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Effectiveness of Acupoint Application in Patients with Pharyngeal Pain: Evidence from CHUNBO, A Prospective Real-World Study

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Chinese Journal of Integrative Medicine 2024年第1期30卷 18-24页

作者： MA Hang-kun WANG Yi-ming GUO Man-ping LI Chen-fei LI Rui GAO Rui Emergency Department Xiyuan Hospital Affiliated to China Academy of Chinese Medical SciencesBeijing(100091)China National Medical products Administration for Laboratory of clinical research and Evaluation of Traditional Chinese Medicine Beijing(100091)China National clinical research Center for Chinese Medicine Cardiology Beijing(100091)China Postdoctoral Workstation of Yabao pharmaceutical Group Co. Ltd.YunchengShanxi Province(044602)China

Objective: To assess the outcomes after acupoint application in patients with pharyngeal pain in a real-world settings, and analyze the characteristics of effective population and prescription characteristics of acupoint application. Methods: Based on CHUNBO platform, patients with pharyngeal pain who were candidates for acupoint application on the basis of physician-evaluation, were enrolled in a nationwide, prospective, 69-week multicenter observational study from August 2020 to February 2022. Propensity score matching(PSM) was used to match the confounding factors and the association rules were used to analyze the characteristics of effective population and prescription characteristics of acupoint application. Outcome assessments included the disappearance rate of pharyngeal pain(within 3, 7, and 14 days), disappearance time of pharyngeal pain, as well as adverse events. Results: Of 7,699 enrolled participants, 6,693(86.9%) received acupoint application and 1,450(21.7%) with non-acupoint application. After PSM, there were 1,004 patients each in the application group(AG) and non-application group(NAG). The disappearance rate of pharyngeal pain in the AG at 3, 7, and 14 days were all higher than those in the NAG(P<0.05). The disappearance time of pharyngeal pain in the AG were shorter than that in the NAG(logrank P<0.001, hazard ratio=1.51, 95% confidence interval: 1.41–1.63). The median age of effective cases was 4 years, mainly 3–6 years old(40.21%). The disappearance rate of pharyngeal pain in the application group with tonsil diseases was 2.19 times higher than that in the NAG(P<0.05). The commonly used acupoints for the effective cases were Tiantu(RN 22), Shenque(RN 8) and Dazhui(DU 14). The commonly used herbs for the effective cases were Natrii sulfas, Radix et Rhizoma Rhei, and Herba Ephedrae. Among them, Natrii sulfas was applied to RN 8 most frequently(support 84.39%). A total of 1,324(17.2%) patients experienced AEs, and mainly occurred in the AG, with significant difference in the incidence of AEs be

关键词： acupoint application Chinese medicine pharyngeal pain multicentre effectiveness characters real-world study

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Mechanism of action of the bile acid receptor TGR5 in obesity

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Acta Pharmaceutica Sinica B 2024年第2期14卷 468-491页

作者： Weijun Lun Qihao Yan Xinghua Guo Minchuan Zhou Yan Bai Jincan He Hua Cao Qishi Che Jiao Guo Zhengquan Su Guangdong Engineering research Center of Natural products and New Drugs Guangdong Provincial University Engineering Technology Research Center of Natural Products and DrugsGuangdong Pharmaceutical UniversityGuangzhou 510006China Guangdong Metabolic Disease research Center of Integrated Chinese and Western Medicine Key Laboratory of Glucolipid Metabolic DisorderMinistry of Education of ChinaGuangdong TCM Key Laboratory for Metabolic DiseasesGuangdong Pharmaceutical UniversityGuangzhou 510006China School of Public Health Guangdong Pharmaceutical UniversityGuangzhou 510310China School of Chemistry and Chemical Engineering Guangdong Pharmaceutical UniversityZhongshan 528458China Guangzhou Rainhome Pharm&Tech Co. Ltd.Science CityGuangzhou 510663China

