1.Artesunate Inhibits the Proliferation and Migration of Cutaneous Squamous Cell Carcinoma by Regulating the SLC7A11-GPX4Pathway via the p300-p53 Axis
Xinyan HUANG ; Wenxi WANG ; Songzhao ZHANG ; Lili LI ; Jihui HUANG
Biomolecules & Therapeutics 2025;33(2):365-377
The incidence of cutaneous squamous cell carcinoma (CSCC) is increasing rapidly. This study discussed the effects of artesunate (ART) on CSCC cell proliferation and migration via the solute carrier family 7 member 11 (SLC7A11)-glutathione peroxidase 4 (GPX4) pathway. MTT assessed cell viability and analyzed the IC50 value (69.26 μM). Accordingly, human CSCC cells (A431) were cultured in vitro, and treated with 70 μM ART, Ferrostatin-1, oe-SLC7A11, and C646, with cell biological behavior assessed.The potential targets of ART were predicted. p53 acetylation and protein stability and ART-p300 binding were examined. Thymusless nude mice were subcutaneously inoculated with A431 cells, and treated with ART and C646. ART-treated A431 cells showed weakened proliferation, migration, lactate dehydrogenase levels, oxidized glutathione/glutathione ratio, reactive oxygen species, malondialdehyde, and active Fe2+ levels, which could be reversed by suppressing ferroptosis. ART promoted p53 acetylation and protein stability and curbed the SLC7A11-GPX4 pathway by targeting p300. ART stimulated ferroptosis via the SLC7A11-GPX4 pathway, thereby repressing CSCC cell proliferation and migration, which were counteracted by p300 inhibition. ART regulated the SLC7A11-GPX4 pathway by up-regulating the p300-p53 axis, thereby hindering tumor growth in vivo. Collectively, ART inhibits CSCC proliferation and migration by modulating the SLC7A11-GPX4 pathway through the p300-p53 axis.
2.Artesunate Inhibits the Proliferation and Migration of Cutaneous Squamous Cell Carcinoma by Regulating the SLC7A11-GPX4Pathway via the p300-p53 Axis
Xinyan HUANG ; Wenxi WANG ; Songzhao ZHANG ; Lili LI ; Jihui HUANG
Biomolecules & Therapeutics 2025;33(2):365-377
The incidence of cutaneous squamous cell carcinoma (CSCC) is increasing rapidly. This study discussed the effects of artesunate (ART) on CSCC cell proliferation and migration via the solute carrier family 7 member 11 (SLC7A11)-glutathione peroxidase 4 (GPX4) pathway. MTT assessed cell viability and analyzed the IC50 value (69.26 μM). Accordingly, human CSCC cells (A431) were cultured in vitro, and treated with 70 μM ART, Ferrostatin-1, oe-SLC7A11, and C646, with cell biological behavior assessed.The potential targets of ART were predicted. p53 acetylation and protein stability and ART-p300 binding were examined. Thymusless nude mice were subcutaneously inoculated with A431 cells, and treated with ART and C646. ART-treated A431 cells showed weakened proliferation, migration, lactate dehydrogenase levels, oxidized glutathione/glutathione ratio, reactive oxygen species, malondialdehyde, and active Fe2+ levels, which could be reversed by suppressing ferroptosis. ART promoted p53 acetylation and protein stability and curbed the SLC7A11-GPX4 pathway by targeting p300. ART stimulated ferroptosis via the SLC7A11-GPX4 pathway, thereby repressing CSCC cell proliferation and migration, which were counteracted by p300 inhibition. ART regulated the SLC7A11-GPX4 pathway by up-regulating the p300-p53 axis, thereby hindering tumor growth in vivo. Collectively, ART inhibits CSCC proliferation and migration by modulating the SLC7A11-GPX4 pathway through the p300-p53 axis.
