1.Identification and drug sensitivity analysis of key molecular markers in mesenchymal cell-derived osteosarcoma
Haojun ZHANG ; Hongyi LI ; Hui ZHANG ; Haoran CHEN ; Lizhong ZHANG ; Jie GENG ; Chuandong HOU ; Qi YU ; Peifeng HE ; Jinpeng JIA ; Xuechun LU
Chinese Journal of Tissue Engineering Research 2025;29(7):1448-1456
BACKGROUND:Osteosarcoma has a complex pathogenesis and a poor prognosis.While advancements in medical technology have led to some improvements in the 5-year survival rate,substantial progress in its treatment has not yet been achieved. OBJECTIVE:To screen key molecular markers in osteosarcoma,analyze their relationship with osteosarcoma treatment drugs,and explore the potential disease mechanisms of osteosarcoma at the molecular level. METHODS:GSE99671 and GSE284259(miRNA)datasets were obtained from the Gene Expression Omnibus database.Differential gene expression analysis and Weighted Gene Co-expression Network Analysis(WGCNA)on GSE99671 were performed.Functional enrichment analysis was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes separately for the differentially expressed genes and the module genes with the highest positive correlation to the disease.The intersection of these module genes and differentially expressed genes was taken as key genes.A Protein-Protein Interaction network was constructed,and correlation analysis on the key genes was performed using CytoScape software,and hub genes were identified.Hub genes were externally validated using the GSE28425 dataset and text validation was conducted.The drug sensitivity of hub genes was analyzed using the CellMiner database,with a threshold of absolute value of correlation coefficient|R|>0.3 and P<0.05. RESULTS AND CONCLUSION:(1)Differential gene expression analysis identified 529 differentially expressed genes,comprising 177 upregulated and 352 downregulated genes.WGCNA analysis yielded a total of 592 genes with the highest correlation to osteosarcoma.(2)Gene Ontology enrichment results indicated that the development of osteosarcoma may be associated with extracellular matrix,bone cell differentiation and development,human immune regulation,and collagen synthesis and degradation.Kyoto Encyclopedia of Genes and Genomes enrichment results showed the involvement of pathways such as PI3K-Akt signaling pathway,focal adhesion signaling pathway,and immune response in the onset of osteosarcoma.(3)The intersection analysis revealed a total of 59 key genes.Through Protein-Protein Interaction network analysis,8 hub genes were selected,which were LUM,PLOD1,PLOD2,MMP14,COL11A1,THBS2,LEPRE1,and TGFB1,all of which were upregulated.(4)External validation revealed significantly downregulated miRNAs that regulate the hub genes,with hsa-miR-144-3p and hsa-miR-150-5p showing the most significant downregulation.Text validation results demonstrated that the expression of hub genes was consistent with previous research.(5)Drug sensitivity analysis indicated a negative correlation between the activity of methotrexate,6-mercaptopurine,and pazopanib with the mRNA expression of PLOD1,PLOD2,and MMP14.Moreover,zoledronic acid and lapatinib showed a positive correlation with the mRNA expression of PLOD1,LUM,MMP14,PLOD2,and TGFB1.This suggests that zoledronic acid and lapatinib may be potential therapeutic drugs for osteosarcoma,but further validation is required through additional basic experiments and clinical studies.
