1.Analysis of clinical characteristics and risk factors for infection in patients with multiple myeloma treated with bortezomib
Wenting JIANG ; Jie ZHOU ; Bo LYU ; Aiming SHI ; Bingzong LI ; Jie PAN
China Pharmacy 2026;37(7):942-948
OBJECTIVE To study the clinical characteristics and potential risk factors for infection in patients with multiple myeloma (MM) following treatment with bortezomib. METHODS Clinical data were retrospectively collected from MM patients who received bortezomib-based treatment regimens at the Department of Hematology, the Second Affiliated Hospital of Soochow University, from October 2021 to February 2025. The collected data primarily included demographic characteristics, disease characteristics of MM, treatment regimens, occurrence of infections and corresponding management measures, and prophylactic medication use. Univariate and multivariate Logistic regression analyses were conducted to identify potential risk factors for MM complicated with infection. RESULTS Among the 284 MM patients treated with bortezomib, 132 patients (46.5%) experienced at least one infection. The predominant types of infections were respiratory tract infections and gastrointestinal infections. Univariate analysis showed that age at initial diagnosis, pathological classification, and grade of myelosuppression were influencing factors for infection in MM patients ( P <0.05). Further analysis of influencing factors for the two main types of infections revealed that sex, age at initial diagnosis, pathological classification, treatment regimen, and smoking history were influencing factor s for respiratory tract infections in MM patients ( P <0.05); BMI, pathological classification, treatment regimen, and grade of myelosuppression were influencing factors for gastrointestinal infections in MM patients ( P <0.05). Multivariate Logistic regression analysis indicated that age≥70 years and the presence of grade Ⅳ myelosuppression before treatment were risk factors for infection in MM patients, while the IgG-λ type was a protective factor against infection ( P <0.05). CONCLUSIONS The incidence of infection is relatively high in MM patients receiving bortezomib-based treatment regimens, with respiratory and gastrointestinal infections being the most common. Age at initial diagnosis, grade of myelosuppression, and pathological classification are influencing factors for infection in MM patients.
2.Long-term survival outcomes and prognostic factors following radical resection of pancreatic body and tail cancer:a retrospective analysis of 992 patients
Dong XU ; Yang WU ; Kai ZHANG ; Nan LYU ; Qianqian WANG ; Pengfei WU ; Jie YIN ; Baobao CAI ; Guodong SHI ; Jianzhen LIN ; Yazhou WANG ; Lingdi YIN ; Zipeng LU ; Min TU ; Jianmin CHEN ; Feng GUO ; Jishu WEI ; Junli WU ; Wentao GAO ; Cuncai DAI ; Yi MIAO ; Kuirong JIANG
Chinese Journal of Surgery 2026;64(1):46-54
Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.
3.Visualization analysis of literature on the effect of lipid metabolism on osteoporosis
Jie HUANG ; Hao ZENG ; Wenchi WANG ; Zhucheng LYU ; Wei CUI
Chinese Journal of Tissue Engineering Research 2026;30(6):1558-1568
BACKGROUND:Studies have shown that lipid metabolism and related diseases can affect the development of osteoporosis.OBJECTIVE:Using bibliometric visualization analysis software to analyze and summarize the frontier content and research hotspots in the field of lipid metabolism affecting osteoporosis.METHODS:Using the Web of Science core collection database as the retrieval platform,relevant literature regarding the effect of lipid metabolism on osteoporosis from 2004 to 2024 was retrieved.VOSviewer and CiteSpace were used for bibliometric and visual analyses.RESULTS AND CONCLUSION:A total of 1 277 articles were included,and the number of articles on the effect of lipid metabolism on osteoporosis at home and abroad was increasing year by year.The number of articles published in China was 417,ranking first,and the United States was 243,ranking second.Shanghai Jiao Tong University ranked first with 30 articles.Professor Rosen Clifford J from Tufts University School of Medicine and Professor Recker Robert R from Clayton University were the most cited authors.The number of documents published in BONE in the Netherlands ranked first,and the JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM in England was the most cited journal.Bone mineral density,bone metabolism,menopause,and obesity were the core keywords,and they were also research hotspots in this field.The above results show that in the past 20 years,research in the field of lipid metabolism affecting osteoporosis has focused on the role of abnormal lipid metabolism in bone mineral density and bone metabolism,thereby regulating osteoporosis and post-menopause osteoporosis.Clarifying the pathway of this mechanism and"bone-lipid balance"is the future research idea and direction.
