1.Treatment Principles and Paradigm of Diabetic Microvascular Complications Responding Specifically to Traditional Chinese Medicine
Anzhu WANG ; Xing HANG ; Lili ZHANG ; Xiaorong ZHU ; Dantao PENG ; Ying FAN ; Min ZHANG ; Wenliang LYU ; Guoliang ZHANG ; Xiai WU ; Jia MI ; Jiaxing TIAN ; Wei ZHANG ; Han WANG ; Yuan XU ; .LI PINGPING ; Zhenyu WANG ; Ying ZHANG ; Dongmei SUN ; Yi HE ; Mei MO ; Xiaoxiao ZHANG ; Linhua ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):272-279
To explore the advantages of traditional Chinese medicine (TCM) and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications (DMC), refine key pathophysiological insights and treatment principles, and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine, hosted by the China Association of Chinese Medicine, was held in Beijing, 2024. Experts in TCM, Western medicine, and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis, diagnostic and treatment challenges, and mechanism research related to DMC, ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development, research prioritization, and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM, strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.
2.Characterization of Animal Models of Type 2 Diabetes Mellitus with Hypertension Based on Clinical Symptoms in Traditional Chinese and Western Medicine
Ziyi WANG ; Xingyu FAN ; Yuzhi JIA ; Qingyong HE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):230-236
Type 2 diabetes mellitus (T2DM) and hypertension are common and frequent chronic non-communicable diseases, which often coexist in clinical practice, resulting in a large number of cardiovascular events and deaths, and their case fatality rate far exceeds that of other factors such as dyslipidemia and obesity. Based on the diagnostic standards, guidelines, and animal model evaluation methods of T2DM with hypertension at home and abroad, this study summarized, evaluated, and analyzed the characteristics of the existing animal models of T2DM with hypertension based on the clinical symptoms in traditional Chinese and Western medicine. The animal models showing high fitting degrees with the clinical symptoms in Western medicine are mainly established by injection of streptozocin (STZ) in SHR rats in the surgical induction and chemical induction methods and feeding a high-fat and high-salt diet combined with STZ injection in SD rats in the dietary induction methods. The models showcasing high fitting degrees with the clinical symptoms in traditional Chinese medicine (TCM) are mainly established by the surgical induction method. Considering the fitting degrees and the advantages and disadvantages, the ideal modeling method for T2DM with hypertension is the two-kidney, one clip (2K1C) method (a surgical induction method) combined with feeding a high-fat and high-sugar diet and STZ injection. However, the available models lack the characteristics of TCM and the evaluation indicators have poor specificity. This study found that there are few animal models of T2DM with hypertension considering the characteristics of both disease and syndrome, which may be related to the identification and attribution of TCM syndromes in animal macroscopic information. In view of this problem, it is suggested that the evaluation criteria should be established and improved for the animal models combining disease and syndrome, which can help to evaluate the fitting degree of the pathological characteristics of different syndromes in the animal models of T2DM with hypertension. In this way, ideal animal models of T2DM with hypertension can be established to simulate the disease occurrence and development in the human body. The animal models are expected to provide an ideal approach for the further research on the pathogenesis of T2DM and its prevention and treatment with TCM, which is of great significance for the treatment and prevention of T2DM with hypertension and the prognosis of its complications. At the same time, breakthroughs in the basic syndrome models of comorbidities are expected to lay a foundation for the leapfrog development of TCM research.