2.Buzhong Yiqitang Induces Ferroptosis by Regulating PCBP1 to Attenuate Cisplatin Resistance in Non-small Cell Lung Cancer
Yuetong LIU ; He LI ; Qirui MU ; Jingyi HUANG ; Haoran CAI ; Chunying LIU ; Yuan GAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):90-97
ObjectiveTo explore the molecular mechanism of Buzhong Yiqitang in attenuating cisplatin resistance in non-small cell lung cancer (NSCLC) by inducing ferroptosis via poly(rC)-binding protein 1 (PCBP1). MethodsThe serum containing Buzhong Yiqitang was prepared and cisplatin-resistant human non-small cell lung cancer (NSCLC) cells (A549/DDP) were cultured and randomly grouped as follows: Blank (10% blank serum), model (10% blank serum+20 mg·L-1 cisplatin), Buzhong Yiqitang (10% serum containing Buzhong Yiqitang+20 mg·L-1 cisplatin), Fe-1 (10% blank serum+20 mg·L-1 cisplatin+5 μmol·L-1 Fe-1), and Buzhong Yiqitang+Fe-1 (10% serum containing Buzhong Yiqitang+20 mg·L-1 cisplatin+5 μmol·L-1 Fe-1). Firstly, PCR Array was used to screen ferroptosis-related genes regulated by Buzhong Yiqitang, and PCBP1 was identified as the target for studying the attenuation of cisplatin resistance by Buzhong Yiqitang. Subsequently, the median inhibitory concentration (IC50) of cisplatin in each group was determined by the cell counting kit-8 (CCK-8) method and the resistance index (RI) was calculated. The ultrastructure of A549/DDP cells in each group was observed by transmission electron microscopy. The protein levels of PCBP1 and glutathione peroxidase 4 (GPX4) were determined by Western blot. The lipid reactive oxygen species (ROS) content in each group was determined by the C11-BODIRY 581/591 fluorescence probe. The ferrous ion assay kit was used to measure the ferrous ion content in each group. The malondialdehyde (MDA) assay kit was used to determine the MDA content in each group. ResultsCompared with model group, the IC50 of cisplatin and the RI of A549/DDP cells decreased in the Buzhong Yiqitang group (P<0.05) but increased in the Fe-1 group (P<0.05). The IC50 of cisplatin and the RI of A549/DDP cells in the Buzhong Yiqitang+Fe-1 group were lower than those in the Fe-1 group (P<0.05). Compared with the model group, the Buzhong Yiqitang group showed obvious mitochondrial ferroptosis, while the mitochondrial damage became less obvious after Fe-1 treatment. Compared with that in the Fe-1 group, the mitochondrial ferroptosis was aggravated after the intervention with Buzhong Yiqitang. Compared with blank group, the model group showed down-regulated expression levels of PCBP1 and GPX4 (P<0.05) and increased content of lipid ROS, ferrous ions, and MDA (P<0.05) in A549/DDP cells. Compared with model group, the Buzhong Yiqitang group showed down-regulated expression levels of PCBP1 and GPX4 (P<0.05) and increased content of lipid ROS, ferrous ions, and MDA (P<0.05), while the Fe-1 group showed up-regulated expression levels of PCBP1 and GPX4 (P<0.05) and reduced content of lipid ROS, ferrous ions, and MDA (P<0.05). Compared with the Fe-1 group, the Buzhong Yiqitang+Fe-1 group showed down-regulated expression levels of PCBP1 and GPX4 and increased content of lipid ROS, ferrous ions, and MDA (P<0.05). ConclusionBuzhong Yiqitang attenuated cisplatin resistance in NSCLC by regulating PCBP1 to induce ferroptosis.
3.Mechanism of Ferroptosis in Myocardial Cells and Protective Effect of Traditional Chinese Medicine
Haoran LI ; Ce CAO ; Lei LI ; Jianxun LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(4):260-270
Ferroptosis is a new type of programmed cell death, characterized by iron overload and lipid peroxidation. Cardiovascular disease (CVD) is an ischemic or hemorrhagic disease of the heart caused by various factors, mainly including myocardial infarction, heart failure, etc. Ferroptosis is involved in the process of myocardial cell damage and plays a driving role in the progression of various CVDs. Its main mechanisms include the destruction of iron homeostasis, the production of reactive oxygen species, the disorder of the antioxidant system, mitochondrial membrane damage, endoplasmic reticulum stress, tumor suppressor gene p53, transcription factor Nrf2 pathway, etc. Myocardial injury is one of the causes of death in many patients with heart disease. Monomers or compounds of traditional Chinese medicine have shown good effects in the treatment of myocardial cell injury caused by ferroptosis, including baicalin protecting cardiac microvascular endothelial cells of myocardial ischemia-reperfusion (I/R) rats through intracellular phosphatidylinositol kinase/phosphokinase B/endothelial nitric oxide synthase (PI3K/Akt/eNOS) pathway, Aralia elata saponin inhibiting myocardial cell ferroptosis through glucocorticoid receptor/p53/solute carrier family 7 members 11 (NR3C1/p53/SLC7A11) pathway, Xinyang tablets improving oxidative stress by regulating phosphorylated serine/threonine protein kinase/stress-activated protein kinase/p53 (MLK3/JNK/p53) signaling pathway. It is of great significance to explore the mechanism of ferroptosis and the protective effect of related traditional Chinese medicine after myocardial cell injury. This article reviews the mechanism of ferroptosis and its relationship with myocardial cells, as well as traditional Chinese medicine monomers and formulas for treating CVDs through the ferroptosis pathway. The article focuses on the pathways and effects of traditional Chinese medicine treatment, so as to provide a reference for the treatment of CVDs with traditional Chinese medicine.
