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Retrospective Analysis of the Use of Oral Ivermectin and 5% Permethrin Cream in Galicia (Spain) 西班牙加利西亚地区口服伊维菌素和5%氯菊酯乳膏使用情况回顾性分析
IF 3.3 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-12-04 DOI: 10.1111/bcpt.70152
S. Vazquez-Prieto, A. Vaamonde, E. Paniagua
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引用次数: 0
Epigallocatechin-3-Gallate Provides Hepatoprotection Through Endoplasmic Reticulum Stress/TXNIP/NLRP3 Axis in Paracetamol-Induced Acute Liver Injury 表没食子儿茶素-3-没食子酸酯通过内质网应激/TXNIP/NLRP3轴在扑热息痛诱导的急性肝损伤中提供肝保护
IF 3.3 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-12-04 DOI: 10.1111/bcpt.70155
Nagihan Demirtas, Busra Sahin Mazlumoglu, Nevra Aydemir Celep, Elif Cadirci, Zekai Halici, Saziye Sezin Palabiyik-Yucelik

Epigallocatechin-3-gallate (EGCG) is a polyphenolic compound with strong antioxidant properties and is abundantly found in green tea. We investigated how EGCG affects the liver injury of high-dose paracetamol in this study. In our study, 56 rats were divided into seven groups (n = 8): healthy control, EGCG (100 mg/kg), paracetamol (2 g/kg), paracetamol + EGCG 25 (2 g/kg + 25 mg/kg), paracetamol + EGCG 50 (2 g/kg + 50 mg/kg), paracetamol + EGCG 100 (2 g/kg + 100 mg/kg) and paracetamol + N-acetyl cysteine (NAC, 2 g/kg + 140 mg/kg). Our findings suggest that high-dose paracetamol induces liver injury through endoplasmic reticulum (ER) stress and that EGCG alleviates liver injury by attenuating ER stress-induced inflammasome signalling.

表没食子儿茶素-3-没食子酸酯(EGCG)是一种多酚化合物,具有很强的抗氧化特性,在绿茶中含量丰富。本研究探讨EGCG对大剂量扑热息痛肝损伤的影响。将56只大鼠分为7组(n = 8):健康对照组、EGCG (100 mg/kg)、扑热息痛(2 g/kg)、扑热息痛+ EGCG 25 (2 g/kg + 25 mg/kg)、扑热息痛+ EGCG 50 (2 g/kg + 50 mg/kg)、扑热息痛+ EGCG 100 (2 g/kg + 100 mg/kg)和扑热息痛+ n -乙酰半胱氨酸(NAC, 2 g/kg + 140 mg/kg)。我们的研究结果表明,大剂量扑热息痛通过内质网(ER)应激诱导肝损伤,而EGCG通过减弱内质网应激诱导的炎症小体信号传导来减轻肝损伤。
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引用次数: 0
Reducing Anticholinergic Burden in Hospitalised Older Adults: Analysis From the INFAR Study 减轻住院老年人抗胆碱能负担:来自INFAR研究的分析
IF 3.3 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-12-04 DOI: 10.1111/bcpt.70160
Romana Santos Gama, Luiz Carlos Passos, Welma Wildes Amorim, Renato Morais Souza, Marcio Galvão Oliveira

This study aimed to evaluate the effectiveness of pharmacist-led medication reviews in reducing the anticholinergic burden of hospitalised patients with cardiovascular diseases (CVDs), to identify which anticholinergic medications were most frequently prescribed or discontinued during hospitalisation and to investigate factors associated with an elevated anticholinergic burden via secondary analysis of the INFAR study. An uncontrolled before-and-after design was used, and medication reviews were performed for all patients so that the anticholinergic burden of medications prescribed to older adults during their hospital stay could be examined. The mean age of the 319 patients was 68.9 years (±6.2), and upon hospital admission, 40.4% were classified as having a high anticholinergic burden, decreasing to 22.6% at discharge. Multivariate analysis at admission indicated that polypharmacy (PR = 2.00; 95% CI = 1.47–2.72) and potentially inappropriate medication (PR = 4.47; 95% CI = 2.10–9.53) were independently associated with a higher anticholinergic burden; however, only inappropriate medication was significantly associated with a high burden (PR = 2.39; 95% CI = 1.54–3.71) at discharge. The results indicate that a clinical pharmacist-led medication review may reduce the anticholinergic burden in older adults with CVD, highlighting the importance of such a review in promoting safer prescribing practices during hospitalisation.

