Ginsenoside C-K

点击蓝字，关注我们 Volume 15 · Issue 10 · October 2025 长按扫码 直接阅读 Review papers The latest progress of personalized drug screening and therapy research for common clinical tumors through the PDX model platform Yitong Yuan, Hongling Gao, Yanhong Li, Xiangying Jiao J. Pharm. Anal. 2025. 15(10) 101225 https://doi.org/10.1016/j.jpha.2025.101225 小鼠肿瘤模型的建立对于发现肿瘤发生与发展的生物学靶点、开展靶向药物临床前试验以及制定个体化治疗方案至关重要。目前，人源肿瘤异种移植（PDX）模型能够在组织病理学、分子及遗传水平层面保留原发肿瘤的特征，并维持肿瘤微环境，被广泛认为是最接近人体真实肿瘤特性的动物模型。近年来，随着PDX模型的应用推动了肿瘤研究在药物开发、肿瘤靶点发现及患者精准治疗等领域的深入探索，但其中仍存在一些共性问题。本篇综述重点介绍了常见临床肿瘤的PDX模型在靶向药物筛选和个体化医疗策略制定中的应用，阐述其最新研究进展与常见问题，并探讨PDX模型在肿瘤治疗应用中面临的挑战、改进方法及未来发展方向，为抗癌药物筛选和临床个体化治疗提供了技术指导与展望。 Highlights The response rate of drugs based on the PDX model was significant correlation with clinical outcomes. The PDX model can provide personalized medical options for cancer patients. The tumor subtype database of patients is an urgent task to achieve precise treatment. Systematic review on the extracellular vesicles in reproductive medicine and gamete union Yutao Wang, Honghao Sun, Fangdie Ye, Zhiwei Li, Zhongru Fan, Xun Fu, Yi Lu, Jianbin Bi, Hongjun Li J. Pharm. Anal. 2025. 15(10) 101261 https://doi.org/10.1016/j.jpha.2025.101261 本文作为关于细胞外囊泡（EVs）在生殖医学和配子结合中的系统综述，系统性梳理了EVs（包括外泌体、微囊泡、微粒）在男女生殖生理中的多维度作用——男性生殖中附睾体和前列腺体调控精子成熟与功能；女性生殖中卵泡液、输卵管及子宫EVs分别参与卵母细胞成熟、受精、胚胎发育及植入，且EVs通过携带生物活性分子调控配子结合与胚胎发育。本文深入解析了EVs作为药物递送系统的独特优势，如生物相容性、靶向递送能力及载荷多样性，并结合具体案例展示其在生殖疾病治疗中的转化潜力，包括小分子药物递送、提升辅助生殖技术（ART）成功率等；还分类阐述了EVs亚型的功能差异与协同作用，前瞻性展望了工程化改造、个性化医疗等未来研究方向，且通过可视化图表增强内容可读性，全面展现了EVs在生殖医学中的基础研究价值与临床转化潜力。 Highlights Impact of iron-overloaded follicular fluid on infertility. Use of mesenchymal stem cell-derived exosomes in inflammatory diseases. Importance of intracytoplasmic sperm injection (ICSI) in male infertility. Role of extracellular vesicles in reproductive physiology and ART. Biomarkers of bipolar disorder in omics and neuroimaging Donglin He, Jingzhi Yang, Zuowei Wang, Xin Dong J. Pharm. Anal. 2025. 15(10) 101264 https://doi.org/10.1016/j.jpha.2025.101264 Highlights Biomarkers may provide objective diagnostic criteria for bipolar disorder (BD). Omics and neuroimaging may advance biomarker research for BD. We conducted an overview of current biomarkers for BD. Genomic, transcriptomic, proteomic, metabolomic, and neuroimaging markers are proposed. Currently no biomarker has been definitely identified, but some hold promise. The role of genetics and epigenetics in breast cancer: A comprehensive review of metastasis, risk factors, and future perspectives Yimeng Chai, Yao Shi J. Pharm. Anal. 2025. 15(10) 101268 https://doi.org/10.1016/j.jpha.2025.101268 尽管抗人类表皮生长因子受体2（HER2）靶向药物曲妥珠单抗和拉帕替尼等对于HER2阳性乳腺癌具有显著疗效，但许多患者仍出现原发性或获得性耐药。