1.Triptolide in the treatment of osteoarthritis:network pharmacology analysis and animal model validation
Yixian CHEN ; Chen CHEN ; Liheng LU ; Jinpeng TANG ; Xiaowei YU
Chinese Journal of Tissue Engineering Research 2026;30(4):805-815
BACKGROUND:Osteoarthritis is a chronic degenerative disease of the joints that can lead to disability.Its main pathological features are persistent inflammation and cartilage destruction.Triptolide has been used to treat a variety of chronic joint diseases.However,the mechanism of triptolide in the treatment of osteoarthritis has not been clarifiedOBJECTIVE:To identify the effective targets of triptolide in the treatment of osteoarthritis by network pharmacology,and to investigate the therapeutic effect of triptolide on osteoarthritis in the osteoarthritis model.METHODS:Network pharmacology was used to anticipate the potential targets and signaling pathways of triptolide in the treatment of osteoarthritis,and molecular docking technology was used to validate the core targets.A rat osteoarthritis model was established by anterior cruciate ligament transection.Eight weeks after modeling,the rats were administered with triptolide and sodium hyaluronate by intra-articular injection for 6 weeks.After 6 weeks of intervention,the pathological changes in rat knee joints were observed by hematoxylin-eosin staining and safranin O-fast green staining.The levels of inflammatory factors in rat serum were detected by enzyme-linked immunosorbent assay.The expression of aggrecan,type Ⅰ platelet-responsive protein-containing desmoglein metalloproteinase 5,type Ⅱ collagen and matrix metalloproteinase 13 proteins in rat articular cartilage was tested by immunohistochemical staining.RESULTS AND CONCLUSION:(1)The results of network pharmacology indicated that the target of triptolide may be related to the inhibition of the release of factors such as interleukin 6,tumor necrosis factor a,interleukin 1β,matrix metalloproteinase 9,and the over-activation of the nuclear factor-κB/JAK2-STAT3 signaling pathway.(2)Triptplide could reduce the degree of joint swelling in osteoarthritic rats;pathologically improve the articular cartilage and maintain the cartilage structure;decrease the serum levels of interleukin 6,tumor necrosis factor a,interleukin 1β,matrix metalloproteinase 9,and matrix metalloproteinase 3 in osteoarthritic rats;reduce the protein expression of matrix metalloproteinase 13 and type Ⅰ platelet-responsive protein-containing desmoglein metalloproteinase 5 in the articular cartilage;and increase the expression of type Ⅱ collagen and aggrecan in the cartilage,thereby achieving cartilage protection.
2.Triptolide in the treatment of osteoarthritis:network pharmacology analysis and animal model validation
Yixian CHEN ; Chen CHEN ; Liheng LU ; Jinpeng TANG ; Xiaowei YU
Chinese Journal of Tissue Engineering Research 2026;30(4):805-815
BACKGROUND:Osteoarthritis is a chronic degenerative disease of the joints that can lead to disability.Its main pathological features are persistent inflammation and cartilage destruction.Triptolide has been used to treat a variety of chronic joint diseases.However,the mechanism of triptolide in the treatment of osteoarthritis has not been clarifiedOBJECTIVE:To identify the effective targets of triptolide in the treatment of osteoarthritis by network pharmacology,and to investigate the therapeutic effect of triptolide on osteoarthritis in the osteoarthritis model.METHODS:Network pharmacology was used to anticipate the potential targets and signaling pathways of triptolide in the treatment of osteoarthritis,and molecular docking technology was used to validate the core targets.A rat osteoarthritis model was established by anterior cruciate ligament transection.Eight weeks after modeling,the rats were administered with triptolide and sodium hyaluronate by intra-articular injection for 6 weeks.After 6 weeks of intervention,the pathological changes in rat knee joints were observed by hematoxylin-eosin staining and safranin O-fast green staining.The levels of inflammatory factors in rat serum were detected by enzyme-linked immunosorbent assay.The expression of aggrecan,type Ⅰ platelet-responsive protein-containing desmoglein metalloproteinase 5,type Ⅱ collagen and matrix metalloproteinase 13 proteins in rat articular cartilage was tested by immunohistochemical staining.RESULTS AND CONCLUSION:(1)The results of network pharmacology indicated that the target of triptolide may be related to the inhibition of the release of factors such as interleukin 6,tumor necrosis factor a,interleukin 1β,matrix metalloproteinase 9,and the over-activation of the nuclear factor-κB/JAK2-STAT3 signaling pathway.(2)Triptplide could reduce the degree of joint swelling in osteoarthritic rats;pathologically improve the articular cartilage and maintain the cartilage structure;decrease the serum levels of interleukin 6,tumor necrosis factor a,interleukin 1β,matrix metalloproteinase 9,and matrix metalloproteinase 3 in osteoarthritic rats;reduce the protein expression of matrix metalloproteinase 13 and type Ⅰ platelet-responsive protein-containing desmoglein metalloproteinase 5 in the articular cartilage;and increase the expression of type Ⅱ collagen and aggrecan in the cartilage,thereby achieving cartilage protection.
