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[Solubilization and permeation enhancement of icariin by Epimedium polysaccharide-mediated self-assembled nanoparticles]. 淫羊藿多糖介导的自组装纳米颗粒对淫羊藿苷的增溶和渗透增强作用。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-12-01 DOI: 10.19540/j.cnki.cjcmm.20250916.302
Bin Huang, Yan-Jun Yang, Bing Yang, Mao-Mao Zhu, Liang Feng, Xiao-Bin Jia

In recent years, self-assembled nanostructures of TCM polysaccharides have attracted widespread attention in drug delivery systems. This study investigated the effects of two Epimedium polysaccharides, a neutral polysaccharide(EPSN) and an acidic polysaccharide(EPSA), on the loading of the active component icariin(ICA) and their influence on biopharmaceutical properties. Structural characterization revealed EPSN as a glucan and EPSA as an acidic heteropolysaccharide, both exhibiting triple-helix conformations. Dynamic light scattering(DLS), critical aggregation concentration(CAC), and electron microscopy demonstrated that the polysaccharides self-assembled into nanoparticles in aqueous solutions. Fourier transform infrared spectroscopy(FT-IR) and differential scanning calorimetry(DSC) revealed that hydrogen bonding and π-π stacking interactions occurred between the polysaccharides and ICA. Solubility testing using the saturation shake-flask method, gastrointestinal stability assays, parallel artificial membrane permeability assay(PAMPA), and single-pass intestinal perfusion(SPIP) in rats were used to evaluate and compare the effects of the two polysaccharides on ICA solubility, stability, and permeability. The results showed that both polysaccharides enhanced ICA solubility, stability, and permeability, with EPSA showing superior solubility and stability enhancement, while EPSN exhibited better permeability-promoting effects.

