1.Mechanisms of Qizhujianwei Granules in Blocking Malignant Progression of Gastric Intraepithelial Neoplasia
Yuling YU ; Yanmin WANG ; Siqi WANG ; Yateng SUN ; Yunhe WANG ; Yonghuang YAN ; Xinyu YANG ; Siqi HAN ; Yuhong SONG ; Yuhan WANG ; Cai ZHANG ; Zeqi SU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):143-151
ObjectiveTo investigate the effects of Qizhujianwei granules (QZJW) on abnormal proliferation and malignant transformation of gastric mucosal cells in rats with gastric intraepithelial neoplasia (GIN) and to explore the related mechanisms. MethodsA total of 80 SPF male Wistar rats were used. A GIN rat model was established using a four-factor comprehensive method consisting of methylnitronitrosoguanidine (MNNG), ranitidine, irregular feeding patterns, and sodium salicylate. Except for the normal group, after successful modeling, the rats were randomly divided according to body weight into a model group, a Moluodan group (0.55 g·kg-1), and a QZJW group (7.34 g·kg-1), with 12 rats in each group. All groups were treated for 8 weeks. The general characteristics of the rats and morphological changes of the gastric mucosa were observed. Histopathological changes of the gastric mucosa were examined by hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of pepsinogenⅠ (PGⅠ), pepsinogenⅡ (PGⅡ), and gastrin (G-17), as well as the expression level of transforming growth factor-β1 (TGF-β1) in gastric mucosal tissue, and the PGⅠ/PGⅡ ratio was calculated. Immunohistochemistry (IHC) was used to detect the localization and expression levels of proliferating cell nuclear antigen (Ki-67) and Vimentin in gastric mucosal tissue. Western blot analysis was used to determine the protein expression levels of Wnt family member 3A (Wnt3a), β-catenin, CyclinD1, proto-oncogene Cmyc, transforming growth factor-β receptor Ⅰ (TGFβRⅠ), intracellular signaling transducers Smad2/3, phosphorylated (p)-Smad2/3, twist family transcription factor (Twist1), and Vimentin in gastric mucosal tissue. ResultsCompared with the normal group, the model group showed characteristic changes including dim eyes, pale ears and claws, dark-red tongue, and reduced luster of the tail. The gastric mucosa appeared pale, with surface congestion and erosion. The gastric mucosal glands were disordered, the nuclear-to-cytoplasmic ratio increased, and local tumor cells were observed. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly decreased (P<0.01), while the level of G-17 was significantly increased (P<0.01). The protein expression levels of Ki-67, Wnt3a, β-catenin, CyclinD1, Cmyc, TGF-β1, TGFβRⅠ, Smad2/3, Twist1, and Vimentin in gastric mucosal tissue were significantly increased (P<0.05, P<0.01), whereas the ratio of p-Smad2/3 to Smad2/3 was significantly decreased (P<0.05). Compared with the model group, the general characteristics and gastric mucosal conditions of rats in the Moluodan group and the QZJW group were improved. HE staining showed that QZJW could effectively block the malignant progression of GIN. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly increased (P<0.05, P<0.01), while the level of G-17 was significantly decreased (P<0.01). The protein expression levels of Ki-67, Wnt3a, β-catenin, CyclinD1, Cmyc, TGF-β1, TGFβRⅠ, Smad2/3, Twist1, and Vimentin in gastric mucosal tissue were significantly decreased (P<0.05, P<0.01). ConclusionQZJW have a therapeutic effect on rats with GIN. The mechanism may involve inhibition of the Wnt/β-catenin signaling pathway to regulate the cell cycle and suppress abnormal cell proliferation. Meanwhile, it may inhibit epithelial-mesenchymal transition by suppressing the TGF-β1/Smad/Twist1 signaling pathway, thereby blocking the malignant progression of GIN.