3.Clinical efficacy analysis of transurethral resection of intramural ureteral tumors
Chen YE ; Yi WANG ; Ruixiang SONG ; Jinpeng ZHU ; Shuxiong ZENG ; Chuanliang XU ; Huiqing WANG
Chinese Journal of Clinical Medicine 2026;33(4):683-688
Objective To explore the efficacy and safety of treatment of intramural ureteral tumors via transurethral resection. Methods A retrospective analysis was conducted on the clinical data of 26 patients with ureteral cancer who underwent transurethral resection of intramural ureteral tumors at the First Affiliated Hospital of Naval Medical University from May 2020 to May 2023. All patients were treated using the “outer-wedge, inner-rotation” resection technique, with ureteral stents placed intraoperatively. Clinical indicators including operation time, intraoperative blood loss, length of postoperative hospital stay, ureteral stent indwelling duration, intraoperative and postoperative complications, postoperative pathological results, and bladder tumor recurrence rate were analyzed. Results All surgeries were successfully completed. The operation time was 45(35, 60) min, intraoperative blood loss was 5(3, 10) mL, length of postoperative hospital stay was 4(3, 5) d, and the ureteral stent indwelling duration was (33.8±9.7) d. All patients did not experience intraoperative complications, the postoperative hydronephrosis rate was 3.8%. Postoperative pathology confirmed urothelial carcinoma in all cases, including 6 cases of stage pTa, 16 cases of pT1, and 4 cases of pT2a. The follow-up period ranged from 12 to 48 months. Intravesical recurrence occurred in 2 patients, and recurrence rate was 7.7%. There were no tumor-related deaths during the follow-up period. Conclusions Transurethral resection of intramural ureteral tumors is minimally invasive, resulting in less blood loss, and has low rates of postoperative complications such as hydronephrosis and hydroureter. It achieves favorable surgical outcomes while better preserving renal function.