近年来,中药多糖的自组装纳米结构在给药系统中引起了广泛的关注。研究了淫羊藿中性多糖(EPSN)和酸性多糖(EPSA)对淫羊藿活性成分淫羊藿苷(ICA)负载的影响及其对生物制药性能的影响。结构表征表明EPSN为葡聚糖,EPSA为酸性杂多糖,均为三螺旋构象。动态光散射(DLS)、临界聚集浓度(CAC)和电子显微镜显示多糖在水溶液中自组装成纳米颗粒。傅里叶变换红外光谱(FT-IR)和差示扫描量热法(DSC)表明,多糖与ICA之间存在氢键和π-π堆积相互作用。采用饱和摇瓶法测定溶解度、胃肠稳定性、平行人工膜通透性测定(PAMPA)、单次肠灌注(SPIP)等方法评价和比较两种多糖对ICA溶解度、稳定性和通透性的影响。结果表明,两种多糖均能提高ICA的溶解度、稳定性和通透性,其中EPSA具有较好的溶解度和稳定性增强作用,EPSN具有较好的通透性促进作用。
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引用次数: 0
[Anti-arthritis effects of total triterpenoids from fruits of Chaenomeles speciosa based on TLR4/NF-κB/NLRP3 signaling pathway]. [基于TLR4/NF-κB/NLRP3信号通路的木瓜果实总三萜抗关节炎作用]。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-12-01 DOI: 10.19540/j.cnki.cjcmm.20250725.708
Zi-Yuan Meng, Jun-Yu He, Jun-Hui Ma, Ting-Yue Gan, Hai-Bo He, Ying Zhang, Jie Liu, Ji-Hong Zhang, Hao-Ran Li, Hui-Lin Qin, Liang-Liang Jia
<p><p>This study aims to investigate the anti-arthritis effects and mechanisms of total triterpenoids from the fruits of Chaenomeles speciosa(TCS) on MH7A cells treated with lipopolysaccharide(LPS) and adenosine triphosphate(ATP) as well as the rat model of adjuvant arthritis(AA) induced by Freund's complete adjuvant(CFA). In the cell experiment, the MTT assay and Transwell assay were employed to test cell viability and migration, respectively; the colorimetric method and ELISA were employed to determine the levels of lactate dehydrogenase(LDH), cyclooxygenase(COX)-1, COX-2, interleukin(IL)-4, IL-1β, IL-6, IL-10, IL-18, prostaglandin E2(PGE2), and tumor necrosis factor-α(TNF-α) in the cell supernatant; immunofluorescence was utilized to detect the co-localization of NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein containing a CARD(ASC), and cysteinyl aspartate-specific proteinase-1(caspase-1). In the animal experiment, the degree of paw swelling and arthritis index in AA rats were tested; hematoxylin-eosin staining was used to observe the morphological changes in the ankle joint tissue, and the joint histological score was calculated; the colorimetric method and ELISA were utilized to assess the levels of LDH, COX-1, COX-2, IL-4, IL-1β, IL-6, IL-10, IL-18, PGE2, and TNF-α in the synovial tissue of ankle joints in AA rats. Real-time PCR was used to determine the mRNA levels of ASC, caspase-1, COX-1, COX-2, myeloid differentiation factor 88(MyD88), NLRP3, PGE2, and Toll-like receptor 4(TLR4) in MH7A cells and ankle synovial tissue. Western blot was utilized to assess the protein expression levels of ASC, caspase-1, cytosolic NF-κB p65, MyD88, NLRP3, nuclear NF-κB p65, pro-caspase-1, pro-IL-18, pro-IL-1β and TLR4 in MH7A cells and ankle synovial tissues. The results manifested that TCS prominently depressed LPS-and ATP-induced migration of MH7A cells, reduced paw swelling degree and joint index in AA rats, alleviated synovial edema and inflammatory cell infiltration, lessened bone erosion, cartilage destruction, and vascular opacity formation, and lowered joint histological scores of joint inflammation, vascular opacities, and cartilage and bone injury. Moreover, TCS prominently reduced the levels of COX-2, IL-6, IL-18, IL-1β, LDH, PGE2, and TNF-α while heightening the levels of COX-1, IL-4, and IL-10 in the supernatant of MH7A cells and the synovial tissue. It dramatically down-regulated the mRNA levels of ASC, caspase-1, COX-2, MyD88, NLRP3, PGE2, and TLR4, as well as the protein levels of ASC, caspase-1, MyD88, NLRP3, nuclear NF-κB p65, pro-caspase-1, pro-IL-18, pro-IL-1β, and TLR4 in the MH7A cells treated with LPS and ATP and the ankle synovial tissue of AA rats, restrained co-localization of NLRP3, ASC, and caspase-1 in the MH7A cells treated with LPS and ATP, and up-regulated the mRNA level of COX-1 and the protein level of cytosolic NF-κB p65 in the MH7A cells treated with LPS and ATP and the ankle synovial tissue
本研究旨在探讨Chaenomeles speciosa(TCS)果实总三萜对脂多糖(LPS)和三磷酸腺苷(ATP)处理的MH7A细胞的抗关节炎作用及其机制,以及Freund's complete佐剂(CFA)诱导的大鼠佐剂性关节炎(AA)模型。在细胞实验中,分别采用MTT法和Transwell法检测细胞活力和迁移能力;采用比色法和ELISA法检测细胞上清液中乳酸脱氢酶(LDH)、环氧化酶(COX)-1、COX-2、白细胞介素(IL)-4、IL-1β、IL-6、IL-10、IL-18、前列腺素E2(PGE2)、肿瘤坏死因子-α(TNF-α)水平;利用免疫荧光检测nod样受体蛋白3(NLRP3)、含有CARD的凋亡相关斑点样蛋白(ASC)和天冬氨酸半胱氨酸特异性蛋白酶-1(caspase-1)的共定位。动物实验中,测定AA大鼠足跖肿胀程度和关节炎指数;采用苏木精-伊红染色法观察踝关节组织形态学变化,计算关节组织学评分;采用比色法和ELISA法测定AA大鼠踝关节滑膜组织中LDH、COX-1、COX-2、IL-4、IL-1β、IL-6、IL-10、IL-18、PGE2、TNF-α水平。Real-time PCR检测MH7A细胞和踝关节滑膜组织中ASC、caspase-1、COX-1、COX-2、髓样分化因子88(MyD88)、NLRP3、PGE2、toll样受体4(TLR4) mRNA水平。Western blot检测MH7A细胞和踝关节滑膜组织中ASC、caspase-1、胞浆NF-κB p65、MyD88、NLRP3、核NF-κB p65、pro-caspase-1、pro-IL-18、pro-IL-1β和TLR4蛋白的表达水平。结果表明,TCS显著抑制lps和atp诱导的MH7A细胞迁移,减轻AA大鼠足跖肿胀程度和关节指数,减轻滑膜水肿和炎症细胞浸润,减轻骨侵蚀、软骨破坏和血管混浊形成,降低关节炎症、血管混浊、软骨和骨损伤的关节组织学评分。此外,TCS显著降低MH7A细胞和滑膜组织上清液中COX-2、IL-6、IL-18、IL-1β、LDH、PGE2和TNF-α的水平,同时提高COX-1、IL-4和IL-10的水平。显著下调LPS和ATP处理的MH7A细胞和AA大鼠踝滑膜组织中ASC、caspase-1、COX-2、MyD88、NLRP3、PGE2、TLR4 mRNA水平,以及ASC、caspase-1、MyD88、NLRP3、核NF-κB p65、pro-caspase-1、pro-IL-18、pro-IL-1β、TLR4蛋白水平,抑制LPS和ATP处理的MH7A细胞中NLRP3、ASC、caspase-1共定位;上调LPS和ATP处理的MH7A细胞和AA大鼠踝关节滑膜组织中COX-1 mRNA水平和胞浆NF-κB p65蛋白水平。上述结果表明,TCS通过抑制TLR4/NF-κB/NLRP3通路激活,减轻炎症反应,对LPS和ATP处理的MH7A细胞和cfa诱导的AA大鼠模型具有良好的抗类风湿关节炎作用。
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引用次数: 0
[Multiscale structure of small-molecule dry gels enhances stability and bioavailability of Borneolum Syntheticum]. [小分子干凝胶的多尺度结构提高了冰片的稳定性和生物利用度]。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-12-01 DOI: 10.19540/j.cnki.cjcmm.20250916.304
Kai-Xuan Zhang, Ya-Jun Shi, Yu-Jie Liang, Yi Jiang, Fei Luan, Lu Sun, Jun-Bo Zou, Liang Feng

The chemical instability of the core active components of Borneolum Syntheticum(borneol and isoborneol) is a key factor limiting its quality improvement. In this study, a series of small-molecule gelators based on a cholesterol skeleton were designed and synthesized, and the optimal gelator was selected through gelation-capacity-guided screening to construct a "Borneolum Syntheticum-gelator" dry gel self-assembly system. The preparation process of the dry gel was determined based on Borneolum Syntheticum loss rate, encapsulation efficiency, drug loading capacity, physicochemical characterization, and stability assessment. RESULTS:: showed that dry gels were successfully formed at mass ratios of 1∶1 and 3∶1(Borneolum Syntheticum to gelator 2), with minimal Borneolum Syntheticum loss(0.7% and 0.8%). Corresponding encapsulation efficiencies and drug loading capacities reached 98.86%, 98.96% and 49.76%, 74.88%, respectively. IR and SEM analyses indicated that hydrogen bonding and other intermolecular forces drove the formation of multi-level fibrous network structures, with the 3∶1 ratio producing a more compact three-dimensional architecture. XRD and DSC confirmed the masking of Borneolum Syntheticum's crystalline structure and the formation of new phases in the dry gel system, suggesting that synergistic stabilization was achieved through crystalline transformation and effective encapsulation. Both formulations exhibited excellent stability under high temperature, high humidity, and intense light. The 3∶1 dry gel was selected for pharmacokinetic studies, revealing that the active components, borneol and isoborneol, in the dry gel exhibited prolonged retention time and more stable release profiles in vivo. This study provides new insights for improving the quality of easily degradable TCM components.