本研究旨在评估药师主导的药物评价在减少心血管疾病(cvd)住院患者抗胆碱能负担方面的有效性,确定住院期间最常开具或停药的抗胆碱能药物,并通过对INFAR研究的二次分析调查与抗胆碱能负担升高相关的因素。采用不受控制的前后对照设计,并对所有患者进行药物评价,以便检查老年人住院期间处方的抗胆碱能药物负担。319例患者的平均年龄为68.9岁(±6.2岁),入院时40.4%的患者被归为抗胆碱能负荷高,出院时降至22.6%。入院时的多因素分析显示,多药(PR = 2.00, 95% CI = 1.47-2.72)和可能不适当的用药(PR = 4.47, 95% CI = 2.10-9.53)与较高的抗胆碱能负担独立相关;然而,只有用药不当与出院时的高负担显著相关(PR = 2.39; 95% CI = 1.54-3.71)。结果表明,临床药师主导的药物审查可能会减少老年心血管疾病患者的抗胆碱能负担,强调了这种审查在促进住院期间更安全的处方实践中的重要性。
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引用次数: 0
Gadoteric Acid Induces Dose-Dependent DNA Damage and Enzyme Binding in Fibroblast Cells gadoteracid诱导成纤维细胞剂量依赖性DNA损伤和酶结合
IF 3.3 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-12-04 DOI: 10.1111/bcpt.70150
İbrahim Halil Kenger

Gadolinium-based contrast agents, widely used in magnetic resonance imaging, raise safety concerns due to their potential cytotoxic and genotoxic effects, especially at high doses or repeated exposures. In this study, the cytogenotoxic potential of gadoteric acid in NIH3T3 fibroblast cells was evaluated using in vitro and in silico approaches. NIH3T3 cells were treated with increasing concentrations of gadoteric acid. Cytotoxicity was evaluated by MTS assay and genotoxicity by comet assay; hydrogen peroxide (75 μM) was used as a positive control. In addition, the interaction of gadoteric acid with DNA topoisomerase IIα, DNA topoisomerase IIβ, DNA polymerase β, and B-DNA was examined by molecular docking. MTS assay results showed a dose-dependent decrease in cell viability with an IC50 of 28.19 mM. Comet assay revealed significant DNA damage only at the highest concentration (56.38 mM) (p < 0.05), which also caused marked cytotoxicity. Thus, the observed DNA damage likely resulted from cytotoxicity stress rather than direct strand breaks. In silico docking predicted a high binding affinity of gadoteric acid for DNA polymerase β (−11.7 kcal/mol) and other DNA-related targets. However, these predictions require experimental validation. Overall, gadoteric acid exhibited dose-dependent cytotoxicity and limited genotoxicity at high concentrations, suggesting that DNA damage occurs secondary to cytotoxic effects rather than a direct genotoxic mechanism.