3.Textual Research of Key Information of Classic Formula Xieqingwan Based on Ancient and Modern Literature
Yujie CHANG ; Lyuyuan LIANG ; Jialei CAO ; Xinghang LYU ; Wenxi WEI ; Xiaofang WANG ; Huizhen ZHANG ; Sai REN ; Mengqi WANG ; Bingqi WEI ; Bingxiang MA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):226-234
ObjectiveThis paper aims to systematically collect and organize ancient and modern clauses and studies containing Xieqingwan, excavate and analyze the key information of Xieqingwan, and provide a reference for facilitating the development of the classic formula Xieqingwan. MethodsThe composition, dosage, decocting methods, usage, and other key information of Xieqingwan in ancient traditional Chinese medicine books were collected and analyzed by means of literature research and metrological methods. The modern clinical application of Xieqingwan was summarized. ResultsA total of 42 pieces of effective data involving 32 ancient traditional Chinese medicine books were collected. Xieqingwan was first recorded in Xiaoer Yaozheng Zhijue. The drug origin of this formula is basically clear in the ancient traditional Chinese medicine books. The modern drug usage and decocting method were as follows: Angelicae Sinensis Radix, Gentianae Radix et Rhizoma, Chuanxiong Rhizoma, Gardenia seeds, Radix et Rhizoma Rhei, Notopterygii Rhizoma et Radix, and Saposhnikoviae Radix were grounded to fine powder, decocted with honey, and finally formed into pills with the size of a chicken head (1.5 g). It was suggested that half a pill or one pill were taken for one dose with warm Lophatheri decoction and sugar. The indications and clinical application had developed from the recordings in Xiaoer Yaozheng Zhijue and evolved from pediatrics to ophthalmic otolaryngology, neurology, dermatology, digestion, and respiratory diseases. The main pathogenesis of these diseases is heat in the liver meridian and is treated. The effect of Xieqingwan is "clearing away heat and toxicity, removing fire and relaxing the bowels, and dispersing swelling and relieving pain". It is recommended to use the corresponding preparation methods in the 2020 Edition of Pharmacopoeia of the People's Republic of China. Modern clinical studies are centered around the clinical application of Xieqingwan, which is often modified and used in treating Tourette syndrome, herpes, febrile convulsion, sleepwalking, and insomnia. ConclusionThis paper conducts a thorough textual research of the key information of Xieqingwan, induces its historic evolution, and confirms its key information, so as to provide a reference for the future development of Xieqingwan.
4.Artesunate Inhibits the Proliferation and Migration of Cutaneous Squamous Cell Carcinoma by Regulating the SLC7A11-GPX4Pathway via the p300-p53 Axis
Xinyan HUANG ; Wenxi WANG ; Songzhao ZHANG ; Lili LI ; Jihui HUANG
Biomolecules & Therapeutics 2025;33(2):365-377
The incidence of cutaneous squamous cell carcinoma (CSCC) is increasing rapidly. This study discussed the effects of artesunate (ART) on CSCC cell proliferation and migration via the solute carrier family 7 member 11 (SLC7A11)-glutathione peroxidase 4 (GPX4) pathway. MTT assessed cell viability and analyzed the IC50 value (69.26 μM). Accordingly, human CSCC cells (A431) were cultured in vitro, and treated with 70 μM ART, Ferrostatin-1, oe-SLC7A11, and C646, with cell biological behavior assessed.The potential targets of ART were predicted. p53 acetylation and protein stability and ART-p300 binding were examined. Thymusless nude mice were subcutaneously inoculated with A431 cells, and treated with ART and C646. ART-treated A431 cells showed weakened proliferation, migration, lactate dehydrogenase levels, oxidized glutathione/glutathione ratio, reactive oxygen species, malondialdehyde, and active Fe2+ levels, which could be reversed by suppressing ferroptosis. ART promoted p53 acetylation and protein stability and curbed the SLC7A11-GPX4 pathway by targeting p300. ART stimulated ferroptosis via the SLC7A11-GPX4 pathway, thereby repressing CSCC cell proliferation and migration, which were counteracted by p300 inhibition. ART regulated the SLC7A11-GPX4 pathway by up-regulating the p300-p53 axis, thereby hindering tumor growth in vivo. Collectively, ART inhibits CSCC proliferation and migration by modulating the SLC7A11-GPX4 pathway through the p300-p53 axis.