合成冰片的核心活性成分(冰片和异冰片)的化学不稳定性是制约其质量提高的关键因素。本研究设计并合成了一系列基于胆固醇骨架的小分子凝胶,并通过凝胶容量引导筛选筛选出最优凝胶,构建了“冰片合成-凝胶”干凝胶自组装体系。以冰片的损失率、包封效率、载药量、理化性质和稳定性评价为指标,确定了干凝胶的制备工艺。结果:合成冰片与凝胶剂2的质量比为1∶1和3∶1,合成冰片的损失最小(0.7%和0.8%)。相应的包封效率和载药量分别达到98.86%、98.96%和49.76%、74.88%。红外和扫描电镜分析表明,氢键和其他分子间作用力驱动了多层次纤维网络结构的形成,3∶1的比例使三维结构更加紧凑。XRD和DSC证实了合成冰片的晶体结构被掩盖,在干凝胶体系中形成了新相,表明通过晶体转变和有效包封实现了协同稳定。两种配方在高温、高湿和强光条件下均表现出优异的稳定性。选择3∶1的干凝胶进行药动学研究,结果表明,该干凝胶中的有效成分冰片和异冰片在体内具有较长的保留时间和较稳定的释放特性。本研究为提高易降解中药成分的质量提供了新的思路。
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引用次数: 0
[Mechanism of Shuangshen Fuzheng Powder in regulating TAMs towards M1 polarization to inhibit lung cancer]. [双参扶正散调节tam向M1极化抑制肺癌的机制]。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-12-01 DOI: 10.19540/j.cnki.cjcmm.20250708.705
Yi Li, Qi-Wei Sun, Tao Xu, Qi Huang, Xi-Yuan Zhang, Qiu-Jun Guo, Bao-Jin Hua, Run-Zhi Qi

This study aims to explore the inhibitory mechanism of Shuangshen Fuzheng Powder(SSG) on the tumor of mice bearing M1 macrophages and Lewis lung cancer cells. Lewis lung cancer cells and polarized RAW264.7 macrophages were mixed for injection to construct a mouse model with lung cancer xenograft. The mice were divided into a Lewis group, an SSG group, a Lewis + M1 macrophage(M1) group, and a Lewis + M1 + SSG group, with 10 mice in each group. The SSG group and the Lewis + M1 + SSG group were administered SSG suspension(208 mg·mL~(-1)) daily by gavage, and the Lewis group and the Lewis + M1 group were given purified water by gavage. The spleen and tumor samples were collected after three weeks of intervention. The volume and weight of subcutaneously transplanted tumors in mice were detected. The proportion of F4/80~+CD86~+ tumor-associated macrophages(TAMs) and the expression of CD206~+ in spleen cells were analyzed by flow cytometry, and the expression of M1 macrophage marker protein inducible nitric oxide synthase(iNOS) in transplanted tumor tissue was detected by immunohistochemical staining(IHC). The expression of iNOS, arginase 1(ARG1), transforming growth factor-β(TGF-β), vascular endothelial growth factor(VEGF), matrix metalloproteinase-9(MMP-9), and macrophage migration inhibition factor(MIF) in transplanted tumor tissue of mice was detected by Western blot(WB), and the chemical constituents of SSG were analyzed by ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap high resolution mass spectrometry(UHPLC-Q-Exactive Orbitrap HR-MS). The results showed that treatment by SSG and co-injection with M1 macrophages could both significantly inhibit the tumor volume and weight, and the inhibitory effects were similar. During treatment by SSG, the tumor burden in the Lewis + M1 + SSG group continued to decrease. The flow cytometry results showed that the SSG group and the Lewis + M1 + SSG group exhibited a significant increase in the CD86~+ expression and a significant decrease in the CD206~+ expression. The IHC results indicated that compared with that of the Lewis group, the expression of iNOS in the SSG group was significantly elevated. The WB assay results showed that the expression of iNOS protein significantly increased, and the expression of ARG1, TGF-β, VEGF, MMP-9, and MIF significantly decreased in the Lewis + SSG group compared with those of the Lewis group. A total of 125 chemical constituents were identified from SSG, mainly including saponins, flavonoids, nucleotides, amino acids, and sugar components. SSG may exert its inhibitory effect on lung cancer by increasing the polarization of macrophages to M1-type TAMs and reducing the polarization to M2-type TAMs. The analysis of the pharmacodynamic components of SSG provides a basis and reference for subsequent research on pharmacokinetics.

本研究旨在探讨双参扶正散对携带M1巨噬细胞小鼠肿瘤和Lewis肺癌细胞的抑制机制。将Lewis肺癌细胞与极化的RAW264.7巨噬细胞混合注射,构建异种肺癌移植小鼠模型。将小鼠分为Lewis组、SSG组、Lewis + M1巨噬细胞(M1)组和Lewis + M1 + SSG组,每组10只。SSG组和Lewis + M1 + SSG组每天灌胃SSG混悬液(208 mg·mL~(-1)), Lewis组和Lewis + M1组灌胃纯净水。干预3周后采集脾脏和肿瘤标本。检测小鼠皮下移植肿瘤的体积和重量。流式细胞术检测脾脏细胞中F4/80~+CD86~+肿瘤相关巨噬细胞(tam)的比例及CD206~+的表达;免疫组化染色(IHC)检测移植瘤组织中M1巨噬细胞标记蛋白诱导型一氧化氮合酶(iNOS)的表达。采用Western blot(WB)检测小鼠移植瘤组织中iNOS、精氨酸酶1(ARG1)、转化生长因子-β(TGF-β)、血管内皮生长因子(VEGF)、基质金属蛋白酶-9(MMP-9)、巨噬细胞迁移抑制因子(MIF)的表达,采用超高高效液相色谱-四极静电场轨道阱高分辨质谱法(UHPLC-Q-Exactive Orbitrap HR-MS)分析SSG的化学成分。结果表明,SSG治疗和与M1巨噬细胞共注射均能显著抑制肿瘤体积和重量,且抑制作用相似。在SSG治疗期间,Lewis + M1 + SSG组的肿瘤负荷持续下降。流式细胞术结果显示,SSG组和Lewis + M1 + SSG组CD86~+表达显著升高,CD206~+表达显著降低。免疫组化结果显示,与Lewis组相比,SSG组iNOS表达明显升高。WB检测结果显示,Lewis + SSG组与Lewis组比较,iNOS蛋白表达显著升高,ARG1、TGF-β、VEGF、MMP-9、MIF表达显著降低。共鉴定出125种化学成分,主要包括皂苷、黄酮类化合物、核苷酸、氨基酸和糖组分。SSG对肺癌的抑制作用可能是通过增加巨噬细胞对m1型tam的极化,减少对m2型tam的极化来实现的。分析SSG的药效学成分,为后续的药代动力学研究提供基础和参考。
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引用次数: 0
[Research advances and prospects in taxonomy of Monascus]. 红曲霉分类学研究进展与展望
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-12-01 DOI: 10.19540/j.cnki.cjcmm.20250908.601
Yi-Wen Wu, Rui Feng, Heng Zhou, Hui-Qin Pan, Shen Ji, Qing Hu