本综述系统探讨了多种耐药机制：核因子κB受体激活剂（RANK）表达通过激活核因子κB（NF-κB）通路，增强肿瘤细胞存活能力，削弱靶向药物疗效；磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（AKT）等替代信号通路的异常激活；以及肿瘤相关成纤维细胞通过受体酪氨酸激酶（RTK）活化驱动耐药等以上机制对于指导新型治疗策略开发具有重要意义。通过识别潜在生物标志物和治疗靶点，将HER2抑制剂与靶向耐药通路的药物联用，有望改善患者预后。本综述揭示了HER2阳性乳腺癌治疗复杂性，并指出需持续探索新型联合方案以突破耐药瓶颈。 Highlights Resistance to HER2 therapies in HER2+ breast cancer remains a major issue. RANK expression and PI3K/AKT signaling contribute to resistance mechanisms. Tumor-associated fibroblasts drive resistance via receptor tyrosine kinase activation. Combining HER2 inhibitors with drugs targeting resistance pathways may improve efficacy. Epimedii Folium flavonoids: A double-edged sword effect on the liver, a dual exploration of efficacy and toxicity Meijun Yue, Yanlu Liu, Xiaoan Feng, Bo Cao, Xiaofei Fei, Guohui Li, Chunyu Li J. Pharm. Anal. 2025. 15(10) 101269 https://doi.org/10.1016/j.jpha.2025.101269 黄酮类成分作为中药淫羊藿中的主要成分，在肝脏中兼具保护和毒性作用。对于保肝作用，其能够减轻多种肝脏疾病，机制可能与减轻脂质蓄积及减轻肝脏氧化应激等有关；其可诱导肝毒性机制的机制目前尚不明确，但也是由多种通路共同作用的结果，可能与氧化应激以及细胞焦亡有关。在药代动力学方面，关于淫羊藿素的研究较多，淫羊藿素在体内会发生异戊烯基脱氢、黄酮类苷元的糖基化和葡萄糖醛酸化反应，进而发挥药效作用，但是淫羊藿素的中间代谢物还会与某些生物大分子结合，可能引起肝毒性。为了预防淫羊藿中黄酮类成分的肝毒性，同时正确认识淫羊藿中黄酮类成分在肝脏中的药理活性，本文对淫羊藿中黄酮类成分对肝脏的“双重”作用进行综述，重点阐其对肝脏的作用和毒性的最新机制发现。本文讨论了关于淫羊藿中黄酮类成分的药代动力学特点，从代谢层面解释了它对肝脏的疗效和毒性，还探讨了如何预防这种肝损伤的策略，为了解淫羊藿这一经典中药提供新的见解。 Highlights Epimedii Folium flavonoids possess both protective and toxic effects on liver. Epimedii Folium flavonoids play different roles in various organism states. The hepatotoxicity of Epimedii Folium flavonoids may be the result of multiple mechanisms. A multi-omics-empowered framework for precision diagnosis and treatment of lysosomal diseases Nguyen Thi Hai Yen, Nguyen Tran Nam Tien, Nguyen Quang Thu, Franklin Ducatez, Wladimir Mauhin, Olivier Lidove, Soumeya Bekri, Abdellah Tebani, Nguyen Phuoc Long J. Pharm. Anal. 2025. 15(10) 101274 https://doi.org/10.1016/j.jpha.2025.101274 Highlights Diagnosis and treatment of lysosomal diseases (LDs) remains challenging. A paradigm shift is needed to deepen LD understanding, enabling actionable insights. Longitudinal study designs with a multi-omics framework are highlighted. The proposed framework can be generalized to other complex diseases. Regulation of iron metabolism in ferroptosis: From mechanism research to clinical translation Xin Zhang, Yang Xiang, Qingyan Wang, Xinyue Bai, Dinglun Meng, Juan Wu, Keyao Sun, Lei Zhang, Rongrong Qiang, Wenhan Liu, Xiang Zhang, Jingling Qiang, Xiaolong Liu, Yanling Yang J. Pharm. Anal. 2025. 15(10) 101304 https://doi.org/10.1016/j.jpha.2025.101304 铁是人体内一种必需的微量元素，在维持正常生理功能方面至关重要。近期研究发现，铁离子是启动铁死亡过程的一个重要因素，铁死亡是一种以铁过载和脂质过氧化物积累为特征的新型程序性细胞死亡方式。