4.Robot system-assisted versus freehand screw revision for ankylosing spondylitis with lower cervical fractures: a multicenter retrospective study
Shuai LI ; Jiaojiao BAI ; Baorong HE ; Yanzheng GAO ; Wei MEI ; Xinyu LIU ; Yue ZHU ; Qingda LI ; Yukuan LEI ; Lei ZHU ; Zhigang ZHAO ; Yunfei HUANG ; Jinpeng DU ; Mingzhe FENG ; Ningbo CHEN ; Yansheng HUANG ; Xuefang ZHANG ; Zhen CHANG
Chinese Journal of Trauma 2025;41(5):440-448
Objective:To compare the efficacy of robot system-assisted versus freehand screw revision for ankylosing spondylitis (AS) with lower cervical fractures.Methods:A multicenter retrospective cohort study was conducted to analyze the clinical data of 57 patients with AS combined with lower cervical fractures admitted to Honghui Hospital Affiliated to Xi'an Jiaotong University School of Medicine, Henan Provincial People's Hospital, Zhengzhou Orthopedic Hospital, and Qilu Hospital of Shandong University, including 46 males and 11 females, aged 38-77 years [(65.4±9.5)years]. Injury segments involved C 3 in 7 patients, C 4 in 13, C 5 in 25, C 6 in 10, and C 7 in 2. All the patients underwent revision surgery, among whom, 22 patients were treated with robot system-assisted cervical pedicle screw placement (robot nailing group, with 190 screws), and 35 with freehand cervical pedicle screw placement (freehand nailing group, with 300 screws). The operative duration, intraoperative bleeding volume, frequency of intraoperative fluoroscopy, incision length, and length of hospital stay of the two groups were compared; the time of single nscrew insertion, the number of single nail revisions, the distance between screws and the anterior cortex, the accuracy of screw placement of grade 0 and grade 0+1 were recorded in the two groups. The visual analogue scale (VAS), Japanese Orthopedic Society (JOA) score, neck dysfunction index (NDI), American Spine Injury Association (ASIA) classification before operation, at 3 days, 3 months after operation and at the last follow-up were compared between the two groups. The complication rate was also noted. Results:All the patients were followed up for 12-16 months [(14.3±2.1)months]. The operative duration, intraoperative bleeding volume, and frequency of intraoperative fluoroscopy were (186.4±12.9)minutes, (486.1±68.6)ml, and (3.4±1.3)times in the robot nailing group, which were shorter or less than (206.7±14.4)minutes, (660.3±45.2)ml, and (13.5±3.6)times in the freehand nailing group ( P<0.01). The incision length was (9.4±2.4)cm in the robot nailing group, longer than (5.6±1.2)cm in the freehand nailing group ( P<0.01), and the length of hospital stay was (3.7±0.4)days, shorter than (4.4±1.4)days in the freehand nailing group ( P<0.01). The length of single nail insertion, the number of single nail revision, and the distance between the screws and the front cortex were (6.5±0.4)minutes, (1.1±0.1)times, and (3.5±1.3)mm in the robot nailing group, which were shorter or less than (11.6±0.2)minutes, (1.5±0.2)times, and (12.4±4.7)mm in the freehand nailing group ( P<0.01). The accuracy of the screw placement in the robot nailing group was 90.0% (171/190) and 95.8% (182/190) with level 0 and 0+1 screws, better than 80.0% (240/300) and 89.0% (267/300) in the freehand nailing group ( P<0.05). There was no significant difference in VAS, JOA score, NDI, or ASIA grading between the two groups before operation ( P>0.05). The VAS, JOA, and NDI scores at 3 days after operation were (3.1±0.6)points, (12.1±1.2)points, and (15.6±2.9)points, respectively in the robot nailing group, which were better than (5.0±1.4)points, (11.3±1.1)points and (22.5±3.7)points, respectively in the freehand nailing group ( P<0.05). No statistically significant difference was observed in the ASIA grade between the two groups at 3 days after operation ( P>0.05). There were no significant differences in VAS, JOA, NDI scores, or ASIA grading between the two groups at 3 months after operation and at the last follow-up ( P>0.05). Compared with those before operation, the VAS, JOA, NDI scores, and ASIA grading were significantly improved at 3 days, 3 months after operation and at the last follow-up in the two groups, which were further improved with the passage of time. Two patients in the robot nailing group had pneumonia, with a complication rate of 9% (2/22), while 2 patients in the freehand nailing group had dural sac rupture and cerebrospinal fluid leakage and 3 had lung infection after operation, with a complication rate of 14% (5/35) ( P<0.05). Conclusion:Compared with freehand nailing, the robot system-assisted nailing revision for AS with lower cervical fracture has more advantages in terms of the operative duration, length of hospital stay, intraoperative bleeding volume, frequency of intraoperative fluoroscopy nailing speed and accuracy, screw holding force, early pain relief, function restoration, and complication rate, despite longer surgical incision.
