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Immunomodulatory Role of Neuropeptide Y in Intestinal Inflammation 神经肽Y在肠道炎症中的免疫调节作用
Pub Date : 2023-02-28 DOI: 10.17480/psk.2023.67.1.1
Yunna Lee, E. Im
Neuropeptide Y (NPY) is a 36-amino acid peptide found in the brain, autonomic nervous system, and different peripheral tissues, including the gastrointestinal (GI) tract. Dysfunction of the NPY or NPY system has been implicated in various tumor microenvironments and cardiovascular and GI disorders, such as inflammatory bowel disease (IBD). IBD, including Crohn’s disease (CD) and ulcerative colitis (UC), is a major health concern due to its increasing incidence globally. Emerging evidence has demonstrated that NPY also acts as a potent immunomodulator by linking the nervous and immune systems. NPY plays an important role in immunopathology during intestinal inflammation. This paper discusses the potential role of NPY as a valuable biomarker for IBD due to its consistent upregulation in both in vivo and clinical studies. Consequently, it confirms the pro-inflammatory effects of NPY, providing a rational basis for targeting NPY signaling as a therapeutic strategy.
神经肽Y (NPY)是一种由36个氨基酸组成的肽,存在于大脑、自主神经系统和不同的外周组织,包括胃肠道。NPY或NPY系统的功能障碍与各种肿瘤微环境、心血管和胃肠道疾病(如炎症性肠病(IBD))有关。IBD,包括克罗恩病(CD)和溃疡性结肠炎(UC),是一个主要的健康问题,由于其全球发病率不断上升。新出现的证据表明,NPY还作为一种有效的免疫调节剂,通过连接神经和免疫系统。NPY在肠道炎症的免疫病理过程中发挥重要作用。本文讨论了NPY作为IBD有价值的生物标志物的潜在作用,因为它在体内和临床研究中都有一致的上调。因此,它证实了NPY的促炎作用,为靶向NPY信号作为治疗策略提供了合理的依据。
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引用次数: 0
Cynara scolymus L. Inhibits the LPS-induced Inflammatory Reaction via Suppression of NF-κB Activity in RAW 264.7 Cells 通过抑制NF-κB活性抑制lps诱导的RAW 264.7细胞炎症反应
Pub Date : 2023-02-28 DOI: 10.17480/psk.2023.67.1.45
Kyung-Jun Boo, K. Lee, Il-Ho Park, T. Kang
Cynara scolymus L. (artichoke) has been traditionally used in the treatment of digestive-related disease, severe hyperlipidemia and liver disease. Recently, anti-inflammatory effect of artichoke has been reported by several studies, but its mechanisms are still unclear. In this study, the anti-inflammatory mechanism of artichoke was studied using an in vitro acute inflammation model. The effect of artichoke on the expression of pro-inflammatory cytokines, such as interleukin- 1beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) in murine macrophage cell line, RAW264.7, was examined by using ELISA and RT-PCR. As a result, artichoke inhibited the expression of IL-1β, IL-6 and TNF-α in macrophages activated by lipopolysaccharide (LPS) at a dose dependent manner. The expression of inflammatory mediators such as NO and PGE2 was next investigated in RAW264.7 cells stimulated with LPS. Artichoke also inhibited the production of NO and PGE2 in the cells at a dose dependent manner. Artichoke suppressed the mRNA expression of iNOS and COX-2 in macrophages by LPS. The effect of artichoke on the activation of NF-κB was examined and LPS-induced NF-κB activation was decreased by treatment of artichoke, suggesting that artichoke has anti-inflammatory effect by inhibiting NF- κB activation.
