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    28 February 2026, Volume 30 Issue 6 Previous Issue    Next Issue
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    Effect and mechanism of beta-caryophyllene in mice with osteoarthritis
    Chen Ju, Zheng Jinchang, Liang Zhen, Huang Chengshuo, Lin Hao, Zeng Li
    2026, 30 (6):  1341-1347.  doi: 10.12307/2025.995
    Abstract ( 5 )   PDF (1902KB) ( 0 )   Save
    BACKGROUND: β-Caryophyllene has a variety of pharmacological activities such as antioxidant, anti-inflammatory and anti-apoptotic, which may have a better therapeutic effect on osteoarthritis.
    OBJECTIVE: To investigate the effect and mechanism of β-caryophyllene on mouse osteoarthritis. 
    METHODS: Forty C57BL/6J mice were randomly divided into sham group, model group, low-dose β-caryophyllene group and high-dose β-caryophyllene group, with 10 mice in each group. Hulth method was used to construct an osteoarthritis model in the latter three groups. Four weeks after modeling, 70 and 
    140 mg/kg/d β-caryophyllene was intragastrically given in the low- and high-dose β-caryophyllene groups, respectively, and normal saline was given by gavage in the sham group and the model group, once a day, for 4 weeks. After administration, knee joint morphological changes were observed by hematoxylin-eosin staining, serum levels of inflammatory factors (tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-10) were detected by ELISA, and oxidative stress indexes (glutathione peroxidase, superoxide dismutase, and malondialdehyde) were detected by chemiluminescence. The expression levels of key proteins in the Sonic hedgehog (Shh)/glioma associated oncogene homolog 1 (Gli1) signaling pathway were detected by immunohistochemistry and western blot. 
    RESULTS AND CONCLUSION: (1) Compared with the sham group, a large number of inflammatory cells infiltrated in the knee joint of mice in the model group, cartilage tissue was seriously damaged, serum levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-10 and malondialdehyde were significantly increased (P < 0.01), the activities of glutathione peroxidase and superoxide dismutase were significantly decreased (P < 0.01), and the relative expression levels of Shh and Gli1 in the knee joint were significantly increased (P < 0.01). (2) Compared with the model group, in the low- and high-dose β-caryophyllene groups, inflammatory cell infiltration in the mouse knee joint was decreased, cartilage tissue injury was alleviated, serum levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 and malondialdehyde were significantly decreased (P < 0.05), the activities of glutathione peroxidase and superoxide dismutase were significantly increased (P < 0.01), and the expression levels of Shh and Gli1 in the knee joint were significantly decreased (P < 0.01). The above-mentioned improvements were more significant in the high-dose β-caryophyllene group than the low-dose β-caryophyllene group. To conclude, β-caryophyllene can improve osteoarthritis, and its mechanism may be related to reducing inflammation and oxidative stress damage by regulating the Shh/Gli1 signaling pathway. 
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    Effects and mechanisms of isoginkgetin on osteoclastogenesis
    Wen Guangwei, Zhen Yinghao, Zheng Taikeng, Zhou Shuyi, Mo Guoye, Zhou Tengpeng, Li Haishan, Lai Yiyi
    2026, 30 (6):  1348-1358.  doi: 10.12307/2026.552
    Abstract ( 5 )   PDF (4053KB) ( 19 )   Save
    BACKGROUND: During bone remodeling, bone formation and bone resorption are spatially and temporally coordinated, involving intricate interactions between osteoclasts and osteoblasts. Isoginkgetin, a flavonoid found in Ginkgo biloba, has a wide range of anticancer activity and anti-reactive oxygen species activity; however, the effect of isoginkgetin on osteoclast differentiation is unknown.
    OBJECTIVE: To study the effect and mechanism of action of isoginkgetin on osteoclastogenesis.
    METHODS: In vitro studies were performed on mouse bone marrow-derived macrophages, and cell counting kit-8 cytotoxicity assay was used to detect the effect of isoginkgetin on cell viability of bone marrow-derived macrophages. Macrophage colony-stimulating factor and receptor activator of nuclear factor kappa-B ligand were used to induce the differentiation of bone marrow-derived macrophages to osteoclasts. Network pharmacology and molecular docking and molecular dynamics simulations were used to predict the processes and targets of the effects of isoginkgetin on the differentiation of osteoclasts. Tartrate-resistant acid phosphatase staining and F-actin staining were used to detect the effects of isoginkgetin on the differentiation and function of osteoclasts. Western blot and RT-PCR were used to detect the effects of isoginkgetin on the expression of genes and proteins related to osteoclast differentiation, reactive oxygen species, and PI3K/AKT pathways. Fluorescent probes were used to detect cellular and mitochondrial reactive oxygen species levels. Flow cytometry technology was used to detect reactive oxygen species levels in cells. 
    RESULTS AND CONCLUSION: (1) Network pharmacology results showed that isoginkgetin affected osteoporosis mainly through the PI3K-AKT pathway and cellular response to drugs and hypoxia, and GSK3β, ESR1, MCL1 and CCNA2 were the key targets. (2) Cell counting kit-8 and tartrate-resistant acid phosphatase staining results showed that isoginkgetin at 8 μmol/L had the most significant inhibitory effect on osteoclastogenesis in vitro, and F-actin results showed that isoginkgetin inhibited osteoclast cytoskeletal actin ring formation in a concentration-dependent manner. (3) Molecular dynamics simulations showed that isoginkgetin bound well to osteoclastogenesis marker proteins (NFATc1, c-Fos, CTSK, and MMP9). Western blot and RT-PCR results indicated that isoginkgetin inhibited the expression of osteoclastogenesis marker proteins and genes (NFATc1, c-Fos, CTSK, and MMP9). (4) Western blot results showed that isoginkgetin inhibited the phosphorylation level of PI3K/AKT/GSK3β and suppressed osteoclastogenesis by activating the PI3K-AKT-GSK3β pathway. (5) The results of reactive oxygen species assay showed that isoginkgetin significantly reduced receptor activator of nuclear factor kappa-B ligand-induced cellular and mitochondrial reactive oxygen species production, and inhibited the differentiation of bone marrow-derived macrophages to osteoclasts.