4.Classification research of TCM pulse conditions based on multi-label voice analysis
Haoran Shen ; Junjie Cao ; Lin Zhang ; Jing Li ; Jianghong Liu ; Zhiyuan Chu ; Shifeng Wang ; Yanjiang Qiao
Journal of Traditional Chinese Medical Sciences 2024;11(2):172-179
Objective:
To explore the feasibility of remotely obtaining complex information on traditional Chinese medicine (TCM) pulse conditions through voice signals.
Methods:
We used multi-label pulse conditions as the entry point and modeled and analyzed TCM pulse diagnosis by combining voice analysis and machine learning. Audio features were extracted from voice recordings in the TCM pulse condition dataset. The obtained features were combined with information from tongue and facial diagnoses. A multi-label pulse condition voice classification DNN model was built using 10-fold cross-validation, and the modeling methods were validated using publicly available datasets.
Results:
The analysis showed that the proposed method achieved an accuracy of 92.59% on the public dataset. The accuracies of the three single-label pulse manifestation models in the test set were 94.27%, 96.35%, and 95.39%. The absolute accuracy of the multi-label model was 92.74%.
Conclusion
Voice data analysis may serve as a remote adjunct to the TCM diagnostic method for pulse condition assessment.
5.Assessment of the health situation of daily learning time for elementary school students in the context of Double Reduction policy
YANG Haoran, LI Jin, LIU Kaiqi, TU Ying, LI Suyun, YANG Xiao, LEI Suwen, LI Jing
Chinese Journal of School Health 2024;45(9):1354-1358
Objective:
To investigate the daily learning time status of elementary school students and understand the implementation of Health Requirements of Daily Learning Time for Secondary and Elementary School Students (GB/T 17223-2012) in schools, so as to provide a reference for strengthening and improving school health and health education in the new era.
Methods:
A stratified cluster random sampling method was used to select 7 776 primary school students in Shandong Province, and a survey questionnaire was designed based on the Health Requirements for Dayily Learning Time for Secondary and Elementary School Students(GB/T 17223-2012) standard to investigate their daily learning arrangements, sleep and physical activities, and breaks between classes. Comparison of intergroup differences were used by Chi square test and Kruskal-Wallis H test.
Results:
About 55.88 % of primary school students for daily learning time met the standard. There was a statistically significant difference in the daily learning time achievement rate among primary school students in three grades for first and second grade, third and fourth grade and fifth and sixth grade ( Z=1 629.47, P <0.01), and the fifth and sixth grade had the highest proportion of achieving the standard (85.92%). Specifically, the proportions of students whose class hours, class numbers and morning reading time meeting the standards were 30.07%, 10.20% and 42.19%, respectively. The sleep deficiency rate of primary school studnets was 58.69%, and the physical activity deficiency rate was 65.78%; and there was a statistically significant difference in the rate of insufficient sleep time and physical activity time among primary school students of different grades ( χ 2=56.39, 95.95, P <0.01), with sixth grade students showing the highest rates for both sleep and physical activity deficiencies (64.35%, 73.37%). Additionally, 49.78% of students had recess time below the standard requirements.
Conclusion
The health status of daily learning time among primary school students in Shandong Province is poor, with insufficient implementation of school standards, and the implementation of standards needs to be further strengthened.
