1.Correlation Analysis of Huanglian Jiedu Wan on Syndrome Improvement and Clinical Biomarkers of "Excess Heat-Toxicity" Based on Machine Learning Model
Qi LI ; Keke LUO ; Baolin BIAN ; Hongyu YU ; Mengxiao WANG ; Mengyao TIAN ; Wen XIA ; Yuan MA ; Xinfang ZHANG ; Pengyue LI ; Nan SI ; Hongjie WANG ; Yanyan ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):162-173
ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally, the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome, such as oral ulcers, sore throat, and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation, oxidative stress, and energy metabolism in the early phase, Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting (XGBoost) algorithm was used to develop a prediction model for main symptom classification, with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers, sore throat, and overall symptoms, with significant effects observed especially in sore throat and overall symptom analyses (P<0.01). Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement, were also called "heat-related biomarkers", including succinic acid, α-ketoglutaric acid, glycine, lactic acid, adenosine monophosphate (AMP), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), and so on. Conversely, clinical biomarkers negatively correlated with symptom severity, were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan, including malic acid, fumaric acid, cis-aconitic acid, adrenocorticotropic hormone (ACTH), IL-1β, IL-4, IL-8, succinic acid, and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables, with importance scores of 0.081 and 0.080, respectively. After screening out 14 key variables and optimizing the parameters, model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables, confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established, achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.
2.Correlation Analysis of Huanglian Jiedu Wan on Syndrome Improvement and Clinical Biomarkers of "Excess Heat-Toxicity" Based on Machine Learning Model
Qi LI ; Keke LUO ; Baolin BIAN ; Hongyu YU ; Mengxiao WANG ; Mengyao TIAN ; Wen XIA ; Yuan MA ; Xinfang ZHANG ; Pengyue LI ; Nan SI ; Hongjie WANG ; Yanyan ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):162-173
ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally, the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome, such as oral ulcers, sore throat, and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation, oxidative stress, and energy metabolism in the early phase, Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting (XGBoost) algorithm was used to develop a prediction model for main symptom classification, with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers, sore throat, and overall symptoms, with significant effects observed especially in sore throat and overall symptom analyses (P<0.01). Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement, were also called "heat-related biomarkers", including succinic acid, α-ketoglutaric acid, glycine, lactic acid, adenosine monophosphate (AMP), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), and so on. Conversely, clinical biomarkers negatively correlated with symptom severity, were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan, including malic acid, fumaric acid, cis-aconitic acid, adrenocorticotropic hormone (ACTH), IL-1β, IL-4, IL-8, succinic acid, and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables, with importance scores of 0.081 and 0.080, respectively. After screening out 14 key variables and optimizing the parameters, model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables, confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established, achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.
3.Molecular Mechanism of Gypenoside L Inducing Ovarian Cancer Cell Apoptosis by Regulating NUF2 and Influencing Magnesium Homeostasis
Yang HONG ; Di ZHANG ; Yuanguang DONG ; Jiaxin WANG ; Lu PAN ; Lijiang ZHOU ; Mingdian YUAN ; Qun WANG ; Nan SONG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):155-165
ObjectiveThis paper aims to investigate the role of NDC80 kinetochore complex component (NUF2) and magnesium homeostasis in ovarian cancer cell apoptosis, as well as the regulatory mechanism of gypenoside L (Gyp-L) on NUF2 and magnesium homeostasis. MethodsOvarian cancer OVCAR3 cells were divided into a blank control group, a low-concentration Gyp-L group (50 µmol·L-1), a high-concentration Gyp-L group (100 µmol·L-1), and a cisplatin (15 µmol·L-1) group. The migration, proliferation, and apoptosis capabilities of OVCAR3 cells were evaluated through cell scratch assays, clonal experiments, and terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining. Differentially expressed genes of ovarian cancer were screened by using the Gene Expression Omnibus (GEO) database. The interaction relationships of differentially expressed genes and proteins were analyzed via the Search Tool for Recurring Instances of Neighbouring Genes (STRING) database. The prognostic survival analysis was performed by using the Tumor Immune Estimation Resource (TIMER) database, and the differential expression levels of genes were validated with the Gene Expression Profiling Interactive Analysis (GEPIA) database. The mRNA expression levels of NUF2, magnesium homeostasis-related indicators, such as magnesium transporter 1 (MAGT1), non-imprinted in Prader-Willi/Angelman syndrome 1 (NIPA1), NIPA-like domain containing 1 (NIPAL1), as well as apoptosis-related indicators