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    Irisin inhibits ferroptosis in human articular chondrocytes: roles and mechanisms
    Lyu Guoqing, Aizimaitijiang·Rouzi, Xiong Daohai
    2026, 30 (6):  1359-1367.  doi: 10.12307/2026.568
    Abstract ( 5 )   PDF (4358KB) ( 7 )   Save
    BACKGROUND: Studies have shown that irisin can delay joint degeneration by modulating the metabolic homeostasis of chondrocytes and inhibiting inflammatory responses and oxidative stress.
    OBJECTIVE: To further explore the mechanism by which irisin exerts therapeutic effects on osteoarthritis. 
    METHODS: (1) Bioinformatics analysis: Gene expression data from cartilage tissues of patients with osteoarthritis and healthy controls were obtained from the GSE51588 and GSE207881 datasets. Gene set variation analysis assessed the activation of programmed cell death in osteoarthritis. Differential expression analysis identified differentially expressed genes between osteoarthritis and control samples, followed by pathway enrichment analysis. Ferroptosis-related differentially expressed genes were further identified, with those having an area under the receiver operating characteristic curve greater than 0.9 designated as core genes. (2) Cell experiment. Human articular chondrocytes were divided into four groups: control (chondrocytes), model (inflammatory models were established in chondrocytes induced by tumor necrosis factor α), model+Erastin (a ferroptosis inducer), and model+Erastin+irisin. ELISA measured glutathione, malondialdehyde and reactive oxygen species levels, while JC-1 assays assessed mitochondrial membrane potential. RT-qPCR quantified mRNA levels of core and ferroptosis-related genes, and western blot analyzed the expression of core genes, ferroptosis-related proteins, ERK pathway components, and apoptotic proteins. 
    RESULTS AND CONCLUSION: (1) Gene set variation analysis indicated significant ferroptosis activation in osteoarthritis. (2) Differential expression analysis highlighted significant enrichment of differentially expressed genes in the ERK signaling pathway. Sixteen ferroptosis-related differentially expressed genes including HMOX1, G6PD, and ALOX5, were identified, all with the area under the curve values above 0.9. (3) In the human articular chondrocytes model+Erastin group, glutathione levels and mitochondrial membrane potential decreased significantly, while malondialdehyde and reactive oxygen species levels increased. The expression of HMOX1, G6PD, ALOX5, glutathione peroxidase 4, and SLC7A11 was significantly downregulated, while p-ERK and Bax levels rose, and Bcl2 decreased (all P < 0.05). Irisin treatment significantly improved ferroptosis-related markers (all P < 0.05). To conclude, HMOX1, G6PD, and ALOX5 may be potential therapeutic targets of osteoarthritis. Irisin offers protective effects in osteoarthritis by modulating ferroptosis-related genes and pathways.

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    Effect of icariin-containing serum on lipopolysaccharide-induced inflammatory damage in human chondrocytes
    Li Linzhen, Jiao Hongzhuo, Chen Weinan, Zhang Mingzhe, Wang Jianlong, Zhang Juntao
    2026, 30 (6):  1368-1374.  doi: 10.12307/2026.556
    Abstract ( 14 )   PDF (1884KB) ( 7 )   Save
    BACKGROUND: Previous studies of the research group have found that icariin-containing serum can delay the progression of knee osteoarthritis, promote chondrocyte proliferation and stem cell cartilage differentiation in rats, but there is still a lack of sufficient basis for clinical application. 
    OBJECTIVE: To investigate the repair effect of icariin-containing serum on lipopolysaccharide-induced inflammatory damage of human chondrocytes. 
    METHODS: The effect of icariin-containing serum on chondrocyte viability was detected by cell counting kit-8 method, and the optimal volume fraction and time of icariin-containing serum were screened. The cells were then divided into blank group, lipopolysaccharide group, icariin-containing serum group and lipopolysaccharide+icariin-containing serum group. After grouping, immunofluorescence was used to detect the secretion of type II collagen in chondrocytes in each group. Real-time PCR was used to detect the expression of related genes. 
    RESULTS AND CONCLUSION: (1) Icariin-containing serum showed good biosafety characteristics for human chondrocytes, and the cell viability reached the highest level after 48 hours of intervention when the icariin-containing serum volume fraction was 15%, and the follow-up experiments were carried out according to the conditions. (2) Compared with the blank group, lipopolysaccharide significantly inhibited the expression of type II collagen in chondrocytes, while icariin-containing serum showed a positive mobilization effect, which could effectively promote the secretion of type II collagen in chondrocytes under normal and inflammatory conditions. (3) The mRNA expression of type II collagen and Aggrecan in chondrocytes decreased significantly under lipopolysaccharide stimulation, and the mRNA expression levels of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 increased significantly. Icariin-containing serum promoted the mRNA expression of type II collagen in human chondrocytes under inflammatory conditions and reduced the mRNA expression of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 in chondrocytes after lipopolysaccharide intervention. Therefore, these findings indicate that the icariin-containing serum has good safety for human chondrocytes and plays an important role in maintaining the normal physiological functions of chondrocytes, promoting the synthesis of extracellular matrix, and inhibiting the secretion of inflammatory factors.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程
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    Mechanical effect of mechanical wear of abutment screws on the Morse taper connection implant system: a three-dimensional finite element analysis
    Xu Hao, Ding Lu, Li Xiao
    2026, 30 (6):  1375-1383.  doi: 10.12307/2026.553
    Abstract ( 2 )   PDF (2143KB) ( 8 )   Save
    BACKGROUND: Abutment screw loosening is one of the most common mechanical complications in implant restoration. Mechanical wear, as a potential cause of thread loosening, warrants attention due to its impact on mechanical performance and long-term stability. However, studies on the mechanical effects of thread wear in abutment screws remain limited, and no definitive conclusions have been reached.