As a fermented rice product by the Monascus fungi, red yeast rice is widely used in the food, pharmaceutical, feed, and cosmetics industries. Since the discovery of monacolin K, a lipid-lowering active component, in the metabolites of red yeast rice in the 1970s, its research value has become increasingly prominent, ushering in a new phase of related studies. However, the taxonomic system of Monascus has long been controversial, which has hindered the fungal resource development and the industrial process standardization to a certain extent. This article systematically reviewed the major advances in the taxonomy and identification techniques of Monascus, highlighting the discrepancies among different classification systems. Specifically, significant differences existed between the classification systems by LI Zhong-qin and Hawksworth, while inconsistencies were also observed between the LI system and DNA sequence analysis results. Based on available evidence, a hypothesis was further proposed that "artificial domestication induces genetic morphological differentiation in Monascus", meaning that strains with the same genetic background may develop stable morphological variations during long-term fermentation and domestication. Multigene phylogenetic analyses(e.g., based on ITS, BenA, RPB2, and other genes) provided preliminary molecular support for this hypothesis, though the underlying mechanisms remain to be further validated through whole-genome comparisons, phenotype-associated gene identification, and other studies. On this basis, this paper proposed the construction of a four-dimensional classification model integrating morphomics, genomics, proteomics, and metabolomics to resolve the taxonomic units and phylogenetic relationships of Monascus more comprehensively and objectively. This taxonomic framework will provide important theoretical support for the scientific utilization, safety evaluation, and industrial application of Monascus resources.

红曲米是由红曲霉发酵而成的大米产品,广泛应用于食品、医药、饲料、化妆品等行业。自20世纪70年代在红曲米代谢物中发现降脂活性成分莫那可林K以来,其研究价值日益凸显,相关研究进入了一个新的阶段。然而,红曲霉的分类体系一直存在争议,这在一定程度上阻碍了真菌资源的开发和工业过程的标准化。本文系统地综述了红曲霉分类学和鉴定技术的主要进展,重点介绍了不同分类体系之间的差异。具体来说,李忠勤和Hawksworth的分类系统之间存在显著差异,LI系统与DNA序列分析结果之间也存在不一致性。在现有证据的基础上,进一步提出了人工驯化诱导红曲霉遗传形态分化的假设,即具有相同遗传背景的菌株可能在长期发酵和驯化过程中形成稳定的形态变异。多基因系统发育分析(如:(基于ITS、BenA、RPB2和其他基因)为这一假设提供了初步的分子支持,尽管其潜在机制仍需通过全基因组比较、表型相关基因鉴定和其他研究进一步验证。在此基础上,提出构建集形态组学、基因组学、蛋白质组学、代谢组学于一体的四维分类模型,更全面、客观地解析红曲霉的分类单位和系统发育关系。该分类框架将为红曲霉资源的科学利用、安全性评价和产业化应用提供重要的理论支持。
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引用次数: 0
[Critical pathways of traditional Chinese medicine and active ingredients for intervention in atherosclerosis: proliferation, migration, and phenotypic transformation of vascular smooth muscle cells]. [中药和有效成分干预动脉粥样硬化的关键途径:血管平滑肌细胞的增殖、迁移和表型转化]。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-12-01 DOI: 10.19540/j.cnki.cjcmm.20250811.602
Ji-Xin Li, Rui-Ling Zhou, Hong-Bo Huang, Yan-Ping Deng, Zi-Rui Wang, Sheng-Jing Liu, Ze-Long Niu, Wen-Ru Wang, Pei-Li Wang

Atherosclerosis, a metabolic disease characterized by the formation of plaques consisting of a combination of cholesterol, calcium, fibrin, and other impurities in blood vessels, is a key risk factor for the development of a variety of cardiovascular and cerebrovascular diseases and a global health problem that needs to be addressed urgently. Vascular smooth muscle cells(VSMCs) are the main cell type in atherosclerotic plaques, and many studies have confirmed that the proliferation, migration, and phenotypic transformation of VSMCs are important driving factors for the development of atherosclerosis. VSMCs have a high degree of plasticity, and in the physiological state, VSMCs are responsible for maintaining vasoconstriction and vasodilation and supporting the normal physiological structure of the blood vessels. In case of tissue injury, abnormal lipid metabolism, and abnormal infiltration of inflammation, VSMCs can be de-differentiated into the synthetic type and possess abnormal proliferation and migration capabilities, which will lead to luminal stenosis, plaque accumulation and even rupture. The multi-target and multi-pathway holistic treatment of traditional Chinese medicine(TCM) is consistent with the complexity of this pathological process. Therefore, the intervention of TCM targeting VSMCs may be a new breakthrough. Based on the existing evidence, this study systematically reviewed the research progress of TCM targeting VSMCs proliferation, migration, and phenotypic transformation to intervene in atherosclerosis, with a view to providing evidence support for the clinical diagnosis and treatment of atherosclerosis with TCM and the exploration of the biological basis of atherosclerosis.