铁代谢途径是调节铁死亡的主要机制之一，因其能维持细胞内的铁稳态。大量研究表明，铁代谢异常可引发芬顿反应，加剧氧化应激，导致细胞膜破裂、细胞功能障碍以及组织结构损伤。因此，调节铁代谢是改善铁死亡的关键策略，也为治疗与铁代谢失衡相关的疾病提供了新的思路。本综述首先总结了铁死亡中调节铁代谢途径的机制，并探讨了各种疾病发病机制与铁代谢之间的联系；随后介绍了能够影响铁代谢的天然和合成的小分子化合物、激素、蛋白质及新型纳米材料；最后，概述了铁调节剂在临床转化中面临的挑战和前景。 Highlights Regulation of iron metabolism as a key strategy to ameliorate ferroptosis. Iron metabolism plays an important role in many diseases mediated by ferroptosis. Utilizing iron regulators to fine-tune cellular iron homeostasis holds promise as a new disease treatment strategy. Brain organoids-on-chip for neural diseases modeling: History, challenges and trends Hongyong Zhang, Nan Huang, Sumin Bian, Mohamad Sawan J. Pharm. Anal. 2025. 15(10) 101323 https://doi.org/10.1016/j.jpha.2025.101323 脑类器官芯片平台已成为神经疾病建模和药物发现领域的开创性工具。该技术是器官芯片与类器官培养两大技术的融合，其充分发挥各自优势，在物理和生物学层面提供了迄今为止最接近体内真实环境的体外模型。本综述系统回顾了脑类器官芯片技术的发展历程、现状与未来趋势。首先介绍了目前公认的通过非定向与定向分化策略培育涵盖多脑区或特定脑域类器官的关键方法。继而介绍了集成微电极与微流控的二维“神经元芯片”，该平台可构建仿生血脑屏障并实现神经元的目标导向学习。文章进一步通过表格梳理了各类芯片模型的技术特点与应用，并图示了该领域的完整发展脉络。最后，展望了集成传感与多器官互作的下一代“四元芯片”在构建全人体生理模型及开发生物智能方面的巨大潜力。本综述为深入理解脑类器官芯片技术在神经科学研究和药物开发中的转化价值奠定了坚实基础。 Highlights Main concepts, history development, and key milestones of brain organoids-on-chip are introduced in the review paper. Recent advancements, limitations, and future perspectives of brain organoids-on-chip are reported. Transformative potentials of brain organoids-on-chip in neural disease modeling and drug discovery field are also emphasized. Original articles Integrating biogravimetric analysis and machine learning for systematic studies of botanical materials: From bioactive constituent identification to production area prediction Sinan Wang, Huiru Xiang, Xinyuan Pan, Jianyang Pan, Lu Zhao, Yi Wang, Shaoqing Cui, Yu Tang J. Pharm. Anal. 2025. 15(10) 101222 https://doi.org/10.1016/j.jpha.2025.101222 Highlights A biogravimetric analysis method is developed to identify bioactive substance group. ML-driven VOCs analysis is established for the identification of production areas. Lobetyolin and codonopsinol B are immune-restoring compounds in Codonopsis Radix. Label-free electrochemical aptasensing of cardiac cell secretomes in cell culture media for the evaluation of drug-induced myocardial injury Zelin Yang, Xilin Chen, Mingang Liao, Feng Liao, Wen Chen, Qian Shao, Bing Liu, Duanping Sun J. Pharm. Anal. 2025. 15(10) 101234 https://doi.org/10.1016/j.jpha.2025.101234 心肌肌钙蛋白I（cTnI）作为心肌损伤的核心生物标志物，具有高特异性和灵敏度，是评估药物心脏毒性的理想指标。然而，现有检测方法，如酶联免疫吸附测定（ELISA）和表面等离子体共振等，存在操作复杂、耗时长及灵敏度有限等问题，难以实现细胞层面的实时监测。为此，本研究开发了一种可实现cTnI的高灵敏度检测的电化学传感平台。该平台基于杂化纳米信号探针与金属有机框架修饰电极的协同作用，能够有效放大检测信号。实验表明，该传感器线性检测范围为0.001–100 ng mL-1，检测限低至0.31 pg mL-1，并能成功应用于阿霉素（DOX）诱导心肌细胞释放cTnI的动态监测，其结果与ELISA方法高度一致，且操作更简便、检测更快。 