1.Mitogen-activated protein kinase signaling pathway regulates the development of osteoarthritis:guiding targeted therapy with traditional Chinese medicine
Hao LI ; Hongcheng TAO ; Ping ZENG ; Jinfu LIU ; Qiang DING ; Chicheng NIU ; Kai HUANG ; Hongyu KANG
Chinese Journal of Tissue Engineering Research 2026;30(6):1476-1485
BACKGROUND:Osteoarthritis is pathologically characterized by progressive degeneration of the articular cartilage and abnormal deformation of the subchondral bone.In recent years,with the deepening of medical research,it has been found that the mitogen-activated protein kinases(MAPK)signaling pathway has a regulatory role in inflammatory cell infiltration,inflammatory factor release,and chondrocyte proliferation,which is particularly important for the treatment of osteoarthritis.OBJECTIVE:To briefly review the main research progress in the mechanism of MAPK signaling pathway regulating osteoarthritis in recent years,aiming to provide new ideas for the treatment of osteoarthritis.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature using the search terms of"mitogen-activated protein kinases,osteoarthritis,extracellular signal-regulated MAP kinases,p38 mitogen-activated protein kinases,JNK mitogen-activated protein kinase"in Chinese and English.Relevant literature published from January 2019 to November 2024 was searched,and 108 articles were finally included for summary analysis.RESULTS AND CONCLUSION:(1)Various stimuli inside and outside the cells activate the MAPK signaling pathway,regulate gene transcription and protein synthesis,and promote the release of inflammatory factors,such as tumor necrosis factor-α,interleukin-1β,and interleukin-6.The release of these inflammatory factors aggravates the progression of osteoarthritis.(2)The active ingredients of traditional Chinese medicine,mainly saponins and flavonoids,as well as Chinese herbal formulas and preparations with the main effects of activating blood circulation and removing blood stasis,tonifying the liver and kidney,can play a therapeutic role in osteoarthritis by inhibiting the MAPK signaling pathway,regulating the release of matrix metalloproteinases,balancing the homeostatic state of osteogenesis and osteoblastogenesis,attenuating the synovial inflammation,decreasing the release of inflammatory factors and inflammatory vesicles,decreasing cellular pyroptosis,promoting autophagy,and ameliorating oxidative stress.(3)Although traditional Chinese medicine has become popular in the treatment of osteoarthritis by virtue of its own advantages of multi-components,multi-targets,multi-pathways,and low side effects,the use of MAPK signaling pathway to guide the treatment of individual osteoarthritis is the difficulty of the technology,which needs to be continuously researched and explored.(4)Therefore,further development of relevant herbal inhibitors that can modulate the MAPK signaling pathway may be a potential drug strategy for the treatment of osteoarthritis in the future.
2.Mitogen-activated protein kinase signaling pathway regulates the development of osteoarthritis:guiding targeted therapy with traditional Chinese medicine
Hao LI ; Hongcheng TAO ; Ping ZENG ; Jinfu LIU ; Qiang DING ; Chicheng NIU ; Kai HUANG ; Hongyu KANG
Chinese Journal of Tissue Engineering Research 2026;30(6):1476-1485
BACKGROUND:Osteoarthritis is pathologically characterized by progressive degeneration of the articular cartilage and abnormal deformation of the subchondral bone.In recent years,with the deepening of medical research,it has been found that the mitogen-activated protein kinases(MAPK)signaling pathway has a regulatory role in inflammatory cell infiltration,inflammatory factor release,and chondrocyte proliferation,which is particularly important for the treatment of osteoarthritis.OBJECTIVE:To briefly review the main research progress in the mechanism of MAPK signaling pathway regulating osteoarthritis in recent years,aiming to provide new ideas for the treatment of osteoarthritis.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature using the search terms of"mitogen-activated protein kinases,osteoarthritis,extracellular signal-regulated MAP kinases,p38 mitogen-activated protein kinases,JNK mitogen-activated protein kinase"in Chinese and English.Relevant literature published from January 2019 to November 2024 was searched,and 108 articles were finally included for summary analysis.RESULTS AND CONCLUSION:(1)Various stimuli inside and outside the cells activate the MAPK signaling pathway,regulate gene transcription and protein synthesis,and promote the release of inflammatory factors,such as tumor necrosis factor-α,interleukin-1β,and interleukin-6.The release of these inflammatory factors aggravates the progression of osteoarthritis.