钆基造影剂广泛应用于磁共振成像,由于其潜在的细胞毒性和基因毒性作用,特别是在高剂量或重复暴露时,引起了安全性问题。在本研究中,采用体外和计算机方法评估了钆乙酸对NIH3T3成纤维细胞的细胞基因毒性潜力。NIH3T3细胞用浓度增加的钆处理。MTS法测定细胞毒性,comet法测定遗传毒性;过氧化氢(75 μM)作为阳性对照。此外,通过分子对接研究了牛乳酸与DNA拓扑异构酶i α、DNA拓扑异构酶i β、DNA聚合酶β和B-DNA的相互作用。MTS实验结果显示细胞活力呈剂量依赖性下降,IC50为28.19 mM。彗星试验显示,仅在最高浓度(56.38 mM)时DNA损伤显著(p < 0.05),并引起显著的细胞毒性。因此,观察到的DNA损伤可能是由细胞毒性应激而不是直接链断裂引起的。在硅对接预测gadoteracid对DNA聚合酶β (- 11.7 kcal/mol)和其他DNA相关靶点具有高结合亲和力。然而,这些预测需要实验验证。总的来说,gadoteracid在高浓度下表现出剂量依赖性的细胞毒性和有限的遗传毒性,这表明DNA损伤是继发于细胞毒性作用,而不是直接的遗传毒性机制。
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引用次数: 0
Proton Pump Inhibitors and Biomarkers of Haemostasis in Postmenopausal Women: The Buffalo OsteoPerio Study 绝经后妇女血液止血的质子泵抑制剂和生物标志物:水牛骨手术研究
IF 3.3 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-12-04 DOI: 10.1111/bcpt.70156
Ahmed I. Soliman, Jean Wactawski-Wende, Amy E. Millen, Kathleen M. Hovey, Michael J. LaMonte

Aims

Examine the association between proton pump inhibitor (PPI) use and plasma levels of four biomarkers of haemostasis: fibrinogen, von Willebrand factor (vWF), high-sensitivity CRP (hs-CRP) and plasminogen activator inhibitor-1 (PAI-1) in postmenopausal women.

Methods

We conducted a cross-sectional analysis on 200 women in the Buffalo Osteoporosis and Periodontitis study Year 17 visit. PPI use was assessed using medication inventories, and biomarkers were measured using frozen plasma samples. Linear regression was used to estimate mean differences for each biomarker according to PPI use (yes/no) and duration (≤ 1 year, > 1 year). Logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (95% CI) for having a high versus low level of each biomarker. Models were adjusted for major cardiovascular risk factors to account for potential confounding.

Results

PPI users had non-statistically significant higher levels of vWF (mean difference = 52.9 mIU/mL, p = 0.38) and log hs-CRP (mean difference = 0.1 mg/L, p = 0.5) compared to non-users. PPI users for > 1 year had non-statistically significant higher odds of having a high level of vWF (OR = 1.08, 95% CI: 0.51–2.31) and hs-CRP (OR = 1.16, 95% CI: 0.58–2.33) compared to non-users.

Conclusions

There was no significant association between PPI use and measured plasma haemostatic markers.

目的探讨绝经后妇女血浆中纤维蛋白原、血管性血友病因子(vWF)、高敏CRP (hs-CRP)和纤溶酶原激活物抑制剂-1 (PAI-1)水平与质子泵抑制剂(PPI)使用的关系。方法我们对布法罗骨质疏松和牙周炎研究17年访问的200名妇女进行了横断面分析。使用药物清单评估PPI使用情况,使用冷冻血浆样本测量生物标志物。根据PPI使用情况(是/否)和持续时间(≤1年,>; 1年),采用线性回归估计每个生物标志物的平均差异。使用逻辑回归来估计每种生物标志物高水平与低水平的比值比(OR)和95%置信区间(95% CI)。对模型进行了主要心血管危险因素调整,以考虑潜在的混杂因素。结果PPI使用者的vWF水平(平均差值为52.9 mIU/mL, p = 0.38)和log hs-CRP水平(平均差值为0.1 mg/L, p = 0.5)高于非PPI使用者,无统计学意义。PPI使用者1年的vWF (OR = 1.08, 95% CI: 0.51-2.31)和hs-CRP (OR = 1.16, 95% CI: 0.58-2.33)高于非PPI使用者,无统计学意义。结论PPI的使用与血浆止血指标之间无显著相关性。
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引用次数: 0
BCPT 2026 Policy for Experimental and Clinical Studies BCPT 2026实验与临床研究政策。
IF 3.3 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-12-03 DOI: 10.1111/bcpt.70159
Pernille Tveden-Nyborg, Troels K. Bergmann, Niels Jessen, Ulf Simonsen, Jens Lykkesfeldt
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引用次数: 0
Significant Antispastic Effect of Combined Fasudil and Isosorbide Dinitrate on Internal Mammary Artery in Coronary Artery Bypass Grafting 法舒地尔联合硝酸异山梨酯对冠状动脉搭桥术中乳腺内动脉的显著抗痉挛作用
IF 3.3 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-12-03 DOI: 10.1111/bcpt.70148
You-Feng Zhang, Hai-Tao Hou, Qin Yang, Guo-Wei He