G protein-coupled receptors(GPCRs)are a large family of membrane protein receptors,and Takeda G protein-coupled receptor 5(TGR5)is a member of this family.As a membrane receptor,TGR5 is widely distributed in different parts of the human body and plays a vital role in regulating metabolism,including the processes of energy consumption,weight loss and blood glucose homeostasis.Recent studies have shown that TGR5 plays an important role in glucose and lipid metabolism disorders such as fatty liver,obesity and diabetes.With the global obesity situation becoming more and more serious,a comprehensive explanation of the mechanism of TGR5 and filling the gaps in knowledge concerning clinical ligand drugs are urgently needed.In this review,we mainly explain the anti-obesity mechanism of TGR5 to promote the further study of this target,and show the electron microscope structure of TGR5 and review recent studies on TGR5 ligands to illustrate the specific binding between TGR5 receptor binding sites and ligands,which can effectively provide new ideas for ligand research and promote drug research.

关键词： Obesity TGR5 Bile acids Ligand Appetite Metabolism GLP-1 Inflammation

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Molecular regulation of the key specialized metabolism pathways in medicinal plants

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Journal of Integrative Plant Biology 2024年第3期66卷 510-531页

作者： Min Shi Siwei Zhang Zizhen Zheng Itay Maoz Lei Zhang Guoyin Kai Zhejiang Provincial International S&T Cooperation Base for Active Ingredients of Medicinal and Edible Plants and Health Zhejiang Provincial Key TCM Laboratory for Chinese Resource Innovation and TransformationSchool of Pharmaceutical SciencesJinhua AcademyZhejiang Chinese Medical UniversityHangzhou 310053China Department of Postharvest Science Agricultural Research OrganizationVolcani CenterRishonLeZion 7505101Israel Department of pharmaceutical Botany School of PharmacyNaval Medical UniversityShanghai 200433China

The basis of modern pharmacology is the human ability to exploit the production of specialized metabolites from medical plants,for example,terpenoids,alkaloids,and phenolic acids.However,in most cases,the availability of these valuable compounds is limited by cellular or organelle barriers or spatio-temporal accumulation patterns within different plant tissues.Transcription factors(TFs)regulate biosynthesis of these specialized metabolites by tightly controlling the expression of biosynthetic genes.Cutting-edge technologies and/or combining multiple strategies and approaches have been applied to elucidate the role of TFs.In this review,we focus on recent progress in the transcription regulation mechanism of representative high-value products and describe the transcriptional regulatory network,and future perspectives are discussed,which will help develop high-yield plant resources.

关键词： biosynthesis medicinal plants omics secondary metabolism transcription factors

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Efficacy and safety of human umbilical cord-derived mesenchymal stem cells in the treatment of refractory immune thrombocytopenia:a prospective,single arm,phase I trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2250-2259页

作者： Yunfei Chen Yanmei Xu Ying Chi Ting Sun Yuchen Gao Xueqing Dou Zhibo Han Feng Xue Huiyuan Li Wei Liu Xiaofan Liu Huan Dong Rongfeng Fu Mankai Ju Xinyue Dai Wentian Wang Yueshen Ma Zhen Song Jundong Gu Wei Gong Renchi Yang Lei Zhang State Key Laboratory of Experimental Hematology National Clinical Research Centre for Blood DiseasesHaihe Laboratory of Cell EcosystemTianjin Key Laboratory of Gene Therapy for Blood DiseasesCAMS Key Laboratory of Gene Therapy for Blood DiseasesInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Tianjin Institutes of Health Science Tianjin 301600China National clinical research Center for Hematologic Diseases Jiangsu Institute of HematologyThe First Affiliated Hospital of Soochow UniversitySuzhou 215006China National Engineering research Centre of Cell products Tianjin Key Laboratory of Engineering Technologies for Cell PharmaceuticalAmCellGene Engineering Co.LtdTianjin 300457China School of Population Medicine and Public Health Chinese Academy of Medical Sciences and Peking Union Medical College100730 BeijingChina