2.Mechanisms of Qizhujianwei Granules in Blocking Malignant Progression of Gastric Intraepithelial Neoplasia
Yuling YU ; Yanmin WANG ; Siqi WANG ; Yateng SUN ; Yunhe WANG ; Yonghuang YAN ; Xinyu YANG ; Siqi HAN ; Yuhong SONG ; Yuhan WANG ; Cai ZHANG ; Zeqi SU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):143-151
ObjectiveTo investigate the effects of Qizhujianwei granules (QZJW) on abnormal proliferation and malignant transformation of gastric mucosal cells in rats with gastric intraepithelial neoplasia (GIN) and to explore the related mechanisms. MethodsA total of 80 SPF male Wistar rats were used. A GIN rat model was established using a four-factor comprehensive method consisting of methylnitronitrosoguanidine (MNNG), ranitidine, irregular feeding patterns, and sodium salicylate. Except for the normal group, after successful modeling, the rats were randomly divided according to body weight into a model group, a Moluodan group (0.55 g·kg-1), and a QZJW group (7.34 g·kg-1), with 12 rats in each group. All groups were treated for 8 weeks. The general characteristics of the rats and morphological changes of the gastric mucosa were observed. Histopathological changes of the gastric mucosa were examined by hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of pepsinogenⅠ (PGⅠ), pepsinogenⅡ (PGⅡ), and gastrin (G-17), as well as the expression level of transforming growth factor-β1 (TGF-β1) in gastric mucosal tissue, and the PGⅠ/PGⅡ ratio was calculated. Immunohistochemistry (IHC) was used to detect the localization and expression levels of proliferating cell nuclear antigen (Ki-67) and Vimentin in gastric mucosal tissue. Western blot analysis was used to determine the protein expression levels of Wnt family member 3A (Wnt3a), β-catenin, CyclinD1, proto-oncogene Cmyc, transforming growth factor-β receptor Ⅰ (TGFβRⅠ), intracellular signaling transducers Smad2/3, phosphorylated (p)-Smad2/3, twist family transcription factor (Twist1), and Vimentin in gastric mucosal tissue. ResultsCompared with the normal group, the model group showed characteristic changes including dim eyes, pale ears and claws, dark-red tongue, and reduced luster of the tail. The gastric mucosa appeared pale, with surface congestion and erosion. The gastric mucosal glands were disordered, the nuclear-to-cytoplasmic ratio increased, and local tumor cells were observed. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly decreased (P<0.01), while the level of G-17 was significantly increased (P<0.01). The protein expression levels of Ki-67, Wnt3a, β-catenin, CyclinD1, Cmyc, TGF-β1, TGFβRⅠ, Smad2/3, Twist1, and Vimentin in gastric mucosal tissue were significantly increased (P<0.05, P<0.01), whereas the ratio of p-Smad2/3 to Smad2/3 was significantly decreased (P<0.05). Compared with the model group, the general characteristics and gastric mucosal conditions of rats in the Moluodan group and the QZJW group were improved. HE staining showed that QZJW could effectively block the malignant progression of GIN. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly increased (P<0.05, P<0.01), while the level of G-17 was significantly decreased (P<0.01). The protein expression levels of Ki-67, Wnt3a, β-catenin, CyclinD1, Cmyc, TGF-β1, TGFβRⅠ, Smad2/3, Twist1, and Vimentin in gastric mucosal tissue were significantly decreased (P<0.05, P<0.01). ConclusionQZJW have a therapeutic effect on rats with GIN. The mechanism may involve inhibition of the Wnt/β-catenin signaling pathway to regulate the cell cycle and suppress abnormal cell proliferation. Meanwhile, it may inhibit epithelial-mesenchymal transition by suppressing the TGF-β1/Smad/Twist1 signaling pathway, thereby blocking the malignant progression of GIN.
3.Effects of Zuogui Pill (左归丸) Decoction on Cerebral Perfusion and Corticospinal Tract Remodeling in Patients With Ischemic Stroke of the Liver-Kidney Yin Deficiency Syndrome
Xinyu XU ; Dan WU ; Xiaohui YAN ; Hao HUA ; Siqi MEI ; Zihan ZHOU ; Jinglin ZHAO ; Shiyu HE ; Xiaoyu FEI ; Yangfan LIU ; Yue SU ; Li LI ; Wenlei LI
Journal of Traditional Chinese Medicine 2026;67(21):2302-2310
ObjectiveTo evaluate the clinical efficacy of Zuogui Pill (左归丸,ZGP) decoction on neurological function, motor function, and activities of daily living in patients with ischemic stroke (IS) of liver-kidney yin deficiency syndrome, and to assess its potential mechanisms from the perspectives of cerebral perfusion and corticospinal tract (CST) remodeling. MethodsA total of 108 patients with IS of liver-kidney yin deficiency syndrome and onset time ≤14 days were enrolled and randomly divided into a control group and a treatment group, with 54 cases in each group. The control group received conventional western medicine, while the treatment group received ZGP decoction (one dose per day) in addition to the conventional treatment. Both groups were treated for 90 days. The National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), modified Barthel Index (MBI), Fugl-Meyer Assessment (FMA), and Chinese medicine syndrome score (CMS) were evaluated before treatment and after (90±3) days of treatment. Three-dimensional arterial spin labeling (3D-ASL) and diffusion tensor imaging (DTI) were performed to obtain ipsilesional cerebral blood flow (CBF) in the unaffected and affected hemispheres, relative CBF (rCBF), and fractional anisotropy (FA) of the CST. Nodal analysis of FA values along the CST was also conducted. Correlation