动脉粥样硬化是一种代谢性疾病,其特征是血管中胆固醇、钙、纤维蛋白和其他杂质形成斑块,是多种心脑血管疾病发展的关键危险因素,是一个迫切需要解决的全球健康问题。血管平滑肌细胞(Vascular smooth muscle cells, VSMCs)是动脉粥样硬化斑块的主要细胞类型,许多研究证实VSMCs的增殖、迁移和表型转化是动脉粥样硬化发展的重要驱动因素。VSMCs具有高度的可塑性,在生理状态下,VSMCs负责维持血管收缩和血管舒张,支持血管的正常生理结构。在组织损伤、脂质代谢异常、炎症浸润异常的情况下,VSMCs可去分化为合成型,具有异常的增殖和迁移能力,导致管腔狭窄、斑块积聚甚至破裂。中医多靶点、多途径的整体治疗与这一病理过程的复杂性是一致的。因此,中医药对VSMCs的干预可能是一个新的突破。本研究在现有证据的基础上,系统综述中医药靶向VSMCs增殖、迁移及表型转化干预动脉粥样硬化的研究进展,以期为临床中医诊治动脉粥样硬化及探索动脉粥样硬化的生物学基础提供证据支持。
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引用次数: 0
[Clinical research evidence map analysis of Chinese patent medicines in treatment of depression]. 中成药治疗抑郁症的临床研究证据图分析。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-12-01 DOI: 10.19540/j.cnki.cjcmm.20250728.501
Yan-Yan Chen, Wu-Jian-Wen Zhai, Tong Zhang, Ju-Hua Pan, Shi-Jing Huang

This study uses evidence mapping to summarize and analyze existing clinical research on Chinese patent medicines(CPMs) for the treatment of depression, aiming to identify strengths and shortcomings in this field and provide references for future research. A systematic search was conducted in eight databases, CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, Cochrane Library, and EMbase, for Chinese and English literature published from database inception to June 1, 2024. The clinical research characteristics and methodological quality of the included studies were evaluated, with results presented through figures and tables. A total of 223 studies involving 6 CPMs were included, comprising 181 randomized controlled trials(RCTs), 29 non-randomized controlled trials(non-RCTs), 12 systematic reviews/Meta-analyses, and 1 expert consensus. Among these 6 CPMs, Shugan Jieyu Capsules were the most widely used clinically for treating depression. The research trend on CPMs for depression showed an initial increase followed by a decline. The studies were mainly single-center, small-sample, and short-term. Outcome measures primarily included depression, anxiety, safety indicators, adverse effects, and total effective rate, while less attention was given to quality of life, follow-up and recurrence rates, and traditional Chinese medicine(TCM) syndrome scores. The overall risk of bias in RCT was high, and the quality of systematic review/Meta-analysis was generally low. Non-RCTs did not report sample size estimation, follow-up, or follow-up duration, and most lacked blinding, significantly lowering the credibility of their findings. Future research should adhere to TCM principles, design clinical studies according to standards, and integrate TCM concepts throughout all stages of clinical research. The application of TCM syndrome scores should be standardized and promoted, and greater attention should be paid to patients' quality of life, to improve the quality of research and development in TCM treatment of depression.

本研究采用证据图谱的方法对现有中成药治疗抑郁症的临床研究进行总结和分析,旨在找出该领域的优势和不足,为今后的研究提供参考。系统检索了中国知网、万方、维普、中国医学信息网、PubMed、Web of Science、Cochrane Library、EMbase等8个数据库,检索了自建库至2024年6月1日发表的中英文文献。对纳入研究的临床研究特点和方法学质量进行评价,并通过图表展示结果。共纳入223项研究,涉及6种cpm,包括181项随机对照试验(rct)、29项非随机对照试验(non- rct)、12项系统评价/ meta分析和1项专家共识。在这6种中药中,舒肝解郁胶囊治疗抑郁症的临床应用最为广泛。抑郁症的cpm研究呈现先上升后下降的趋势。这些研究主要是单中心、小样本和短期的。结局指标主要包括抑郁、焦虑、安全指标、不良反应和总有效率,而对生活质量、随访率、复发率和中医证候评分的关注较少。RCT的总体偏倚风险较高,系统评价/ meta分析的质量普遍较低。非随机对照试验没有报告样本量估计、随访或随访时间,大多数缺乏盲法,显著降低了其研究结果的可信度。未来的研究应坚持中医原则,按标准设计临床研究,将中医理念贯穿于临床研究的各个阶段。规范和推广中医证候评分的应用,更加重视患者的生活质量,提高中医药治疗抑郁症的研发质量。
{"title":"[Clinical research evidence map analysis of Chinese patent medicines in treatment of depression].","authors":"Yan-Yan Chen, Wu-Jian-Wen Zhai, Tong Zhang, Ju-Hua Pan, Shi-Jing Huang","doi":"10.19540/j.cnki.cjcmm.20250728.501","DOIUrl":"10.19540/j.cnki.cjcmm.20250728.501","url":null,"abstract":"<p><p>This study uses evidence mapping to summarize and analyze existing clinical research on Chinese patent medicines(CPMs) for the treatment of depression, aiming to identify strengths and shortcomings in this field and provide references for future research. A systematic search was conducted in eight databases, CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, Cochrane Library, and EMbase, for Chinese and English literature published from database inception to June 1, 2024. The clinical research characteristics and methodological quality of the included studies were evaluated, with results presented through figures and tables. A total of 223 studies involving 6 CPMs were included, comprising 181 randomized controlled trials(RCTs), 29 non-randomized controlled trials(non-RCTs), 12 systematic reviews/Meta-analyses, and 1 expert consensus. Among these 6 CPMs, Shugan Jieyu Capsules were the most widely used clinically for treating depression. The research trend on CPMs for depression showed an initial increase followed by a decline. The studies were mainly single-center, small-sample, and short-term. Outcome measures primarily included depression, anxiety, safety indicators, adverse effects, and total effective rate, while less attention was given to quality of life, follow-up and recurrence rates, and traditional Chinese medicine(TCM) syndrome scores. The overall risk of bias in RCT was high, and the quality of systematic review/Meta-analysis was generally low. Non-RCTs did not report sample size estimation, follow-up, or follow-up duration, and most lacked blinding, significantly lowering the credibility of their findings. Future research should adhere to TCM principles, design clinical studies according to standards, and integrate TCM concepts throughout all stages of clinical research. The application of TCM syndrome scores should be standardized and promoted, and greater attention should be paid to patients' quality of life, to improve the quality of research and development in TCM treatment of depression.</p>","PeriodicalId":52437,"journal":{"name":"Zhongguo Zhongyao Zazhi","volume":"50 23","pages":"6760-6769"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145935865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Prevention and treatment of acute kidney injury, renal interstitial fibrosis, and diabetic kidney disease by regulating endoplasmic reticulum stress with traditional Chinese medicine: a review]. [中药调节内质网应激防治急性肾损伤、肾间质纤维化及糖尿病肾病:综述]。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-11-01 DOI: 10.19540/j.cnki.cjcmm.20250725.701
Si-Yu Huang, Xi-Xi Wang, Guan-Ting Chen, Kai-Li Chen, Xu Chen, Lin-Qi Zhang