Patients with refractory immune thrombocytopenia(ITP)frequently encounter substantial bleeding risks and demonstrate limited responsiveness to existing therapies.Umbilical cord-derived mesenchymal stem cells(UC-MSCs)present a promising alternative,capitalizing on their low immunogenicity and potent immunomodulatory effects for treating diverse autoimmune disorders.This prospective phase I trial enrolled eighteen eligible patients to explore the safety and efficacy of UC-MSCs in treating refractory ITP.The research design included administering UC-MSCs at escalating doses of 0.5×10^(6)cells/kg,1.0×10^(6)cells/kg,and 2.0×10^(6)cells/kg weekly for four consecutive weeks across three cohorts during the dose-escalation phase,followed by a dose of 2.0×10^(6)cells/kg weekly for the dose-expansion phase.Adverse events,platelet counts,and changes in peripheral blood immunity were monitored and recorded throughout the administration and follow-up period.Ultimately,12(with an addition of three patients in the 2.0×10^(6)cells/kg group due to dose-limiting toxicity)and six patients were enrolled in the dose-escalation and dose-expansion phase,respectively.Thirteen patients(13/18,72.2%)experienced one or more treatment emergent adverse events.Serious adverse events occurred in four patients(4/18,22.2%),including gastrointestinal hemorrhage(2/4),profuse menstruation(1/4),and acute myocardial infarction(1/4).The response rates were 41.7%in the dose-escalation phase(5/12,two received 1.0×10^(6)cells/kg per week,and three received 2.0×10^(6)cells/kg per week)and 50.0%(3/6)in the dose-expansion phase.The overall response rate was 44.4%(8/18)among all enrolled patients.To sum up,UC-MSCs are effective and well tolerated in treating refractory ITP(clinicalTrials.gov ID:NCT04014166).

关键词： doses immunity treatment

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Balancing efficacy and safety of doxorubicin-loaded albumin nanoparticles utilizing pH-sensitive doxorubicin-fatty acid prodrugs

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Nano research 2024年第6期17卷 5491-5500页

作者： Yuanhao Yu Shiyi Zuo Jiaxuan Song Lingxiao Li Tian Liu Jiayu Guo Yaqiao Li Danping Wang Qi Lu Helin Wang Dun Zhou Zhonggui He Xiaohong Liu Bingjun Sun Jin Sun School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China Department of Pharmacy The First Affiliated Hospital of Jinzhou Medical UniversityJinzhou 121001China Joint International research Laboratory of Intelligent Drug Delivery Systems Ministry of EducationShenyang 110016China

Albumin nanoparticles(ANPs)offer unique advantages for antitumor drug delivery system,including non-immunogenicity and inherent tumor-targeting capacity.At present,only a few products,such as ABRAXANE®and FYARRO™,have been approved for clinical applications.The poor affinity of doxorubicin(DOX)for albumin,coupled with its numerous severe adverse reactions,poses challenges in the fabrication of desirable albumin nanoparticles loaded with DOX.In this study,we developed prodrugs by conjugating fatty acids of varying lengths with DOX.Our aim was to investigate the balance between efficacy and safety through the selection of appropriate modules.We synthesized five pH-sensitive doxorubicin-fatty acid prodrugs.Compared to free DOX,all DOX prodrug ANPs exhibited a uniform size distribution with desirable sizes of 150 nm.Additionally,DOX prodrugs with hydrazone bonds remained intact in blood circulation while releasing DOX within tumor cells.Significantly,the characteristics of prodrug ANPs were considerably influenced by the length of fatty acids,impacting their in vivo pharmacokinetics,antitumor effectiveness and tumor accumulation.This research offers a detailed understanding of the length of fatty acid influence on DOX-fatty acid prodrug-based ANPs,and it builds a good platform for creating ANPs which prioritize high drug loading,high efficiency,and minimal side effects.

