trace P-450HSj, (2) the rule of distribution of P-450HSj, and (3) the relationship between the isozyme and the occurrence of gastric cancer caused by nitrosa-mines. 展开更多
关键词 IN HUMAN GASTRIC MUCOSA AND GASTRIC CARCINOMA AN enzyme RELATED TO NITROSAMINE METABOLISM IMMUNOCHEMICAL IDENTIFICATION AND LOCALIZATION OF cytochrome p-450HSjISOZYME NDEA
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Effects of Tianma(Rhizoma Gastrodiae)and Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)on cytochrome P450 enzyme activities in rats 被引量:3
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作者 LIU Xin WANG Xinyu +1 位作者 PENG Yinxuan WANG Xing 《Journal of Traditional Chinese Medicine》 SCIE CSCD 2021年第2期284-292,共9页
OBJECTIVE:To investigate the efficacy of Tianma(Rhizoma Gastrodiae)and Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)on cytochrome P450(CYP450)enzyme activities in rats.METHODS:A cocktail strategy was followed to ... OBJECTIVE:To investigate the efficacy of Tianma(Rhizoma Gastrodiae)and Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)on cytochrome P450(CYP450)enzyme activities in rats.METHODS:A cocktail strategy was followed to evaluate the influence of Tianma(Rhizoma Gastrodiae)and Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)on the activities of CYP450 isoforms(CYP1A2,CYP3A4,CYP2E1,CYP2C19,CYP2C9,CYP2D6),which were determined by changes in the pharmacokinetic parameters of six probe drugs,theophylline,dapsone,chlorzoxazone,omeprazole,tolbutamide and dextromethorphan.Study groups included,Control group(CG),Tianma(Rhizoma Gastrodiae)group(TM),Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)group(GT)and Tianma Gouteng(Gastrodia Uncaria)group(TMGT).RESULTS:No significant differences between Tianma(Rhizoma Gastrodiae)and control groups were found.Compared with the control group,in the Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)group both the AUC and t1/2 of dapsone and tolbutamide were reduced,whereas the CL(clearance rate)of dapsone and tolbutamide were increased.Compared with the control group,in the Tianma Gouteng group,the AUC and t1/2 of dapsone and tolbutamide were reduced,the CL of dapsone and tolbutamide were increased,and the AUC and t1/2 of chlorzoxazone were increased and the CL of chlorzoxazone was reduced.CONCLUSION:Tianma(Rhizoma Gastrodiae)has no significant effect on the six CYP450 subtypes.The activities of CYP3A4 and CYP2C9 were increased by Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis).The activities of CYP3A4 and CYP2C9 were increased,whereas the activity of CYP32E1 was reduced by combined Tianma(Rhizoma Gastrodiae)and Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis). 展开更多
关键词 Gastrodiae Elata Ramulus Uncariae Cum Uncis cytochrome p-450 enzyme system cocktail probe drug
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Immunohistochemical localization of cytochrome P450 enzymes 2C and 4A in the normal rat brain
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作者 黄存斌 《Chinese Medical Journal》 SCIE CAS CSCD 1998年第11期48-53,共6页