3.Application of Huangkui Capsules in Diabetic Kidney Disease: A Review
Jia LUO ; Beile JIANG ; Qiuxiang HE ; Shilong LU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):314-324
Diabetic kidney disease (DKD) is a kidney disease caused by hyperglycemia,which is one of the most common microvascular complications of diabetes. Due to the high incidence of diabetes,the incidence of DKD has also increased year by year,and DKD has become a global public health problem. The pathogenesis of DKD is related to mechanisms such as oxidative stress,inflammation,renal fibrosis,and decreased mitophagy activity,which are developed under a variety of complex mechanisms. In traditional Chinese medicine,it is believed that the incidence of DKD is closely related to damp heat. Therefore,it is necessary to grasp the treatment method of clearing heat and removing dampness in clinical medication. Huangkui Capsules (HKC) have the effect of clearing damp heat,detoxifying, and detumescence. Because of its unique curative effect on DKD,HKC is often used in the treatment of DKD. HKC plays a role in the treatment of DKD with a variety of pharmacokinetic and pharmacodynamic processes. In many laboratory studies,it has been found that the specific mechanisms of HKC in the treatment of DKD include increasing mitophagy,reducing mitochondrial damage,reducing renal fibrosis,controlling inflammatory response,and inhibiting oxidative stress,which can achieve the purpose of reducing renal damage and promoting renal function. Some clinical studies have also verified that the application of HKC alone can exert renal protective function through anti-inflammatory,anti-oxidative stress,anti-renal fibrosis effects,as well as reduction of urinary protein. Since DKD is not a single injury of renal function,it is often accompanied by problems in blood pressure,blood lipids,blood circulation,body immunity, and other aspects. Therefore,the combination of HKC with other drugs can often achieve more comprehensive results,improve the advantages of various drugs,and improve the therapeutic effect. The combination of drugs such as antihypertensive,lipid-lowering, vascular circulation improvement,immunity inhibition,and anti-oxidative stress with HKC has achieved good results. In addition,HKC is often used in combination with other Chinese patent medicines in clinics. The application of HKC in the treatment of DKD has made some progress,but there are still many places worthy of further study,and the research on the mechanism of HKC is not comprehensive enough. The research on its long-term effect and safety in clinical application is relatively lacking,and the drug variety is relatively single when combined with certain drugs. These problems deserve further attention. Finally,it is necessary to pay attention to the promotion and application of HKC in clinical practice so that HKC can be better applied in clinical practice and better solve practical problems for patients.
4.Characterization of Animal Models of Type 2 Diabetes Mellitus with Hypertension Based on Clinical Symptoms in Traditional Chinese and Western Medicine
Ziyi WANG ; Xingyu FAN ; Yuzhi JIA ; Qingyong HE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):230-236
Type 2 diabetes mellitus (T2DM) and hypertension are common and frequent chronic non-communicable diseases, which often coexist in clinical practice, resulting in a large number of cardiovascular events and deaths, and their case fatality rate far exceeds that of other factors such as dyslipidemia and obesity. Based on the diagnostic standards, guidelines, and animal model evaluation methods of T2DM with hypertension at home and abroad, this study summarized, evaluated, and analyzed the characteristics of the existing animal models of T2DM with hypertension based on the clinical symptoms in traditional Chinese and Western medicine. The animal models showing high fitting degrees with the clinical symptoms in Western medicine are mainly established by injection of streptozocin (STZ) in SHR rats in the surgical induction and chemical induction methods and feeding a high-fat and high-salt diet combined with STZ injection in SD rats in the dietary induction methods. The models showcasing high fitting degrees with the clinical symptoms in traditional Chinese medicine (TCM) are mainly established by the surgical induction method. Considering the fitting degrees and the advantages and disadvantages, the ideal modeling method for T2DM with hypertension is the two-kidney, one clip (2K1C) method (a surgical induction method) combined with feeding a high-fat and high-sugar diet and STZ injection. However, the available models lack the characteristics of TCM and the evaluation indicators have poor specificity. This study found that there are few animal models of T2DM with hypertension considering the characteristics of both disease and syndrome, which may be related to the identification and attribution of TCM syndromes in animal macroscopic information. In view of this problem, it is suggested that the evaluation criteria should be established and improved for the animal models combining disease and syndrome, which can help to evaluate the fitting degree of the pathological characteristics of different syndromes in the animal models of T2DM with hypertension. In this way, ideal animal models of T2DM with hypertension can be established to simulate the disease occurrence and development in the human body. The animal models are expected to provide an ideal approach for the further research on the pathogenesis of T2DM and its prevention and treatment with TCM, which is of great significance for the treatment and prevention of T2DM with hypertension and the prognosis of its complications. At the same time, breakthroughs in the basic syndrome models of comorbidities are expected to lay a foundation for the leapfrog development of TCM research.