6.Application of computer-aided design modified 3D printing model in video-assisted thoracoscopic sublobular resection for early lung cancer: A retrospective cohort study
Xinyu ZHANG ; Linqian LI ; Haoran LI ; Qiang GUO ; Hongli YAN ; Jinghua LI ; Shujie CHENG ; Hefei LI ; Ke ZHANG ; Jihong YANG ; Jianguo WU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(09):1266-1273
Objective To compare the effect of three-dimensional visual (3DV) model, three-dimensional printing (3DP) model and computer-aided design (CAD) modified 3DP model in video-assisted thoracoscopic surgery (VATS) sublobular resection. Methods The clinical data of patients who underwent VATS sublobular resection in the Affiliated Hospital of Hebei University from November 2021 to August 2022 were retrospectively analyzed. The patients were divided into 3 groups including a 3DV group, a 3DP group and a CAD-3DP group according to the tools used. The perioperative indexes and subjective evaluation of operators, patients and their families were compared. Results A total of 22 patients were included. There were 5 males and 17 females aged 32-77 (56.95±12.50) years. There were 9 patients in the 3DV group, 6 patients in the 3DP group, and 7 patients in the CAD-3DP group. There was no statistical difference in the operation time, intraoperative blood loss, drainage volume, hospital stay time or postoperative complications among the groups (P>0.05). Based on the subjective evaluations of 4 surgeons, the CAD-3DP group was better than the 3DV group in the preoperative planning efficiency (P=0.025), intuitiveness (P=0.045) and doctor-patient communication difficulty (P=0.034); the CAD-3DP group was also better than the 3DP group in the overall satisfaction (P=0.023), preoperative planning difficulty (P=0.046) and efficiency (P=0.014). Based on the subjective evaluations of patients and their families, the CAD-3DP group was better than the 3DP group in helping understand the vessel around the tumor (P=0.016), surgical procedure (P=0.020), procedure selection (P=0.029), and overall satisfaction (P=0.048); the CAD-3DP group was better than the 3DV group in helping understand the tumor size (P=0.038). Conclusion CAD-modified 3DP model has certain advantages in pre-planning, intraoperative navigation and doctor-patient communication in the VATS sublobectomy.
7.Da Chaihutang Treats Digestive System Tumors: A Review
Ranpei ZHU ; Tianqing SANG ; Hui XIE ; Tingting SUN ; Haoran QU ; Shanshan LI ; Yuling ZHENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):251-260
Da Chaihutang from the Treatise on Febrile Disease (Shanghanlun) has the function of harmonizing lesser Yang and discharging internal heat. It is formulated by ZHANG Zhongjing for the concurrent diseases of lesser Yang and Yang brightness and has been widely used in the treatment of digestive system diseases, especially malignant tumors. By review of the articles published in the last 20 years, this paper summarizes the application of Da Chaihutang in treating digestive system tumors from syndrome analysis, clinical research, and mechanism research. Da Chaihutang can treat the syndrome involving lesser Yang and Yang brightness in the digestive system, release interior and exterior to expel pathogen, and remove obstruction by conforming to the descending nature of the six fu-organs. In clinical practice, Da Chaihutang can directly treat digestive system malignant tumors such as liver cancer, pancreatic cancer, intestinal cancer, gastric cancer, and gallbladder cancer. In addition, it can relieve common complications of digestive system malignant tumors, such as cancerous fever, malignant obstructive jaundice, and constipation. Moreover, it can alleviate the adverse reactions caused by Western medical treatment, such as post-embolization syndrome, side effects of chemotherapy, and incomplete postoperative obstruction. Da Chaihutang is effective when used alone as it can relieve clinical symptoms, improve prognosis, and prolong survival of advanced patients and is safe and non-toxic, suitable for long-term use by tumor patients. Regarding the mechanism, Da Chaihutang can promote the apoptosis and inhibit the proliferation of tumor cells, reduce inflammation and inflammatory injury, and improve the liver function. The clear effect and mechanism confirms the anti-tumor effect of Da Chaihutang. This paper comprehensively describes the current research status of Da Chaihutang in the treatment of digestive system tumors and puts forward the deficiencies and improvement measures for the current research, aiming to provide reference for the application of this formula in treating digestive system tumors, the establishment of Chinese and Western medicine treatment schemes of tumors, and the research and development of anti-tumor drugs.