Highlights A label-free electrochemical aptasensor was proposed for analysis of cTnI from cells. The assembled nanoprobe (Cu-MOF@AuPt@HRP) can co-catalyze the HQ-H2O2 system. NiCoCu MOFs@AuNPs and NTH were used as electrode substrate to improve sensitivity. The aptasensor showed high selectivity and sensitivity with detection limit of 0.31 pg mL−1. The sensor provides a cost-effective way for cardiotoxicity evaluation of antitumor drugs. Tumor cells targetable graphene oxide doped microneedle for synergistic photothermal-chemotherapy treatment of melanoma Zhiqiang Zhang, Junfang Ke, Yuxin Dai, Chenxi Fang, Yunfeng Dai, Chen Wang, Meitao Duan, Jungang Ren, Ming Chen, Chen Wang J. Pharm. Anal. 2025. 15(10) 101270 https://doi.org/10.1016/j.jpha.2025.101270 本研究针对黑色素瘤开发了一种创新的微针药物递送系统，通过整合化疗药物多柔比星、光热治疗剂吲哚菁绿、氧化石墨烯及靶向肽cRGD，实现了对皮下肿瘤的多模式协同治疗。该微针系统可突破皮肤屏障，将药物精准递送至皮下病灶，并在局部形成药物储库。体外实验证实，微针可高效穿透皮肤角质层，促进肿瘤细胞对药物的摄取；负载吲哚菁绿的微针在近红外激光照射下可产生可控光热效应，联合化疗显著增强肿瘤细胞的杀伤效果。体内实验表明，该系统通过光热-化疗协同作用使肿瘤抑制率达98.15%，且由于药物的局部递送特性，显著降低了对心、肾等器官的毒性。这一原位靶向治疗策略为恶性黑色素瘤治疗提供了高疗效、低毒副作用的突破性方案，具有重要转化价值。 Highlights The microneedle transdermal drug delivery system based on graphene oxide loaded with DOX and ICG was established. In situ drug release, chemotherapy, dual photothermal therapy work together enhanced the anti-melanoma efficiency. The synergistic photothermal-chemotherapy perfected anti-melanoma efficiency while minimizing side effects. Ginsenoside CK potentiates SIRT1 to alleviate lupus nephritis through compensating for XBP1-mediated endoplasmic reticulum stress in plasma cells Ziyu Song, Ying Li, Sumei Xu, Shuowen Qian, Wangda Xu, Li Xu, Fengyuan Tian J. Pharm. Anal. 2025. 15(10) 101245 https://doi.org/10.1016/j.jpha.2025.101245 狼疮性肾炎（LN）作为系统性红斑狼疮最常见且最严重的并发症之一，是导致终末期肾脏病甚至死亡的主要原因。近年来研究提示，靶向浆细胞的单克隆抗体疗法为难治性LN提供了潜在新策略。人参皂苷Compound K（CK）作为人参在体内的主要活性代谢产物，已在多种急慢性肾损伤模型中均表现出明确的肾脏保护作用。本研究基于单细胞测序技术，系统阐明了人参皂苷CK通过调控SIRT1/XBP1信号通路在缓解内质网应激中的关键作用。实验结果表明，人参皂苷CK不仅能显著降低血清抗dsDNA抗体水平、改善肾功能指标、促进肾脏免疫复合物清除，还可有效抑制B细胞向浆细胞的异常分化。机制层面进一步揭示，人参皂苷CK通过激活SIRT1、抑制XBP1剪接及其乙酰化修饰，从而显著缓解内质网应激。本研究为LN的靶向治疗提供了新的分子理论依据和潜在候选药物。 Highlights CK effectively improves renal function and clear deposited immune complexes. CK delays the conversion from activated B cells to plasma cells leaning on B cell-specific SIRT1 activation. CK promotes the activation of SIRT1 and inhibits the splicing of XBP1, thereby attenuating plasma cell accumulation. CK enhances SIRT1 function and promotes the deacetylation of XBP1, thereby compensating for ER stress. Prrx1 promotes mesangial cell proliferation and kidney fibrosis through YAP in diabetic nephropathy Liu Xu, Jiasen Shi, Huan Li, Yunfei Liu, Jingyi Wang, Xizhi Li, Dongxue Ren, Sijie Liu, Heng Wang, Yinfei Lu, Jinfang Song, Lei Du, Qian Lu, Xiaoxing Yin J. Pharm. Anal. 2025. 