洋蓟(Cynara scolymus L.)传统上用于治疗消化相关疾病,严重高脂血症和肝病。近年来,一些研究报道了洋蓟的抗炎作用,但其作用机制尚不清楚。本研究采用体外急性炎症模型研究洋蓟的抗炎作用机制。采用ELISA和RT-PCR检测了洋蓟对小鼠巨噬细胞RAW264.7中促炎细胞因子IL-1β (IL-1β)、IL-6、TNF-α表达的影响。结果表明,洋蓟抑制脂多糖激活巨噬细胞IL-1β、IL-6和TNF-α的表达呈剂量依赖性。然后在LPS刺激的RAW264.7细胞中研究NO和PGE2等炎症介质的表达。洋蓟还能抑制细胞中NO和PGE2的产生,并呈剂量依赖性。洋蓟通过LPS抑制巨噬细胞iNOS和COX-2 mRNA的表达。通过观察洋蓟对NF-κB活化的影响,发现lps诱导的NF-κB活化降低,提示洋蓟可能通过抑制NF-κB活化而具有抗炎作用。
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引用次数: 0
Consumers’ Knowledge and Perceptions on Generic Medicines 消费者对仿制药的知识和认知
Pub Date : 2023-02-28 DOI: 10.17480/psk.2023.67.1.23
Nagyeong Lee, Sylvia Park
This study aimed to understand the general public’s perception of the definition and equivalence of generic medicines, and to identify factors associated with the perception. We conducted a nationwide survey of the general public who are currently taking prescription drugs for chronic conditions or who filled at least one prescription in the prior 3 months. A total of 2,026 people were included in the analysis. Of the respondents, 21.0% knew the definition of generic medicines. Less than half of respondents considered generic medicines to be as effective (42.8%) as their original counterparts, and to have same side effects (37.1%) and same quality (35.0%). Also, respondents who were men, taking prescription drugs, and those of higher income or higher levels of education were more likely to know the definition of generic drugs. Higher trust in pharmaceutical equivalence of generic medicines were associated with being male, higher education and knowing the definition of generic medicines. This result implies that consumers having more ability to acquire information tend to have more knowledge on generic medicines. Consumers’ trust in generic medicines seems to build from their knowledge rather than experience of using generic medicines. Information should be given to consumers more effectively in order to enhance their knowledge and perceptions on generic medicine.
本研究旨在了解公众对仿制药的定义和等效性的认知,并确定与认知相关的因素。我们在全国范围内进行了一项调查,调查对象是目前正在服用慢性病处方药或在过去3个月内至少服用过一种处方药的公众。共有2026人参与了分析。21.0%的受访者知道仿制药的定义。不到一半的受访者认为仿制药与原药一样有效(42.8%),具有相同的副作用(37.1%)和相同的质量(35.0%)。此外,服用处方药的男性受访者以及收入较高或受教育程度较高的受访者更有可能知道仿制药的定义。对仿制药等效性的较高信任度与男性、高等教育程度和了解仿制药定义相关。这一结果表明,拥有更多信息获取能力的消费者往往对仿制药有更多的了解。消费者对仿制药的信任似乎建立在他们的知识基础上,而不是建立在使用仿制药的经验基础上。应更有效地向消费者提供信息,以提高他们对仿制药的认识和认知。
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引用次数: 0
Development and Evaluation of Implant using Hot-Melt Extrusion 热熔挤压种植体的研制与评价
Pub Date : 2023-02-28 DOI: 10.17480/psk.2023.67.1.32
S. Lee, Geunjeong Lee, Young Jin Kim, Young ho Cho, Gye-Won Lee
In this study, poly(lactic-co-glycolic acid) (PLGA)-based subcutaneous implant containing metformin HCl was prepared by hot-melt extrusion (HME). This study aimed to evaluate swelling and dissolution behavior for application as subcutaneous implant. Implants containing metformin HCl were fabricated successfully at 30 rpm, 90oC by HME. Drugexcipient compatibility studies through FT-IR and DSC revealed the absence of any interaction between the drug and polymers. Dissolution rate and swelling ratio of metformin HCl was significantly affected by the type of PLGA. Dissolution rate increased as the ratio of -COOH terminal group and GA. By the results, we could confirm that the mechanism of drug release from implants is Korsmeyer-Peppas model (n=0.14~0.71) by combination of non-fickian diffusion and erosion. The formulation F7 with 65% of RG 752H and 5% of RG 502 was showed excellent swelling ratio with drug release control. In this study, mixing 5~10% of RG 502 with RG 752H can be expected to develop optimal implants exhibiting diffusion-controlled release for 3 months without initial burst release.
