OBJECTIVE To establish drug utilization evaluation （DUE） criteria for pyrotinib to promote its appropriate application in clinical practice. METHODS Based on the label of Pyrotinib maleate tablets， with relevant guiding principles and diagnostic and treatment guidelines as the evaluation basis， DUE criteria for pyrotinib were determined through the Delphi method. Attribute hierarchical model （AHM） and entropy weight method （EWM） were used to combine and assign weights to each indicator within the DUE criteria. Additionally， the weighted technique for order preference by similarity to an ideal solution （TOPSIS） method was applied to perform rationality evaluation of medication in archived medical records from Hainan Provincial Tumor Hospital and Hainan Western Central Hospital regarding the use of pyrotinib from November 2019 to November 2023. RESULTS The established DUE criteria for pyrotinib included 4 primary indicators （prescription authority， indications for use， medication process， and medication outcomes） and 11 secondary indicators. The secondary indicators with higher weights were the route of administration and dosage （0.257） and indications in the label （0.241）. Among the 88 archived cases included， there were 28 cases of inappropriate medication （31.82%）， 43 cases of generally appropriate medication （48.86%）， and 17 cases of appropriate medication （19.32%）. The main issues related to inappropriate medication involved off-label use （42.05%） and inappropriate routes of administration and dosage （43.18%）. CONCLUSIONS DUE criteria for pyrotinib established using the AHM-EWM-weighted TOPSIS method is highly operational and results in quantifiable evaluation outcomes. The overall rationality of the use of pyrotinib in the above hospitals remains to be improved， and there are some issues， like the off-label use，and inappropriate routes of administration and dosage being liaoyylyy@163.com unreasonable.

OBJECTIVE To construct an evaluation index system for the core competencies of ethics committee members of drug clinical trial institution， providing a basis for optimizing the training system for committee members， improving the quality of ethical review， and fully safeguarding the safety and rights of subjects. METHODS Using methods such as literature research and expert consultation， a preliminary core competency evaluation index system was constructed. The Delphi method was employed to revise and validate it， ultimately forming an evaluation index system for the core competencies of ethics committee members. Based on this system， a questionnaire survey was conducted among 90 ethics committee members from 29 drug clinical trial institutions nationwide， comparing their importance rating and self-assessment scores of the core competency indexes. RESULTS The evaluation system constructed included 4 primary indicators （ethics and professional knowledge， ethics review ability， communication and expression ability， moral integrity and work style） and 39 secondary indicators （familiarity with the content of clinical trial-related laws and regulations， ability to complete project ethics review and identify ethical defects in research protocols within a short period of time， ability to judge the scientific value of clinical research， etc.）. The results of questionnaire survey showed that the interviewed ethics committee members had significant capability gaps in dimensions such as regulatory knowledge， ethical norms， review efficiency， risk judgment， and problem analysis. The differences between the importance rating scores of corresponding secondary indicators and the self-assessment scores were all no less than 0.38. CONCLUSIONS This study has developed a quantifiable and stratified core competency assessment tool for ethics committee members. It can provide a scientific framework for committee member training， qualification certification， and standardized management of ethics committees.

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

BackgroundPatients demonstrating depressive disorder with psychotic symptoms often have increased risk of death and poor prognosis. A large amount of research has explored the factors influencing psychotic symptoms in adult patients with depressive disorder， but few has focused on adolescent patients. ObjectiveTo explore the influencing factors of psychotic symptoms in adolescent patients with depressive disorder， so as to provide references for early screening and intervention in clinic. MethodsA total of 96 adolescent patients who met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） for depressive disorder and were seen in the psychiatry departments of Chaohu Hospital of Anhui Medical University and The Fourth People's Hospital of Hefei from September 2022 to January 2023 were included. Another 56 healthy individuals from the health examination center of Chaohu Hospital of Anhui Medical University were concurrently recruited as control group. Patients were assigned into psychotic group （n=32） and non-psychotic group （n=64） according to the presence or absence of psychotic symptoms. Hamilton Depression Scale-24 item （HAMD-24）， Positive and Negative Syndrome Scale （PANSS）， Positive and Negative Suicide Ideation （PANSI） and Childhood Trauma Questionnaire-Short Form （CTQ-SF） were used for evaluation. Plasma brain-derived neurotrophic factor （BDNF） concentration was obtained using Meso Scale Discovery electrochemiluminescence assay. Pearson and Spearman correlation analysis were adopted to determine the correlation of PANSS positive symptom subscale score with plasma BDNF concentration and clinical characteristics of adolescent depression patients with psychotic symptoms. Binary Logistic regression analysis was used to identify the factors influencing the presence of psychotic symptoms in adolescent patients with depressive disorder， and multiple linear regression analysis was utilized to screen the factors affecting the severity of psychotic symptoms. ResultsThe plasma BDNF concentration of adolescent patients with depressive disorder was lower than that of control group （t=-3.080， P<0.01）.The plasma BDNF concentration of psychotic group was lower than that of non-psychotic group （t=2.418， P<0.05）， while the body mass index （BMI） PANSI scores， CTQ-SF scores and HAMD-24 total scores were all higher than those of non-psychotic group （t=-2.024， -2.530， -2.187， -4.977， P<0.05 or 0.01）. Correlation analysis showed that PANSS positive symptom subscale scores were negatively correlated with anxiety/somatization factor score and weight factor score in HAMD-24 of psychotic group （r=-0.438， -0.498， P<0.05 or 0.01）. Binary Logistic regression showed that BMI， plasma BDNF concentration， HAMD-24 total scores and cognitive dysfunction factor score were the influencing factors of psychotic symptoms in adolescent patients with depressive disorder. Multiple linear regression analysis demonstrated that weight factor scores （β=-0.349， P<0.05） and anxiety/somatization factor score （β=-0.433， P<0.05） in HAMD-24 were the factors influencing the severity of psychotic symptoms. ConclusionHigh BMI， low plasma BDNF concentration， severe depressive symptoms and cognitive dysfunction may be the risk factors of psychotic symptoms in adolescent patients with depressive disorder， furthermore， BMI and anxiety symptoms are found to be associated with the severity of psychotic symptoms. ［Funded by Scientific Research Fund Project of Anhui Institute of Translational Medicine （number， 2022zhyx-B01）； Central Finance Supported Provincial Key Clinical Specialty Construction Project of Anhui Province in 2019］