Objective To localize cytochrome P450 enzymes 4A and 2C in central nervous cells of normal male rats.Methods Eight drug/alcohol untreated normal male rats (150-200 g of body weight) were treated by the optimized perfu... Objective To localize cytochrome P450 enzymes 4A and 2C in central nervous cells of normal male rats.Methods Eight drug/alcohol untreated normal male rats (150-200 g of body weight) were treated by the optimized perfusion technique, then brain tissues were postfixed, paraffin-embedded and cut into series sections, which were labeled by the improved strept-avidin-biotin complex DAB-nickel enhancer (SABC-DAB-Ni) immunohistochemistry and hematoxylin & eosin (H & E) stain techniques.Results The immunohistochemical results indicated that P450 2C-11 enzyme was localized in diverse numbers of neurons as well as some neuroglial cells, with focal or defuse distribution in many brain regions such as cerebrum, thalamus, olfactory bulb, hypothalamus, brain-stem, hippocampus, cerebellum, interpositus nucleus, caudate-putamen, and globus pallidus. In contrast, no positive findings of P450 4A-2, 3 and 8 enzymes were obtained in the same animals. With high magnification, 2C-11 protein was able to be roughly observed on the endoplasmic reticulum of the rat neurons.Conclusions P450 2C-11 protein, rather than P450 4A-2, 3 and 8, may be a candidate of brain P450 enzymes in the normal male rats. 展开更多
关键词 Aryl Hydrocarbon Hydroxylases Steroid 16-alpha-Hydroxylase Animals BRAIN cytochrome p-450 enzyme System Immunohistochemistry Male RATS Rats Sprague-Dawley Steroid Hydroxylases
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来氟米特对急性化学性肝损伤小鼠肝Cyt.P450酶含量及CYP2E1 mRNA表达的影响 被引量:4
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作者 郭安平 李俊 +1 位作者 吕雄文 司洪芳 《安徽医科大学学报》 CAS 北大核心 2008年第1期58-61,共4页
目的观察来氟米特(Lef)作用前后急性化学性肝损伤小鼠肝微粒体细胞色素P450(Cyt.P450)、细胞色素b5(Cyt.b5)含量及P4502E1(CYP2E1)mRNA表达水平的变化,进一步研究其治疗机制。方法采用CCl4诱导小鼠急性化学性肝损伤模型,检测血清丙氨酸... 目的观察来氟米特(Lef)作用前后急性化学性肝损伤小鼠肝微粒体细胞色素P450(Cyt.P450)、细胞色素b5(Cyt.b5)含量及P4502E1(CYP2E1)mRNA表达水平的变化,进一步研究其治疗机制。方法采用CCl4诱导小鼠急性化学性肝损伤模型,检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)活性,肝匀浆丙二醛(MDA)、谷胱甘肽(GSH)含量以及肝微粒体细胞色素P450(Cyt.P450)和细胞色素b5(Cyt.b5)含量,RT-PCR法检测小鼠肝脏细胞色素P4502E1(CYP2E1)mRNA表达水平,并作肝组织切片病理观察。结果Lef明显降低CCl4急性肝损伤小鼠血清ALT、AST水平;降低肝匀浆MDA含量;提高GSH含量并提高肝微粒体Cyt.P450、Cyt.b5含量;抑制CYP2E1 mRNA表达;减轻肝脏病理损伤。结论Lef治疗CCl4所致小鼠急性化学性肝损伤,可能与其诱导肝微粒体Cyt.P450表达,抑制CYP2E1 mRNA转录及抗脂质过氧化有关。 展开更多
关键词 肝疾病/化学诱导 肝疾病/治疗 细胞色素P450酶系统 细胞色素P450 CYP2E1 异恶唑类
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细胞色素P450基因多态性与药物性肝损伤的关系 被引量:7
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作者 王巧玲 邹正升 《临床肝胆病杂志》 CAS 北大核心 2020年第5期1150-1153,共4页
随着药物性肝损伤患病率的逐年上升,药物性肝损伤发病机制成为了关注的焦点。CYP450酶作为一个庞大的家族,参与了药物在人体肝脏内的几乎所有氧化代谢反应。近年来发现CYP450酶的基因多态性导致了药效动力学在不同个体中的代谢差异性,... 随着药物性肝损伤患病率的逐年上升,药物性肝损伤发病机制成为了关注的焦点。CYP450酶作为一个庞大的家族,参与了药物在人体肝脏内的几乎所有氧化代谢反应。近年来发现CYP450酶的基因多态性导致了药效动力学在不同个体中的代谢差异性,故探索CYP450酶基因多态性在药物性肝损伤中的作用,可促进对药物性肝损伤发病机制的了解。对已发现与药物性肝损伤相关的CYP450酶基因多态性进行综述。 展开更多