5.Application of Huangkui Capsules in Diabetic Kidney Disease: A Review
Jia LUO ; Beile JIANG ; Qiuxiang HE ; Shilong LU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):314-324
Diabetic kidney disease (DKD) is a kidney disease caused by hyperglycemia,which is one of the most common microvascular complications of diabetes. Due to the high incidence of diabetes,the incidence of DKD has also increased year by year,and DKD has become a global public health problem. The pathogenesis of DKD is related to mechanisms such as oxidative stress,inflammation,renal fibrosis,and decreased mitophagy activity,which are developed under a variety of complex mechanisms. In traditional Chinese medicine,it is believed that the incidence of DKD is closely related to damp heat. Therefore,it is necessary to grasp the treatment method of clearing heat and removing dampness in clinical medication. Huangkui Capsules (HKC) have the effect of clearing damp heat,detoxifying, and detumescence. Because of its unique curative effect on DKD,HKC is often used in the treatment of DKD. HKC plays a role in the treatment of DKD with a variety of pharmacokinetic and pharmacodynamic processes. In many laboratory studies,it has been found that the specific mechanisms of HKC in the treatment of DKD include increasing mitophagy,reducing mitochondrial damage,reducing renal fibrosis,controlling inflammatory response,and inhibiting oxidative stress,which can achieve the purpose of reducing renal damage and promoting renal function. Some clinical studies have also verified that the application of HKC alone can exert renal protective function through anti-inflammatory,anti-oxidative stress,anti-renal fibrosis effects,as well as reduction of urinary protein. Since DKD is not a single injury of renal function,it is often accompanied by problems in blood pressure,blood lipids,blood circulation,body immunity, and other aspects. Therefore,the combination of HKC with other drugs can often achieve more comprehensive results,improve the advantages of various drugs,and improve the therapeutic effect. The combination of drugs such as antihypertensive,lipid-lowering, vascular circulation improvement,immunity inhibition,and anti-oxidative stress with HKC has achieved good results. In addition,HKC is often used in combination with other Chinese patent medicines in clinics. The application of HKC in the treatment of DKD has made some progress,but there are still many places worthy of further study,and the research on the mechanism of HKC is not comprehensive enough. The research on its long-term effect and safety in clinical application is relatively lacking,and the drug variety is relatively single when combined with certain drugs. These problems deserve further attention. Finally,it is necessary to pay attention to the promotion and application of HKC in clinical practice so that HKC can be better applied in clinical practice and better solve practical problems for patients.
6.Influencing factors for whole-eye astigmatism after pterygium excision combined with autologous limbal stem cell transplantation
Yanru HE ; Wanyue LI ; Jia LIU ; Yingwei WANG ; Zifeng ZHANG
International Eye Science 2025;25(2):286-291
AIM: To explore the factors affecting the whole-eye astigmatism after pterygium excision combined with autologous limbal stem cell transplantation.METHODS: A retrospective analysis was conducted on the medical records of 42 patients(42 eyes)with primary pterygium admitted in the ophthalmology department of Xijing Hospital from January 2023 to October 2023. They underwent pterygium excision combined with autologous limbal stem cell transplantation. The maximum invasion depth of pterygium into the cornea was measured with anterior segment optical coherence tomography(AS-OCT)before operation, the length of the pterygium invading cornea, the width of the limbus and the area of the invading cornea were measured during the operation, and three-dimensional values of corneal astigmatism of anterior segment, index of surface variance(ISV), index of vertical asymmetry(IVA), best corrected visual acuity(BCVA)and whole-eye astigmatism were collected before and at 1 mo after surgery. Patients with astigmatism ≤0.50 D or >0.50 D of the whole eye at 1 mo after surgery were assigned to group A and B, respectively. The differences of clinical data before and at 1 mo after surgery between the two groups, and the correlation between pre-operative clinical indicators and whole-eye astigmatism were analyzed. The decision tree algorithm was performed to explore the influencing factors of whole-eye astigmatism at 1 mo postoperatively.RESULTS: The maximum invasion depth of pterygium in the group A was significantly less than that in the group B [80.00(40.00, 180.00)μm vs 175.00(123.00, 190.00)μm, P=0.002]. Preoperative BCVA(LogMAR), whole-eye astigmatism, cornea astigmatism, ISV, IVA and maximum invasion depth of pterygium were positively correlated with whole-eye astigmatism at 1 mo after surgery(rs=0.317, P=0.041; rs=0.545, P<0.001; rs=0.448, P=0.003; rs=0.389, P=0.011; rs=0.382, P=0.013; rs=0.391, P=0.010). The decision tree algorithm screened out two influential factors: the maximum invasion depth of pterygium into the cornea and preoperative whole-eye astigmatism. The risk of whole-eye astigmatism >0.50 D at 1 mo after operation was higher with maximum invasion depth of pterygium into the cornea >95 μm than that with ≤95 μm. Among the patients with whole-eye astigmatism >2.63 D before operation, the probability of residual whole-eye astigmatism >0.50 D was 88.9%, and the predictive model AUC was 0.804.CONCLUSION: The whole-eye astigmatism after pterygium resection is mainly affected by the maximum invasion depth of pterygium into the cornea and preoperative whole-eye astigmatism. When the maximum invasion depth of pterygium into the corneal is >95 μm and the whole-eye stigmatism is >2.63 D before surgery, the patient should receive surgical treatment as soon as possible in order to obtain good clinical benefits.