B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) in OVCAR3 cells, were detected by real-time quantitative polymerase chain reaction (Real-time PCR). The protein expression levels of NUF2, MAGT1, NIPA1, NIPAL1, Bcl-2, and Bax in OVCAR3 cells were quantitatively analyzed by ProteinSimple WES. A model of overexpression of NUF2 was constructed, and Gyp-L intervention was performed. The molecular mechanism by which Gyp-L induces ovarian cancer cell apoptosis by regulating NUF2 and influencing magnesium homeostasis was quantitatively analyzed and detected through cell cloning, TUNEL staining, Real-time PCR, and ProteinSimple WES. Finally, the Mg2+ content and protein synthesis efficiency were detected by immunofluorescence. ResultsGyp-L significantly inhibited the migration and proliferation capabilities of OVCAR3 cells and promoted their apoptosis (P<0.05). Overexpression of NUF2 markedly increased the expression levels of MAGT1, NIPA1, NIPAL1, and Bcl-2, while reducing the expression level of Bax (P<0.05). It also significantly elevated intracellular Mg2+ content and protein synthesis efficiency and simultaneously inhibited apoptosis (P<0.05). Gyp-L could reverse the magnesium homeostasis imbalance and apoptosis inhibition caused by the overexpression of NUF2, downregulating the expression levels of NUF2, MAGT1, NIPA1, NIPAL1, and Bcl-2 (P<0.05), while upregulating the expression level of Bax (P<0.05). ConclusionGyp-L can inhibit the occurrence of ovarian cancer, and its mechanism may involve inhibiting the expression of NUF2 to maintain magnesium homeostasis and inducing apoptosis of ovarian cancer cells.
4.Umbrella decision-making model for diagnosis and treatment of elderly lung cancer patients: Construction and practice
Lunxu LIU ; Jian ZHOU ; Xiang DING ; Nan CHEN ; Jianxin XUE ; Xuelei MA ; Ye WANG ; Weiya WANG ; Liqing PENG ; Xin YOU ; Minggang SU ; Xu CHENG ; Jiao WANG ; Ning GE ; Deying KANG ; Yuchen HUANG ; Jinghan WANG ; Yu TONG ; Yaoxi ZHANG ; Jirong YUE ; Hu LIAO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(06):833-839
With the accelerating trend of population aging, the number of elderly patients with lung cancer continues to rise, and the disease burden is becoming increasingly heavy. The clinical management of these patients faces severe challenges due to their decreased physiological reserve, complex comorbidities, and significant individual heterogeneity. Consequently, under traditional diagnosis and treatment models, doctors often struggle to identify the individualized risks of elderly patients in a timely and comprehensive manner, which can easily lead to decision biases such as undertreatment or overtreatment. In view of this, this study advocates for the establishment of an umbrella decision-making model specifically tailored for elderly lung cancer patients. Grounded in a multidisciplinary team (MDT) platform, this model deeply integrates oncological indicators with the comprehensive geriatric assessment (CGA) system. By holistically considering multidimensional variables including tumor burden, organ function, frailty index, cognitive status, and social support, the model establishes an operational mechanism characterized by "single entry, precise stratification, and targeted selection". Accordingly, patients can be scientifically triaged into distinct intervention tiers, such as active surveillance, minimally invasive surgery, drug therapy, radiotherapy, and best supportive care, thereby achieving real-time alignment between treatment intensity and patient fitness. This article elaborates on the construction logic and key operational procedures of this novel decision-making framework, aiming to guide clinical practice beyond the limitations of a tumor-centric perspective toward a holistic, dynamic, whole-course management strategy. This transition seeks to ensure optimal quality of life and clinical net benefit for elderly patients alongside survival prolongation.
5.Cross-sectional survey of healthcare-associated infection in 5 736 medical institutions across China in 2024
Cui ZENG ; Wuqiang GAO ; Fu QIAO ; Hui ZHAO ; Xu FANG ; Linping LI ; Xiuwen CHEN ; Jiansen CHEN ; Dan LI ; Yuan ZHOU ; Lingli YU ; Qinglan MENG ; Xia MOU ; Lijuan XIONG ; Weiguang LI ; Ding LIU ; Jiaqing XIAO ; Limei OU ; Baozhen LI ; Jun YIN ; Haojun ZHANG ; Qiang FU ; Qun LU ; Biao WU ; Ya-wei XING ; Shumei SUN ; Shuncai WANG ; Longmin DU ; Jingping ZHANG ; Wen-ying HE ; Gui CHENG ; Nan REN ; Xun HUANG ; Anhua WU
Chinese Journal of Infection Control 2025;24(11):1572-1583
Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27%.The number of HAI episodes was 38 032,and case prevalence rate was 1.38%.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66%to 2.35%.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65%.The most common infection site was the lower respiratory tract(44.66%),followed by the urinary tract(12.94%),surgical site(9.32%),upper respiratory tract(7.02%),and bloodstream infection(5.78%).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02%),department of neurosurgery(5.51%),and department(group)of hematology(5.34%).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10%)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76%),Pseudomonas aeruginosa(13.33%),Escherichia coli(12.79%),Acinetobacter baumannii(9.23%),and Staphylococcus aureus(7.88%).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71%.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18%.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46%.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.