5.Efficacy and Safety of Qihuang Acupuncture Theory Combined with Opioid Analgesics in the Treatment of Moderate to Severe Cancer Pain in Lung Cancer Patients:a Randomize-Controlled Trial
Yingqi WANG ; Ruifang YU ; Jinpeng HUANG ; Guiya LIAO ; Ziyan GAN ; Zhenhu CHEN ; Xiaobing YANG ; Chunzhi TANG
Journal of Traditional Chinese Medicine 2025;66(4):358-366
ObjectiveTo observe the analgesic efficacy and safety of Qihuang acupuncture theory combined with opioid analgesics in patients with moderate to severe cancer pain due to lung cancer. MethodsPatients with moderate to severe cancer pain from lung cancer were randomly divided into Qihuang acupuncture group and control group, with 33 cases in each group. The control group was treated with long-acting opioid analgesics at maintenance doses and supplementary analgesic medications as needed. In case of breakthrough pain, short-acting opioids were used for rescue. The Qihuang acupuncture group received Qihuang acupuncture treatment in addition to the treatment used in the control group, administered once every other day, with 3 sessions constituting one treatment course. The treatment duration for both groups was 5 days. The primary outcome was the change in pain intensity, measured using the numerical rating scale (NRS) before and after treatment, and the NRS change rate was calculated. Secondary endpoints included the daily NRS change rate, the Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score, the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) score, and the 24-hour equivalent hydrocodone sustained-release tablet dose. Laboratory tests, including routine blood, urine, stool, liver function, and kidney function, were performed before and after treatment. Adverse events were recorded throughout the trial. ResultsAll patients completed the trial, and both groups showed a decrease in average NRS scores and PS scores after treatment, with the Qihuang acupuncture group showing lower average NRS scores and PS scores than the control group (P<0.05 or P<0.01). After treatment, the NRS change rate in the Qihuang acupuncture group was (0.42±0.17), significantly higher than that in the control group (0.14±0.27, P<0.01). The daily NRS change rate during treatment was also higher in the Qihuang acupuncture group compared to the control group (P<0.01). The Qihuang acupuncture group showed an increase in overall health status and functional scores in the EORTC QLQ-C30, and a decrease in symptom scores for fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, and financial difficulties. In contrast, overall health status and constipation scores in the control group increased, while scores of fatigue, nausea and vomiting, pain, and appetite loss decreased (P<0.05 or P<0.01). After treatment, the 24-hour equivalent hydrocodone sustained-release tablet dose did not show significant difference in the Qihuang acupuncture group (P>0.05), while the control group showed a significant increase in the 24-hour dose (P<0.01). No significant abnormalities were observed in laboratory tests before and after treatment in either group. During the study, the incidence of nausea and vomiting as well as constipation in the Qihuang acupuncture group was both 3.03% (1/33), while the incidence in the control group was 27.27% (9/33) and 36.36% (12/33), respectively, with the Qihuang acupuncture group showing significantly lower incidence (P<0.01). No serious adverse reactions were observed in either group. ConclusionQihuang acupuncture therapy combined with opioid analgesics is more effective than using opioids alone in relieving pain in patients with moderate to severe cancer pain due to lung cancer. It can improve the patients' physical condition and quality of life, reduce the dose of opioid analgesics, and has good safety.