15(10) 101247 https://doi.org/10.1016/j.jpha.2025.101247 糖尿病肾病（DN）是糖尿病最严重的并发症之一，严重影响患者的生存质量，但其发病机制尚不明确。本研究发现，在DN状态下，肾小球系膜细胞中配对相关同源框1（Prrx1）的表达显著上调，且与细胞增殖及纤维化标志物呈正相关。体内外实验显示，Prrx1异常升高可促进db/m小鼠系膜细胞增殖与肾纤维化，减少Prrx1的表达则抑制db/db小鼠高糖诱导的系膜细胞增殖并减轻肾纤维化。在机制上，Prrx1可直接结合Yes相关蛋白1（YAP）启动子，上调YAP表达，促进其核转位并与TEAD结合，激活下游细胞周期调控蛋白，进而引发系膜细胞增殖与细胞外基质积累。Prrx1通过调控YAP转录诱导DN肾纤维化，靶向Prrx1或将成为DN相关肾纤维化的潜在治疗策略。 Highlights Prrx1 exhibited elevated expression levels in diabetic nephropathy, which stimulated mesangial cell proliferation. Renal specific knockdown of Prrx1 improves renal function in diabetic nephropathy mice. Prrx1 binds to YAP promoter to promote YAP transcription and induce mesangial cell proliferation. Metformin alleviates renal tubular injury in diabetic kidney disease by activating mitophagy and inhibiting ferroptosis via HIF-1α/MIOX axis Qinrui Wu, Yanyan Zhao, Fengjuan Huang J. Pharm. Anal. 2025. 15(10) 101284 https://doi.org/10.1016/j.jpha.2025.101284 糖尿病肾病（DKD）作为糖尿病的严重微血管并发症，以进行性蛋白尿和肾功能减退为特征，已成为导致终末期肾病的主要病因之一。本研究聚焦肾小管损伤机制，旨在探索二甲双胍（Metformin）延缓DKD进展的新途径。研究发现，Metformin通过抑制缺氧诱导因子α（HIF-1α），激活糖尿病小鼠肾脏的线粒体自噬，并抑制铁死亡，从而减轻肾脏纤维化进程。进一步的体外实验证实，HIF-1α通过直接结合肌醇加氧酶（MIOX）启动子区域，正向调控MIOX表达，进而驱动线粒体自噬抑制与铁死亡激活。Metformin则通过抑制HIF-1α/MIOX轴，通过恢复线粒体自噬活性并抑制铁死亡，最终延缓DKD病理进展。本研究首次揭示了Metformin通过协同调控铁死亡与线粒体自噬，改善DKD的新机制，突显了其在延缓DKD进展中的潜在治疗价值。 Highlights Metformin mitigates renal injury by modulating mitophagy and ferroptosis in DKD. HIF-1α overexpression enhances MIOX expression, increasing ferroptosis. MET treatment reverses mitochondrial dysfunction and ferroptosis in DKD models. Chromatin immunoprecipitation confirms HIF-1α interacts with the MIOX promoter. Under high glucose, MET activates mitophagy and reduces ferroptosis in RTECs. Integrating gas-chromatographical analyses with nuclear-magnetic-resonance spectroscopy to elucidate anti-microbial profile of oleoresins isolated from Rauvolfia serpentina seeds by supercritical–(CO2)–fluid extraction Acharya Balkrishna, Monali Joshi, Yash Varshney, Manisha Kabdwal, Himanshu Jangid, M. Priya Rani, Pardeep Nain, Savita Lochab, Anurag Varshney J. Pharm. Anal. 2025. 15(10) 101299 https://doi.org/10.1016/j.jpha.2025.101299 Highlights Pioneer supercritical (CO2) extraction was done on seeds of Rauvolfia serpentina L. Utilised GC-FID and GC-MS/MS platforms for the identification of active biomarkers. Quantified phytometabolites using HPTLC, and validated by IR, and NMR techniques. Revealed strong bactericidal effects with non-genotoxic properties on various strains. Foremost studies on Rauvolfia serpentina seeds