本研究采用热熔挤压(HME)法制备了含二甲双胍的聚乳酸-羟基乙酸(PLGA)皮下植入物。本研究旨在评估其作为皮下植入物的溶胀和溶解行为。含二甲双胍HCl的植入物在30 rpm, 90℃的HME下成功制备。通过FT-IR和DSC进行的药物赋形剂相容性研究显示药物和聚合物之间没有任何相互作用。PLGA类型对盐酸二甲双胍溶出率和溶胀率有显著影响。溶解速率随-COOH末端基团与GA的比值增大而增大。结果表明,种植体的药物释放机制为Korsmeyer-Peppas模型(n=0.14~0.71),为非黏性扩散和侵蚀相结合的释放机制。F7中RG 752H含量为65%,RG 502含量为5%,具有良好的溶胀率和控释效果。在本研究中,将5~10%的RG 502与RG 752H混合,有望开发出最佳的植入物,具有3个月的扩散控制释放,没有初始爆裂释放。
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引用次数: 0
Impact of Collaboration on Clinical Development Time 协作对临床开发时间的影响
Pub Date : 2022-12-30 DOI: 10.17480/psk.2022.66.6.310
Y. Park, Sang-Won Lee
This research investigated how collaborations affect drug development, including innovation speed and productivity in the field of new drug development. Two-hundred and twenty new drugs approved by the Food and Drug Administration (FDA) between 2015 and 2019 were analyzed for the duration of each clinical phase using the Clinicaltrials.gov database. Collaborative drug development projects were associated with longer clinical development than independent projects. The largest differences were seen in phases 2 and 3. Collaborations between small firms were associated with longer clinical development times than other types of collaboration. This result suggests consideration should be given, when devising a new drug development strategy, to the fact that collaborative development can slow down the clinical development process.
本研究调查了合作如何影响药物开发,包括新药开发领域的创新速度和生产力。2015年至2019年间,美国食品和药物管理局(FDA)批准的220种新药使用Clinicaltrials.gov数据库对每个临床阶段的持续时间进行了分析。与独立项目相比,合作药物开发项目的临床开发时间更长。最大的差异出现在第二阶段和第三阶段。小公司之间的合作比其他类型的合作需要更长的临床开发时间。这一结果提示,在制定新药开发策略时,应考虑到协同开发可能会减缓临床开发过程。
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引用次数: 0
Ameliorating Effect of Lespedeza cuneata Extract on Male Menopause in Wistar Rats by Increasing Androgen Receptor 胡枝子提取物通过增加雄激素受体改善Wistar大鼠雄性更年期的作用
Pub Date : 2022-12-30 DOI: 10.17480/psk.2022.66.6.316
S. Lee, S. Choung, Changhee Kim, Hyung Jee Kim, SangJoon Mo, Sun-Hyang Choi, Eun Young Kim, Dahye Kang, Eun Jin Kim, Jin Chul Ahn
Male menopause, also referred to as late-onset hypogonadism or andropause, is a clinical syndrome characterized by sexual dysfunction, depressive disorder, and insomnia secondary to a testosterone deficiency in older men. Lespedeza cuneata, which belongs to the Fabaceae family, possesses several biological properties, including antiinflammatory, anti-oxidant, and antidiabetic effects. We investigated the inhibitory effect of standardized L. cuneata extract (LCE) on andropause symptoms in vivo. LCE administration significantly increased serum levels of total testosterone without any effects on serum estrogen levels. Additionally, LCE significantly increased serum 17-beta hydroxysteroid dehydrogenase 13 protein levels and reduced levels of sex hormone-binding globulin (SHBG), a protein that blocks free testosterone movement into the cytosol. LCE significantly upregulated the expression of cAMP response element binding protein and androgen receptor (AR), which functions as a transcription factor to stimulate spermatogenesis-associated genes and results in increased numbers of AR-positive cells, such as Leydig and Sertoli cells in the testis. To summarize, LCE administration increases serum testosterone, reduces SHBG levels and upregulates AR expression. Therefore, LCE may be useful as alternative therapy for andropause in older men.