(2)The active ingredients of traditional Chinese medicine,mainly saponins and flavonoids,as well as Chinese herbal formulas and preparations with the main effects of activating blood circulation and removing blood stasis,tonifying the liver and kidney,can play a therapeutic role in osteoarthritis by inhibiting the MAPK signaling pathway,regulating the release of matrix metalloproteinases,balancing the homeostatic state of osteogenesis and osteoblastogenesis,attenuating the synovial inflammation,decreasing the release of inflammatory factors and inflammatory vesicles,decreasing cellular pyroptosis,promoting autophagy,and ameliorating oxidative stress.(3)Although traditional Chinese medicine has become popular in the treatment of osteoarthritis by virtue of its own advantages of multi-components,multi-targets,multi-pathways,and low side effects,the use of MAPK signaling pathway to guide the treatment of individual osteoarthritis is the difficulty of the technology,which needs to be continuously researched and explored.(4)Therefore,further development of relevant herbal inhibitors that can modulate the MAPK signaling pathway may be a potential drug strategy for the treatment of osteoarthritis in the future.
3.Panax notoginseng saponins regulate differential miRNA expression in osteoclast exosomes and inhibit ferroptosis in osteoblasts
Hongcheng TAO ; Ping ZENG ; Jinfu LIU ; Zhao TIAN ; Qiang DING ; Chaohui LI ; Jianjie WEI ; Hao LI
Chinese Journal of Tissue Engineering Research 2025;29(19):4011-4021
BACKGROUND:Steroid-induced femoral head necrosis is mostly caused by long-term and extensive use of hormones,but its specific pathogenesis is not yet clear and needs further study. OBJECTIVE:To screen out the differential miRNAs in osteoclast exosomes after the intervention of Panax notoginseng saponins,and on this basis,to further construct an osteogenic-related ferroptosis regulatory network to explore the potential mechanism and research direction of steroid-induced osteonecrosis of the femoral head. METHODS:MTT assay was used to detect the toxic effects of different concentrations of dexamethasone and different mass concentrations of Panax notoginseng saponins on Raw264.7 cell line.Tartrate resistant acid phosphatase staining and TUNEL assay were used to detect the effects of Panax notoginseng saponins on osteoclast inhibition and apoptosis.Exosomes were extracted from cultured osteoclasts with Panax notoginseng saponins intervention.Exosomes from different groups were sequenced to identify differentially expressed miRNAs.CytoScape 3.9.1 was used to construct and visualize the regulatory network between differentially expressed miRNAs and mRNAs.Candidate mRNAs were screened by GO analysis and KEGG analysis.Finally,the differential genes related to ferroptosis were screened out,and the regulatory network of ferroptosis-related genes was constructed. RESULTS AND CONCLUSION:(1)The concentration of dexamethasone(0.1 μmol/L)and Panax notoginseng saponins(1 736.85 μg/mL)suitable for intervention of Raw264.7 cells was determined by MTT assay.(2)Panax notoginseng saponins had an inhibitory effect on osteoclasts and could promote their apoptosis.(3)Totally 20 differentially expressed miRNAs were identified from osteoclast-derived exosome samples,and 11 differentially expressed miRNAs related to osteogenesis were predicted by target mRNAs.The regulatory networks of 4 up-regulated differentially expressed miRNAs corresponding to 155 down-regulated candidate mRNAs and 7 down-regulated differentially expressed miRNAs corresponding to 238 up-regulated candidate mRNAs were constructed.(4)Twenty-four genes related to ferroptosis were screened out from the differential genes.Finally,12 networks were constructed(miR-98-5p/PTGS2,miR-23b-3p/PTGS2,miR-425-5p/TFRC,miR-133a-3p/TFRC,miR-185-5p/TFRC,miR-23b-3p/NFE2L2,miR-23b-3p/LAMP2,miR-98-5p/LAMP2,miR-182-5p/LAMP2,miR-182-5p/TLR4,miR-23b-3p/ZFP36,and miR-182-5p/ZFP36).These results indicate that Panax notoginseng saponins may regulate osteoblast ferroptosis by regulating the expression of miRNAs derived from osteoclast exosomes,thus providing a new idea for the study of the mechanism of steroid-induced femoral head necrosis.