highlights its novel therapeutic role. Chemical analysis, antihyperglycemic properties and enzyme inhibition of Opuntia dillenii (Ker Gawl.) Haw.: A detailed analysis of pulp and peel extracts El Hassania Loukili, Amal Elrherabi, Asmae Hbika, Amine Elbouzidi, Mohamed Taibi, Mohammed Merzouki, Mohamed Bouhrim, Abdelaaty A. Shahat, Omar M. Noman, Abdellah Azougay, Bruno Eto, Mohamed Bnouham, Belkheir Hammouti, Mohammed Ramdani J. Pharm. Anal. 2025. 15(10) 101320 https://doi.org/10.1016/j.jpha.2025.101320 Highlights Opuntia dillenii extracts show unique chemical profiles in juice and peel. p-coumaric acid dominates in both juice and peel, with notable concentrations. Strong inhibition of α-amylase, lipase, and α-glucosidase in vitro. In vivo, antihyperglycemic effects observed in diabetic rats, without toxicity. Molecular docking shows potent enzyme interactions, outperforming acarbose. A novel approach to assessing quality issues and component annotation in TCM prescription: Insights from 100 common TCM products Huiting Ou, Chunxiang Liu, Saiyi Ye, Lin Yang, Qirui Bi, Wenlong Wei, Hua Qu, Yaling An, Jianqing Zhang, De-an Guo J. Pharm. Anal. 2025. 15(10) 101332 https://doi.org/10.1016/j.jpha.2025.101332 中药复方的质量直接影响临床疗效，然而其质量评价和质量差异成因追溯面临挑战。本研究对市售100个大宗中药复方（共645批）进行了质量评价。通过通用色谱方法结合聚类分析和相似度热图等统计方法，发现19%的复方存在化学成分不一致现象。相关性分析表明，该问题与贵重原料、产品低定价及不同厂家售价差异呈正相关。当单价超过7元、售价低于0.5元或不同生产商价格差异超过两倍时，多厂家产品更易出现质量问题。为了探究质量问题成因，本研究采用液相色谱-高分辨质谱联用技术，结合天然产物高分辨质谱数据库，对100种复方进行了化学成分快速自动鉴定，并通过成分追溯到可能的投料药味，锁定质量一致性差的成因。共在正离子模式下鉴定761个化合物，负离子鉴定673个化合物，其中73个复方的化学成分为首次报道。以P93为例，三个厂家样品轮廓不一致，数据库追溯到差异色谱峰来自大黄，通过自制样本验证不同厂家使用了不同的基原。本研究为大规模中药的质量评价提供了方法学支持。 Highlights First large-scale quality consistency study on 100 TCM prescriptions (645 batches). 19% of prescriptions exhibited inconsistencies, associated with price disparities. Simultaneous annotation of chemicals in 100 prescriptions, 73 newly reported. Case study: TCM-PCDL for compound annotation and ingredient tracing. DHGT-DTI: Advancing drug-target interaction prediction through a dual-view heterogeneous network with GraphSAGE and Graph Transformer Mengdi Wang, Xiujuan Lei, Ling Guo, Ming Chen, Yi Pan J. Pharm. Anal. 2025. 15(10) 101336 https://doi.org/10.1016/j.jpha.2025.101336 本文提出了一种基于双视角异质网络的药物-靶标相互作用（DTI）预测新方法。该方法构建了一个涵盖药物、靶标、疾病和副作用四类节点的多层次异构网络，并融合了药物的分子指纹与靶标的序列特征。在核心特征学习阶段，采用双视角深度表征学习框架：在局部视角，采用异构图的GraphSAGE方法，对节点的直接邻域进行采样与聚合，捕捉其局部拓扑特征；在全局视角，选取了多个元路径，并利用带残差连接的图Transformer网络捕获更高级别的元路径依赖关系。最终整合这两个视角学习到的特征并重构DTI矩阵完成预测任务。实验结果表明该方法能有效协同局部与全局信息并提升DTI预测性能。针对帕金森病药物的案例研究进一步验证了该方法的应用价值与潜力。 