    OBJECTIVE: To investigate the effect of different degrees of mechanical wear on the spatial stress distribution of the Morse taper connection implant system, with a view to providing a theoretical basis for the clinical assessment of the long-term stability of dental implants.
    METHODS: Three-dimensional finite element models of Morse taper implants with central screw thread wear levels of 0, 0.1, 1, 10, and 100 μm were established using SolidWorks software, and simulation analysis with Ansys Workbench software was performed. The implant models were inserted into artificial bone blocks (simulating type II bone, with a cortical bone thickness of 2 mm on the outer layer and cancellous bone inside). An alternating load of 300 N in the buccolingual direction was applied at the centroid of the abutment (forming an angle of 30° with the long axis of the implant). The von Mises stress, principal stress, displacement, and fatigue life of the abutment, central screw, implant, and bone tissue in the five groups of models were analyzed.
    RESULTS AND CONCLUSION: (1) As the degree of mechanical wear on the central screw thread increased, the von Mises stress, principal stress, and strain in the implant and abutment also increased. The stress in the model was concentrated at the top of the implant, at the shoulder level of the implant, at the neck of the abutment, and at the bottom edge of the abutment. (2) Under moderate wear conditions (≥ 10 μm), the fatigue life of the implant system decreased by 30%, and the maximum von Mises stress of the central screw decreased by 37%, with the stress still primarily concentrated at the transition area between the head and the body of the central screw. (3) Under significant wear conditions (≥ 100 μm), the von Mises stress of the central screw decreased by 98%, with the stress concentrated at the screw head, and the fatigue life of the implant system decreased by 63%. Therefore, when the wear level of the central screw thread reaches ≥ 10 μm, the risk of screw loosening is significantly increased, and the fatigue life of the implant system is markedly reduced, warranting clinical attention.

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    Feasibility of optimizing radiation dose for three-dimensional printing of the maxillofacial bone based on low-dose CT technology
    Li Guan, Wang Haopeng, Wang Jinbao, Song Xinhao, Qin Guochu, Shao Yang
    2026, 30 (6):  1384-1389.  doi: 10.12307/2026.557
    Abstract ( 7 )   PDF (1335KB) ( 1 )   Save
    BACKGROUND: Maxillofacial bone three-dimensional (3D) printing technology has been widely used in clinical diagnosis and treatment, but the data source before performing maxillofacial bone 3D printing mainly comes from the CT scanning data. The lens, thyroid and other parts of the human body are extremely sensitive to X-rays; therefore, it is particularly important to effectively reduce the dose of CT radiation when acquiring the data source.
    OBJECTIVE: To explore the feasibility of low-dose CT technology in optimizing radiation dose for maxillofacial bone 3D printing. 
    METHODS: The medical records of 65 patients who underwent maxillofacial bone 3D printing in the Department of Stomatology at the General Hospital of Northern Theater Command from March 2021 to December 2023 were retrospectively collected and categorized into a conventional CT-dose 3D printing group (conventional CT-dose, 120 kVp, automated tube current modulation, n=32) and a low-CT-dose 3D printing group (low-CT-dose group, 80 kVp, automated tube current modulation, n=33). The effective dose of radiation was calculated and compared between the two groups. A Likert scale was used to evaluate the quality of 3D printing in the two groups, and the measurement bias and consistency between evaluators were measured using the Bland-Altman method. 
    RESULTS AND CONCLUSION: (1) There was no significant difference in the general demographic characteristics (age, height, weight, body mass, sex, and body mass index) between the two groups (all P > 0.05). (2) The effective dose value of the low CT-dose 3D printing group was (0.3±0.1) mSv, which was about 62.5% lower than that in the conventional CT-dose 3D printing group [(0.8±0.1) mSv]. (3) There was no significant difference in the subjective scoring of 3D printing quality between the two groups (all P > 0.05). The subjective consistency among evaluators was good, with Kappa values of 0.85, 0.80, and 0.76. The scatter points in the Bland-Altman for both protocols were uniformly distributed within the standard deviation line, indicating good consistency between the two groups. To conclude, low-dose CT technology can be effectively applied in maxillofacial bone 3D printing, reducing radiation dose without affecting the quality of 3D printing.
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    Inhibitory effects of different concentrations of auranofin on M1 macrophage function and its therapeutic potential in diabetic wound healing 
    Pan Hongfei, Zhuang Zhenbing, Xu Baiyun, Yang Zhangyang, Lin Kairui, Zhan Bingqing, Lan Jinghan, Gao Heng, Zhang Nanbo, Lin Jiayu
    2026, 30 (6):  1390-1397.  doi: 10.12307/2026.555
    Abstract ( 6 )   PDF (2133KB) ( 2 )   Save
    BACKGROUND: During diabetic wound healing, the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair. Auranofin, an anti-inflammatory drug, has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.
    OBJECTIVE: To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing. 
    METHODS: RAW264.7 and THP-1 cells were used as research models. M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide. M1 macrophages were treated with 1 and 2 μmol/L auranofin. Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.  Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β, interleukin-6, and tumor necrosis factor-α. ELISA was employed to measure the levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α in the supernatant. Western blot analysis was used to assess the expression of nuclear factor-κB (p65), phosphorylated mitogen-activated protein kinases (MAPK), and total MAPK proteins. Additionally, 6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments, with the mice divided into C57 control, db/db control and auranofin treatment groups, each containing six animals. Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.