As the primary excretory organ responsible for maintaining internal homeostasis, renal dysfunction constitutes the pathological foundation of kidney injury. Renal cells are rich in endoplasmic reticulum(ER) structures, making endoplasmic reticulum stress(ERS) a central mechanism in regulating renal homeostasis. Numerous studies have revealed that aberrant activation of ERS leads to abnormal programmed cell death(PCD) in intrinsic renal cells and is closely associated with the progression of various kidney diseases. Consequently, suppressing ERS has emerged as a promising therapeutic direction in renal disease research. TCM offers wide clinical applicability and demonstrates advantages such as multi-target regulation, efficacy enhancement, and toxicity reduction. Accumulating research demonstrates that TCM ameliorates pathological renal damage by modulating ERS in kidney cells, thereby attenuating disease progression. Based on the regulatory mechanisms of ERS signaling pathways, this review focuses on the mechanistic actions of TCM in modulating ERS and its downstream PCD. It summarizes current evidence on the roles of Chinese herbal monomers and compound formulas for treating acute kidney injury(AKI), renal interstitial fibrosis(RIF), and diabetic kidney disease(DKD) by targeting ERS, aiming to provide novel perspectives for innovative clinical prevention and treatment strategies in renal diseases.

肾功能不全是维持体内稳态的主要排泄器官,是肾损伤的病理基础。肾细胞具有丰富的内质网结构,内质网应激(endoplasmic reticulum stress, ERS)是调节肾脏稳态的主要机制。大量研究表明,ERS异常激活可导致肾内生性细胞的异常程序性细胞死亡(PCD),并与各种肾脏疾病的进展密切相关。因此,抑制ERS已成为肾脏疾病研究中一个有前景的治疗方向。中医药具有广泛的临床适用性,具有多靶点调节、增效减毒等优势。越来越多的研究表明,中药通过调节肾细胞内ERS改善病理性肾损害,从而减缓疾病进展。本文从ERS信号通路的调控机制出发,对中药对ERS及其下游PCD的调控机制进行综述。本文综述了中药单体及复方靶向ERS治疗急性肾损伤(AKI)、肾间质纤维化(RIF)和糖尿病肾病(DKD)的研究进展,旨在为创新肾脏疾病的临床防治策略提供新的视角。
{"title":"[Prevention and treatment of acute kidney injury, renal interstitial fibrosis, and diabetic kidney disease by regulating endoplasmic reticulum stress with traditional Chinese medicine: a review].","authors":"Si-Yu Huang, Xi-Xi Wang, Guan-Ting Chen, Kai-Li Chen, Xu Chen, Lin-Qi Zhang","doi":"10.19540/j.cnki.cjcmm.20250725.701","DOIUrl":"https://doi.org/10.19540/j.cnki.cjcmm.20250725.701","url":null,"abstract":"<p><p>As the primary excretory organ responsible for maintaining internal homeostasis, renal dysfunction constitutes the pathological foundation of kidney injury. Renal cells are rich in endoplasmic reticulum(ER) structures, making endoplasmic reticulum stress(ERS) a central mechanism in regulating renal homeostasis. Numerous studies have revealed that aberrant activation of ERS leads to abnormal programmed cell death(PCD) in intrinsic renal cells and is closely associated with the progression of various kidney diseases. Consequently, suppressing ERS has emerged as a promising therapeutic direction in renal disease research. TCM offers wide clinical applicability and demonstrates advantages such as multi-target regulation, efficacy enhancement, and toxicity reduction. Accumulating research demonstrates that TCM ameliorates pathological renal damage by modulating ERS in kidney cells, thereby attenuating disease progression. Based on the regulatory mechanisms of ERS signaling pathways, this review focuses on the mechanistic actions of TCM in modulating ERS and its downstream PCD. It summarizes current evidence on the roles of Chinese herbal monomers and compound formulas for treating acute kidney injury(AKI), renal interstitial fibrosis(RIF), and diabetic kidney disease(DKD) by targeting ERS, aiming to provide novel perspectives for innovative clinical prevention and treatment strategies in renal diseases.</p>","PeriodicalId":52437,"journal":{"name":"Zhongguo Zhongyao Zazhi","volume":"50 22","pages":"6227-6233"},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145936274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Ganoderma lucidum spore polysaccharides regulate JAK2/STAT3 pathway to alleviate cancer-related fatigue in mouse model of spleen deficiency syndrome]. [灵芝孢子多糖调节JAK2/STAT3通路减轻脾虚证小鼠模型癌相关性疲劳]。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-11-01 DOI: 10.19540/j.cnki.cjcmm.20250609.705
Jing He, Lin-Yuan Wang, Ya-Wen Chen, Hao-Yi Qiao, Xiao-Fang Wu, Feng-Wei Zhang, Ming-Hui Jiang, Ying-Li Zhu, Zhen-Hao Li, Jian-Jun Zhang