4.Visualization analysis of literature on the effect of lipid metabolism on osteoporosis
Jie HUANG ; Hao ZENG ; Wenchi WANG ; Zhucheng LYU ; Wei CUI
Chinese Journal of Tissue Engineering Research 2026;30(6):1558-1568
BACKGROUND:Studies have shown that lipid metabolism and related diseases can affect the development of osteoporosis.OBJECTIVE:Using bibliometric visualization analysis software to analyze and summarize the frontier content and research hotspots in the field of lipid metabolism affecting osteoporosis.METHODS:Using the Web of Science core collection database as the retrieval platform,relevant literature regarding the effect of lipid metabolism on osteoporosis from 2004 to 2024 was retrieved.VOSviewer and CiteSpace were used for bibliometric and visual analyses.RESULTS AND CONCLUSION:A total of 1 277 articles were included,and the number of articles on the effect of lipid metabolism on osteoporosis at home and abroad was increasing year by year.The number of articles published in China was 417,ranking first,and the United States was 243,ranking second.Shanghai Jiao Tong University ranked first with 30 articles.Professor Rosen Clifford J from Tufts University School of Medicine and Professor Recker Robert R from Clayton University were the most cited authors.The number of documents published in BONE in the Netherlands ranked first,and the JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM in England was the most cited journal.Bone mineral density,bone metabolism,menopause,and obesity were the core keywords,and they were also research hotspots in this field.The above results show that in the past 20 years,research in the field of lipid metabolism affecting osteoporosis has focused on the role of abnormal lipid metabolism in bone mineral density and bone metabolism,thereby regulating osteoporosis and post-menopause osteoporosis.Clarifying the pathway of this mechanism and"bone-lipid balance"is the future research idea and direction.
5.Long-term survival outcomes and prognostic factors following radical resection of pancreatic body and tail cancer:a retrospective analysis of 992 patients
Dong XU ; Yang WU ; Kai ZHANG ; Nan LYU ; Qianqian WANG ; Pengfei WU ; Jie YIN ; Baobao CAI ; Guodong SHI ; Jianzhen LIN ; Yazhou WANG ; Lingdi YIN ; Zipeng LU ; Min TU ; Jianmin CHEN ; Feng GUO ; Jishu WEI ; Junli WU ; Wentao GAO ; Cuncai DAI ; Yi MIAO ; Kuirong JIANG
Chinese Journal of Surgery 2026;64(1):46-54
Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.
6.Polydatin Delays Progression of Colitis-associated Colorectal Cancer by Modulating IL-17A/Wnt/β-catenin Signaling Pathway
Jie LIU ; Mengmeng LYU ; Yanfei HONG ; Xinmei NAN ; Jialong SU ; Huachen LIU ; Qing WANG ; Guiying PENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):144-154
ObjectiveTo investigate the effects and underlying mechanisms of polydatin in delaying the progression of colitis-associated colorectal cancer (CAC) by constructing an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC mouse model and conducting in vitro experiments. MethodsFifty-four male C57BL/6J mice were randomly divided into normal, model, and polydatin groups (0.045 g·kg-1). The CAC mouse model was established using AOM/DSS, and samples were collected at 4, 7, and 10 weeks. Body weight change rate, disease activity index (DAI), and tumor formation were assessed. Hematoxylin-eosin (HE) staining was used to observe pathological injury in intestinal tissues. Immunohistochemistry (IHC) was performed to detect zonula occludens-1 (ZO-1) expression in colonic tissues, and Western blot was used to detect the expression of E-cadherin, N-cadherin, and Vimentin in colonic epithelial cells. Real-time PCR was used to measure mRNA expression of interleukin-17A (IL-17A), Wnt3a, β-catenin, T cell factor 1 (Tcf1), E-cadherin, N-cadherin, and Vimentin in colonic tissues. Flow cytometry was used to analyze the proportion of CD8+T cells and the expression of exhaustion-related molecules