5.Textual Research and Ancient and Modern Application of Classical Prescription Sinisan
Lyuyuan LIANG ; Qing TANG ; Jialei CAO ; Wenxi WEI ; Yuxin ZHANG ; Jinyu CHEN ; Hejia WAN ; Chen CHEN ; Ruiting SU ; Bingqi WEI ; Shen'ao DING ; Bingxiang MA ; Wenli SHI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):182-193
Sinisan is a classical prescription developed and applied by ancient medical experts and it is first recorded in the Treatise on Cold Damage written by ZHANG Zhongjing in the Eastern Han Dynasty. Later physicians have modified this prescription based on this original one. The bibliometrics methods were used to analyze the key information and research trend of Sinisan. According to the inclusion and exclusion criteria, 69 pieces of effective data were extracted, involving 67 ancient traditional Chinese medicine (TCM) books. The results showed that the name, composition, and decocting methods of Sinisan in later generations were inherited from the original record in the Treatise on Cold Damage. The original plants of medicinal materials used in Sinisan are basically clear. We recommend Bupleuri Radix as the dried root of Bupleurem scorzonerifolium, Paeoniae Radix Alba as the dried root of Paeonia lactiflora, Aurantii Fructus as the dried fruit of Citrus aurantium, Glycyrrhizae Radix et Rhizoma as the dry root and rhizome of Glycyrrhiza uralensis. Raw materials of Bupleuri Radix and Paeoniae Radix Alba, Aurantii Fructus stir-fried with bran, and stir-fried Glycyrrhizae Radix et Rhizoma should be used for preparation of Sinisan. According to measurement system in the Han Dynasty, a bag of Sinisan is composed of 1.25 g Bupleuri Radix, 1.25 g Paeoniae Radix Alba, 1.25 g Aurantii Fructus, and 1.25 g Glycyrrhizae Radix et Rhizoma. The materials should be grounded into coarse powder and taken with a proper amount of rice soup, 3 times a day. Sinisan has the effects of regulating qi movement and harmonizing the liver and spleen. It can be used for treating reversal cold in limbs and cold damage. In modern clinical practice, Sinisan can be used to treat chronic gastritis, irritable bowel syndrome, and dyspepsia. The above research results provide scientific reference for the future research and development of Sinisan.
6.Establishment and Implementation of Post-marketing Benefit-risk Assessment Strategy for Traditional Chinese Medicine
Meng QIAO ; Wenxi PENG ; Qiang ZHANG ; Chao LEI ; Yanming XIE ; Zhifei WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):253-260
The field of post-marketing benefit-risk assessment for traditional Chinese medicine(TCM) is still in its nascent stage, lacking a universally accepted and cohesive evaluation framework and standards. This study presented a strategy developed for the benefit-risk assessment of post-marketing of TCM, and explored the critical techniques and specific implementation steps involved in the assessment process. Initially, appropriate qualitative assessment frameworks and quantitative analysis models were selected for the integrated qualitative and quantitative benefit-risk assessment. Subsequently, key technologies were outlined, including the establishment of a benefit-risk indicator system, the assignment of indicator weights, and the definition of criteria attributes. Furthermore, the implementation steps were elaborated, which involved defining decision-making issues, data collection, evaluation methodologies, variability factors, and sensitivity analysis. Finally, a case study of the benefit-risk assessment of a TCM injection for hepatitis B treatment was conducted to validate the feasibility of the proposed strategy. The objective of this research was to provide theoretical support and practical references for the development of a comprehensive post-marketing benefit-risk assessment system for TCM.