Ganoderma lucidum spore polysaccharides(GLSP) are the main active ingredients of G. lucidum spores and have pharmacological effects of regulating immunity and inhibiting tumor growth. Cancer-related fatigue is a common concomitant symptom in cancer patients, with no safe and effective therapy. This study established a mouse model of cancer-related fatigue with spleen deficiency syndrome to investigate the effect and mechanism of GLSP in alleviating cancer-related fatigue. First, GLSP was obtained by water extraction and alcohol precipitation, and its content was measured to be approximately 75% by the anthrone sulfate method. GLSP was found to be composed of 10 monosaccharides including glucose, galactose, and mannose by 1-phenyl-3-methyl-5-pyrazolone(PMP) derivatization-HPLC. Using a mouse model of cancer-related fatigue due to spleen deficiency, this study showed that GLSP significantly reduced the tumor volume and weight, prolonged the running time, increased the motilin and gastrin content in the antral tissue, and improved the gastrointestinal digestive function in mice. Moreover, GLSP lowered the serum lactic acid level, increased the ATP concentration in the skeletal muscle, raised the levels of mitochondrial respiratory enzymes Ⅰ and Ⅳ, and promoted material and energy metabolism in the body. In addition, GLSP significantly alleviated the abnormal spleen tissue structure, promoted tumor tissue necrosis, lowered the serum levels of inflammatory factors [interleukin(IL)-1β, tumor necrosis factor(TNF)-α)], increased CD4~+ expression in the spleen tissue, reduced CD8~+ expression, and down-regulated the protein and mRNA levels of JAK2/STAT3 pathway-related factors in model mice. To sum up, GLSP can inhibit Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3) activation by reducing IL-6 expression, raise the CD4~+/CD8~+ level, regulate the tumor microenvironment, enhance immunity, improve gastrointestinal absorption and digestion, promote energy metabolism, and increase the skeletal muscle energy storage level, thereby relieving cancer-related fatigue in mice with the spleen deficiency syndrome.