analysis was used to assess the relationships between post-treatment cerebral perfusion parameters (CBF and rCBF), and FA values with clinical neurological function scores. ResultsAfter treatment, both groups showed significantly decreased NIHSS, mRS and CMS scores, together with significantly increased FMA and MBI scores (P<0.01). Intergroup comparison showed that NIHSS, mRS, and CMS scores in the treatment group were significantly lower than those in the control group , while MBI and FMA scores were significantly higher (P<0.01). The 3D-ASL results revealed that CBF and rCBF values in the affected hemisphere significantly increased in both groups after treatment, and the treatment group had significantly higher values (P<0.01). DTI showed that the FA value of the CST on the affected side in the treatment group was significantly higher than that in the control group after treatment (P<0.05). Nodal analysis along the CST further demonstrated that the continuity of FA values at lesion-related nodes 45~99 in the treatment group was significantly better than that in the control group (P<0.01), with significant increases at nodes 65~71 and 76~81 compared with baseline (P<0.05 or P<0.01), whereas the control group showed a decreasing trend at nodes 80~93 (P<0.05). Correlation analysis indicated that CBF and rCBF values in the affected hemisphere were negatively correlated with NIHSS and mRS scores and positively correlated with MBI score (P<0.05). FA value of the CST on the affected side, both before and after treatment, were negatively correlated with NIHSS score and positively correlated with FMA score (P<0.05 or P<0.01). ConclusionZGP decoction can effectively improve neurological function, motor function, and activities of daily living in IS patients with liver-kidney yin deficiency syndrome, and its mechanism may be related to enhanced cerebral perfusion in the affected hemisphere and corticospinal tract structural remodeling.
4.Quantification of in vivo biomechanics and analysis of influencing factors in cervical spine fixed-point rotation manipulation
Jiyao LIANG ; Honghai ZHOU ; Guikang WEI ; Shaoting SU ; Longhao CHEN ; Xinyu HE ; Liangpu LIU
Chinese Journal of Tissue Engineering Research 2025;29(3):486-492
BACKGROUND:Fixed-point rotation manipulation of cervical spine is a mechanical operation with high technical requirements,but the biomechanics of fixed-point manipulation of cervical spine still lacks relevant quantitative data.Moreover,the research on the influencing factors of cervical fixed-point rotation manipulation includes many parameters and there are differences,so it is necessary to further analyze its influencing factors to improve its related data. OBJECTIVE:To quantify the biomechanical parameters of cervical spine fixed-point rotation manipulation,explore the correlation between different biomechanical parameters,and the influence of individual characteristics of the subjects on the biomechanical parameters of cervical spine fixed-point rotation manipulation. METHODS:Totally 35 cases of cervical spondylosis were Outpatients from Orthopedic Department of Renai Branch of the First Affiliated Hospital of Guangxi University of Chinese Medicine and selected as the subjects investigated.Wearable mechanical measuring gloves were used to collect biomechanical parameters of cervical spine fixed-point rotation manipulation,including:thumb preload,thumb maximum thrust,palm preload,palm wrench force,and palm wrench maximum force.Personal characteristic parameters were collected,including age,height,weight,and neck circumference.The key biomechanical parameters in the process of cervical spine fixed-point rotation manipulation were analyzed and different individual characteristics were quantified.The results of biomechanical parameters were analyzed using Spearman correlation analysis.The possible effects of different individual characteristic parameters on biomechanics were analyzed. RESULTS AND CONCLUSION:(1)Compared with bilateral mechanical parameters,there was no significant difference between left manipulation and right manipulation(P>0.05).(2)The average of thumb preload force was(7.21±1.19)N;the average of thumb maximum thrust was(28.40±4.48)N;the average of palm preload was(5.67±2.49)N;the average of palm wrench force was(10.90±5.11)N,and the average of palm wrench maximum force was(16.00±7.27)N.(3)There was a significant positive correlation between palm preload and palm wrench force(Rs=0.812,P<0.01).There was a significant positive correlation between palm preload and palm wrench maximum force(Rs=0.773,P<0.01).There was a significant positive correlation between palm wrench force and palm wrench maximum force(Rs=0.939,P<0.01).(4)The weight was positively correlated with thumb preload,palm preload,palm wrench force and palm wrench maximum force(P<0.05).(5)These findings confirm that there is a certain biomechanical standard value in the operation of cervical spine fixed-point rotation manipulation to treat cervical spondylosis.There is no significant difference between the left and right manipulations,which indicates that the manipulation has good consistency and repeatability.There is consistency and coordination among palm preload force,palm wrench force,and palm wrench maximum force.Their contributions to the therapeutic effect are similar.Body weight is an important factor affecting cervical spine fixed-point rotation manipulation.