    RESULTS AND CONCLUSION: (1) Cell experiments showed that co-treatment with interferon-γ (10 ng/mL) and lipopolysaccharide (100 ng/mL) significantly induced M1 polarization in RAW264.7 and THP-1 cells, resulting in increased mRNA expression of interleukin-1β, interleukin-6, and tumor necrosis factor-α. Treatment with auranofin (1 and 2 μmol/L) reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant. (2) Auranofin treatment significantly suppressed the activation of nuclear factor-κB (p65) and phosphorylated MAPK signaling pathways. (3) Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice, suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.
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    Luteolin promotes wound healing in diabetic mice: roles and mechanisms
    Peng Zhiwei, Chen Lei, Tong Lei
    2026, 30 (6):  1398-1406.  doi: 10.12307/2026.558
    Abstract ( 4 )   PDF (3129KB) ( 0 )   Save
    BACKGROUND: Luteolin has a variety of pharmacological activities such as antibacterial, anti-inflammatory, antioxidant, etc., which can inhibit the release of cellular inflammatory factors, promote cell proliferation, and improve the cellular microenvironment.
    OBJECTIVE: To explore the potential roles and mechanisms of luteolin in promoting diabetic chronic wound healing using network pharmacology and in vivo experiments.
    METHODS: Potential targets of luteolin were screened using multiple databases, systemic pharmacology of Chinese medicines database, PubChem and UniProt databases. Genes related to wound healing were identified through the GeneCards database. A protein-protein interaction network was constructed to screen core targets, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to explore the biological pathways that luteolin may affect. In vivo experiments in mice were conducted to observe the effects of luteolin on wound healing. Eighteen C57BL/6 mice were randomly divided into three groups. A 1 cm diameter full skin defect wound was made on the back of the control group (n=6), and a 1 cm diameter full skin defect wound was made on the back of the model group (n=6) and the treatment group (n=6) after the establishment of the diabetes model. The treatment group was given 200 mg/kg luteolin by gavage once a day for 9 consecutive days after the operation, and the wound healing was observed. At the end of drug administration, the samples were taken for hematoxylin-eosin and Masson staining. qRT-PCR was used to detect the mRNA expression of interleukin 6 and tumor necrosis factor α, and western blot was used to detect the protein expression of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway.
    RESULTS AND CONCLUSION: (1) Network pharmacological analysis identified 56 potential target genes associated with luteolin for the treatment of chronic wounds, of which the AKT gene was most closely linked to other target genes. Gene Ontology analysis indicated that luteolin could have antioxidant and anti-stress effects and have the potential to act as a multi-targeted drug. Kyoto Encyclopedia of Genes and Genomes analysis indicated that the target genes of luteolin were mainly enriched in the PI3K/AKT signaling pathway. (2) On the 9th day of drug administration, the remaining wound area of mice in the control and treatment groups was smaller than that of the model group (P < 0.05). Hematoxylin-eosin and Masson staining results showed that compared with the model group, the number of trabecular granulation tissues and collagen deposition were increased in the treatment group, and the degree of epithelialization was higher and close to that of the control group. The mRNA expression of interleukin 6 and tumor necrosis factor α on the wound surface was lower in the treatment group than the model group (P < 0.05), while the protein expression of p-PI3K and p-AKT was higher in the treatment group than the model group (P < 0.05). To conclude, luteolin inhibits wound inflammatory response and promotes healing of diabetic wounds by modulating the PI3K/AKT signaling pathway.
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    Simulation and force characterization of the lower limbs in elderly people from sitting to standing
    Zhang Zihua
    2026, 30 (6):  1407-1416.  doi: 10.12307/2026.506
    Abstract ( 5 )   PDF (2075KB) ( 2 )   Save
    BACKGROUND: Falls are an urgent health concern globally and the most common cause of injury-related death in older adults.
    OBJECTIVE: To analyze the characteristics of lower limb muscle exertion and the mechanical mechanisms affecting the risk of falls from sitting to standing. 
    METHODS: Forty-five subjects recruited from current college students and retired employees over 65 years between July and September 2023 were divided into a young adult group, an elderly group of 65-69.9 years old and an elderly group of 70-75 years old. A three-dimensional infrared motion capture system and a dynamometer platform were used to capture the movements from sitting to standing. C3D files were input into AnyBody7.2 simulation software to simulate and process the lower limb muscles after completing the motion. A one-way analysis of variance was used to analyze the differences in lower limb muscle strength, contribution, active muscle, antagonistic muscle and functional ratios between the two groups.
    RESULTS AND CONCLUSION: (1) Compared with the young adult group, the completion time of the elderly groups was significantly higher than that of the young adult group (P < 0.05). (2) There were significant differences in the strength of the adductor longus, adductor brevis, adductor maximus, obturator lateralis, quadratus femoris, piriformis, plantaris, biceps femoris brevis, femoris medialis, femoris lateralis, gastrocnemius lateralis, soleus lateralis, peroneus longus, and tibialis anterior muscles (P < 0.05). (3) There were significant differences in hip joint antagonistic muscle and functional ratio, knee joint active muscle, antagonistic muscle and functional ratio, and ankle joint active muscle and functional ratio (P < 0.05). (4) There were significant differences in the peak sagittal torque of the hip, knee, and ankle joints (P < 0.05). These two elderly groups showed significant differences in the strength of the pyriformis, tibialis anterior muscles, and ankle extensors (P < 0.05). To conclude, the main joints that exert force in the movement are the knee and ankle joints, with the hip joint playing a controlling role. The high contribution rate of deep muscle groups in the ankle joint can increase the stability of completing movements. Weakness in hip joint antagonistic muscle group strength, knee joint active muscle group strength, and ankle joint active muscle group strength leads to an imbalance in the human-machine performance ratio of older adults. The contribution rate of the deep adductor muscle group in the hip joint is low, and the strength of the antagonistic muscle group is insufficient, resulting in uneven coordination of muscle action. When completing movements, the body’s ability to control balance is weakened, the completion time is prolonged, and the risk of falls in older adults is increased.