灵芝孢子多糖(GLSP)是灵芝孢子的主要活性成分,具有调节免疫和抑制肿瘤生长的药理作用。癌症相关性疲劳是癌症患者常见的伴随症状,目前尚无安全有效的治疗方法。本研究建立小鼠癌性疲劳脾虚证模型,探讨GLSP减轻癌性疲劳的作用及机制。首先通过水提醇沉得到GLSP,用硫酸蒽酮法测定其含量约为75%。通过1-苯基-3-甲基-5-吡唑啉酮(PMP)衍生-高效液相色谱法发现GLSP由葡萄糖、半乳糖和甘露糖等10种单糖组成。本研究通过小鼠脾虚癌相关性疲劳模型,发现GLSP显著降低肿瘤体积和重量,延长小鼠运行时间,增加小鼠胃窦组织胃动素和胃泌素含量,改善小鼠胃肠消化功能。此外,GLSP降低血清乳酸水平,增加骨骼肌ATP浓度,提高线粒体呼吸酶Ⅰ和Ⅳ水平,促进机体物质和能量代谢。此外,GLSP可显著缓解模型小鼠脾组织结构异常,促进肿瘤组织坏死,降低血清炎症因子[白细胞介素(IL)-1β、肿瘤坏死因子(TNF)-α]水平,升高脾组织CD4~+表达,降低CD8~+表达,下调JAK2/STAT3通路相关因子蛋白和mRNA水平。综上所述,GLSP可通过降低IL-6的表达,抑制Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)的激活,提高CD4~+/CD8~+水平,调节肿瘤微环境,增强免疫力,改善胃肠道吸收消化,促进能量代谢,增加骨骼肌能量储存水平,从而缓解脾虚证小鼠的癌相关性疲劳。
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引用次数: 0
[Mechanism of Liuwei Dihuang Pills in enhancing GPNMB expression to regulate FcγRⅡB/c-Src pathway for prevention and treatment of Alzheimer's disease]. [六味地黄丸增强GPNMB表达调控FcγRⅡB/c-Src通路防治阿尔茨海默病的机制]。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-11-01 DOI: 10.19540/j.cnki.cjcmm.20250805.401
Wen-Xiao Hou, Yu-Xi Liu, Jia-Rui Miao, Zhong-Kang Zhu, Ye Yin, Jia-Li Liu, Dan-Yu Zhao
<p><p>This study investigated the effect of Liuwei Dihuang Pills on the Fcγ receptor Ⅱ-b(FcγRⅡB)/c-Src tyrosine kinase(c-Src) pathway in senescence-accelerated mouse prone 8(SAMP8) by regulating the expression of the glycoprotein non-metastatic melanoma protein B(GPNMB) and explored the mechanism of the kidney-tonifying and essence-strengthening therapy in the treatment of Alzheimer's disease.(1) For the effects of Liuwei Dihuang Pills on the learning and memory ability, hippocampal β-amyloid protein(Aβ), GPNMB, and autophagy function in SAMP8 mice, eight seven-month-old male senescence-accelerated mouse resistant 1(SAMR1) mice were used as a control group, and 16 male SAMP8 mice of the same age were randomly divided into a model group and a Liuwei Dihuang Pills group. The Liuwei Dihuang Pills group was given 2.36 g·kg~(-1) concentrated Liuwei Dihuang Pills solution by gavage, while the control group and the model group were given the same volume of normal saline twice a day for four consecutive weeks. The learning and memory ability of mice in each group was detected by the Morris water maze experiment; the expression level of Aβ in the hippocampus of mice were detected by enzyme-linked immunosorbent assay(ELISA) and immunohistochemistry; the expression of GPNMB in the hippocampus of mice was detected by immunofluorescence and Western blot; the expression level of ubiquitin-binding protein p62 and microtubule-associated protein light chain 3(LC3) Ⅱ/LC3Ⅰ in the hippocampus of mice was measured by Western blot.(2) For the regulatory effect of GPNMB on the FcγRⅡB/c-Src pathway, eight seven-month-old male SAMR1 mice were used as a control group, and 24 male SAMP8 mice of the same age were randomly divided into a model group, an LV-Vector group, and an LV-GPNMB~(OE) group. The bilateral hippocampus of the LV-Vector group and LV-GPNMB~(OE) group was injected with LV-Vector and LV-GPNMB~(OE) of 2 μL/each side, respectively. Western blot was used to detect the expression level of p62, LC3Ⅱ/LC3Ⅰ, FcγRⅡB, Src homology 2 protein tyrosine phosphatase 1(SHP-1), and c-Src proteins in the hippocampus of mice.(3) For the effect of Liuwei Dihuang Pills in regulating the FcγRⅡB/c-Src pathway by increasing the GPNMB expression, 32 seven-month-old male SAMP8 mice were randomly divided into a model group, a Liuwei Dihuang Pills group, a Liuwei Dihuang Pills + LV-NC group, and a Liuwei Dihuang Pills + LV-shGPNMB group. The bilateral hippocampus of the Liuwei Dihuang Pills + LV-NC group and Liuwei Dihuang Pills + LV-shGPNMB group was injected with LV-NC and LV-shGPNMB, respectively, before the drug treatment. Western blot was used to detect the expression level of p62, LC3Ⅱ/LC3Ⅰ, FcγRⅡB, SHP-1, and c-Src proteins in the hippocampus of mice. The results showed that(1) compared with those of the control group, the escape latency of the model group was significantly increased, and the time spent in the target quadrant and the effective area was significantly decreased. T
本研究通过调节糖蛋白非转移性黑色素瘤蛋白B(GPNMB)的表达,探讨六味地黄丸对衰老加速小鼠易感8(SAMP8)中Fcγ受体Ⅱ-b(Fcγ rⅡB)/c-Src酪氨酸激酶(c-Src)通路的影响,探讨补肾益精疗法治疗阿尔茨海默病的作用机制。(1)为研究六味地黄丸对SAMP8小鼠学习记忆能力、海马β-淀粉样蛋白(a β)、GPNMB及自噬功能的影响,以8只7月龄雄性衰老加速小鼠抗1(SAMR1)小鼠为对照组,16只同龄雄性SAMP8小鼠随机分为模型组和六味地黄丸组。六味地黄丸组大鼠灌胃2.36 g·kg~(-1)浓缩六味地黄丸溶液,对照组和模型组大鼠ig等量生理盐水,每天2次,连续4周。采用Morris水迷宫实验检测各组小鼠的学习记忆能力;采用酶联免疫吸附法(ELISA)和免疫组织化学检测小鼠海马组织中Aβ的表达水平;免疫荧光和Western blot检测小鼠海马组织中GPNMB的表达;Western blot检测小鼠海马组织中泛素结合蛋白p62和微管相关蛋白轻链3(LC3)Ⅱ/LC3Ⅰ的表达水平。(2)为研究GPNMB对FcγRⅡB/c-Src通路的调控作用,以8只7月龄雄性SAMR1小鼠为对照组,24只同龄雄性SAMP8小鼠随机分为模型组、LV-Vector组和LV-GPNMB~(OE)组。LV-Vector组和LV-GPNMB~(OE)组双侧海马分别注射2 μL/侧的LV-Vector和LV-GPNMB~(OE)。Western blot检测小鼠海马组织中p62、LC3Ⅱ/LC3Ⅰ、FcγRⅡB、Src同源2蛋白酪氨酸磷酸酶1(SHP-1)、c-Src蛋白的表达水平。(3)为研究六味地黄丸通过增加GPNMB表达调节FcγRⅡB/c-Src通路的作用,将32只7月龄雄性SAMP8小鼠随机分为模型组、六味地黄丸组、六味地黄丸+ LV-NC组、六味地黄丸+ LV-shGPNMB组。在药物治疗前,六味地黄丸+ LV-NC组和六味地黄丸+ LV-shGPNMB组双侧海马分别注射LV-NC和LV-shGPNMB。Western blot检测小鼠海马组织中p62、LC3Ⅱ/LC3Ⅰ、FcγRⅡB、SHP-1、c-Src蛋白的表达水平。结果显示:(1)与对照组相比,模型组小鼠的逃逸潜伏期明显增加,在目标象限和有效面积停留的时间明显减少。海马组织中Aβ、GPNMB、p62表达水平显著升高,LC3Ⅱ/LC3Ⅰ表达水平显著降低。与模型组比较,六味地黄丸组大鼠逃避潜伏期明显缩短,靶象限停留时间和有效面积明显增加。Aβ水平显著降低,GPNMB表达水平显著升高。p62表达水平显著降低,LC3Ⅱ/LC3Ⅰ表达水平显著升高。(2)与对照组比较,模型组海马组织中p62、FcγRⅡB、SHP-1、c-Src蛋白表达水平显著升高,LC3Ⅱ/LC3Ⅰ表达水平显著降低。与模型组比较,LV-GPNMB~(OE)组p62、FcγRⅡB、SHP-1、c-Src表达水平显著降低,LC3Ⅱ/LC3Ⅰ表达水平显著升高。(3)与模型组比较,六味地黄丸组p62、FcγRⅡB、SHP-1、c-Src表达水平显著降低,LC3Ⅱ/LC3Ⅰ表达水平显著升高。与六味地黄丸组比较,六味地黄丸+ LV-shGPNMB组p62、FcγRⅡB、SHP-1、c-Src表达水平显著升高,LC3Ⅱ/LC3Ⅰ表达水平显著降低。上述结果提示六味地黄丸可通过上调GPNMB表达抑制FcγRⅡB/c-Src通路,从而增加自噬水平,增强神经保护能力,缓解阿尔茨海默病。
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Zhongguo Zhongyao Zazhi
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