5.Discovery of selective HDAC6 inhibitors driven by artificial intelligence and molecular dynamics simulation approaches.
Xingang LIU ; Hao YANG ; Xinyu LIU ; Minjie MOU ; Jie LIU ; Wenying YAN ; Tianle NIU ; Ziyang ZHANG ; He SHI ; Xiangdong SU ; Xuedong LI ; Yang ZHANG ; Qingzhong JIA
Journal of Pharmaceutical Analysis 2025;15(8):101338-101338
Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC50 = 5.41 nM) than that of tubastatin A (TubA) (IC50 = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC50 = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.
6.Risk factors analysis of non-small cell lung cancer immune checkpoint inhibitor-related pneumonia and the construction and validation of nomogram prediction model
Xinyu MA ; Kaituo ZHANG ; Xin SONG ; Qiaona SU ; Jianfeng ZHANG ; Haifeng ZHAO ; Jinfang ZHAI ; Jianchun DUAN ; Jianxin ZHANG
Cancer Research and Clinic 2025;37(8):584-590
Objective:To analyze risk factors for immune checkpoint inhibitor-related pneumonitis (CIP) in non-small cell lung cancer (NSCLC) patients based on clinical and radiological characteristics, and to develop and validate a nomogram model for predicting the risk of CIP.Methods:A retrospective case-controlled study was conducted. The clinical data of 159 patients diagnosed with NSCLC in Shanxi Province Cancer Hospital between January 2020 and December 2023 who received immune checkpoint inhibitor (ICI) therapy were retrospectively analyzed. Based on the development of CIP after immunotherapy, the patients were divided into the CIP group (30 cases) and the control group (129 cases). The clinical data of NSCLC patients, hematological indicators and the data of imaging characteristics before their first ICI treatment were collected. Quantitative assessments were performed on pretreatment chest CT images, including lung total tumor volume, number of involved lung segments, and pulmonary infection index. Logistic regression analysis was used to screen out the factors influencing the development of CIP. R 4.3.0 statistical software was used to construct a nomogram model for predicting CIP based on the statistically significant risk factors identified in the multivariate logistic regression analysis. The predictive performance of the model was evaluated by using receiver operating characteristic (ROC) curves and the area under the curve (AUC). Calibration curves and decision curve analysis (DCA) were employed to assess the model's consistency and clinical benefit.Results:There were statistically significant differences in the proportions of patients with a history of chest radiotherapy and those receiving different immunotherapy regimens between the control group and the CIP group (both P < 0.001). The difference in the lactate dehydrogenase (LDH) [ M ( IQR)] between the both groups was statistically significant [211.00 U/L (57.00 U/L) vs. 276.00 U/L (136.00 U/L), Z = -3.41, P < 0.001]; additionally, the difference in lung status score between the 2 groups was statistically significant ( P < 0.001). Multivariate logistic regression analysis revealed that a history of chest radiotherapy (with vs. without: OR = 4.200, 95% CI: 1.466-12.036), the combination of immunotherapy (monotherapy vs. the combined therapy: OR = 0.106, 95% CI: 0.022-0.509), LDH ≥ 255.5 U/L (< 255.5 U/L vs. ≥ 255.5 U/L: OR = 0.988, 95% CI: 0.981-0.995), and severe lung status score(mild vs. moderate vs. severe: OR = 0.187, 95% CI: 0.059-0.593) were independent risk factors for CIP development in NSCLC patients after immunotherapy (all P < 0.05). A nomogram model for predicting CIP occurrence was constructed based on chest radiotherapy history, immunotherapy regimen, LDH, and lung status score. ROC curve analysis showed the AUC was 0.878 (95% CI: 0.813-0.942). The calibration curve demonstrated the good consistency between the predicted risk probability of CIP and the observed outcomes; DCA indicated that the model had favorable clinical benefits. Conclusions:The constructed nomogram prediction model shows a good predictive performance.