4.IsoVISoR: Towards 3D Mesoscale Brain Mapping of Large Mammals at Isotropic Sub-micron Resolution.
Chao-Yu YANG ; Yan SHEN ; Xiaoyang QI ; Lufeng DING ; Yanyang XIAO ; Qingyuan ZHU ; Hao WANG ; Cheng XU ; Pak-Ming LAU ; Pengcheng ZHOU ; Fang XU ; Guo-Qiang BI
Neuroscience Bulletin 2025;41(2):344-348
5.Construction of a prediction model for muscular invasion in upper urinary tract urothelial carcinoma based on preoperative MRI features
Haonan CHEN ; Lingkai CAI ; Hongyuan DING ; Hao JI ; Tianxiao HONG ; Hao YU ; Qikai WU ; Chaoran ZHAO ; Xiao YANG ; Qiang CAO ; Xiancheng ZHAO ; Pengchao LI ; Qiang LYU
Chinese Journal of Urology 2025;46(9):661-668
Objective:To construct a nomogram based on preoperative MRI imaging features for the prediction of muscle-invasive upper urinary tract urothelial carcinoma(UTUC)and evaluate its performance.Methods:This retrospective cohort study analyzed the clinical data of 99 UTUC patients treated at the First Affiliated Hospital of Nanjing Medical University from April 2018 to May 2024. Among them,69(69.7%)were male and 30(30.3%)were female,with a median age of 67.0 years. All patients underwent preoperative MRI and radical nephroureterectomy. According to postoperative pathology,tumors staged ≥ T 2 were assigned to the muscle-invasive group,and those staged ≤ T 1 were assigned to the non-muscle-invasive group. Baseline data,pathological information,and imaging characteristics were collected and compared between the two groups. Logistic regression analysis was performed to identify risk factors for muscle-invasive UTUC,and a nomogram was constructed. The diagnostic performance of the model was assessed using receiver operating characteristic(ROC)curves,calibration curves,and decision curve analysis(DCA). Results:Among the 99 patients,70(70.7%)were diagnosed with muscle-invasive UTUC,and 29(29.3%)with non-muscle-invasive UTUC. The muscle-invasive group had significantly larger tumor size[4.5(2.8,7.0)cm vs. 3.0(2.3,4.5)cm, P = 0.029],a higher incidence of multifocal tumors[37.1%(26/70)vs. 3.5%(1/29), P < 0.001],patchy tumors[30.0%(21/70)vs. 6.9%(2/29), P = 0.019],spiculated tumor margins[52.9%(37/70)vs. 17.2%(5/29), P = 0.001],tumor compression on renal parenchyma or periureteral/peripelvic fat[68.6%(48/70)vs. 10.3%(3/29), P < 0.001],high-grade pathology[92.9%(65/70)vs. 75.9%(22/29), P = 0.043],lymph node metastasis[28.6%(20/70)vs. 0, P = 0.001],and lymphovascular invasion[42.9%(30/70)vs. 10.3%(3/29), P=0.002]. The apparent diffusion coefficient(ADC)values[0.9(0.8,1.1)× 10 -3 mm2/s vs. 1.1(1.0,1.4)× 10 -3 mm2/s, P < 0.001]and normalized ADC(NADC)values[0.8(0.7,1.0)vs. 0.9(0.8,1.1), P = 0.002]were significantly lower in the muscle-invasive group. Univariate logistic regression identified multifocality,patchy tumor patterns,spiculated tumor margins,tumor compression on renal parenchyma or periureteral/peripelvic fat,and low NADC values as risk factors for muscle-invasive UTUC(all P < 0.05). Multivariate analysis revealed multifocality( OR = 17.903,95% CI 1.650 - 194.253, P = 0.018),tumor compression on renal parenchyma or perirenal / ureteral fat( OR = 14.690,95% CI 3.069 - 70.323, P < 0.001),and low NADC value( OR = 0.016,95% CI 0.001 - 0.471, P = 0.017)as independent risk factors. A nomogram was constructed based on these factors. The area under the ROC curve(AUC)of the model was 0.898(95% CI 0.838 - 0.957),with an optimal cutoff value of 0.639. The model showed an accuracy of 83.8%,sensitivity of 81.4%,and specificity of 89.7%. Calibration curves indicated good calibration,and DCA showed that the model provided substantial clinical net benefit. Conclusions:This study constructed a nomogram based on preoperative MRI features,including tumor multifocality,compression on renal parenchyma or periureteral/peripelvic fat and NADC value,which demonstrates good predictive performances for muscle-invasive UTUC.