Highlights A novel model called DHGT-DTI is proposed for drug-target interaction prediction. DHGT-DTI employs GraphSAGE to extract local features from neighboring nodes and Graph Transformer with residual connections to extract higher-order features from meta-paths, comprehensively capturing the information of heterogeneous networks. Experimental results show that the dual-perspective heterogeneous network feature extraction method effectively improves prediction performance. Fast-adapting graph neural network with prior knowledge for drug response prediction across preclinical and clinical data Hui Guo, Xiang Lv, Shenghao Li, Daichuan Ma, Yizhou Li, Menglong Li J. Pharm. Anal. 2025. 15(10) 101386 https://doi.org/10.1016/j.jpha.2025.101386 高效的药物反应预测对降低药物研发成本、缩短研发周期具有关键意义，但现有计算模型仍面临实验数据稀缺、体外与体内场景间分布偏移等核心挑战。为此，本研究提出一种新的药物反应元学习模型metaDRP，旨在在小样本条件下提升不同药物组织水平任务的预测精度。在癌症药物敏感性基因组学（GDSC）药物筛选数据集及体内数据集中，metaDRP 的性能均达到当前最优模型水平，同时有效缓解分布偏移问题，为将体外控制实验成果转化至临床应用提供了可靠工具。此外，metaDRP 具备内在可解释性，能够为药物作用机制研究提供可信见解，例如阐明埃博霉素 B、培美曲塞等药物的作用通路及分子靶点。该研究为克服药物反应预测中的数据稀缺与分布偏移难题提供了极具潜力的解决方案，同时推动少样本学习在该领域的融合应用。 Highlights MAML-based bilevel optimization framework to boost drug response prediction model’s generalization in low-sample settings. Prior knowledge-driven model with graph neural networks and sparse linear layers for biomolecular network topological information. Attention and bio-annotated weights endow model with interpretability to find key drug-related pathways and target genes. Short communications Suppression of LIF in tumor-associated macrophages contributing to the PD-1/PD-L1 blockade in hepatocellular carcinoma Shuangshuang Yin, Yanming Luo, Miaomiao Jiang, Lifeng Han, Sibao Chen, Leilei Fu, Yuling Qiu, Haiyang Yu J. Pharm. Anal. 2025. 15(10) 101286 https://doi.org/10.1016/j.jpha.2025.101286 肝癌是全球高发的恶性肿瘤，每年新发患者超86万，其中中国占比居世界首位。在原发性肝癌中，肝细胞癌（HCC）占比高达 75%～85%，成为威胁国民健康的主要 “杀手”。传统靶向治疗与免疫治疗作为肝癌治疗的重要手段，面临响应率低、易产生耐药性等难题，亟需寻求更有效的治疗策略。作为传统中药复方制剂，康艾注射液在调节肿瘤免疫微环境方面展现出独特优势。本研究系统揭示其核心作用机制：通过调控 LIF/HMGA2/CYR61 信号轴，抑制巨噬细胞的脂质合成与代谢，推动 M2 型巨噬细胞复极化，同时增强 PD-1 阻滞剂的敏感性，显著提升 PD-1/PD-L1 阻断剂的治疗效果。在动物模型中，康艾注射液与 PD-1 阻滞剂联合使用显著抑制肿瘤生长，更有效减轻 PD-1阻滞剂单药治疗引发的心脏毒性。这一研究成果为肝癌免疫联合治疗提供了新策略与实验依据。 Highlights Effective therapy is achieved as Kang Ai (KA) injection significantly increases the proportion of pro-inflammatory macrophages and CD8+ T cells. PD-1/PD-L1 blockade demonstrates increased responsiveness and decreased immunotoxicity when used in combination with KA injection. Activation of the LIF/HMGA2/CYR61 pathway promotes macrophages M2 polarization, while KA injection inactivates this pathway. A high throughput strategy for traditional Chinese medicine active compound screening based on Raman spectroscopy Mengyin Tian, Xiaobo Ma, Yuandong Li, Hengchang Zang, Lian Li J. Pharm. Anal. 2025. 