男性更年期,也被称为迟发性性腺功能减退或男性更年期,是一种临床综合征,以性功能障碍、抑郁障碍和失眠为特征,继发于老年男性睾酮缺乏。胡枝子属豆科植物,具有抗炎、抗氧化、抗糖尿病等多种生物学特性。我们在体内研究了标准山羊草提取物(LCE)对男性更年期症状的抑制作用。LCE显著提高了血清总睾酮水平,但对血清雌激素水平没有影响。此外,LCE显著增加血清17- β羟基类固醇脱氢酶13蛋白水平,降低性激素结合球蛋白(SHBG)水平,SHBG是一种阻止游离睾酮进入细胞质的蛋白。LCE显著上调cAMP反应元件结合蛋白和雄激素受体(AR)的表达,雄激素受体作为一种转录因子刺激精子发生相关基因,导致睾丸中AR阳性细胞(如Leydig和Sertoli细胞)数量增加。综上所述,LCE可增加血清睾酮,降低SHBG水平,上调AR表达。因此,LCE可能是老年男性更年期的替代疗法。
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引用次数: 1
Discovery of 2-Anilinopyrimidine-based Selective Inhibitors against Non-small Cell Lung Cancer Cell Line H1975 基于2-苯胺嘧啶的非小细胞肺癌H1975细胞选择性抑制剂的发现
Pub Date : 2022-12-30 DOI: 10.17480/psk.2022.66.6.345
Jinyoung Lee, S. Kim, Seung-Tae Kim, Heegyu Kim, Huu Long Nguyen, Young-Suk Jung, Hwayoung Yun
Small molecular EGFR-tyrosine kinase inhibitors (EGFR-TKIs) have been proved as a successful and powerful strategy for the treatment of non-small-cell lung cancer (NSCLC). Recent studies have reported that the T790M mutation in EGFR is the most prevalent factor in acquired resistance for NSCLC patients. In an effort to identify small molecules for the inhibition of T790M mutant EGFR, a screening of our in-house chemical library was conducted by an MTT assay. A set of 2-anilinopyrimidine derivatives was rationally selected and then evaluated for their antiproliferative activities against three different type of NSCLC cell lines H358 (EGFR wild-type), HCC827 (EGFR exon 19 deletion) and H1975 (EGFR L858R/T790M double-mutant). Compounds 9, possessing a piperidine in the part A and a 4-methylpiperidine in the part B, selectively showed inhibitory activity in the T790M mutant cell line. In addition, in silico studies of 9 utilizing a SwissADME tool exhibited good drug-like properties.
小分子egfr -酪氨酸激酶抑制剂(EGFR-TKIs)已被证明是治疗非小细胞肺癌(NSCLC)的一种成功而有力的策略。最近的研究报道,EGFR中的T790M突变是NSCLC患者获得性耐药的最普遍因素。为了鉴定抑制T790M突变EGFR的小分子,我们通过MTT试验对我们内部的化学文库进行了筛选。合理选择一组2-苯胺嘧啶衍生物,对3种不同类型的NSCLC细胞系H358 (EGFR野生型)、HCC827 (EGFR外显子19缺失)和H1975 (EGFR L858R/T790M双突变)进行抗增殖活性评价。化合物9在T790M突变细胞系中选择性地表现出抑制活性,其中a部分含有一个哌啶,B部分含有一个4-甲基哌啶。此外,利用SwissADME工具进行的9项计算机研究显示出良好的药物样性质。
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引用次数: 0
Comparative Study on the Extended Patent Term to Restrain Patent Owners from Obtaining the Excessive Market Exclusivity Regarding Pharmaceuticals in Korea, the US, Japan, the UK, France, and Germany 韩国、美国、日本、英国、法国、德国延长专利期限限制专利权人获得药品市场专有权的比较研究
Pub Date : 2022-12-30 DOI: 10.17480/psk.2022.66.6.350
Sohee Kim, Daesung Lee, Hyungbin Choi, Kyenghee Kwon
The extended patent term or exclusivity period from pharmaceuticals’ approval date is limited to 14 years in the US or 15 years in the EU. However there are no such restrictions in Korea, so the market exclusivity can be excessively extended. Therefore, the status of extension of patent term in Korea was analyzed and the patent term from the product’s approval date in Korea, the US, Japan, the UK, France, and Germany were compared. For that, the following information from NEDRUG or KIPRIS were collected and analyzed: the filing date of the patent, whether the patent term has been extended, the expiration date of the patent term, approval date, the products’ name, and representative claims. Alecensa, Xalkori, Biktarvy, and Champix were selected for the comparison. Among 597 patents in Korea, 90.1% (538) were extended and 17.1% (102) of patents exceeded 14 years from the approval date. There were 81 and 60 products that have patents whose term exceeds 14 and 15 years from the approval date, respectively. In the comparative cases of 4 products, the patent term from products’ approval date in Korea is longer than 14 or 15 years, whereas the US, the UK, France, and Germany comply with the regulated limitation. The excessive patent protection delays the market entry of lower-cost generics and leads to an increase in financial burden on healthcare cost. To address such problems, a proper limitation on the extension of the patent term from the product’s approval date needs to be established.