Pulmonary hypertension(PH)is the pulmonary vascular remodeling caused by endothe-lial dysfunction and other factors,which leads to the increase of pulmonary artery pressure and finally right heart failure and patient death.Medications can significantly improve the symptoms of patients with pulmonary hypertension,but drugs can't cure vascular remodeling and right heart failure once for all,so it is urgent to find new treatments.Endothelial cells can obtain mesenchymal phenotypes after hypoxia stimulation,that is,endothelial-to-mesenchymal transition(EndMT).Increasing studies have shown that EndMT plays an important role in pulmonary vascular remodeling of PH.In this review,three signaling pathways related to induction of endothelial-to-mesenchymal transition under hypoxic conditions and research progress in related drugs are elaborated:① Transforming growth factor-β/bone morphogenetic protein(TGF-β/BMP)signaling pathway.The TGF-β/BMP pathway is mediated by Smad,and hypoxia regulates the expressions of EndMT-related genes by inhibiting or inducing the phosphorylation level of Smad in the downstream medium.② Notch signaling pathway.Hypoxia can enhance Jagged/Notch signaling pathway and promote the EndMT process.③Wnt/β-catenin signaling pathway.Hypoxia increases the expression of β-catenin,activates the Wnt signaling pathway,and regulates the expressions of EndMT regulatory genes.The significance of hypoxia-induced EndMT as an impor-tant pathogenic factor in PH is clarified in order to provide new ideas for the improvement of pulmonary vascular remodeling and recommend new effective strategies for the prevention and treatment of PH.

Objective To understand the research status,hotspots and trends of Wuzhuyu Decoction;To provide reference for relevant research.Methods The literature related to Wuzhuyu Decoction was retrieved from CNKI,VIP,Wanfang Data and CBM databases from the establishment to February 28,2023.NoteExpress 3.6 was used to merge and deduplicate,and the author,organization and keywords were mapped and interpreted by CiteSpace 6.1.R6 software.Results A total of 822 articles were included,and the number of publications showed a wave upward trend;the top journals were New Chinese Medicine,Henan Traditional Chinese Medicine and Sichuan Traditional Chinese Medicine;the main research institutions were Beijing University of Chinese Medicine,China Academy of Chinese Medical Sciences and Shandong University of Traditional Chinese Medicine;a total of 566 authors were involved,and the authors with more publications included Wang Zhimin(12),Gong Muxin(9)and Bi Kaishun(5);high-frequency keywords included"headache","Shang Han Lun","TCM therapy"and so on.Conclusion Wuzhuyu Decoction is effective in treating chronic gastritis,hypertension and other primary diseases,which is a research hotspot in this field.It is a research trend in this field to explore its active components by high performance liquid chromatography and explain its action mechanism and target at the molecular level.