6.Clinical value of evaluation of anatomical position of inferior mesenteric artery and vein as well as left colic artery in laparoscopic radical resection of colorectal
Bo ZHANG ; Tao WU ; Shuai ZHOU ; Ling DANG ; Jiaxing HE ; Ying YANG ; Zhuo HAN ; Longlong ZHENG ; Nan WANG
Chinese Journal of Digestive Surgery 2025;24(6):754-761
Objective:To investigate the clinical value of laparoscopic evaluation of anato-mical position of inferior mesenteric artery (IMA), inferior mesenteric vein (IMV) and left colic artery (LCA).Methods:The prospective one-arm study was conducted. The clinical data of 229 pati-ents who underwent laparoscopic left hemicolectomy for left colon or laparoscopic radical resection of rectal cancer in The Second Affiliated Hospital of Air Force Medical University from December 2022 to December 2023 were selected. The distance between the origin point of IMA and the origin point of the first branch (L1) as well as the distance from the origin point of LCA root to the junction of LCA and IMV (L2) were measured during the operation. IMA classification, the location relation-ship of LCA and IMV junction were recorded. Observation indicators: (1) situations of enrolled patients; (2) difference analysis between L1, L2 and clinical features; (3) distribution characteristics of the location relationship between LCA and IMV in different types of IMA. Mann-Whitney U test was used for comparison of measurement data with skewed distribution between groups, Kruskal-Wallis H test was used for comparison between multiple groups, and Dunn-Bonferroni test was used for pairwise comparison. Comparison of count data between groups was performed by chi-square test. Pearson or Spearman correlation analysis was conducted for correlation of continuous variables. Results:(1) Situations of enrolled patients. A total of 229 eligible patients were screened out, including 146 males and 83 females, aged 64(range, 55-71)years. The height of 229 patients was 168(range, 160-172)cm, the weight was 65.0(55.5,71.5)kg, the body surface area was (1.68±0.17)m 2, the tumor maximum diameter was 3.0(2.5,4.0)cm. The total number of lymph nodes dissected was 19(17,21), and the number of No.253 lymph node dissected was 4(3,5). The L1 was 3.50(1.20,8.00)cm, and the L2 was 2.20(0.50,7.30)cm. There were 58, 31, 32, 71, 22, 90, 26 and 212 patients with smoking, alcohol drinking, diabetes, hypertension, coronary heart disease, neoadjuvant chemo-therapy, neoadjuvant radiotherapy and preservation of the LCA, respectively. Among 229 patients, cases with BMI <18.5 kg/m 2, 18.5-23.9 kg/m 2 and >23.9 kg/m 2 were 11, 133 and 85, respectively. There were 153 cases in pathological stage Ⅰ-Ⅱ and 76 cases in stage Ⅲ. There were 168 cases of Dixon operation, 6 cases of Miles operation and 55 cases of sigmoid colon resection. There were 135 cases of IMA type 1, 44 cases of IMA type 2, 23 cases of IMA type 3, 2 cases of IMA type 4, and 25 cases of IMA type unable to judge. (2) Difference analysis between L1, L2 and clinical features.Correlation analysis showed negative correlation between the height, body surface area and L1 ( r=-0.17, -0.15, P<0.05). The L1 was 3.20(2.68,4.00)cm for male patients and 3.60(3.00,4.20)cm for female patients, respectively, showing a significant difference between the two groups ( Z=-2.37, P<0.05). The L1 of patients with IMA type 1, 2, and 3 was 3.20(2.80,4.00)cm, 3.85(3.00,4.48)cm, and 3.20(2.50,4.30)cm, respectively, showing a significant difference among them ( H=7.54, P<0.05). Further pairwise com-parison showed that there was a significant difference in L1 between patients with IMA type 2 and those with IMA type 1 ( P<0.05). The L2 of smokers and non-smokers were 2.50(1.95,3.20)cm and 2.20(1.60,2.80)cm, respectively, showing a significant difference between the two groups ( Z=-2.24, P<0.05). (3)Distribution characteristics of the location relationship between LCA and IMV in different types of IMA. There was no significant difference in LCA distribution between the anterior and posterior positions of IMV among the three IMA types (type 1, 2, 3) ( χ2=1.63, P>0.05). Conclusions:Patients with greater height have larger body surface area and shorter L1. L1 is significantly longer in female patients than in male patients. L1 is significantly longer in patients with IMA type 2 than in those with type 1. L2 is significantly longer in smokers than in non-smokers. There was no significant difference in the distribution location between LCA and IMV among patients of IMA type 1, 2 and 3.