从药品批准之日起延长的专利期限或独占期在美国限制为14年,在欧盟限制为15年。但是韩国没有这样的限制,因此市场独占权有可能被过度延长。因此,分析了韩国专利期限延长的现状,并对韩国、美国、日本、英国、法国和德国自产品批准之日起的专利期限进行了比较。为此,从NEDRUG或KIPRIS收集并分析了以下信息:专利申请日期、专利期限是否延长、专利期限截止日期、批准日期、产品名称、代表性权利要求。选取Alecensa、Xalkori、Biktarvy和Champix进行比较。在韩国国内的597件专利中,90.1%(538件)的专利被延长,17.1%(102件)的专利从批准之日起超过14年。自批准之日起,专利有效期超过14年的有81种,超过15年的有60种。在4种产品的比较案例中,韩国的专利期限从产品批准之日起超过14年或15年,而美国、英国、法国、德国则符合规定的期限。过度的专利保护延迟了低成本仿制药的市场进入,并导致医疗成本的财务负担增加。为了解决这些问题,需要对专利期限从产品批准之日起的延长设定适当的限制。
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引用次数: 0
The Efficacy of Potassium Competitive Acid Blocker-based First-line Triple Therapy on Helicobacter pylori Eradication as Compared to Proton Pump Inhibitor-based Treatment: A Systematic Review and Meta-analysis 与基于质子泵抑制剂的治疗相比,基于钾竞争酸阻滞剂的一线三联疗法对幽门螺杆菌根除的疗效:系统回顾和荟萃分析
Pub Date : 2022-12-30 DOI: 10.17480/psk.2022.66.6.374
Miryoung Kim, Sola Han, H. S. Suh
Although randomized controlled trials (RCTs) comparing potassium competitive acid blockers (PCABs) and proton-pump inhibitors (PPIs) have been previously conducted, systematic reviews are lacking. In this systematic review and meta-analysis, we searched the CENTRAL, EMBASE, MEDLINE, KMBASE, and KoreaMed databases for relevant RCTs up to October 3, 2020. We assessed the Helicobacter pylori eradication rate of PCAB-based first-line triple therapy and compared it with that of PPI-based therapy. In all five of the included studies comprising a total of 1542 patients, the intervention used was vonoprazan (VPZ)-based therapy, and there were no studies on tegoprazan (TPZ)-based therapy. The pooled risk ratios (RRs) for the eradication rate of VPZ-based therapy as compared to those of PPI-based therapies was 1.17 (95% confidence interval (CI): 1.10–1.26, P<0.00001 for overall effect, I2=41%, P=0.15 for heterogeneity). The RR of VPZ-based therapy compared to that of PPI-based for clarithromycin (CAM)-resistant strains was 1.29 (95% CI: 1.12– 1.48, P<0.0003 for overall effect, I2=0%, P=0.78 for heterogeneity). VPZ-based first-line triple therapy shows a significant H. pylori eradication rate compared to that of the PPI-based. Notably, VPZ-based therapy shows a better eradication rate than that PPI-based therapy, even in patients with CAM-resistant strains.