关键词 细胞色素P450酶系统 多态现象 遗传 化学性与药物性肝损伤
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药物性肝损伤的免疫学研究进展 被引量:11
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作者 周璐 王邦茂 《胃肠病学》 2014年第11期641-643,共3页
药物性肝损伤(DILI)的发病机制未明,近年来的研究发现,免疫因素在DILI的发病中起重要作用。本文阐述免疫因素参与DILI发病的最新研究成果,探讨免疫因素参与DILI发病的机制,并比较免疫介导的DILI与药物诱发的自身免疫性肝炎的异同。DILI... 药物性肝损伤(DILI)的发病机制未明,近年来的研究发现,免疫因素在DILI的发病中起重要作用。本文阐述免疫因素参与DILI发病的最新研究成果,探讨免疫因素参与DILI发病的机制,并比较免疫介导的DILI与药物诱发的自身免疫性肝炎的异同。DILI免疫学研究的开展对DILI和自身免疫性肝炎的防治均具有重要意义。 展开更多
关键词 药物性肝损伤 自身免疫 细胞色素P450酶系统 肝炎 自身免疫性
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高强度阿托伐他汀致肝损伤小鼠肠道菌群的改变及其与肝脏CYP2E 1的关系
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作者 宋冰雪 宋雨晴 +3 位作者 刘鑫 于海初 辛辉 梁惠 《精准医学杂志》 2023年第6期494-498,共5页
目的探讨高强度阿托伐他汀(ATO)导致肝损伤小鼠肠道菌群的改变及其与肝组织中CYP2E1的关系。方法C57BL/6小鼠40只,按照处理方式不同分为4组,每组10只,低强度ATO组(ATO-L组)、中强度ATO组(ATO-M组)、高强度ATO组(ATO-H组)小鼠每天分别灌... 目的探讨高强度阿托伐他汀(ATO)导致肝损伤小鼠肠道菌群的改变及其与肝组织中CYP2E1的关系。方法C57BL/6小鼠40只,按照处理方式不同分为4组,每组10只,低强度ATO组(ATO-L组)、中强度ATO组(ATO-M组)、高强度ATO组(ATO-H组)小鼠每天分别灌胃含有10、20、30 mg/kg ATO的生理盐水1 mL,对照组(CON组)小鼠每天灌胃等量生理盐水,持续4周。HE染色后透射电镜下观察各组小鼠肝脏病理状态,检测各组小鼠血清中ALT、AST、TNF-α、IL-6和IL-10水平以及肝脏组织中SOD活力、CYP2E 1的mRNA水平,采用16SrDNA测序法分析小鼠新鲜粪便中肠道菌群分布,将差异有显著意义的菌属的相对丰度与肝脏组织中CYP2E 1 mRNA水平及SOD活力进行相关性分析。结果经HE染色及透射电镜下观察显示,ATO-M组、ATO-H组小鼠肝脏均出现不同程度的损伤现象;各组小鼠血清中ALT、AST、IL-6、TNF-α和肝脏组织中SOD活力差异有显著性(F=4.57~7.74,P<0.05)。ATO-H组小鼠肠道菌群稳态失衡,ATO-H组拟杆菌门、厚壁菌门、变形菌门和脱铁杆菌门的相对丰度与CON组比较,差异有显著性(t=2.89~5.22,P<0.05);两组紫单孢菌科、普氏菌科、乳杆菌科、毛螺菌科、螺杆菌科的相对丰度差异有显著性(t=2.45~5.46,P<0.05);两组螺杆菌属、拟普雷沃菌属、普氏菌属和乳杆菌属的相对丰度差异具有显著性(t=2.46~7.41,P<0.05)。乳杆菌属的相对丰度与肝脏组织SOD活力呈正相关(r=0.48,P<0.05),与肝组织中CYP2E 1的mRNA水平呈负相关(r=-0.62,P<0.05)。结论高强度他汀类药物可导致小鼠肠道菌群稳态失衡,抗氧化应激能力下降,肠道菌群乳杆菌属的减少可能会促进肝脏的氧化应激反应。 展开更多
关键词 胃肠道微生物组 阿托伐他汀 化学性与药物性肝损伤 细胞色素P450酶系统 RNA 信使 超氧化物歧化酶 乳杆菌属
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Herb-drug enzyme-mediated interactions and the associated experimental methods: a review
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作者 Li Bo Zhao Baosheng +4 位作者 Liu Yang Tang Mingmin Lǚe Beiran Luo Zhiqiang Zhai Huaqiang 《Journal of Traditional Chinese Medicine》 SCIE CAS CSCD 2016年第3期392-408,共17页
OBJECTIVE: To review the interactions between herbs and widely used drugs and summarize the associated experimental methods.METHODS: Definite herb-drug interactions were obtained by searching Pub Med, other large over... OBJECTIVE: To review the interactions between herbs and widely used drugs and summarize the associated experimental methods.METHODS: Definite herb-drug interactions were obtained by searching Pub Med, other large overseas databases and summarizing new researches from China. We summarize some methods to assess the interaction between herbs and drugs involving microsomal, cell culture and animal experiments, and clinical trials, classifying this method as single ingredient herbs, crude herb extracts, andherbal formulae.RESULTS: Many herbs interact with drugs through a complex cytochrome P450 and/or P-glycoprotein mechanism. Herb-induced enzyme inhibition and/or induction may result