7.The scope of application of sexual dysfunction intervention in cervical cancer patients and nursing inspira-tion
Nan ZHOU ; Shihan ZHI ; Meng WANG ; Hui ZHANG ; Lihong ZHANG ; Maoyu LUO ; Ying HE ; Wei GU
Chinese Journal of Nursing 2025;60(7):890-896,后插1
Objective To review the application of sexual dysfunction intervention in cervical cancer patients,and refine the intervention elements,so as to provide ideas and methods for the development of personalized intervention measures.Methods Guided by the 2021 updated methodological guidelines for scoping reviews from the Joanna Briggs Institute in Australia,CINAHL,PubMed,Web of Science,Embase,Cochrane Library,CNKI,Wanfang and VIP databases were systematically searched from inception to February 29,2024,and the included literature were analyzed and summarized.Results A total of 17 studies were included,involving 9 randomized controlled trials,7 quasi-experimental studies and 1 pilot study.The theoretical basis of the intervention includes PLISSIT model,BETTER model,FOCUS program,PERMA flourish theory,empowerment theory,the trans-theoretical model and narrative therapy.The intervention content involves 4 themes:sexual problem disclosing,sexual science education,sexual physiological rehabilitation and sexual psychological rehabilitation.The main forms are offline and online independent or combined intervention.The outcomes include sexual health function,social function,psychological status and self-management.Conclusion Sexual dysfunction interventions have a positive impact on cervical cancer patients.Future research should develop sexual dysfunction interventions with more comprehensive content,richer forms and more accurate evaluation based on the in-depth understanding of the theoretical connotation,and play the role of nurse-led multidisciplinary teams to maintain the long-term sexual and reproductive health of cervical cancer patients.
8.Effects of scaffolding teaching mode from the perspective of deep learning in basic nursing techniques course
Fangman CHENG ; Han LYU ; Nan SHENG ; Binqian GE ; Ying LIU ; Chunmei ZHANG ; Ping ZHOU
Chinese Journal of Modern Nursing 2025;31(32):4464-4469
Objective:To explore the effectiveness of the scaffolding teaching mode from the perspective of deep learning in basic nursing techniques course.Methods:From September 2023 to June 2024, 324 nursing students at Suzhou Vocational Health College in the 2023 cohort were selected as research subjects using convenience sampling. Three classes were designated as experimental group ( n=167), and three classes were designated as control group ( n=157). Control group received the traditional teaching mode, while experimental group received a scaffolding teaching mode from the perspective of deep learning on the basis of control group. Teaching effectiveness was evaluated using course grades, the Academic Self-Efficacy Scale, and the Measure Scale of Autonomous Learning Competencies of Nursing Undergraduates. Results:A total of 324 questionnaires were distributed and 324 valid questionnaires were collected, with a valid response rate of 100.00% (324/324). After teaching, the experimental group's nursing course grades were statistically higher than those of the control group ( P<0.05). After teaching, the experimental group's nursing students demonstrated statistically higher total scores and scores across all dimensions on the Academic Self-Efficacy Scale compared to the control group ( P<0.01). After teaching, the experimental group of nursing students scored statistically higher than the control group on the total score of the Measure Scale of Autonomous Learning Competencies of Nursing Undergraduates, as well as on the dimensions of self-management and learning cooperation ability ( P<0.01) . Conclusions:The implementation of the scaffolding teaching mode from the perspective of deep learning for basic nursing techniques course enhances vocational nursing students' academic performance, academic self-efficacy, and autonomous learning competencies.