in tumors. Human colon cancer DLD-1 cells were cultured in a polydatin-containing medium, and wound healing assays were performed to observe migration changes. Real-time PCR was used to detect mRNA expression of interleukin-17 receptor A (IL-17RA), Wnt3a, β-catenin, Tcf1, E-cadherin, N-cadherin, and Vimentin in DLD-1 cells. ResultsCompared with the normal group, the model group at all three time points showed significantly decreased body weight change rate (P<0.01), significantly shortened colon length (P<0.01), and markedly increased DAI scores (P<0.01). HE staining revealed significant inflammatory cell infiltration in the submucosa of the colon in the model group, accompanied by epithelial dysplasia. ZO-1 expression in colonic tissues was significantly reduced (P<0.01). The mRNA expression of the pro-inflammatory factor IL-17A and key molecules of the Wnt/β-catenin pathway (Wnt3a, β-catenin, Tcf1) was significantly elevated (P<0.05). The mRNA and protein expression of epithelial-mesenchymal transition (EMT) markers N-cadherin and Vimentin was significantly upregulated (P<0.05), while E-cadherin expression was significantly downregulated (P<0.05). The proportion of tumor-infiltrating CD8+T cells expressing immunosuppressive molecules (TIM-3, LAG-3, PD-1) was significantly increased (P<0.05). Compared with the model group, the polydatin group showed significant improvement in body weight and DAI score (P<0.01), as well as recovery of colon length and tissue injury. ZO-1 expression in colonic tissue was significantly increased (P<0.01), while IL-17A, Wnt3a, β-catenin, Tcf1, N-cadherin, and Vimentin expression levels were significantly decreased (P<0.05), and E-cadherin expression was significantly increased (P<0.01). Tumor-infiltrating CD8+ T cells expressing immunosuppressive molecules were significantly reduced (P<0.05). In vitro experiments showed that polydatin significantly inhibited migration of DLD-1 cells (P<0.01) and reversed the upregulation of IL-17RA, Wnt3a, β-catenin, N-cadherin, and Vimentin mRNA, as well as the downregulation of E-cadherin mRNA (P<0.05). ConclusionPolydatin inhibits IL-17A secretion and IL-17RA expression, improves the immune microenvironment, blocks activation of the Wnt/β-catenin signaling pathway, suppresses EMT markers (N-cadherin and Vimentin), and restores tight junction protein expression in intestinal epithelial cells, thereby delaying the progression from colitis to colorectal cancer in mice.
7.Bioinformatics analysis of efferocytosis-related genes in diabetic kidney disease and screening of targeted traditional Chinese medicine.
Yi KANG ; Qian JIN ; Xue-Zhe WANG ; Meng-Qi ZHOU ; Hui-Juan ZHENG ; Dan-Wen LI ; Jie LYU ; Yao-Xian WANG
China Journal of Chinese Materia Medica 2025;50(14):4037-4052
This study employed bioinformatics to screen the feature genes related to efferocytosis in diabetic kidney disease(DKD) and explores traditional Chinese medicine(TCM) regulating these feature genes. The GSE96804 and GSE30528 datasets were integrated as the training set, and the intersection of differentially expressed genes and efferocytosis-related genes(ERGs) was identified as DKD-ERGs. Subsequently, correlation analysis, protein-protein interaction(PPI) network construction, enrichment analysis, and immune infiltration analysis were performed. Consensus clustering was conducted on DKD patients based on the expression levels of DKD-ERGs, and the expression levels, immune infiltration characteristics, and gene set variations between different subtypes were explored. Eight machine learning models were constructed and their prediction performance was evaluated. The best-performing model was evaluated by nomograms, calibration curves, and external datasets, followed by the identification of efferocytosis-related feature genes associated with DKD. Finally, potential TCMs that can regulate these feature genes were predicted. The results showed that the training set contained 640 differentially