6.Research progress on the application of intelligent medical treatment in abdominal war trauma
Si-Zhe WANG ; Xu SUN ; Ding-Chang LI ; Xian-Qiang LIU ; Wen-Xing GAO ; Wen ZHAO ; Hao LIU ; Guang-Long DONG
Medical Journal of Chinese People's Liberation Army 2025;50(1):22-27
Abdominal war trauma is a common and high-risk type of injury in the modern battlefield,with rapid changes in condition and a high mortality rate.There is an urgent need for emerging medical technologies to improve the efficiency and success rate of first aid for military casualties.With the development of artificial intelligence(AI),5G,and other emerging technologies,the concept of intelligent medical treatment is gradually forming and can assist in the diagnosis and treatment of abdominal trauma.This paper reviews the characteristics of abdominal war trauma in modern wars,discusses the application of intelligent medical treatment for abdominal war trauma and its drawbacks to be solved,aiming to provide reference for research related to abdominal war trauma.
7.Construction of a prediction model for muscular invasion in upper urinary tract urothelial carcinoma based on preoperative MRI features
Haonan CHEN ; Lingkai CAI ; Hongyuan DING ; Hao JI ; Tianxiao HONG ; Hao YU ; Qikai WU ; Chaoran ZHAO ; Xiao YANG ; Qiang CAO ; Xiancheng ZHAO ; Pengchao LI ; Qiang LYU
Chinese Journal of Urology 2025;46(9):661-668
Objective:To construct a nomogram based on preoperative MRI imaging features for the prediction of muscle-invasive upper urinary tract urothelial carcinoma(UTUC)and evaluate its performance.Methods:This retrospective cohort study analyzed the clinical data of 99 UTUC patients treated at the First Affiliated Hospital of Nanjing Medical University from April 2018 to May 2024. Among them,69(69.7%)were male and 30(30.3%)were female,with a median age of 67.0 years. All patients underwent preoperative MRI and radical nephroureterectomy. According to postoperative pathology,tumors staged ≥ T 2 were assigned to the muscle-invasive group,and those staged ≤ T 1 were assigned to the non-muscle-invasive group. Baseline data,pathological information,and imaging characteristics were collected and compared between the two groups. Logistic regression analysis was performed to identify risk factors for muscle-invasive UTUC,and a nomogram was constructed. The diagnostic performance of the model was assessed using receiver operating characteristic(ROC)curves,calibration curves,and decision curve analysis(DCA). Results:Among the 99 patients,70(70.7%)were diagnosed with muscle-invasive UTUC,and 29(29.3%)with non-muscle-invasive UTUC. The muscle-invasive group had significantly larger tumor size[4.5(2.8,7.0)cm vs. 3.0(2.3,4.5)cm, P = 0.029],a higher incidence of multifocal tumors[37.1%(26/70)vs. 3.5%(1/29), P < 0.001],patchy tumors[30.0%(21/70)vs. 6.9%(2/29), P = 0.019],spiculated tumor margins[52.9%(37/70)vs. 17.2%(5/29), P = 0.001],tumor compression on renal parenchyma or periureteral/peripelvic fat[68.6%(48/70)vs. 10.3%(3/29), P < 0.001],high-grade pathology[92.9%(65/70)vs. 75.9%(22/29), P = 0.043],lymph node metastasis[28.6%(20/70)vs. 0, P = 0.001],and lymphovascular invasion[42.9%(30/70)vs. 10.3%(3/29), P=0.002]. The apparent diffusion coefficient(ADC)values[0.9(0.8,1.1)× 10 -3 mm2/s vs. 1.1(1.0,1.4)× 10 -3 mm2/s, P < 0.001]and normalized ADC(NADC)values[0.8(0.7,1.0)vs. 0.9(0.8,1.1), P = 0.002]were significantly lower in the muscle-invasive group. Univariate logistic regression identified multifocality,patchy tumor patterns,spiculated tumor margins,tumor compression on renal parenchyma or periureteral/peripelvic fat,and low NADC values as risk factors for muscle-invasive UTUC(all P < 0.05). Multivariate analysis revealed multifocality( OR = 17.903,95% CI 1.650 - 194.253, P = 0.018),tumor compression on renal parenchyma or perirenal / ureteral fat( OR = 14.690,95% CI 