7.Mahoniae Caulis Alkaloids Ameliorate Depression by Regulating Synaptic Plasticity via cAMP Pathway
Junhui HE ; Chunlian JIA ; Kedao LAI ; Guili ZHOU ; Rongfei ZHOU ; Yi LI ; Dongmei LI ; Jiaxiu XIE ; Guining WEI ; Juying ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):132-140
ObjectiveTo explore the mechanisms associated with Mahoniae Caulis alkaloids (MA) in ameliorating depression by network pharmacology, molecular docking, and animal experiments. MethodsThe component targets of MA were obtained through Swiss Target Prediction and TCMIP database. The depression targets were collected through TCMIP, Genecards, HPO, DrugBank and OMIM database. The depression targets were collected through TCMIP, Genecards, HPO, DrugBank and OMIM database. Protein-protein interaction (PPI) network was constructed by protein interaction analysis (STRING) database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed through Bioinformatics (DAVID) database. The docking of components and targets was performed by AGFR. The mouse model of depression was established by intraperitoneal injection of corticosterone (CORT) once a day for 35 consecutive days. Sixty mice were randomly allocated into control (0.9% normal saline), model (CORT, 20 mg·kg-1), positive control (fluoxetine hydrochloride, 3.6 mg·kg-1), and MA (10, 5, and 2.5 mg·kg-1) groups. Each group was administrated with corresponding medicine or normal saline once a day for 28 consecutive days. The depression-like behavior of mice was observed. The pathological changes of prefrontal cortex in mice were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl dUTP transferase nick end labeling (TUNEL) was employed to observe the apoptosis of neurons in the prefrontal cortex. Enzyme-linked immunosorbent assay was employed to assess the serum levels of brain-derived neurotrophic factor (BDNF), dopamine (DA), 5-hydroxytryptamine (5-HT), and norepinephrine (NE) in mice. The mRNA levels of cyclic adenosine monophosphate (cAMP) pathway-related factors and inflammatory factors were determined by Real-time PCR. Western blot was employed to determine the expression of cAMP pathway-related factors and connexin 43 (Cx43). ResultsA total of 434 component targets and 545 depression targets were obtained, including 84 common targets, among which 10 core targets were screened out. GO analysis predicted 34 biological processes, 15 cell components, and 11 molecular functions. The KEGG pathways were mainly related to gap junction and cAMP signaling pathway. The core components had good binding affinity with the core targets. The results of animal experiments showed that compared with the control group, CORT prolonged the immobility time of mice in forced swimming and tail suspension tests (P<0.01), lowered the serum levels of NE, BDNF, and 5-HT (P<0.05), up-regulated the mRNA levels of nuclear factor-κB (NF-κB) and interleukin-6 (IL-6) in the brain tissue (P<0.05), and down-regulated the mRNA levels of cyclic adenosine monophosphate effector binding protein (CREB) and BDNF (P<0.05) and the protein levels of protein kinase (PRKACA), phosphorylation (p)-CREB/CREB, BDNF, and Cx43 (P<0.05) in the brain tissue. Compared with the model group, high-dose MA reduced the immobility time of mice in forced swimming (P<0.05) and tail suspension (P<0.01) tests, raised the serum levels of NE, BDNF, and 5-HT (P<0.01), down-regulated the mRNA level of NF-κB (P<0.01), and up-regulated the mRNA level of BDNF (P<0.01) and protein levels of PRKACA, p-CREB/CREB, BDNF, and Cx43 (P<0.05). ConclusionMA alleviates the CORT-induced depressive behavior of mice. It may play an antidepressant role by regulating cAMP signaling pathway and gap junction pathway, improving synaptic plasticity and gap junction function, and reducing neuroinflammation.