Background

Vasospasm of arterial grafts remains a critical problem in coronary artery bypass grafting (CABG), contributing to perioperative ischemia and graft failure. This study evaluates the antispastic effects of combining the ROCK inhibitor fasudil and isosorbide dinitrate (ISDN) on the human internal mammary artery (IMA).

Methods

IMA rings (n = 208) from 94 CABG patients were investigated in a myograph. Relaxation to fasudil (−3.5 log M), ISDN (−4 log M) and their combination (FI solution) was assessed after precontraction with potassium chloride (KCl 30 mM) or U46619 (10−8 M). The preventive effects of FI solution on the contraction induced by KCl or U46619 were studied. ROCK2 protein and cGMP levels were measured using Western blot and ELISA.

Results

FI solution demonstrated superior relaxation compared to either drug alone against KCl or U46619 (p < 0.001). Pretreatment with FI inhibited the contraction by KCl and U46619, significantly higher than that with either drug alone (p < 0.0001). FI also reduced ROCK2 expression (p = 0.0001) and elevated cGMP levels (p = 0.0002).

Conclusions

The combination of fasudil and ISDN effectively prevents and relieves IMA vasospasm mediated by both voltage-operated and receptor-operated calcium channels, with a long-lasting vasorelaxing effect. The FI solution offers a novel approach for preventing and relieving IMA spasm in CABG.

背景在冠状动脉旁路移植术(CABG)中,血管痉挛仍然是一个关键问题,导致围手术期缺血和移植失败。本研究评价了ROCK抑制剂法舒地尔和硝酸异山梨酯(ISDN)联合应用对人乳腺内动脉(IMA)的抗痉挛作用。方法对94例冠脉搭桥患者的IMA环(208个)进行肌图检查。用氯化钾(KCl 30 mM)或U46619(10−8 M)预收缩后,评估法舒地尔(−3.5 log M)、ISDN(−4 log M)及其组合(FI溶液)的松弛度。研究了FI溶液对KCl和U46619诱导的收缩的预防作用。Western blot和ELISA检测各组小鼠ROCK2蛋白和cGMP水平。结果与单独使用KCl或U46619的药物相比,FI溶液表现出更好的松弛作用(p < 0.001)。FI预处理对KCl和U46619的收缩抑制作用显著高于单独用药(p < 0.0001)。FI还降低了ROCK2的表达(p = 0.0001),升高了cGMP水平(p = 0.0002)。结论法舒地尔联合ISDN可有效预防和缓解电压型和受体型钙通道介导的IMA血管痉挛,并具有持久的血管舒张作用。FI解决方案为预防和缓解CABG的IMA痉挛提供了一种新的方法。
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引用次数: 0
Impact of Sex, Age, Body Composition and Kidney Function on the Relationship Between Self-Reported Alcohol Consumption and Phosphatidylethanol—Data From the HUNT Study 性别、年龄、身体组成和肾功能对自我报告饮酒与磷脂酰乙醇关系的影响——来自HUNT研究的数据
IF 3.3 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-12-01 DOI: 10.1111/bcpt.70141
Ragnhild Bergene Skråstad, Øyvind Salvesen, Trine Naalsund Andreassen, Trond Oskar Aamo, Kristian Hveem, Steinar Krokstad, Olav Spigset

Background

Phosphatidylethanol 16:0/18:1 (PEth) is a widely used alcohol marker, but how sex, body size and composition and kidney function affect the dose–response relationship between alcohol consumption and PEth is not fully understood.