8.Research progress on running-related joint injuries and rehabilitation treatment
Yumin LI ; Jie LYU ; Peipei HAN ; Ruiqin WANG ; Haoran XU ; Panjing GUO ; Duoduo WANG
International Journal of Biomedical Engineering 2024;47(1):93-98
Under the backdrop of the "Healthy China 2030" strategy, running has become the most common form of exercise. Fitness running is a kind of endurance aerobic exercise. Compared with swimming, aerobics, and other sports with high activity and intensity, the risk of lower limb fatigue injury during fitness running is higher. In this review paper, the risk factors for running-related injuries were summarized by consulting and analyzing the database and focuses on discussing and analyzing the impact of running on joints. The results showed that hip adduction, knee bending, and ankle joint abnormalities are the three joint-related factors that cause the main injuries during running. Four rehabilitation intervention methods for running-related injuries were proposed, that can guide patients to generate personalized rehabilitation treatment plans through training.
9.Research progress in mitochondrial quality control in schizophrenia
Haoran CHU ; Cuicui CUI ; Xianbiao SU ; Hongchang ZHANG ; Jiashu MA ; Houming ZHU ; Ludong BAI ; Ranran LI
Journal of Central South University(Medical Sciences) 2024;49(1):128-134
Mitochondria are the main site of energy metabolism within cells,generating a substantial amount of ATP to supply energy to the human body.Research has shown that alterations in mitochondrial structure and function exist in individuals with schizophrenia,suggesting their potential impact on the onset of psychiatric disorders and clinical treatment efficacy.Therefore,understanding the research progress on the genetic mechanisms,pathological processes,image manifestations of schizophrenia and mitochondrial quality control,and summarizing the relevant evidence of mitochondrial-related targets as potential therapeutic targets for schizophrenia,can provide references for further research.
10.Potential mechanism of Babao Dan in the treatment of hepatocellular carcinoma based on network pharmacology
Xinyu ZHU ; Haoran BAI ; Naping ZHAO ; Dachuan QI ; Lixin WEI ; Li ZHANG
Journal of Pharmaceutical Practice and Service 2024;42(4):157-164
Objective To explore the potential mechanism of Babao Dan on primary liver cancer based on network pharmacology. Methods First, the diethylnitrosamine-induced hepatocellular carcinoma rat(HCC)model was used to observe the effects of Babao Dan. Then, the effective components in Babao Dan were detected by UPLC-MS, and the potential target sites of these effective components were predicted in the Swiss Target Prediction databases, etc. The corresponding target sites for HCC were screened using GeneCards, OMIM and Therapeutic Target Database, and the common target sites between Babao Dan and HCC were obtained after getting the intersection. The protein-protein interaction network was drawn by Cytoscape software and the STRING database, and the key molecules regulating HCC by Babao Dan were screened out. The effective target sites were subjected to GO analysis in the DAVID database and enrichment analysis in the Pathway’s KEGG. Finally, the clinical relevance of key molecules to liver cancer patients was verified by the TCGA database. Results Babao Dan could slow down the tumor development. 851 chemical components were detected in BaBao Dan by UPLC-MS , 9 major active components and 285 target sites were identified. 637 hepatocellular carcinoma-related targets were screened out, and 16 targets of Babao Dan regulating HCC were identified. GO enrichment analysis showed 802 biological processes, 11 cell compositions, and 43 molecular functions, while KEGG pathway enrichment analysis identified a total of 90 pathways. Correlation analysis of TCGA identified three key molecules associated with the survival of liver cancer patients. Conclusion In the primary rat liver cancer model, Babao Dan was found to significantly prolong the survival of cancer-induced rats and reduce tumor burden. The initial prediction of the mechanism by which Babao Dan regulating liver cancer was made through UPLC-MS analysis and network pharmacology methods, indicating that Babao Dan has the characteristics of multi-component, multi-pathway, and multi-target regulation of primary liver cancer, which could provide a reference for further relevant experimental research.


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