6.Xiaozhong Zhitong Mixture(消肿止痛合剂)Combined with Antibiotic Bone Cement in the Treatment of Diabetic Foot Ulcers with Damp-Heat Obstructing Syndrome:A Randomized Controlled Trial of 35 Patients
Xiaotao WEI ; Zhijun HE ; Tao LIU ; Zhenxing JIANG ; Fei LI ; Yan LI ; Jinpeng LI ; Wen CHEN ; Bihui BAI ; Xuan DONG ; Bo SUN
Journal of Traditional Chinese Medicine 2025;66(7):704-709
ObjectiveTo observe the clinical effectiveness and safety of Xiaozhong Zhitong Mixture (消肿止痛合剂) combined with antibiotic bone cement in the treatment of diabetic foot ulcer (DFU) with damp-heat obstructing syndrome. MethodsA total of 72 DFU patients with damp-heat obstructing syndrome were randomly assigned to treatment group (36 cases) and the control group (36 cases). Both groups received standard treatment and topical antibiotic bone cement for ulcer wounds, while the treatment group received oral Xiaozhong Zhitong Mixture (50 ml per time, three times daily) in additionally. Both groups underwent daily wound dressing changes for 21 consecutive days. Ulcer healing rate, serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), malondialdehyde (MDA), superoxide dismutase (SOD), C-reactive protein (CRP), and white blood cell (WBC) count were observed before and after treatment, and visual analog scale (VAS) scores for wound pain, traditional Chinese medicine (TCM) syndrome scores, and the DFU Healing Scale (DMIST scale) were also compared. Liver and kidney function were evaluated before and after treatment, and adverse events such as allergic reactions, worsening ulcer pain were recorded. ResultsTotally 35 patients in the treatment group and 33 in the control group were included in the final analysis. The ulcer healing rate in the treatment group was (87.93±9.34)%, significantly higher than (81.82±12.02)% in the control group (P = 0.035). Compared to pre-treatment levels, both groups showed significant reductions in serum CRP, WBC, MDA, IL-1β, and TNF-α levels, with an increase in SOD level (P<0.05). TCM syndrome scores, VAS, and DMIST scores also significantly decreased in both groups (P<0.05), with greater improvements in the treatment group (P<0.05). No significant adverse reactions were observed in either group during treatment. ConclusionXiaozhong Zhitong Mixture combined with antibiotic bone cement has significant advantages in promoting DFU healing, reducing inflammatory response, and alleviating oxidative stress in DFU patients with damp-heat obstructing syndrome, with good safety for DFU patients with damp-heat obstructing syndrome.
7."Compatibility" Relationship of Active Components and Heat-clearing and Blood-cooling Effect of Rehmannia glutinosa Roots
Yaman CHEN ; Jinpeng CUI ; Juan ZHANG ; Qingpu LIU ; Haiyan GONG ; Jingwei LEI ; Fengqing WANG ; Caixia XIE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):193-201
ObjectiveTo analyze the "compatibility" relationship of sugars and glycosides and the heat-clearing and blood-cooling effect of the roots of four varieties of Rehmannia glutinosa and provide a basis for research on the pharmacodynamic material basis and quality control of R. glutinosa. MethodsThe content of sugars and glycosides in the roots of four varieties of R. glutinosa was determined during the growth period. The principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA), and the "compatibility" relationship of active components were employed to screen out the differential samples. A rat model of bleeding due to blood heat was used to verify the pharmacodynamic differences and the potential active components of differential samples. ResultsThe content and proportion characteristics of various components in roots of the four varieties of R. glutinosa during the expansion stage and the maturity stage had obvious differences. The proportion of phenylethanoid glycosides at the maturity stage was higher than that at the expansion stage. The R. glutinosa variety 85-5 had special quality characteristics among the tested varieties. All the samples alleviated the symptoms in the rat model. The effect of clearing heat and cooling blood was different between the maturity stage and the expansion stage, as well as between 85-5 samples at the maturity stage and other samples. The effect of clearing heat and cooling blood of R. glutinosa roots was the result of the combined action of multiple components in R. glutinosa roots and might be related to the high proportions of polysaccharides, iridoid glycosides, and phenylethanoid glycosides. ConclusionThe growth stage and variety affect the quality of R. glutinosa roots. The effect of clearing heat and cooling blood of R. glutinosa roots was related to the content and proportions of various components. The study can provide a basis for the basic research on the active components and quality control of R. glutinosa.