7.Clinical guideline for diagnosis and treatment of nonunion of osteoporotic vertebral fractures (version 2025)
Haipeng SI ; Le LI ; Junjie NIU ; Wencan ZHANG ; Fuxin WEI ; Jinqiu YUAN ; Qiang YANG ; Hongli WANG ; Guangchao WANG ; Shihong CHEN ; Yunzhen CHEN ; Xiaoguang CHENG ; Jianwen DONG ; Shiqing FENG ; Rui GU ; Yong HAI ; Tianyong HOU ; Bo HUANG ; Xiaobing JIANG ; Lei ZANG ; Chunhai LI ; Nianhu LI ; Hua LIN ; Hongjian LIU ; Peng LIU ; Xinyu LIU ; Sheng LU ; Shibao LU ; Chunshan LUO ; Lvy CHAOLIANG ; Lvy WEIJIA ; Xuexiao MA ; Wei MEI ; Chunyang MENG ; Cailiang SHEN ; Chunli SONG ; Ruoxian SONG ; Jiacan SU ; Honglin TENG ; Hui SHENG ; Beiyu WANG ; Bingwu WANG ; Liang WANG ; Xiangyang WANG ; Nan WU ; Guohua XU ; Yayi XIA ; Jin XU ; Youjia XU ; Jianzhong XU ; Cao YANG ; Maowei YANG ; Zibin YANG ; Xiaojian YE ; Hailong YU ; Xijie YU ; Hua YUE ; Zhili ZENG ; Xinli ZHAN ; Hui ZHANG ; Peixun ZHANG ; Wei ZHANG ; Zhenlin ZHANG ; Jianguo ZHANG ; Tengyue ZHU ; Qiang LIU ; Huilin YANG
Chinese Journal of Trauma 2025;41(10):932-945
Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.
8.Discovery of selective HDAC6 inhibitors driven by artificial intelligence and molecular dynamics simulation approaches
Xingang LIU ; Hao YANG ; Xinyu LIU ; Minjie MOU ; Jie LIU ; Wenying YAN ; Tianle NIU ; Ziyang ZHANG ; He SHI ; Xiangdong SU ; Xuedong LI ; Yang ZHANG ; Qingzhong JIA
Journal of Pharmaceutical Analysis 2025;15(8):1860-1872
Increasing evidence showed that histone deacetylase 6(HDAC6)dysfunction is directly associated with the onset and progression of various diseases,especially cancers,making the development of HDAC6-targeted anti-tumor agents a research hotspot.In this study,artificial intelligence(AI)technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline,which combined Voting strategy based on compound-protein interaction(CPI)prediction models,cascade molecular docking,and molecular dynamic(MD)simulations.The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays.Among the identified compounds,Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity(IC50=5.41 nM)than that of tubastatin A(TubA)(IC50=15.11 nM),along with a favorable subtype selectivity profile(selectivity index ≈ 117.23 for HDAC1),which was further verified by the Western blot analysis.Additionally,Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells,exerting desirable antiproliferative activity(IC50=2.59 μM).Furthermore,based on long-term MD simulation trajectory,the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis,thereby elucidating its binding mechanism.Moreover,the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation,thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.
9.Screening of Anti-breast Cancer Active Ingredients in Famous Classical Formula Yanghetang
Sijia SU ; Xinyu ZHAO ; Jingna ZHOU ; Junfeng GAO ; Xu TANG ; Binyu WEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):21-30
ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS), the combination of serum pharmacochemistry, response profile of absorbed components in serum, network pharmacology and drug-likeness prediction was used to screen the potential active ingredients of Yanghetang against breast cancer. MethodsUPLC-Q-TOF-MS/MS was used to identify the main components in different solvent extracts of Yanghetang, and serum pharmacochemistry was applied to analyze the absorbed components from the serum of female SD rats after 0.5, 1, 2 h of administration. Combined with the response characteristic values of serum drug components obtained from UNIFI 1.8.2, the absorbed prototype components and metabolites were screened to get the absorbed components of Yanghetang with a significant patterns of elimination and growth. Network pharmacology was applied to construct a drug-component-pathway-target-disease network, and molecular docking was performed between absorbed components and key targets of breast cancer, and the drug similarity was analyzed by SwissADME. ResultsForty-two compounds were identified in Yanghetang samples extracted with different solvents, of which 16 compounds were common to the three different extraction solvents(methanol, 50% methanol and water). The results of drug-containing serum analysis showed that there were 16 absorbed components in serum, including 5 prototypes and 11 metabolites. Network pharmacology results showed that Yanghetang against breast cancer involved 15 key targets such as proto-oncogene tyrosine-protein kinase Src(SRC), epidermal growth factor receptor(EGFR) and phosphoinositide 3 kinase catalytic alpha polypeptide(PIK3CA). Molecular docking results showed that 16 potential active ingredients were well combined with the predicted targets. Combined with drug likenesses, 12 compounds in the absorbed components of Yanghetang were considered to have potential for anti-breast cancer activity, mainly including α-pinene and γ-eudesmol and their metabolites, of which one was from Ephedrae Herba, one was from Rehmanniae Radix, and eight were from Cinnamomi Cortex. ConclusionThe chemical components of Yanghetang mainly include polysaccharides, monoterpene glycosides and coumarins, and its prototype components mainly undergo oxidation, hydrolysis and acetylation after entering the blood. Its anti-breast cancer mechanism may be related to the regulation of signaling pathways such as the mitogen-activated protein kinase(MAPK) and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt). The results of this study can lay a foundation for further exploration of Yanghetang in the treatment of breast cancer.