in enhanced and / or decreased plasma, tissue, urine and bile drug concentrations, leading to a change in a drug's pharmacokinetic parameters and resulting in the improper treatment of patients and potentially severe side effects. Use of an appropriate method for comprehensively assessing herb-drug interactions can minimize clinical risks. Different methods were used by researchers to assess the pharmacological changes of drugs in vivo and in vitro and the mechanisms of the interactions from microsomal, cell culture and animal experiments, and clinical trials are discussed in this review.CONCLUSION: Co-medication with herbs can result in changes in pharmacological effects of many drugs. This review describes the assessment of single-ingredient herbs, crude herb extracts, and herbal formulae. When choosing a research method to investigate herb-drug interactions, the properties of the drugs and herbs should be considered. 展开更多
关键词 Herb-drug interaction METABOLISM cytochrome p-450 enzyme system p-GLYCOPROTEIN REVIEW
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利福平的肝药酶诱导作用对右美托咪定麻醉效果的影响 被引量:1
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作者 何婉雯 温海明 +4 位作者 代冬梅 孔德煜 邵琤 连贵勇 郭瑞 《中国新药与临床杂志》 CAS CSCD 北大核心 2021年第11期760-763,共4页
目的观察利福平的肝药酶诱导作用对右美托咪定麻醉效果的影响。方法选择拟行肺大疱手术患者40例设为对照组,经利福平治疗9~12个月拟行结核性肺纤维板剥脱术患者40例设为观察组。2组均采用全身麻醉,右美托咪定0.2μg·kg^(-1)·h... 目的观察利福平的肝药酶诱导作用对右美托咪定麻醉效果的影响。方法选择拟行肺大疱手术患者40例设为对照组,经利福平治疗9~12个月拟行结核性肺纤维板剥脱术患者40例设为观察组。2组均采用全身麻醉,右美托咪定0.2μg·kg^(-1)·h^(-1)静脉输注10 min后进行麻醉诱导,气管插管成功后予1.7%七氟烷吸入,瑞芬太尼0.2μg·kg^(-1)·min^(-1)、右美托咪定0.2μg·kg^(-1)·h^(-1)静脉维持。采用序贯法测定右美托咪定抑制插管应激反应的半数有效剂量(EC_(50))及其95%置信区间(CI)。观察2组平均动脉压(MAP)和心率(HR),并检测血促肾上腺皮质激素(ACTH)和皮质醇(COR)水平。结果对照组右美托咪定抑制插管应激反应的EC_(50)(95%CI)为0.246μg·kg^(-1)·h^(-1)(0.227~0.266μg·kg^(-1)·h^(-1)),观察组为0.332μg·kg^(-1)·h^(-1)(0.310~0.358μg·kg^(-1)·h^(-1)),观察组显著高于对照组(P=0.0001)。插管时、插管后5 min、切皮时、术毕、苏醒期观察组ACTH、COR、MAP和HR均较诱导前显著升高(P<0.05),且高于同时点对照组值(P<0.05)。结论利福平可引起右美托咪定麻醉效果下降,进而减弱右美托咪定消除应激的效能,增加使用耐量。 展开更多
关键词 利福平 右美托咪定 酶诱导 细胞色素P450酶诱导剂
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反应性代谢产物致药物性肝损伤的机制研究进展
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作者 边诣聪 缪丽燕 肇丽梅 《药物不良反应杂志》 CSCD 2022年第11期599-603,共5页
药物反应性代谢产物是导致药物性肝损伤(DILI)的主要原因之一。某些药物进入体内后,可经肝脏代谢生成反应性代谢产物,耗竭谷胱甘肽,进而与体内蛋白或核酸等大分子结合,改变生物大分子功能,诱导细胞氧化应激和机体免疫反应,干扰机体正常... 药物反应性代谢产物是导致药物性肝损伤(DILI)的主要原因之一。某些药物进入体内后,可经肝脏代谢生成反应性代谢产物,耗竭谷胱甘肽,进而与体内蛋白或核酸等大分子结合,改变生物大分子功能,诱导细胞氧化应激和机体免疫反应,干扰机体正常生理功能并产生肝毒性。反应性代谢产物介导的DILI可能不是某一种机制单独作用的结果,而是多种机制共同作用的结果。本文综述了药物反应性代谢产物的产生过程、致肝损伤的机制和防治手段,为临床安全用药提供重要参考。 展开更多
关键词 化学和药物性肝损伤 药物和物质代谢的副作用 细胞色素P450酶系统 氧化应激 免疫反应
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Effect of Yajieshaba,a preparation of Dai indigenous medicine,on enhanced liver detoxification 被引量:1
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作者 Duan Xiaohua Zheng Jin +3 位作者 Wang Hui Cheng Haifeng Zhang Chao Yu Zepu 《Journal of Traditional Chinese Medicine》 SCIE CAS CSCD 2015年第2期197-205,共9页