3.069 - 70.323, P < 0.001),and low NADC value( OR = 0.016,95% CI 0.001 - 0.471, P = 0.017)as independent risk factors. A nomogram was constructed based on these factors. The area under the ROC curve(AUC)of the model was 0.898(95% CI 0.838 - 0.957),with an optimal cutoff value of 0.639. The model showed an accuracy of 83.8%,sensitivity of 81.4%,and specificity of 89.7%. Calibration curves indicated good calibration,and DCA showed that the model provided substantial clinical net benefit. Conclusions:This study constructed a nomogram based on preoperative MRI features,including tumor multifocality,compression on renal parenchyma or periureteral/peripelvic fat and NADC value,which demonstrates good predictive performances for muscle-invasive UTUC.
8.Research focus and future trend of Chinese hospital supply chain management: a literature review based on bibliometric analysis
Baoyang DING ; Zheng LIU ; Wei HAO ; Liujin ZHANG ; Xiaohan YANG ; Qiang SUN
Chinese Journal of Hospital Administration 2024;40(1):53-58
Objective:To reveal the research hotspots in hospital supply chain management in China and explore how supply chain management can facilitate the high-quality development of public hospitals.Methods:Bibliometric analysis method was employed, retrieving the Chinese literature on hospital supply chain management from 2000 to 2022 from CNKI, WeiPu, and WanFang databases. Descriptive analysis and cluster analysis of high-frequency keywords were conducted.Results:Through cluster analysis of 34 high-frequency keywords in the 1 113 Chinese literature, it was found that current research on hospital supply chain management mainly focused on 7 research hotspots: big data information systems, procurement management, risk management, refined management, inventory management, supplier management, and traceability management.Conclusions:Future research could focus on construction of hospital supply chain performance evaluation systems, digital technology-driven supply chain transformation and upgrading, enhancing hospital supply chain resilience under risks, and sustainable supply chain management.
9.Molecular mechanism of PANoptosis in diagnostic markers and subtyping of osteoporosis
Qiang DING ; Bo XIONG ; Jinfu LIU ; Zhao TIAN ; Xiangbin RONG ; Limin CHEN ; Hongcheng TAO ; Hao LI ; Ping ZENG
Chinese Journal of Tissue Engineering Research 2024;28(28):4505-4510
BACKGROUND:It has been hypothesized that PANoptosis may be involved in the pathologic process of osteoporosis,but there have been no studies addressing the mechanisms of PANoptosis genes in osteoporosis. OBJECTIVE:To analyze the biological mechanism of PANoptosis regulators in the occurrence and development of osteoporosis. METHODS:The GSE56815 dataset was obtained from the Gene Expression Omnibus database and PANoptosis genes were extracted for differential analysis.The key genes of PANoptosis were screened by random forest tree model to construct a disease risk prediction model.Consensus clustering algorithm,single sample genome enrichment analysis and immune infiltration analysis were used to explore the differences between different PANoptosis molecular subtypes.Herbal drugs that regulate the key genes of PANoptosis were predicted through Coremine medical database,a medical ontology information retrieval platform. RESULTS AND CONCLUSION:Based on the four PANoptosis key genes(CASP1,CASP10,MEFV,and TNF),the diagnostic markers of osteoporosis were determined,and the risk prediction model was constructed and verified.Osteoporosis was divided into two different PANoptosis subtypes(clusters A,B and gene clusters A,B),and the PANoptosis scores of cluster B and gene cluster B were higher than those of cluster A and gene cluster A,respectively.Traditional Chinese drugs such as ginseng which can regulate the key genes of PANoptosis were predicted by the Coremine medical database.