Objective To understand the research status,hotspots and trends of animal medicinal materials;To provide reference for future research.Methods The literature related to animal medicinal materials was retrieved from CNKI,VIP,Wanfang Data and CBM from January 1,2000 to April 30,2023.NoteExpress 3.6 was used to merge and deduplicate,and the author,institution and keywords were mapped and interpreted by CiteSpace 6.1.R6 software.Results A total of 1 169 articles were included,and the overall publication quantity in this field showed a stable fluctuation trend;the top journals were Lishizhen Medicine and Materia Medica Research,China Journal of Chinese Materia Medica and Modern Chinese Medicine;the main research institutions were China Academy of Chinese Medical Sciences,Changchun University of Chinese Medicine and Chinese Academy of Medical Sciences;a total of 676 authors were involved,and the authors with more publications included Zhang Hui(22),Liu Rui(15),Lin Zhe and Ma Shuangcheng(14);high-frequency keywords included"identification","TCM resources","clinical application"and so on.Conclusion Resource survey of animal medicinal materials,standardized breeding of medicinal animals,development of alternatives to rare medicinal animal resources,and construction of quality standard system for animal medicinal materials are the research hotspots in this field.The basic research of pharmacodynamic substances of animal medicinal materials based on the integrated analysis strategies of proteomics,peptideomics and transcriptomics,and the revelation of the signaling pathways and targets of animal medicinal materials from the molecular biology level are the research trends in this field.

Objective To understand the current status and development trend of the research on Prunellae Spica;To provide reference for the subsequent research.Methods The research literature related to Prunellae Spica was searched in China Knowledge Resources Database(CNKI),Chinese Science and Technology Journal Database(VIP),Chinese Academic Journal Database(Wanfang Data),and Chinese Biomedical Literature Database(CBM)from January 1,2002 to March 23,2023.After merging and removing duplicates using NoteExpress 3.7.0.9258 software,CiteSpace 6.2.R1 software was used to visualize and analyze authors,institutions and keywords.Results Totally 3 136 articles were included,and the annual number of publications showed a fluctuating upward trend.Shaanxi Journal of Traditional Chinese Medicine had the most publications(93).The core authors included Lin Limei(34),Guo Qiaosheng(27),and Zhang Mingzhi(20),and core research institutions included Shandong University of Traditional Chinese Medicine(37),Tianjin University of Traditional Chinese Medicine(30),and Nanjing University of Chinese Medicine(28),with less cooperation among authors and institutions.The analysis of keywords showed that the research on the treatment of diseases were mainly"hypertension","breast cancer","hyperplasia of mammary glands","vertigo","insomnia".The chemical composition studies were mainly on"rosmarinic acid"and"ursolic acid".The type of literature was mainly"experience of famous doctors"and"clinical observation".Conclusion The research field of Prunellae Spica is in the rising stage of development,and the research content mainly focuses on clinical application and chemical composition research,etc.Summarizing the law of medication,exploring its mechanism of action and action target through data mining and molecular docking technology are the research trends.

Objective To understand the research hotspots and trend of Scrophulariae Radix from 2000 to 2023;To provide reference for related research.Methods The relevant literature of Scrophulariae Radix were retrieved from CNKI,VIP,Wanfang Data and CBM from January 1,2000 to June 1,2023.NoteExpress 3.7.0.9296 software was used to manage files and weight,and CiteSpace 6.2.R4 software was used for visualization analysis of authors,institutions and keywords.Results A total of 2 240 articles were included,and the annual number of publications showed a dynamic upward trend.The source journals with more publications included Shaanxi Journal of Traditional Chinese Medicine,Journal of Traditional Chinese Medicine,Shizhen Journal of Traditional Chinese Medicine Research and so on.The core authors were Zhang Ning,Liu Shumin,Liu Bin,etc;the main research institutions included Beijing University of Chinese Medicine,Nanjing University of Chinese Medicine,Guangzhou University of Chinese Medicine,etc.;high-frequency keywords were"harpagoside","quality standard","clinical observation"and so on.Conclusion The research of Scrophulariae Radix mainly focuses on chemical composition,disease treatment and compatibility application.It is a research trend in recent years to explore the medication law and mechanism of Scrophulariae Radix by using data mining,network pharmacology and molecular docking.

Objective To analyze the research hotspots and trend of Raphani Semen from 2000 to 2023;To provide reference and direction for the follow-up research.Methods The literature related to Raphani Semen was retrieved from CNKI,VIP,Wanfang Data and CBM from January 1,2000 to July 20,2023.NoteExpress 3.7 software was used to organize the bibliothems,and CiteSpace 6.2.R2 software was used to visualize the authors,research institutions and keywords.Results After screening,a total of 1 023 articles were included,and the annual publication volume showed a trend of first fluctuating and then slowly decreasing.The source journals were 421,and the journal with the most articles was Shaanxi Journal of Traditional Chinese Medicine(75 articles).It involved 682 authors,the core authors included Zhou Honglei,Lü Wenhai,Zhu Liqiao,etc.Core research institutions included Shandong University of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,etc.High-frequency keywords included"constipation","data mining","clinical observation"and so on.Conclusion The current research hotspots in Raphani Semen are disease treatment,chemical composition,compatibility of prescriptions,related prescriptions and so on.The key research trend in this field is to summarize the clinical medication law by data mining technology and the treatment of spleen and stomach diseases.