7.Analysis and comparison of health education on respiratory infectious diseases at home and abroad
Yan GUAN ; Xili CHEN ; Wenxi WANG ; Ming LI ; Yueming SU ; Zhenyu LIANG ; Dongying ZHANG
Chinese Journal of Health Management 2024;18(11):869-875
Objective:To analyze and compare the health education efforts of respiratory infectious diseases at home and abroad.Methods:The literature related to health education and popular science of respiratory infectious diseases included in the databases of China National Knowledge Infrastructure (CNKI) and Web of Science (WOS) from January 1, 2003 to December 31, 2023 was searched. A total of 4 686 articles were retrieved in CNKI, 1 540 articles unrelated to the theme were excluded, and 3 146 Chinese articles were obtained. In the WOS database, 7 724 articles were retrieved, 3 685 articles about the clinical mechanism of diseases, pharmacology, and other research topics were excluded, and 4 039 English articles were obtained. The information of annual publications, institutions, authors and keywords was analyzed by using CiteSpace visualization software, and the publication status, research hotspots and development trends of health education related to respiratory infectious diseases at home and abroad were analyzed.Results:Since 2003, the number of publications in health education on respiratory infectious diseases at home and abroad had shown a fluctuating growth trend, and in 2020, the field showed a sharp growth trend at home and abroad. There was no core author group in this field in China, and the network density of domestic authors was 0.006 5, and the network density of foreign authors was 0.009 6. The domestic institutions were mainly the Center for Disease Control and Prevention and medical institutions, including Guangzhou Chest Hospital (29 articles) and the Chinese Center for Disease Control and Prevention (10 articles); Foreign research institutions were mainly higher education institutions, including the University of London (91 articles) and Harvard University (67 articles). The network density of domestic was 0.001 3, and the network density of foreign publishing institutions was 0.026 3, the network density was greater than that of Chinese publishing institutions. The emergence of "COVID-19" "Avian influenza" "Knowledge, Attitude, Practice" and "mental health" in China had strong burst (burst intensity: 46.41, 12.12, 10.33, 8.5); "Coronavirus" "coverage" "Avian influenza" and "COVID-19 vaccine" in foreign countries had strong burst (burst intensity: 14.34, 11.06, 10.73, 10.02).Conclusions:At present, the health education of respiratory infectious diseases at home and abroad has received great attention. But the cooperation between domestic authors and research institutions is loose, and the close collaboration needs to be strengthened. There are differences in the research focus of health education on respiratory infectious diseases at home and abroad.
8.Requirements and countermeasures for continuing review in the Ethical Review Measures for Life Science and Medicine Research involving Humans
Pei ZHANG ; Wenxi WANG ; Xiaohui QIU ; Jun CHEN ; Jiyin ZHOU
Chinese Journal of Medical Science Research Management 2024;37(3):192-197
Objective:This paper analyzed the current situation of clinical research continuing review in China, and puts forward countermeasures to strengthen continuing review in combination with the requirements of the Measures for the Ethical Review of Life Science and Medical Research Involving Humans, so as to provide a certain reference for standardizing the ethical continuing review of research institutions.Methods:Through literature research, this paper systematically sorted out the current situation of continuing review, and analyzed many problems and related reasons in the process of continuing review of clinical research in China based on the practical experience of ethical review.Results:The requirements for continuing review in the Measures for Ethical Review of Life Science and Medical Research Involving Humans included demphasizing the implementation of continuing review, the entrusted ethics committee should be responsible for continuing review, clarifying the responsibility for continuing review of cooperative research, clarifying the responsibility of participating research institutions for continuing review, and increasing the responsibility of the ethics committee to supervise the submission of continuing review. Countermeasures to strengthen continuing review included the health authorities urging research institutions to strengthen continuing review, research institutions to increase efforts to implement continuing review, establishing a standardized continuing review process, strengthening the ethics training of researchers and other relevant personnel, establishing a multi-channel communication and consultation method between the ethics committee and researchers, strengthening the review capacity of ethics committee members, allocating a corresponding number of ethics committee staff, and using information technology to improve quality and efficiency.Conclusions:Continuing review is indispensable in the whole process of research development, and all parties should take measures to ensure the quality and efficiency of continuing review, standardize continuing review, and promote the healthy development of life science and medical research.