关键词： fatty acid prodrug albumin doxorubicin pH-sensitive bond nanomedicines

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Cancer treatment with biosimilar drugs:A review

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Cancer Innovation 2024年第2期3卷 45-62页

作者： Shilpa Malakar Emmanuel Nuah Gontor Moses YDugbaye Kamal Shah Sakshi Sinha Priya Sutaoney Nagendra Singh Chauhan Department of Microbiology Kalinga UniversityRaipurChhattisgarhIndia Institute of pharmaceutical research GLA UniversityMathuraUttar PradeshIndia Drug Testing Laboratory Avam Anusandhan KendraRaipurChhattisgarhIndia

Biosimilars are biological drugs created from living organisms or that contain living components.They share an identical amino-acid sequence and immunogenicity.These drugs are considered to be cost-effective and are utilized in the treatment of cancer and other endocrine disorders.The primary aim of biosimilars is to predict biosimilarity,efficacy,and treatment costs;they are approved by the Food and Drug Administration(FDA)and have no clinical implications.They involve analytical studies to understand the similarities and dissimilarities.A biosimilar manufacturer sets up FDA-approved reference products to evaluate biosimilarity.The contribution of next-generation sequencing is evolving to study the organ tumor and its progression with its impactful therapeutic approach on cancer patients to showcase and target rare mutations.The study shall help to understand the future perspectives of biosimilars for use in gastro-entero-logic diseases,colorectal cancer,and thyroid cancer.They also help target specific organs with essential mutational categories and drug prototypes in clinical practices with blood and liquid biopsy,cell treatment,gene therapy,recombinant therapeutic proteins,and personalized medications.Biosimilar derivatives such as monoclonal antibodies like trastuzumab and rituximab are common drugs used in cancer therapy.Escherichia coli produces more than six antibodies or antibody-derived proteins to treat cancer such as filgrastim,epoetin alfa,and so on.

关键词： biologics biosimilars cancer Escherichia coli monoclonal antibody next-generation sequencing pharmacovigilance

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Combination strategies for first-line treatment of patients with unresectable hepatocellular carcinoma:prospect of natural products

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Chinese Journal of Natural Medicines 2024年第1期22卷 1-3页

作者： ZHANG Lele LU Jinjian School of Basic Medical Sciences Chengdu UniversityChengdu 610106China State Key Laboratory of Quality research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078China Department of pharmaceutical Sciences Faculty of Health SciencesUniversity of MacaoMacao 999078China

Liver cancer stands as a significant global health concern,contributing substantially to cancer incidence and mortality,particularly in Asian countries[1].Hepatocellular carcinoma(HCC)accounts for approximately 90%of all liver cancer cases and is characterized by a high-risk profile and a generally poor prognosis[2].To address advanced HCC,systemic therapy has been recommended,leading to the approval of a range of treatment regimens in clinical practice.Traditionally,first-line therapy involved the use of multitargeted tyrosine kinase inhibitors(TKIs)such as sorafenib or lenvatinib,while cabozantinib,ramucirumab.

关键词： Unresectable hepatocellular carcinoma Combination strategies Immunotherapy PD-1/PD-L1 Natural products

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Identifying the geographical origin and processing technology of Moyao(Myrrh) on the basis of near-infrared spectroscopy combined with chemometrics

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Journal of Traditional Chinese Medicine 2024年第3期44卷 505-514页

作者： XU Ningning YAN Ganming XU Fengjie DENG Linfeng QIAO Xinjiang LU Changzheng CHENG Shaomin TCM Diagnosis Institute College of Traditional Chinese MedicineJiangxi University of Chinese Medicine TCM Processing Institute Pharmaceutical CollegeJiangxi University of Chinese medicine School of Electronic Information and Artificial Intelligence Shaanxi University of Science and Technology Jiangzhong pharmaceutical Co. Ltd. Jiangxi Guhan Refined Chinese Herbal Pieces Co. Ltd.