8."Compatibility" Relationship of Active Components and Heat-clearing and Blood-cooling Effect of Rehmannia glutinosa Roots
Yaman CHEN ; Jinpeng CUI ; Juan ZHANG ; Qingpu LIU ; Haiyan GONG ; Jingwei LEI ; Fengqing WANG ; Caixia XIE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):193-201
ObjectiveTo analyze the "compatibility" relationship of sugars and glycosides and the heat-clearing and blood-cooling effect of the roots of four varieties of Rehmannia glutinosa and provide a basis for research on the pharmacodynamic material basis and quality control of R. glutinosa. MethodsThe content of sugars and glycosides in the roots of four varieties of R. glutinosa was determined during the growth period. The principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA), and the "compatibility" relationship of active components were employed to screen out the differential samples. A rat model of bleeding due to blood heat was used to verify the pharmacodynamic differences and the potential active components of differential samples. ResultsThe content and proportion characteristics of various components in roots of the four varieties of R. glutinosa during the expansion stage and the maturity stage had obvious differences. The proportion of phenylethanoid glycosides at the maturity stage was higher than that at the expansion stage. The R. glutinosa variety 85-5 had special quality characteristics among the tested varieties. All the samples alleviated the symptoms in the rat model. The effect of clearing heat and cooling blood was different between the maturity stage and the expansion stage, as well as between 85-5 samples at the maturity stage and other samples. The effect of clearing heat and cooling blood of R. glutinosa roots was the result of the combined action of multiple components in R. glutinosa roots and might be related to the high proportions of polysaccharides, iridoid glycosides, and phenylethanoid glycosides. ConclusionThe growth stage and variety affect the quality of R. glutinosa roots. The effect of clearing heat and cooling blood of R. glutinosa roots was related to the content and proportions of various components. The study can provide a basis for the basic research on the active components and quality control of R. glutinosa.
9.Pathogenesis and treatment progress of flap ischemia-reperfusion injury
Bo HE ; Wen CHEN ; Suilu MA ; Zhijun HE ; Yuan SONG ; Jinpeng LI ; Tao LIU ; Xiaotao WEI ; Weiwei WANG ; Jing XIE
Chinese Journal of Tissue Engineering Research 2025;29(6):1230-1238
BACKGROUND:Flap transplantation technique is a commonly used surgical procedure for the treatment of severe tissue defects,but postoperative flap necrosis is easily triggered by ischemia-reperfusion injury.Therefore,it is still an important research topic to improve the survival rate of transplanted flaps. OBJECTIVE:To review the pathogenesis and latest treatment progress of flap ischemia-reperfusion injury. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature published from 2014 to 2024.The search terms used were"flap,ischemia-reperfusion injury,inflammatory response,oxidative stress,Ca2+overload,apoptosis,mesenchymal stem cells,platelet-rich plasma,signaling pathways,shock wave,pretreatment"in Chinese and English.After elimination of irrelevant literature,poor quality and obsolete literature,77 documents were finally included for review. RESULTS AND CONCLUSION:Flap ischemia/reperfusion injury may be related to pathological factors such as inflammatory response,oxidative stress response,Ca2+overload,and apoptosis,which can cause apoptosis of vascular endothelial cells,vascular damage and microcirculation disorders in the flap,and eventually lead to flap necrosis.Studies have found that mesenchymal stem cell transplantation,platelet-rich plasma,signaling pathway modulators,shock waves,and pretreatment can alleviate flap ischemia/reperfusion injuries from different aspects and to varying degrees,and reduce the necrosis rate and necrosis area of the grafted flap.Although there are many therapeutic methods for skin flap ischemia/reperfusion injury,a unified and effective therapeutic method has not yet been developed in the clinic,and the advantages and disadvantages of various therapeutic methods have not yet been compared.Most of the studies remain in the stage of animal experiments,rarely involving clinical observations.Therefore,a lot of research is required in the future to gradually move from animal experiments to the clinic in order to better serve the clinic.
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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