Objective

The aim of the study was to investigate whether sex, age, body size and composition and kidney function influence the estimate of alcohol consumed at a given PEth concentration.

Methods

This is a longitudinal population-based cohort study including 24 902 participants from the Trøndelag Health Study (HUNT4). Associations were assessed using a regression model.

Findings

When analysed together, sex and soft lean mass were statistically significant independent predictors of alcohol consumption at a given PEth concentration. To achieve the same PEth concentration as a female, a male with identical body composition could on average consume 21% more alcohol, according to our model. Independent of sex, a person with 10% higher soft lean mass could consume 3.9% more alcohol to achieve the same PEth concentration. When soft lean mass was excluded, height and body weight became significant predictors.

Conclusions

Sex, body composition and body size may have an impact on the dose–response relationship between alcohol consumption and PEth concentration. Thus, these factors will contribute to the uncertainty when estimating ethanol intake from a given PEth concentration.

背景:磷脂酰乙醇(phosphatidyle16:0 /18:1, PEth)是一种广泛使用的酒精标志物,但性别、体型和组成以及肾功能如何影响饮酒与PEth之间的剂量-反应关系尚不完全清楚。目的:本研究的目的是调查性别、年龄、体型、身体成分和肾功能是否会影响给定浓度下的酒精摄入量。方法:这是一项基于人群的纵向队列研究,包括来自Trøndelag健康研究(HUNT4)的24902名参与者。使用回归模型评估相关性。结果:当一起分析时,性别和软瘦质量是在给定的聚醚浓度下酒精消费量的统计显著的独立预测因子。根据我们的模型,为了达到与女性相同的白思浓度,身体成分相同的男性平均需要多摄入21%的酒精。与性别无关,如果一个人的软瘦体重高出10%,那么他可能会多消耗3.9%的酒精来达到相同的PEth浓度。当排除软瘦质量时,身高和体重成为显著的预测因子。结论:性别、身体组成和体型可能会影响饮酒与PEth浓度的剂量-反应关系。因此,这些因素在估计从给定的聚醚浓度中摄入的乙醇时将造成不确定性。
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引用次数: 0
Exosomes in Cardiovascular Disease: Emerging Roles, Therapeutic Potential and Translational Challenges 外泌体在心血管疾病中的作用、治疗潜力和转化挑战。
IF 3.3 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-11-30 DOI: 10.1111/bcpt.70151
Adnan Taan Al Khafaji, Ali Mohammed Barakat, Akram Jooda Al Zaidy, Ali Adnan Taan, Raed Fanoukh Aboqader Al-Aouadi

Cardiovascular diseases (CVDs) remain a leading global cause of mortality, necessitating novel therapeutic strategies to address myocardial injury, adverse remodelling and impaired cardiomyocyte regeneration. Exosomes, nanoscale extracellular vesicles secreted by nearly all cell types, have emerged as pivotal mediators of intercellular communication, influencing cardiac physiology and pathology through their cargo of nucleic acids, proteins and lipids. These vesicles participate actively in processes such as cytoprotection, angiogenesis, apoptosis regulation and immune modulation, which are critical for cardiac repair and regeneration. Recent preclinical and clinical studies highlight the promising regenerative capabilities of exosomes, especially those derived from stem cells and immune cells, positioning them as innovative therapeutic tools and diagnostic biomarkers in CVD management. Despite their potential advantages over traditional cell therapies, including lower immunogenicity and enhanced targeting, several hurdles remain before exosomes can be routinely applied in clinical practice. Challenges include the lack of standardized isolation and characterization protocols, heterogeneity of exosome populations, inefficient cargo loading methods, off-target biodistribution and safety concerns related to immune response and infectious risk. Ongoing research aims to overcome these obstacles to realize exosomes' full potential in cardiovascular regenerative medicine, with diagnostic applications currently representing a nearer-term goal.