expressed genes, and after intersecting with ERGs, 12 DKD-ERGs were obtained, which demonstrated mutual regulation and immune modulation effects. Consensus clustering divided DKD into two subtypes, C1 and C2. The support vector machine(SVM) model had the best performance, predicting that growth arrest-specific protein 6(GAS6), S100 calcium-binding protein A9(S100A9), C-X3-C motif chemokine ligand 1(CX3CL1), 5'-nucleotidase(NT5E), and interleukin 33(IL33) were the feature genes of DKD. Potential TCMs with therapeutic effects included Astragali Radix, Trionycis Carapax, Sargassum, Rhei Radix et Rhizoma, Curcumae Radix, and Alismatis Rhizoma, which mainly function to clear heat, replenish deficiency, activate blood, resolve stasis, and promote urination and drain dampness. Molecular docking revealed that the key components of these TCMs, including β-sitosterol, quercetin, and sitosterol, exhibited good binding activity with the five target genes. These results indicated that efferocytosis played a crucial role in the development and progression of DKD. The feature genes closely related to both DKD and efferocytosis, such as GAS6, S100A9, CX3CL1, NT5E, and IL33, were identified. TCMs such as Astragali Radix, Trionycis Carapa, Sargassum, Rhei Radix et Rhizoma, Curcumae Radix, and Alismatis Rhizoma may provide a new therapeutic strategy for DKD by regulating efferocytosis.
Humans
;
Computational Biology
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Diabetic Nephropathies/physiopathology*
;
Protein Interaction Maps
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Medicine, Chinese Traditional
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Drugs, Chinese Herbal
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Phagocytosis/genetics*
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Efferocytosis
8.A method for emotion transition recognition using cross-modal feature fusion and global perception.
Lilin JIE ; Yangmeng ZOU ; Zhengxiu LI ; Baoliang LYU ; Weilong ZHENG ; Ming LI
Journal of Biomedical Engineering 2025;42(5):977-986
Current studies on electroencephalogram (EEG) emotion recognition primarily concentrate on discrete stimulus paradigms under controlled laboratory settings, which cannot adequately represent the dynamic transition characteristics of emotional states during multi-context interactions. To address this issue, this paper proposes a novel method for emotion transition recognition that leverages a cross-modal feature fusion and global perception network (CFGPN). Firstly, an experimental paradigm encompassing six types of emotion transition scenarios was designed, and EEG and eye movement data were simultaneously collected from 20 participants, each annotated with dynamic continuous emotion labels. Subsequently, deep canonical correlation analysis integrated with a cross-modal attention mechanism was employed to fuse features from EEG and eye movement signals, resulting in multimodal feature vectors enriched with highly discriminative emotional information. These vectors are then input into a parallel hybrid architecture that combines convolutional neural networks (CNNs) and Transformers. The CNN is employed to capture local time-series features, whereas the Transformer leverages its robust global perception capabilities to effectively model long-range temporal dependencies, enabling accurate dynamic emotion transition recognition. The results demonstrate that the proposed method achieves the lowest mean square error in both valence and arousal recognition tasks on the dynamic emotion transition dataset and a classic multimodal emotion dataset. It exhibits superior recognition accuracy and stability when compared with five existing unimodal and six multimodal deep learning models. The approach enhances both adaptability and robustness in recognizing emotional state transitions in real-world scenarios, showing promising potential for applications in the field of biomedical engineering.