9.Current situation, legal requirements and management countermeasures of ethics committee archives management
Pei ZHANG ; Jiyin ZHOU ; Wenxi WANG ; Xiaohui QIU ; Jun CHEN
Chinese Journal of Medical Science Research Management 2024;37(4):269-277
Objective:To analyze the current situation of the archives management of ethics committees in China, combine the requirements of the Implementation Regulations of the Archives Law of the People′s Republic of China and the ethics review regulations, and propose countermeasures to strengthen the archives management of ethics committees, thereby further standardizing the archives management of ethics committees.Methods:Through the literature research method, this study systematically reviewed the current situation of the archives management of ethics committees and analyzed its problems and causes in China in combination with related practice experiences.Results:The requirements for ethics committee archives included supervision and management, the establishment of rules and regulations, personnel, site and environment, storage period, confidentiality, and information construction. Countermeasures to strengthen the archives management of ethics committees were suggested including strict daily supervision, strengthening management awareness, establishing and improving the scientific management system and standard operating procedures, setting up independent ethics committee offices and dedicated archives, strictly implementing the confidentiality system, strengthening information construction, and improving utilization rate.Conclusions:To better construct and manage ethics committee archives, a standardized archives management system should be established to effectively evaluate the quality of ethics review and ensure the proper functions of the ethics committee.
10.Exploring the Mechanism of Action of Guhuaisi Kangfu Pill for Treating Steroid-induced Osteonecrosis of the Femoral Head Based on WGCNA and Animal Experiment Validation
Wenxi LI ; Liangyu TIAN ; Jin ZHANG ; Caihong SHEN ; Zhimin YANG ; Jiaqiao GUO ; Yuju CAO
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(9):1306-1318
Objective To investigate the main pharmacological basis and mechanism of action of Guhuaisi Kangfu Pill(GHSKF)in the treatment of steroid-induced osteonecrosis of the femoral head(SONFH).Methods The active constituents and targets of GHSKF were screened by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and other databases.The speculative targets of SONFH were screened out based on GeneCards and Online Mendelian Inheritance in Man(OMIM)databases.The gene modules and hub genes of SONFH were identified using a weighted gene co-expression network analysis(WGCNA).The intersection of the two targets and the result of WGCNA was taken to obtain the potential targets of GHSKF for the treatment of SONFH.The key active constituents were screened with the"active constituent-target"network,which was constructed by the Cytoscape software.Then,the STRING database was used to construct the protein interaction network to screen the key targets.The Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of key targets was performed,and the relationship between key active constituent,key targets and key signaling pathways was explored.Finally,the molecular docking between key active constituents and key targets was verified.In addition,the SONFH rat model was used for experimental verification.Results A total of 146 compounds and the corresponding 346 targets were identified based on the TCMSP database.A total of 4 187 targets of SONFH were obtained based on GeneCards and OMIM databases.In addition,twelve gene modules and 2 556 hub genes of SONFH were screened out based on WGCNA.Quercetin,luteolin and kaempferol were key active ingredients for the treatment of SONFH.Various signaling pathways such as PI3K/AKT were involved.Molecular docking showed the key active ingredients had good binding activity with the key targets.The results of animal experiments demonstrated that GHSKF could improve bone biological alterations by up-regulating AKT1,PI3K,RUNX2,and down-regulating the expression of Caspase-3 and IL-6(P<0.01),which verified some results of the network pharmacology prediction.Conclusion We analyzed the potential mechanism of action of GHSKF for the treatment of SONFH using network pharmacology and animal experiments,which may provide a reference for further research on its pharmacological basis and targets.

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