8.The Experience of Retention Enema with Traditional Chinese Medicine for Ulcerative Colitis Based on the Theory of Sweat Pore
Zifu HONG ; Yinghua HE ; Lipeng FENG ; Fei JIA ; Mouwen QYU ; Liang YUAN ; Mingwen JIA
Journal of Traditional Chinese Medicine 2025;66(6):634-637
This paper discussed the nature of ulcerative colitis, that is deficiency of the root and excess of the branch, from the theory of sweat pore, and to explore the theoretical basis and experience of treating this disease with retention enema of traditional Chinese medicine (TCM). The main location of this disease is in the intestine. As a part of sweat pore, the intestinal sweat pore serves as the gateway for the ascending, descending, exiting and entering of qi movement in the zang fu (脏腑) organs, meridians and collaterals, as well as the channel for the transportation of qi, blood and body fluids. The constraint and closure of the intestinal sweat pore are the main pathological basis of ulcerative colitis. According to the manifestations of colonoscopy, and the different etiological factors and pathogenesis that lead to the constraint and closure of sweat pore, there should be different treatment focuses such as expelling wind to open sweat pore, clearing fire to open sweat pore, promoting blood circulation to open sweat pore, for which wind-dispersing herbs, heat-clearing herbs, and blood-activating herbs are used accordingly. The method of retention enema can directly induce Chinese medicinal herbs to the affected part, so as to diffuse and unblock the sweat pore, regulate qi and blood, and thus restore the normal function of the intestinal sweat pore.
9.Gut microbiota and osteoporotic fractures
Wensheng ZHAO ; Xiaolin LI ; Changhua PENG ; Jia DENG ; Hao SHENG ; Hongwei CHEN ; Chaoju ZHANG ; Chuan HE
Chinese Journal of Tissue Engineering Research 2025;29(6):1296-1304
BACKGROUND:Osteoporotic fracture is the most serious complication of osteoporosis.Previous studies have demonstrated that gut microbiota has a regulatory effect on skeletal tissue and that gut microbiota has an important relationship with osteoporotic fracture,but the causal relationship between the two is unclear. OBJECTIVE:To explore the causal relationship between gut microbiota and osteoporotic fractures using Mendelian randomization method. METHODS:The genome-wide association study(GWAS)datasets of gut microbiota and osteoporotic fracture were obtained from the IEU Open GWAS database and the Finnish database R9,respectively.Using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,Mendelian randomization analyses with random-effects inverse variance weighted,MR-Egger regression,weighted median,simple model,and weighted model methods were performed to assess whether there is a causal relationship between gut microbiota and osteoporotic fracture.Sensitivity analyses were performed to test the reliability and robustness of the results.Reverse Mendelian randomization analyses were performed to further validate the causal relationship identified in the forward Mendelian randomization analyses. RESULTS AND CONCLUSION:The results of this Mendelian randomization analysis indicated a causal relationship between gut microbiota and osteoporotic fracture.Elevated abundance of Actinomycetales[odds ratio(OR)=1.562,95%confidence interval(CI):1.027-2.375,P=0.037),Actinomycetaceae(OR=1.561,95%CI:1.027-2.374,P=0.037),Actinomyces(OR=1.544,95%CI:1.130-2.110,P=0.006),Butyricicoccus(OR=1.781,95%CI:1.194-2.657,P=0.005),Coprococcus 2(OR=1.550,95%CI:1.068-2.251,P=0.021),Family ⅩⅢ UCG-001(OR=1.473,95%CI:1.001-2.168,P=0.049),Methanobrevibacter(OR=1.274,95%CI:1.001-1.621,P=0.049),and Roseburia(OR=1.429,95%CI:1.015-2.013,P=0.041)would increase the risk of osteoporotic fractures in patients.Elevated abundance of Bacteroidia(OR=0.660,95%CI:0.455-0.959,P=0.029),Bacteroidales(OR=0.660,95%CI:0.455-0.959,P=0.029),Christensenellacea(OR=0.725,95%CI:0.529-0.995,P=0.047),Ruminococcaceae(OR=0.643,95%CI:0.443-0.933,P=0.020),Enterorhabdus(OR=0.558,95%CI:0.395-0.788,P=0.001),Eubacterium rectale group(OR=0.631,95%CI:0.435-0.916,P=0.016),Lachnospiraceae UCG008(OR=0.738,95%CI:0.546-0.998,P=0.048),and Ruminiclostridium 9(OR=0.492,95%CI:0.324-0.746,P=0.001)would reduce the risk of osteoporotic fractures in patients.We identified 16 gut microbiota associated with osteoporotic fracture by the Mendelian randomization method.That is,using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,eight gut microbiota showed positive causal associations with osteoporotic fracture and another eight gut microbiota showed negative causal associations with osteoporotic fracture.The results of this study not only identify new biomarkers for the early prediction of osteoporotic fracture and potential therapeutic targets in clinical practice,but also provide an experimental basis and theoretical basis for the study of improving the occurrence and prognosis of osteoporotic fracture through gut microbiota in bone tissue engineering.
10.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.

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