15(10) 101334 https://doi.org/10.1016/j.jpha.2025.101334 传统中药活性成分筛选耗时费力，已严重制约中药研发进程。本研究以安宫牛黄丸（AGNHP）为研究对象，提出一种基于拉曼光谱的高通量筛选策略，为解决中药复杂体系活性成分鉴定难题提供新方案。本研究结合高效液相色谱-串联质谱、网络药理学、单细胞拉曼光谱与机器学习构建-判别模型，并搭配细胞功能试验进行验证。结果成功鉴定出AGNHP中47种化合物，筛选出小檗碱、黄芩素等 4 种核心活性成分，这些成分能有效修复脂多糖诱导的细胞损伤，调节脂质代谢与炎症因子水平。该策略无需标记、预处理简单， 预测模型准确率达98.3%，可快速捕获细胞表型，显著降低假阳性率，大幅提升中药活性成分筛选的效率与准确性。 Highlights Single-cell Raman technology was applied to screen the critical active compounds in AGNHP. Berberine, baicalein, epiberberine, and cholic acid in AGNHP may play a more critical role in the treatment of stroke. We developed an integrated strategy combining multiple technologies for efficient screening of critical active ingredients in TCM. Emodin is a novel phosphatidylethanolamine anabolism inhibitor that reprograms lipid metabolism to overcome 5-fluorouracil resistance in colorectal cancer Yanyan Chen, Yanchen Liu, Zhicheng Gong, Zhaohui Huang J. Pharm. Anal. 2025. 15(10) 101343 https://doi.org/10.1016/j.jpha.2025.101343 结直肠癌（CRC）是全球面临的重大公共卫生挑战，其发病率在恶性肿瘤中位居第三，死亡率高居第二。5-氟尿嘧啶（5-Fu）是结直肠癌治疗中的核心化疗药物。然而，患者几乎不可避免地出现耐药性，严重限制了其临床疗效。因此，本研究首次揭示，在5-Fu耐药的CRC细胞中，5-Fu处理可引发独特的脂代谢重编程，导致多种磷脂酰乙醇胺（PE）显著积聚。这些积聚的PE能够改变磷脂酰乙醇胺结合蛋白1（PEBP1）的结合偏好，使其从RAF1转向IKKα/β，进而释放RAF1并激活MAPK信号通路，最终维持耐药细胞在药物压力下的存活。进一步研究发现，天然化合物大黄素可通过直接靶向丝氨酸/苏氨酸激酶PIM1，抑制PE合成，恢复PEBP1与RAF1的结合，从而阻断MAPK通路并逆转5-Fu耐药。综上所述，本研究为克服结直肠癌化疗耐药提供了新的联合治疗策略与理论依据。 Highlights Emodin overcomes 5-Fu resistance in colorectal cancer. 5-Fu drives PE accumulation to shift PEBP1 binding partners and activate MAPK signaling, which maintains drug resistance. Emodin acts as a novel PE anabolism inhibitor by directly targeting PIM1. Emodin reverses 5-Fu-induced PE accumulation to restore the PEBP1-RAF1 interaction to inactivate MAPK signaling. 近期阅读： JPA文章推荐 | 汕头大学李吉林/侯凯健科研团队成果：肠道抗炎药物靶点作为心血管疾病风险潜在调节因子 JPA文章推荐 | 北京大学张亮仁科研团队成果——DTLCDR：一种基于靶标信息的多模态抗癌药物反应预测模型 期刊简介 Journal of Pharmaceutical Analysis（JPA,《药物分析学报（英文）》）创刊于2011年，由教育部主管，西安交通大学主办，是国内第一本有关药物分析的专业英文学术期刊，JPA 始终秉承服务国家重大战略需求、建设世界一流科技期刊的办刊宗旨，重点报道药物发现与药品全生命周期质量控制的新理论、新技术、新方法，临床精准用药，以及药物与生物、人工智能等交叉领域的技术方法方面的最新研究成果，为全球药物研发和药品质量控制提供高水平的国际学术交流平台，持续推动药物分析学科以及药学领域的快速发展。 JPA目前已组建一支以主编贺浪冲教授为核心的国际化的学术团队和专业的编辑出版团队，已实现编委国际化、稿源国际化、同行评议国际化、读者国际化和出版国际化。已被SCIE、PubMed、Scopus、DOAJ、中国科学引文数据库（CSCD）等多种重要国际和国内数据库和评价体系定为刊源。JPA连续7年入选“中国最具国际影响力学术期刊”。2019年入选“中国科技期刊卓越行动计划”重点期刊，2024年入选“中国科技期刊卓越行动计划二期”英文领军期刊。2024年影响因子 8.9，位于全球药理学和药学类学术期刊第14位（14/352），进入药学与药理学前4%，继续稳居于Q1区前列。2025年中科院1区，Top期刊。 收稿范围 药物分析新技术、新方法，分析药理学，药物代谢与递送，中药与天然药物，生物传感，可视化分析，生物功能分析，生物技术药物，药物分析装备，人工智能应用 收稿栏目 原创论文、综述、快报、展望、观点、新闻、社评等 期刊官网 https://www.journals.elsevier.com/journal-of-pharmaceutical-analysis 投稿网址 https://www.editorialmanager.com/jpa/Default.aspx  编辑 | 李   蕾  校对 | 朱丹丹 审核 | 王梦杰、马维娜 阅读原文 了解更多