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    Biomechanical mechanism of sports-related patellar tendinitis
    Zhong Caihong, Xiao Xiaoge, Li Ming, Lin Jianhong, Hong Jing
    2026, 30 (6):  1417-1423.  doi: 10.12307/2026.551
    Abstract ( 5 )   PDF (1728KB) ( 4 )   Save
    BACKGROUND: Patellar tendonitis can present as tendon degeneration that fails to heal due to tissue overload and incomplete recovery. Patellar tendonitis is a predisposition to high jumping and its pathogenesis has not been clearly defined.
    OBJECTIVE: To explore the stress-strain relationship of patellar tendon in the take-off technique of high jump through the finite element model with accurate human anatomical structure, so as to provide ideas for the prevention and rehabilitation of patellar tendinitis.
    METHODS: Based on the CT and MRI imaging data of the lower extremity (including the knee and ankle) of one subject (22 years old, 183 cm height, 70 kg body mass), a three-dimensional finite element model of the lower extremity was reconstructed using medical imaging software, reverse engineering software and modeling software. The plantar pressure of the take-off leg was collected in eight subjects by gait testing system, and the technical action of high jump take-off was collected by motion capture system. The captured data were imported into human sports biomechanics software for analysis, and kinematic and kinetic data were obtained as the boundary conditions of finite element model for finite element simulation analysis.
    RESULTS AND CONCLUSION: The force borne by the patellar tendon reached 3.29 times of its own body mass when the subjects took off. In the take-off stage, the peak values of normal equivalent stress, strain and shear stress of the patellar tendon were 127.76 MPa, 0.81 and 37.69 MPa, respectively, which were in the nonlinear region of the stress-strain curve, and the peak values were distributed in the proximal and posterior parts of patellar tendon. To conclude, the high patellar tendon force, strain and shear stress caused by the load of 3.29 times its own body mass during take-off are related to the induction of patellar tendinitis.
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    Mechanism by which hairless gene mutation promotes white adipose tissue browning in hairless mice
    Zhu Kuicheng, Du Chunyan, Zhang Jintao
    2026, 30 (6):  1424-1430.  doi: 10.12307/2026.554
    Abstract ( 4 )   PDF (2014KB) ( 2 )   Save
    BACKGROUND: In mammals, white adipose tissue stores energy, whereas brown adipose tissue dissipates energy. Conversion from White to brown/beige adipocytes is a potential therapeutic strategy to fight obesity, but the molecular mechanisms that drive this process is unclear.  
    OBJECTIVE: To reveal the potential relationship between Hr mutation and adipocyte browning.
    METHODS: Ten 10-week-old male Yuyi hairless mice and 10 littermate wild-type controls were selected and changes in food intake, body mass and inguinal white adipose tissue mass were recorded. Serum levels of leptin and adiponectin were estimated by ELISA. Glucose tolerance test was used to assess glucose metabolic function and insulin tolerance test was performed to analyze insulin sensitivity. Hematoxylin-eosin staining was performed to observe pathological changes of inguinal white adipose tissue in mice. Real-time fluorescence quantitative PCR and immunofluorescent staining were performed to analyze the expression of genes and proteins associated with browning of white adipose tissue in the groin.
    RESULTS AND CONCLUSION: (1) Compared with wild-type mice, Yuyi hairless mice had increased brown fat content and ultimately increased glucose tolerance and insulin sensitivity. Hr mutation reduced body mass and inguinal adipose mass in mice, but food intake did not change significantly compared with wild-type mice, suggesting that there was a reduction in body mass and adipose mass but not in food intake. (2) Hematoxylin-eosin staining results showed browning of adipocytes in the inguinal white adipose tissue of Yuyi hairless mice, which became smaller, rounder and accompanied by the appearance of multilocular cells. (3) There was increased level of peroxisome proliferator-activated receptor γ coactivator 1α and activation of thyroid hormone receptor α, uncoupling protein 1, and the mitochondria-shaping genes (nuclear respiratory factor 1 and mitochondrial transcription factor A), thereby promoting browning of adipocytes. Thus, Hr mutation activates the peroxisome proliferator-activated receptor γ coactivator 1α/thyroid hormone receptorα/uncoupling protein 1 signaling pathway and increases brown adipose content in mice, thereby promoting energy expenditure and thermogenesis and inhibiting obesity.
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    Construction of craniocerebral tissue segmentation model based on texture feature retrieval enhancement
    Li Jinqian, Wang Chao, Dou Zhuangzhuang, Jin Xiaoke, Ruan Shijie, Li Jia
    2026, 30 (6):  1431-1438.  doi: 10.12307/2026.569
    Abstract ( 5 )   PDF (1726KB) ( 0 )   Save
    BACKGROUND: Rapid and accurate segmentation of brain tissue in medical images is of great significance for three-dimensional biomechanical modeling and diagnosis of craniocerebral injuries. Currently, artificial intelligence (AI)-based baseline models exhibit excellent generalization capabilities on large-scale datasets. However, due to the specificity and complexity of craniocerebral tissues, these models have certain limitations in their application to craniocerebral tissue segmentation. Additionally, the scarcity of craniocerebral tissue samples makes it difficult for baseline models to achieve precise segmentation results through fine-tuning.
    OBJECTIVE: To construct a craniocerebral tissue segmentation model based on texture feature retrieval enhancement to improve segmentation accuracy under a small number of samples.