OBJECTIVE: To evaluate the quality of Moyao(Myrrh) in the identification of the geographical origin and processing of the products. METHODS: Raw Moyao(Myrrh) and two kinds of Moyao(Myrrh) processed with vinegar from three countries were identified using near-infrared(NIR) spectroscopy combined with chemometric techniques. Principal component analysis(PCA) was used to reduce the dimensionality of the data and visualize the clustering of samples from different categories. A classical chemometric algorithm(PLS-DA) and two machine learning algorithms [K-nearest neighbor(KNN) and support vector machine] were used to conduct a classification analysis of the near-infrared spectra of the Moyao(Myrrh) samples, and their discriminative performance was evaluated. RESULTS: Based on the accuracy, precision, recall rate, and F1 value in each model, the results showed that the classical chemometric algorithm and the machine learning algorithm obtained positive results. In all of the chemometric analyses, the NIR spectrum of Moyao(Myrrh) preprocessed by standard normal variation or Multivariate scattering correction combined with KNN achieved the highest accuracy in identifying the geographical origins, and the accuracy of identifying the processing technology established by the KNN method after first-order derivative pretreatment was the best. The best accuracy of geographical origin discrimination and processing technology discrimination were 0.9853 and 0.9706 respectively. CONCLUSIONS: NIR spectroscopy combined with chemometric technology can be an important tool for tracking the origin and processing technology of Moyao(Myrrh) and can also provide a reference for evaluations of its quality and the clinical use.

关键词： Moyao () geographical origin near-infrared spectroscopy processing technology

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Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome-wide association and whole genome sequencing analyses

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Cancer Communications 2024年第2期44卷 287-293页

作者： Kouya Shiraishi Atsushi Takahashi Yukihide Momozawa Yataro Daigo Syuzo Kaneko Takahisa Kawaguchi Hideo Kunitoh Shingo Matsumoto Hidehito Horinouchi Akiteru Goto Takayuki Honda Kimihiro Shimizu Masahiro Torasawa Daisuke Takayanagi Motonobu Saito Akira Saito Yuichiro Ohe Shun-ichi Watanabe Koichi Goto Masahiro Tsuboi Katsuya Tsuchihara Sadaaki Takata Tomomi Aoi Atsushi Takano Masashi Kobayashi Yohei Miyagi Kazumi Tanaka Hiroyuki Suzuki Daichi Maeda Takumi Yamaura Maiko Matsuda Yoko Shimada Takaaki Mizuno Hiromi Sakamoto Teruhiko Yoshida Yasushi Goto Tatsuya Yoshida Taiki Yamaji Makoto Sonobe Shinichi Toyooka Kazue Yoneda Katsuhiro Masago Fumihiro Tanaka Megumi Hara Nobuo Fuse Satoshi S.Nishizuka Noriko Motoi Norie Sawada Yuichiro Nishida Kazuki Kumada Kenji Takeuchi Kozo Tanno Yasushi Yatabe Kuniko Sunami Tomoyuki Hishida Yasunari Miyazaki Hidemi Ito Mitsuhiro Amemiya Hirohiko Totsuka Haruhiko Nakayama Tomoyuki Yokose Kazuyoshi Ishigaki Toshiteru Nagashima Yoichi Ohtaki Kazuhiro Imai Ken Takasawa Yoshihiro Minamiya Kazuma Kobayashi Kenichi Okubo Kenji Wakai Atsushi Shimizu Masayuki Yamamoto Motoki Iwasaki Koichi Matsuda Johji Inazawa Yuichi Shiraishi Hiroyoshi Nishikawa Yoshinori Murakami Michiaki Kubo Fumihiko Matsuda Yoichiro Kamatani Ryuji Hamamoto Keitaro Matsuo Takashi Kohno Division of Genome Biology National Cancer Center Research InstituteTokyoJapan Department of clinical Genomics National Cancer Center Research InstituteTokyoJapan Laboratory for Statistical Analysis Center for Integrative Medical SciencesRIKENYokohamaJapan Department of Genomic Medicine Research InstituteNational Cerebral and Cardiovascular CenterOsakaJapan Laboratory for Genotyping Development Center for Integrative Medical SciencesRIKENYokohamaJapan Center for Antibody and Vaccine Therapy Research HospitalInstitute of Medical ScienceThe University of TokyoTokyoJapan Department of Medical Oncology and Cancer Center and Center for Advanced Medicine against CancerShiga University of Medical ScienceOtsuJapan Division of Medical AI research and Development National Cancer Center Research InstituteTokyoJapan Center for Genomic Medicine Graduate School of MedicineKyoto UniversityKyotoJapan Department of Medical Oncology Japanese Red Cross Medical CenterTokyoJapan Department of Thoracic Oncology National Cancer Center Hospital EastJapan Department of Thoracic Oncology National Cancer Center HospitalTokyoJapan Department of Cellular and Organ Pathology Graduate School of MedicineAkita UniversityAkitaJapan Department of Respiratory Medicine Tokyo Medical and Dental UniversityBunkyo-kuTokyoJapan Division of General Thoracic Surgery Department of SurgeryShinshu University School of MedicineMatsumotoNaganoJapan Department of General Surgical Science Division of General Thoracic SurgeryGunma University Graduate School of MedicineIntegrative Center of General SurgeryGunma University HospitalGunmaJapan Department of Gastrointestinal Tract Surgery Fukushima Medical University School of MedicineFukushimaJapan StaGen Co. LtdTokyoJapan Division of Thoracic Surgery National Cancer Center HospitalTokyoJapan Department of Thoracic Surgery National Cancer Center Hospital EastChibaJapan Division of Translational Informatics Exploratory Oncology Research and Clinical Trial Center(EPOC