10.Surgical treatment for obstructive hypertrophic cardiomyopathy: a five-year single-center experience of 421 cases.
Fang Yu LIU ; Qiang JI ; Yu Lin WANG ; Jin Miao CHEN ; Li Li DONG ; Wen Jun DING ; Hao LAI ; Chun Sheng WANG
Chinese Journal of Surgery 2023;61(3):201-208
Objectives: To examine the short-term and mid-term effects of surgical treatment of obstructive hypertrophic cardiomyopathy (HCM) in one center. Methods: The perioperative data and short-term follow-up outcomes of 421 patients with obstructive HCM who received surgical treatment at Department of Cardiac Surgery, Zhongshan Hospital, Fudan University from January 2017 to December 2021 were analyzed retrospectively. There were 207 males and 214 females, aged (56.5±11.7) years (range: 19 to 78 years). Preoperative New York Heart Association (NYHA) classification included 45 cases of class Ⅱ, 328 cases in class Ⅲ, and 48 cases in class Ⅳ. Fifty-eight patients were diagnosed with latent obstructive HCM and 257 patients had moderate or more mitral regurgitation with 56 patients suffering from intrinsic mitral valve diseases. All procedures were completed by a multidisciplinary team, including professional echocardiologists involving in preoperative planning for proper mitral valve management strategies and intraoperative monitoring. A total of 338 patients underwent septal myectomy alone, and 59 patients underwent mitral valve surgery along with myectomy. A single transaortic approach was used in 355 patients, and a right atrial-atrial septal/atrial sulcus approach was used in 51 other patients. Long-handled minimally invasive surgical instruments were used for the procedures. Student t test, Wilcoxon rank sum test, χ2 test or Fisher exact test were used to compare the data before and after surgery. Results: The aortic cross-clamping time of septal myectomy alone was (34.3±8.5) minutes (range: 21 to 94 minutes). Eighteen patients had intraoperative adverse events and underwent immediate reoperation, including residual obstruction (10 patients), left ventricular free wall rupture (4 patients), ventricular septal perforation (3 patients), and aortic valve perforation (1 patient). Four patients died during hospitalization, and 11 patients developed complete atrioventricular block requiring permanent pacemaker implantation. After discharge, 384 (92.1%) patients received a follow-up visit with a median duration of 9 months. All follow-up patients survived with significantly improved NYHA classifications: 216 patients in class Ⅰ and 168 patients in class Ⅱ (χ2=662.73, P<0.01 as compared to baseline). At 6 months after surgery, follow-up echocardiography showed that the thickness of the ventricular septum ((13.6±2.5) mm vs. (18.2±3.0) mm, t=23.51, P<0.01) and the peak left ventricular outflow tract gradient ((12.0±6.3) mmHg vs. (93.4±19.8) mmHg, 1 mmHg=0.133 kPa, t=78.29, P<0.01) were both significantly lower than baseline values. Conclusion: The construction of the surgical team (including echocardiography experts), proper mitral valve management strategies, identification and management of sub-mitral-valve abnormalities, and application of long-handled minimally invasive surgical instruments are important for the successful implementation of septal myectomy with satisfactory short-and medium-term outcomes.
Male
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Female
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Humans
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Retrospective Studies
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Atrial Fibrillation
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Treatment Outcome
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Cardiomyopathy, Hypertrophic/surgery*
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Mitral Valve Insufficiency/surgery*
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Ventricular Septum

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