    METHODS: Segment Anything in Medical Images (MedSAM) model was selected as the basic framework, and texture features were combined with deep learning to build a brain tissue segmentation model based on texture feature retrieval enhancement (DP-MedSAM). Dice Coefficient and mean intersection over union (MIoU) were selected to evaluate the efficiency of image segmentation results. In comparison with the original MedSAM model, the ablation experiment systematically evaluated the influence of key components on the model performance. The sensitivities of MedSAM, the Segment Anything Model (SAM) for medical image segmentation (SAM-Med2D) and DP-MedSAM in the mandible, left optic nerve, and left parotid gland were compared.
    RESULTS AND CONCLUSION: (1) By verifying the impact of the number of point prompts on segmentation results on the HaN-Seg dataset, the experimental results indicated that the optimal Dice score was achieved with the addition of three points. (2) DP-MedSAM demonstrated performance improvements compared with MedSAM and SAM-Med2D on two datasets (HaN and Public Domain Database for Computational Anatomy). Especially on the Public Domain Database for Computational Anatomy dataset, in terms of the MIoU metric, DP-MedSAM outperformed MedSAM by 6.59% and SAM-Med2D by 37.35%; in terms of the Dice metric, DP-MedSAM outperformed MedSAM and SAM-Med2D by 4.34% and 25.32%, respectively. (3) The ablation experiment results showed that removing the texture feature extraction module in the DP-MedSAM model, relying solely on original image features, led to a significant decrease in results on the test set. Furthermore, removing the vector cache database and its retrieval enhancement function from the model, which deprived the ability of the model to perform similarity retrieval using an external knowledge base, further reduced model performance. (4) Under conditions of limited data resources, the DP-MedSAM model outperformed the other two models in all evaluation metrics. The DP-MedSAM model performed excellently when processing simple and moderately difficult samples, demonstrating a clear advantage over the other two models and indicating good generalization ability. Processing the fine structures of difficult samples placed higher demands on the model’s segmentation capabilities. Although the performance of the DP-MedSAM model declined slightly, it still outperformed the other two models. (5) This study proposes an innovative craniocerebral tissue segmentation model, DP-MedSAM, which improves the baseline model’s performance in capturing local details and global structural information in medical images by introducing target region texture feature extraction. Through vector similarity retrieval technology, DP-MedSAM can retrieve the feature vector most similar to the current target region from a pre-constructed vector database, providing more precise guiding information for the segmentation process.
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    Effects of EP300 on autophagy and apoptosis related to allergic rhinitis in rats
    Jia Jinwen, Airefate·Ainiwaer, Zhang Juan
    2026, 30 (6):  1439-1449.  doi: 10.12307/2026.601
    Abstract ( 2 )   PDF (8356KB) ( 46 )   Save
    BACKGROUND: As a multifunctional histone acetyltransferase, E1A binding protein P300 (EP300) is widely involved in biological processes such as gene expression regulation, cell growth and differentiation, and has been associated with a variety of inflammatory and immune-related diseases. However, its specific role in the pathogenesis of allergic rhinitis is unclear.
    OBJECTIVE: To explore the changes in gene expression related to allergic rhinitis, analyze its association with programmed cell death, and search for potential biomarkers and therapeutic targets. 
    METHODS: (1) Gene expression data of patients with allergic rhinitis and the control group were collected from the GSE51392, GSE43523 and GSE206149 datasets. Differentially expressed genes were screened and weighted gene co-expression network analysis was performed. (2) From March 2022 to May 2024, 10 patients with allergic rhinitis who underwent vidian neurectomy and 10 healthy controls were recruited from the Fifth Affiliated Hospital of Xinjiang Medical University. Blood and nasal mucosal tissue samples were collected from the patients before and after surgery. (3) A rat model of allergic rhinitis was established and EP300 was knocked down. The rats were divided into control group, model group, model+shEP300-NC group, and model+shEP300 group. ELISA, hematoxylin-eosin staining, RT-qPCR and western blot assay were used to detect the levels of inflammatory factors, pathological changes in nasal mucosal tissues, and the expression of related genes and proteins. 
    RESULTS AND CONCLUSION: (1) A total of 43 intersection genes were identified between allergic rhinitis and the control group. Weighted gene co-expression network analysis revealed that the Green module was strongly correlated with allergic rhinitis. Through intersection analysis with genes related to programmed cell death and common differentially expressed genes, the key gene EP300 was obtained. (2) Compared with the preoperative status of patients with allergic rhinitis, the levels of interleukin-4, interleukin-5, interleukin-13, EP300, LC3B, Beclin1, cleaved-Caspase were significantly decreased, while the expressions of p62 and Bcl2 in nasal mucous tissue were significantly increased after surgery. (3) Compared with the control group, the levels of interleukin-4, interleukin-5, interleukin-13, EP300, LC3B, Beclin1, and cleaved-Caspase were significantly increased, while the expressions of p62 and Bcl2 in nasal mucous tissue were significantly decreased in the model group. Compared with the model group, the above indicators had opposite changes. To conclude, EP300 can participate in allergic rhinitis by regulating inflammation, autophagy and apoptosis.
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    Screening of diagnostic markers for endothelial cell Senescence in mice with radiation-induced heart disease and analysis of immune infiltration
    Lai Jiaming, , Song Yuling, Chen Zixi, Wei Jinghuan, Cai Hao, , Li Guoquan,
    2026, 30 (6):  1450-1463.  doi: 10.12307/2026.573
    Abstract ( 4 )   PDF (6596KB) ( 0 )   Save
    BACKGROUND: Radiotherapy significantly improves survival rates in patients with various malignant tumors. However, with prolonged post-treatment survival, many patients face the risk of radiation-related cardiac toxicity. This is especially true after chest radiotherapy, where the risk of radiation-induced heart disease significantly increases, becoming one of the most severe complications affecting prognosis survival. 