虽然之前已经进行了比较钾竞争性酸阻滞剂(pcab)和质子泵抑制剂(PPIs)的随机对照试验(rct),但缺乏系统评价。在本系统综述和荟萃分析中,我们检索了截至2020年10月3日的CENTRAL、EMBASE、MEDLINE、KMBASE和KoreaMed数据库中的相关rct。我们评估了以ppab为基础的一线三联治疗的幽门螺杆菌根除率,并将其与以ppi为基础的治疗进行了比较。在所有纳入的5项研究中,总共有1542名患者,使用的干预措施是vonoprazan (VPZ)为基础的治疗,没有关于替戈拉赞(TPZ)为基础的治疗的研究。与基于ppi的治疗相比,基于vpz的治疗根除率的合并风险比(rr)为1.17(95%置信区间(CI): 1.10-1.26,总体效果P<0.00001, I2=41%,异质性P=0.15)。基于vpz的治疗与基于ppi的治疗对克拉霉素耐药菌株的RR为1.29 (95% CI: 1.12 - 1.48,总体效果P<0.0003, I2=0%,异质性P=0.78)。与基于ppi的一线三联疗法相比,基于vpz的一线三联疗法显示出显著的幽门螺杆菌根除率。值得注意的是,基于vpz的治疗显示出比基于ppi的治疗更好的根除率,即使在具有cam耐药菌株的患者中也是如此。
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引用次数: 0
Factors Associated with Unused Medicine Occurrences in Long-term Care Facilities 与长期护理机构未用药事件相关的因素
Pub Date : 2022-12-30 DOI: 10.17480/psk.2022.66.6.364
S. Jang, Cinoo Kang
As the number of elderly living in long-term care facilities increases, unused medicines are also increasing. This study investigated the status of unused medicines in long-term care facilities and the factors affecting it. Using National Health Insurance Claims Database(NHICB) and Long-term Care Insurance Claims Database(LTCHCD), 137,309 people who lived only in long-term care facilities and took prescription drugs in 2019 were analyzed in this study. Most of them were prescribed by the clinic (41%), and the days per prescription were 25 days in average. Only 1.8% of prescriptions were from tertiary general hospitals, but the days per prescription reached 85 days, accounting for 67% of prescriptions for more than 60 days. The average age of long-term care facility residents was 84.8 years, and 22.6% of them deceased in 2019. 33.7% of the subjects had unused medicines. The days of unused medicines due to duplication in pharmacologically equivalent groups were 13 days in average. The average days of unused medicine due to death were comparatively longer, which was 75.5 days. Unused medicine costs were about 0.9% of the total pharmaceutical expenditures and 77.8% of the costs was caused by death. Unused medicines increased as the number of outpatient visits increased (Relative Risk (RR): 1.14) or when the days per prescription were long (RR: 1.16). Older adults who died were 15 times more likely to have unused medicines than those who were alive. The amount of unused medicines in long-term care facilities is substantial, so it is necessary to establish appropriate policies to reduce it.
随着生活在长期护理机构的老年人数量的增加,未使用的药物也在增加。本研究旨在调查长期照护机构未使用药物的现况及影响因素。本研究利用国家健康保险索赔数据库(NHICB)和长期护理保险索赔数据库(LTCHCD),对2019年仅居住在长期护理机构并服用处方药的137309人进行了分析。以门诊处方为主(41%),处方天数平均为25天。来自三级综合医院的处方仅占1.8%,但每张处方的天数达到85天,占60天以上处方的67%。2019年,长期护理机构居民的平均年龄为84.8岁,其中22.6%的人去世。33.7%的受试者有未使用的药物。药理学等效组重复用药天数平均为13天。死亡未使用药物的平均天数相对较长,为75.5天。未用药费约占总药费的0.9%,其中死亡费用占77.8%。未使用的药物随着门诊次数的增加而增加(相对风险(RR): 1.14)或当每个处方的天数较长(RR: 1.16)。已死亡的老年人未使用药物的可能性是活着的老年人的15倍。长期护理机构中未使用药物的数量很大,因此有必要制定适当的政策来减少这一数量。
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引用次数: 0
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