10.Design of customized Gyroid condylar prosthesis and finite element analysis of articular disc
Tingting JIANG ; Danyu LIU ; Zhixiu JIANG ; Yuchen JI ; Yilin CAO ; Yucheng SU ; Xinyu WANG
Chinese Journal of Tissue Engineering Research 2025;29(28):6003-6011
BACKGROUND:Condylar prosthesis replacement,as one of the surgical methods for the treatment of temporomandibular joint diseases,not only needs to restore the morphology and function,but also needs to ensure long-term stable application.OBJECTIVE:To design finite element analysis of a customized Gyroid condylar prosthesis.METHODS:Gyroid structure specimens with different wall thicknesses(250,350,450,550,650,and 750 μm)were designed by software.Finite element simulation compression experiments were carried out to test the elastic modulus of the specimens.The Gyroid structure wall thickness range that matches the elastic modulus of mandibular cancellous bone and whose pore size meets the osteogenesis conditions was screened out.This range was subdivided and Gyroid structure specimens were made using 3D printing technology.Mechanical compression experiments were carried out on a universal testing machine.The Gyroid structure wall thickness that meets the mechanical properties of mandibular bone,has an easier osteogenesis and a smaller strength was screened out by elastic modulus and compressive strength,and subsequent experiments were carried out.A three-dimensional model of a customized Gyroid condylar prosthesis was designed,and the finite element analysis of the blade jaw position and cusp interdigitation position of the model under natural occlusion was simulated.RESULTS AND CONCLUSION:(1)Finite element analysis results showed that with the increase of wall thickness,the elastic modulus of Gyroid structure specimens increased.The elastic modulus of Gyroid structure specimens with wall thickness of 350,450,550,650,and 750 μm matched the elastic modulus of mandibular cancellous bone.Since the subsequent experiments needed to be subdivided into groups and the pore size of the 550,650,and 750 μm wall thickness group(pore size 800-1 000 μm)was within the osteogenesis range.Gyroid structure specimens with wall thickness of 550,600,650,700,and 750μm were selected for mechanical compression experiments on a universal testing machine.(2)The results of mechanical compression experiments showed that with the increase of wall thickness,the elastic modulus and compressive strength of Gyroid structure specimens increased.The elastic modulus of Gyroid structure specimens with wall thickness of 550,600,and 650 μm was within the elastic modulus of the mandibular cancellous bone.Finally,the wall thickness of 650 μm and the pore size of 900 μm were selected to construct the three-dimensional model of the mandibular customized Gyroid condylar prosthesis.(3)The results of finite element analysis of three-dimensional model of the mandibular customized Gyroid condylar prosthesis showed that the stress of the articular disc in the edge-to-edge occlusion was mainly concentrated on the lower surface of the anterior middle band,and the stress of the articular disc in the interposition of tooth tips was mainly concentrated on the lateral surface of the lower surface.The maximum displacement and the maximum equivalent stress of the left and right articular discs in the edge-to-edge occlusion and the interposition of tooth tips were similar.The maximum displacement was 0.031,0.030,0.028,and 0.018 mm,and the maximum equivalent stress was 2.87,2.30,2.73,and 1.71 MPa,respectively.(4)The results showed that the Gyroid structure with a wall thickness of 650 μm was consistent with the mechanical properties of the mandible,which reduced the strength of the titanium alloy and reduced the damage of the articular disc caused by the customized Gyroid condylar prosthesis.

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