    OBJECTIVE: To identify diagnostic markers of endothelial cellular senescence in radiation-induced heart disease through systematic transcriptomic analysis.
    METHODS: Firstly, genes associated with cellular senescence were screened from the CellAge database and intersected with the transcriptomic training dataset of a mouse model of radiation-induced heart disease to identify differentially expressed senescence-related genes. Secondly, weighted gene co-expression network analysis and machine learning were used to identify key hub genes that play critical roles in radiation-induced heart disease. The expression of these genes was validated using a dataset of radiation-induced endothelial injury. Additionally, the quanTIseq method was employed to assess the immune infiltration status related to radiation-induced heart disease. The expression levels of key genes and their association with survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy were explored through the analysis of The Cancer Genome Atlas database.
    RESULTS AND CONCLUSION: (1) Systematic transcriptomic analysis identified CCND1 as the core gene of endothelial cellular senescence in radiation-induced heart disease, and this finding was validated in the mouse model of radiation-induced heart disease. (2) The diagnostic model constructed from these data indicated that CCND1 had high specificity and sensitivity for diagnosing radiation-induced heart disease. (3) Immune infiltration analysis revealed significant immune response dysregulation in the mouse model of radiation-induced heart disease, and CCND1 was closely related to various immune cells. (4) Kaplan-Meier survival analysis showed that CCND1 was associated with poorer disease-specific survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy. This study systematically uncovers, for the first time, the pivotal role of CCND1 in endothelial cell senescence associated with radiation-induced heart disease. CCND1, a gene integral to cell cycle regulation, can induce cellular senescence when abnormally expressed. Furthermore, the findings highlight its potential as an early diagnostic marker.
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    Main physiological changes in skeletal muscle aging and the multimechanism regulatory role of exercise
    Hou Chaowen, Li Zhaojin, Kong Jianda, Zhang Shuli
    2026, 30 (6):  1464-1475.  doi: 10.12307/2026.571
    Abstract ( 3 )   PDF (2042KB) ( 1 )   Save
    BACKGROUND: Skeletal muscle aging is associated with various chronic diseases. Exercise is considered an important means to delay this process, but the multimechanism regulation of exercise intervention strategies still requires in-depth exploration.
    OBJECTIVE: To systematically outline the main physiological changes in skeletal muscle aging and explore the multiple mechanisms by which exercise regulates these changes, thereby providing a theoretical basis for basic research and clinical applications.
    METHODS: By searching databases such as Web of Science, PubMed, Embase, CNKI, WanFang, and VIP, relevant literature from database inception to October 2024 was retrieved by the first author, including original research articles and reviews. The search terms were “skeletal muscle aging, sarcopenia, exercise regulation, physical activity, chronic inflammation, inflammaging, mitochondrial dysfunction, extracellular matrix fibrosis, lipid mediators, satellite cells” in English and Chinese. Literature was screened based on inclusion and exclusion criteria, and the included 95 articles underwent quality assessment and data extraction.
    RESULTS AND CONCLUSION: (1) The core manifestations of skeletal muscle aging are the decline in muscle mass, strength, and function, closely related to various physiological changes. The decreased protein synthesis capacity and accelerated degradation rate in muscles lead to muscle atrophy and functional decline. Additionally, dysfunction of satellite cells is considered a key factor in the reduced regenerative capacity of muscles. Mitochondrial dysfunction is another important factor leading to muscle fatigue and energy metabolism disorders, directly affecting the metabolic activity and endurance of skeletal muscles. Chronic inflammatory responses and extracellular matrix fibrosis further exacerbate muscle aging. These factors interact synergistically, collectively resulting in skeletal muscle degeneration. (2) Exercise is widely recognized as an important means to delay skeletal muscle aging. Exercise alleviates chronic low-grade inflammatory responses in skeletal muscle by regulating the immune system, increasing the secretion of anti-inflammatory factors, and inhibiting the expression of pro-inflammatory factors, thereby mitigating the damage of inflammation to muscles. Exercise also enhances mitochondrial biogenesis and function, improves the muscle’s energy metabolism capacity, and consequently increases endurance and strength. Furthermore, exercise regulates lipid metabolism and the synthesis of lipid mediators, reduces fat accumulation and alleviates fat-induced inflammatory responses, thereby further protecting skeletal muscles. The mechanical stimulation from exercise promotes the remodeling of the extracellular matrix, reduces fibrosis occurrence, and improves muscle structure and function. Additionally, exercise activates satellite cells, enhancing the regenerative capacity of skeletal muscles, especially notable with strength training and high-intensity interval training. (3) Future research should include large-scale, multicenter clinical trials to evaluate the comprehensive effects of long-term exercise interventions on skeletal muscle aging. By analyzing data from genomics, metabolomics, and other fields, exploring individual differences in responses to exercise interventions can provide more precise theoretical bases for personalized exercise strategies. Besides exercise, the impacts of other interventions such as nutritional supplementation and pharmacological treatments on skeletal muscle aging should not be overlooked. Future studies can explore the combined use of exercise with these interventions to achieve more significant effects.
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    Mitogen-activated protein kinase signaling pathway regulates the development of osteoarthritis: guiding targeted therapy with traditional Chinese medicine
    Li Hao, Tao Hongcheng, Zeng Ping, Liu Jinfu, Ding Qiang, Niu Chicheng, Huang Kai, Kang Hongyu
    2026, 30 (6):  1476-1485.  doi: 10.12307/2026.577
    Abstract ( 3 )   PDF (1572KB) ( 5 )   Save
    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.