Humans
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Emotions/physiology*
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Electroencephalography
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Neural Networks, Computer
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Eye Movements
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Perception
9.Distribution characteristics and heritability of alcohol consumption behavior in adult twins in China
Yuanchen LI ; Wenjing GAO ; Weihua CAO ; Jun LYU ; Canqing YU ; Shengfeng WANG ; Tao HUANG ; Dianjianyi SUN ; Chunxiao LIAO ; Yuanjie PANG ; Ruqin GAO ; Min YU ; Jinyi ZHOU ; Xianping WU ; Zhong DONG ; Fan WU ; Dezheng WANG ; Zhihua XU ; Yu LIU ; Yanxia MA ; Jie YIN ; Shengli YIN ; Liming LI
Chinese Journal of Epidemiology 2025;46(1):73-80
Objective:To describe the distribution characteristics of alcohol consumption in adult twins in the Chinese National Twin Registry (CNTR), and further explore the influence of genetic factors on alcohol consumption in adult twins.Methods:The subjects of the study were twins registered by CNTR in 11 project areas across China from 2010 to 2018. A total of 56 966 twins (28 483 pairs) aged 18 years and above who answered questions about drinking behavior were included, and the random effect model was used to describe the population and regional distribution characteristics of alcohol consumption. Intra-pair analysis was performed to calculate the concordance rate and heritability of their alcohol consumption.Results:The age of all subjects was (36.6±12.0) years, and current drinkers accounted for 16.6% (9 461/56 966) of all subjects. In men, those aged 50-59 years, those in northern China, those living in rural area, those with low education level and those with high BMI, the proportions of current drinkers were higher. After excluding 468 pairs of twins who had stopped alcohol use and 21 764 pairs of twins who had no drink or had small amount drink, an intra-pair analysis was conducted in 4 929 pairs of same-sex twins, and found that the concordance rate of alcohol consumption was 64.0% (2 059/3 215) in monozygotic twins, and 52.6% (902/1 714) in dizygotic twins, the difference was significant ( P<0.001), and the heritability of alcohol consumption was 24.1% (95% CI: 18.9%- 29.3%). The further stratified analysis found that in southern men, the heritability was highest in those aged 40-49 years (36.1%, 95% CI: 21.6%-50.7%), while in northern men, the heritability was highest in those aged 50-59 years (34.2%, 95% CI: 18.1%-50.3%). Conclusions:In adult twins in China, there were population and regional differences in the distribution of alcohol consumption behavior, and alcohol consumption was influenced by genetic factors, and gender, age and region had potential modifying effects.
10.Effects of sesquiterpene lactones from Ixeris sonchifolia on bone metabolism and lipid metabolism in ApoE-/-mice
Kui-mao WANG ; Xin PANG ; Jia-hao LYU ; Jian LIU ; Yang HU ; Yu-jie ZHU ; Li-hong HU
Chinese Pharmacological Bulletin 2025;41(8):1492-1499
Aim To investigate the effects of Ixerin Z,a sesquiterpene lactone from Ixeris sonchifolia,on bone-lipid metabolic imbalance in ApoE-/-mice and to elu-cidate its molecular mechanisms.Methods A mouse model of ApoE-/-was induced using a high-fat diet,followed by eight weeks of Ixerin Z administration at doses of 1 and 10 mg·kg-1.Serum markers related to bone-lipid metabolism and inflammatory cytokines were quantified.Bone mineral density,biomechanical prop-erties,bone tissue morphology,and bone microstructure changes were analyzed.Computational molecular doc-king was performed to identify potential target proteins of Ixerin Z,and its regulatory effects on bone-lipid me-tabolism were investigated.Results Treatment with Ixerin Z markedly decreased the serum levels of total cholesterol,triglycerides,TNF-α,and IL-1β in ApoE-/-mice.It significantly improved bone mineral density,enhanced biomechanical strength,restored tra-becular structure,and reduced fat accumulation in bone tissue.Investigations revealed that Ixerin Z activated PPARα,thereby promoting fatty acid β-oxidation in bone tissue,and stimulating the Wnt/β-Catenin signa-ling pathway to facilitate bone formation.Furthermore,Ixerin Z suppressed the OPG/RANKL/NF-κB signaling pathway,leading to reduced bone resorption,independ-ent of PPARα activation.Conclusions Ixerin Z dem-onstrates potent therapeutic effects on bone-lipid meta-bolic imbalance in ApoE-/-mice.The mechanism in-volves activating PPARα to promote fatty acid β-oxida-tion in bone tissue,activating PPARα/Wnt/β-Catenin signaling pathway to promote bone formation,and in-hibiting OPG/RANKL/NF-κB signaling pathway to re-duce bone resorption.

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