心血管疾病(cvd)仍然是全球主要的死亡原因,需要新的治疗策略来解决心肌损伤、不良重构和心肌细胞再生受损。外泌体是由几乎所有细胞类型分泌的纳米级细胞外囊泡,已成为细胞间通讯的关键介质,通过其核酸、蛋白质和脂质的装载影响心脏生理和病理。这些囊泡积极参与细胞保护、血管生成、细胞凋亡调节和免疫调节等过程,对心脏修复和再生至关重要。最近的临床前和临床研究强调了外泌体的再生能力,特别是那些来自干细胞和免疫细胞的外泌体,将它们定位为心血管疾病管理的创新治疗工具和诊断生物标志物。尽管与传统细胞疗法相比,外泌体具有潜在的优势,包括较低的免疫原性和增强的靶向性,但在将外泌体常规应用于临床实践之前,仍存在一些障碍。挑战包括缺乏标准化的分离和表征方案、外泌体种群的异质性、低效的货物装载方法、脱靶生物分布以及与免疫反应和感染风险相关的安全问题。目前正在进行的研究旨在克服这些障碍,实现外泌体在心血管再生医学中的全部潜力,目前的诊断应用代表了一个较近期的目标。
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引用次数: 0
Beyond Preservation: Propyl Gallate's Evolving Story as a Metabolic Precursor and Bioactive Compound 超越保存:没食子酸丙酯作为代谢前体和生物活性化合物的进化故事
IF 3.3 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-11-27 DOI: 10.1111/bcpt.70153
Woo Hyun Park

Propyl gallate (PG), a long-standing synthetic antioxidant, is integral to the food, cosmetic and pharmaceutical industries for its established effectiveness in inhibiting lipid peroxidation. This review synthesizes the evolving scientific narrative of PG, reframing it from a simple preservative to a multifaceted bioactive compound and metabolic precursor. It details PG's physicochemical properties, chain-breaking antioxidant mechanism and applications in advanced active packaging. A central focus is its metabolic fate: PG is rapidly and extensively hydrolyzed to gallic acid (GA) upon ingestion. This transformation is critical, as the systemic biological activities and toxicological profile are largely attributable to its metabolites, positioning PG as a pro-drug. This metabolic context clarifies the historical discrepancy between in vitro genotoxicity, driven by reactive oxygen species (ROS) generation, and its general lack of in vivo genotoxicity. The review examines PG's dual bioactivity, where its pro-oxidant potential underlies promising anti-cancer effects via the induction of apoptosis in various cancer cell lines and restores antibiotic efficacy against resistant bacteria. By summarizing current toxicological data, including its role as a contact allergen, this work highlights the urgent need for future research designed to precisely differentiate the in vivo activities of PG from GA, enabling a more nuanced understanding of its complex and often paradoxical biological role.

没食子酸丙酯(PG)是一种历史悠久的合成抗氧化剂,是食品、化妆品和制药行业不可或缺的一部分,因为它在抑制脂质过氧化方面具有既定的有效性。本综述综合了PG不断发展的科学叙述,将其从简单的防腐剂重新定义为多方面的生物活性化合物和代谢前体。详细介绍了PG的理化性质、断链抗氧化机理及其在先进活性包装中的应用。一个中心焦点是它的代谢命运:PG在摄入后迅速而广泛地水解成没食子酸(GA)。这种转变是至关重要的,因为其系统生物活性和毒理学特征主要归因于其代谢物,将PG定位为前药物。这种代谢背景澄清了由活性氧(ROS)产生驱动的体外遗传毒性与体内普遍缺乏遗传毒性之间的历史差异。该综述研究了PG的双重生物活性,其中其促氧化潜力通过诱导各种癌细胞系的凋亡而具有潜在的抗癌作用,并恢复抗生素对耐药细菌的功效。通过总结目前的毒理学数据,包括其作为接触过敏原的作用,这项工作强调了未来研究的迫切需要,旨在精确区分PG和GA的体内活性,从而更细致地了解其复杂且经常矛盾的生物学作用。
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引用次数: 0
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