OBJECTIVE:To explore the mechanistic effects of Yajieshaba(YJSB) on enhanced liver detoxification.METHODS:The effects of YJSB on alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were assayed in five a... OBJECTIVE:To explore the mechanistic effects of Yajieshaba(YJSB) on enhanced liver detoxification.METHODS:The effects of YJSB on alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were assayed in five acute chemical liver injury models[carbon tetrachloride(CCU),D-galactosamine(D-Glan),4-acetamidophenol(AAP),thioacetamide(TAA) and 1-naphthyl isothiocyanate(ANIT)].Sleep latency and sleep time of pentobarbital sodium were tested in control mice and CCL model miceafter oral YJSB administration.The effects of YJSB on drug metabolism enzymes of liver microsomes were tested in control rats and CCI_4model rats.The levels of cytochrome P450(CYP450) and Cyt b5 in liver microsomes were assayed using the method by Omura and Sato,and activities of erythromycin N-demethylase(ERD)and aminopyrine N-demethyl(ADM) were evaluated by Nash colorimetry.Probe substrate-based high performance liquid chromatography(HPLC)methods were established for CYP3A4 and CYP1A2.RESULTS:The level of serum ALT was reduced by YJSB at 3.51 g/kg in the five models as follows:CCl_4 > D-Glan,AAP,ANIT > TAA.YJSB treatment did not reduce the level of serum AST.YJSB at 3.51 g/kg prolonged the sleep latency in control mice and shortened the sleep time of control mice and CCl_4 model mice.For control rats,YJSB at 2.43 g/kg increased the levels of CYP450 and Cyt b5 and induced the activities of ERD and ADM;for liver injuries induced by CCI_4 in rats,YJSB at 2.43 g/kg increasedthe levels of CYP450 and Cyt b5.These results suggest that YJSB at 2.43 g/kg induces CYP3A4 and CYP1A2.CONCLUSION:These results suggest that YJSB enhanced liver detoxification and the mechanisms may be partially related to CYP3A4 and CYP1A2 induction. 展开更多
关键词 cytochrome p-450 enzyme system Chromatography high pressure liquid Liver detoxification Yajieshaba
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药物临床试验中健康受试者依非韦伦相关皮疹分析及文献回顾
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作者 王琎 张兰 胡朝英 《药物不良反应杂志》 CSCD 2023年第9期521-526,共6页
目的探讨依非韦伦(EFV)在药物临床试验中致健康受试者皮疹的发生情况。方法对首都医科大学宣武医院药学部Ⅰ期临床研究中心2020年11月及2021年10月开展的2项以EFV为酶诱导剂的临床试验中,健康受试者EFV相关皮疹的发生情况进行回顾性分... 目的探讨依非韦伦(EFV)在药物临床试验中致健康受试者皮疹的发生情况。方法对首都医科大学宣武医院药学部Ⅰ期临床研究中心2020年11月及2021年10月开展的2项以EFV为酶诱导剂的临床试验中,健康受试者EFV相关皮疹的发生情况进行回顾性分析。检索国内外相关数据库,收集以健康受试者为研究对象、以EFV为研究药物或酶诱导剂的研究文献,回顾文献中报道的EFV相关皮疹病例资料,并与本院2项临床试验中的数据汇总,进行描述性统计分析。结果2项临床试验共纳入40例健康受试者,5例(12.5%)发生EFV相关皮疹。从服药至出现皮疹的时间平均为8 d;皮疹首发症状均为皮肤瘙痒,出现部位主要为四肢和背部,主要形态为斑丘疹,无伴随其他症状及实验室检查异常。4例受试者退出试验,给予抗过敏及对症治疗5~7 d后皮疹消退;1例因皮疹较轻,给予炉甘石洗剂外用,继续参加试验,皮疹于17 d后(停用EFV 5 d)消退。检索到18篇以健康受试者为研究对象、以EFV为研究药物或酶诱导剂的文献。汇总后,18篇文献及本院研究共包括健康受试者403例,19例发生皮疹,皮疹发生率为4.7%。按EFV日剂量,600 mg/d组皮疹的发生率高于<600 mg/d组,但差异无统计学意义[5.5%(18/329)比1.4%(1/74),P=0.131];按服药时间,单次给药组和连续给药组皮疹的发生率相近[4.1%(4/97)比4.9%(15/306),P=0.753]。结论皮疹是健康受试者服用依非韦伦后常见的不良反应,严重程度一般较轻,及时发现和处理均可恢复。 展开更多
关键词 健康志愿者 临床试验 药代动力学 药物相互作用 依非韦伦 药疹 安全性 细胞色素p-450酶诱导剂
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