9.Analysis and suggestions for the FDA drug labeling rules on cardiac safety risk warnings
Wei LIU ; Xiao-qing XING ; Yu-qing REN ; Qian SHEN ; Yue ZHOU ; Nan ZHANG ; Fu-meng LIANG ; Fang-fang WANG ; Hai-yan LI
The Chinese Journal of Clinical Pharmacology 2025;41(2):235-239
Objective To improve and refine the relevant regulations and guiding principles of warnings on drug instructions and labels in China.Methods This paper sorted out the drug instructions of small molecule anti-tumor drugs listed by the U.S.Food and Drug Administration(FDA)from 2005 to 2022,included the drugs mentioned in the QT interval prolongation risk,analyzed the clinical research and QT research results,and sorted out the identification and warning rules of the instructions.Results A total of 35 drugs were included,4 drugs wrote the risk of QT interval prolongation in the black box warning,21 drugs were wrote in the warning and precautions position,6 drugs were wrote in the adverse reaction section,and 2 drugs were only described under clinical pharmacology section.According to the severity of the QT interval prolongation caused by the drug and whether there were serious clinical consequences,they were displayed in the warnings(black box warnings),precautions(warnings and precautions)and adverse reactions in the instructions.Conclusion The aim of this article is to provide a reference for the writing of QT risk warning information of the instructions of domestic drug production enterprises and regulatory departments.It is recommended to clarify the severity of drug safety and the location of the instructions in clinical research,and continue to carry out safety monitoring and update the instructions in time after listing.
10.Mechanism of Compound Fufangteng Mixture in improving isoproterenol-induced myocardial fibrosis by regulating HSPA8
Fengjie ZHOU ; Yafang CHEN ; Jianlong NAN ; Yuhong LI ; Jun HE ; Han ZHANG ; Wei LEI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(8):1081-1094
Objective This study aims to evaluate the therapeutic efficacy of Compound Fufangteng Mixture(CFM)on myocardial fibrosis(MF)and explore its action targets and mechanisms through a combination of animal pharmacodynamics,cell biology,and network pharmacology approaches.Methods Thirty-five male C57BL/6J mice were divided into the normal group,model group,CFM low-dose(0.72 g/kg)group,CFM high-dose(1.44 g/kg)group,and sacubitril valsartan sodium group(20 mg/kg)based on random number table,with 7 mice in each group.Except for the normal group,the mice in the other groups were subcutaneously injected with isoproterenol(20 mg/kg)at multiple points once daily for 21 consecutive days to establish the MF model.The CFM groups were pre-administered by gavage 3 days before modeling,the sacubitril valsartan sodium group was administered starting from the day of modeling,and the normal group and model group were given an equal volume of distilled water.The active ingredients in CFM were analyzed using ultra-performance liquid chromatography(UPLC).On days 7,14,and 21 of modeling,the left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),left ventricular end-diastolic diameter(LVIDd),and left ventricular end-systolic diameter(LVIDs)of mice were detected by ultrasound.The degree of myocardial fibrosis in mice was assessed by Masson staining.The levels of transforming growth factor-β1(TGF-β1),α-smooth muscle actin(α-SMA),type I collagen(COL I),and type Ⅲcollagen(COL Ⅲ)in the myocardial tissue of mice were detected by enzyme-linked immunosorbent assay(ELISA).The average fluorescence intensity of α-SMA in myocardial tissue was detected by immunofluorescence.In addition,by integrating Cellular Thermal Shift Assay(CETSA),QE proteomic analysis,and network pharmacology techniques,we systematically explored the potential core targets and mechanisms of action by which CFM improves MF,and validated these findings using western blotting analysis.Results Main eight chemical components were identified from CFM.Compared with the normal group,the model group exhibited a decrease in LVEF and LVFS,an increase in LVIDd and LVIDs,a higher heart weight to tibia length ratio,and an increased collagen volume fraction(P<0.05),along with aggravated MF.Concurrently,the myocardial tissue showed elevated levels of TGF-β1,α-SMA,COL I,and COL Ⅲ(P<0.05),with enhanced α-SMA fluorescence signal intensity.In comparison to the model group,all groups of CFM and the sacubitril valsartan sodium group demonstrated an increase in LVEF and LVFS,and a decrease in LVIDd,LVIDs,and the heart weight to tibia length ratio(P<0.05).Simultaneously,the collagen volume fraction decreased,and the levels of TGF-β1,α-SMA,COL I,and COL Ⅲ in myocardial tissue were down-regulated(P<0.05).The degree of MF was reduced,and the fluorescence signal intensity of α-SMA expression was weakened.Furthermore,the combined analysis of CETSA,QE proteomics,and network pharmacology revealed that heat shock protein A family member 8(HSPA8)may be a potential core target for CFM in ameliorating MF.CETSA-western blotting analysis further confirmed that CFM could enhance the thermal stability of HSPA8 protein and down-regulate the relative expression level of HSPA8 protein in mouse myocardial tissue(P<0.05).Conclusion CFM can ameliorate isoproterenol-induced cardiac dysfunction in mice,reduce collagen deposition,and reverse the pathological progression of MF.The underlying mechanism may be associated with the regulation of HSPA8.

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