Dear editor,Lung carcinoma is responsible for the highest fatal-ity rate among cancer-related deaths globally,with lung adenocarcinoma(LADC)emerging as the prevailing sub-type.

关键词： adenocarcinoma lung Lung

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Rapid characterization of non-volatile phenolic compounds reveals the reliable chemical markers for authentication of traditional Chinese medicine Xiang-ru among confusing Elsholtzia species

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Chinese Journal of Natural Medicines 2024年第4期22卷 375-384页

作者： ZENG Zhen ZHANG Chen HU Jiadong WANG Feiyan WU Ziding WANG Jing ZHANG Jun YANG Shuda CHEN Junfeng LI Mingming TONG Qi QIU Shi CHEN Wansheng The SATCM Key Laboratory for New Resources&Quality Evaluation of Chinese Medicine Institute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201203China Department of Pharmacy Second Affiliated Hospital of Navy Medical UniversityShanghai 200003China Kunming Plant Classification Biotechnology Co. Ltd.Kunming 650500China School of pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural products Kunming Medical UniversityKunming 650500China State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Beijing100700China

The aerial parts of Mosla chinensis Maxim.and Mosla chinensis cv.'Jiangxiangru'(MCJ)are widely utilized in traditional Chinese medicine(TCM),known collectively as Xiang-ru.However,due to clinical effectiveness concerns and frequent misidentification,the original plants have increasingly been substituted by various species within the genera Elsholtzia and Mosla.The challenge in distinguishing between these genera arises from their similar morphological and metabolic profiles.To address this issue,our study introduced a rapid method for metabolic characterization,employing high-resolution mass spectrometry-based metabolomics.Through detailed biosynthetic and chemometric analyses,we pinpointed five phenolic compounds—salviaflaside,cynaroside,scutellarein-7-O-D-glucoside,rutin,and vicenin-2—among 203 identified compounds,as reliable chemical markers for distinguishing Xiang-ru from closely related Elsholtzia species.This methodology holds promise for broad application in the analysis of plant aerial parts,especially in verifying the authenticity of aromatic traditional medicinal plants.Our findings underscore the importance of non-volatile compounds as dependable chemical markers in the authentication process of aromatic traditional medicinal plants.

关键词： Genus Elsholtzia Genus Mosla Traditional Chinese medicine Xiang-ru Non-volatile phenolic compounds Liquid chromatography-mass spectrometry

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