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    Potential mechanisms by which exercise regulates iron metabolism in immune inflammatory diseases
    Sun Yaotian, Xu Kai, Wang Peiyun
    2026, 30 (6):  1486-1498.  doi: 10.12307/2026.585
    Abstract ( 5 )   PDF (1481KB) ( 0 )   Save
    BACKGROUND: Abnormal iron metabolism is closely related to immune inflammatory diseases. Exercise intervention is a potentially effective treatment that can reduce inflammation by regulating iron metabolism and improving immune response. However, how exercise regulates immune system function through iron metabolism still needs to be further explored.
    OBJECTIVE: To review and summarize the research progress of iron metabolism in immune inflammatory diseases, analyze the regulatory effect of exercise intervention on iron metabolism and the potential mechanism by which exercise regulates immune inflammatory diseases, thereby providing new ideas for the treatment of immune inflammatory diseases in the future.
    METHODS: The data sources included CNKI and PubMed databases. The retrieval time was from January 2010 to June 2024. The keywords were “iron metabolism, iron homeostasis, hepcidin, immune inflammation, rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), systemic lupus erythematosus (SLE), exercise” in Chinese and English, respectively. Finally, 101 articles were included for review. 
    RESULTS AND CONCLUSION: (1) Abnormal iron metabolism is closely related to the occurrence and development of a variety of immune inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease. Iron overload or iron deficiency can lead to dysfunction of the immune system, and thereby triggers or aggravates the inflammatory response. (2) Exercise intervention is an important means to regulate iron metabolism. Short-term aerobic exercise or strenuous exercise may lead to short-term iron metabolism disorders. Long-term aerobic exercise can promote the recovery of iron homeostasis. Regular aerobic exercise can reduce serum iron concentration, reduce iron storage in liver and muscle, and improve iron distribution in the body. Long-term exercise can help restore the balance of iron metabolism, thereby reducing the inflammatory response caused by iron metabolism disorders. Exercise types such as strength training and flexibility training also have a significant effect on iron metabolism. The effect of exercise on immune diseases has individual differences. Exercise intensity, duration, frequency and other factors may have different effects on iron metabolism. (3) In general, exercise intervention plays a role in the prevention and treatment of immune inflammatory diseases. However, there are still some limitations in the mechanism elucidation, long-term effects and individual differences in the existing studies. In the future, it is necessary to further explore the specific regulatory mechanism of exercise on iron metabolism and the individualized therapeutic effects of different types of exercise.
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    Potential target values of low temperature and cold receptor transient receptor potential M8 and glutamate receptor-3/glutamate receptor ionotropic, kainate 2 in the treatment of hypertension
    Wang Jingfeng, Xia Fan, Mao Sujie, Li Xiaolin
    2026, 30 (6):  1499-1507.  doi: 10.12307/2026.570
    Abstract ( 2 )   PDF (1565KB) ( 3 )   Save
    BACKGROUND: Low temperatures have detrimental effects on the human cardiovascular system, with a higher prevalence of hypertension and related cardiovascular diseases, especially among people living in cold climates. Transient receptor potential M8 (TRPM8) is often recognized as a physiological sensor of environmental cold, and glutamate receptor-3 (GLR-3)/glutamate receptor ionotropic, kainate 2 (GluK2) is also cold-sensitive. However, the specific molecular mechanisms of cold-associated TRPM8 and GLR-3/GluK2 in regulating hypertension remain puzzling. 
    OBJECTIVE: Through a review of the literature in this field, to find out the general pattern of TRPM8 and GLR-3/GluK2 in regulating the body’s cold response, as well as the specific mechanism of action in hypertension, thereby providing a theoretical basis for subsequent research on the treatment of hypertension based on cold-stimulation-related targets, and further expanding the new ideas and methods for the treatment of hypertension. 
    METHODS: We searched, reviewed and screened the relevant literature on “cold stimulation, TRPM8, GLR-3/GluK2 and hypertension” to lay the theoretical foundation for the analysis of the whole article. Comparative analysis method, through reading and analyzing the obtained literature, comparing the similarities and differences between the literature, was performed to provide reasonable theoretical support for the argument. Through further comparative analysis of the literature, the relationship between the relevant indicators was clarified, and the ideas were clarified for the analysis of the full text. 
    RESULTS AND CONCLUSION: (1) TRPM8 can be activated by cold and mainly mediates cool temperature perception in mammals. Its activation can trigger neurogenic inflammatory response and indirectly affect the inflammatory process. Abnormal TRPM8 signal can lead to excessive activation of immune cells, which is significantly associated with the occurrence and development of hypertension. (2) The activation threshold of GLR-3/GluK2 is lower than that of TRPM8, which may preferentially respond to noxious cold stimulation rather than ordinary cool temperature. In cold environment, GLR-3/GluK2 activation enhances sympathetic nerve excitability by regulating interneuron signal transduction and causes peripheral vascular constriction. Long-term effects can lead to increased peripheral vascular resistance. To conclude, TRPM8 and GLR-3/GluK2 are involved in the interaction of the nerve-immune-vascular system by sensing different cold stimuli. Abnormal TRPM8 signaling indirectly promotes the progression of hypertension through inflammation and immune dysregulation, while GLR-3/GluK2 directly exacerbates vascular constriction and resistance by enhancing sympathetic nerve activity. The combination of the two factors may constitute the key molecular mechanism of the occurrence and development of hypertension in cold environment, and provide a potential target for the intervention of cold-related cardiovascular diseases.
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    Mitochondrial mechanism and intervention therapy in diabetic cystopathy
    Lyu Xiaofan, Huang Yi, Ding Liucheng
    2026, 30 (6):  1508-1515.  doi: 10.12307/2026.576
    Abstract ( 0 )   PDF (1172KB) ( 0 )   Save
    BACKGROUND: Mitochondrial dysfunction is a key mechanism underlying the pathogenesis and progression of diabetic cystopathy. Recent studies have suggested that drugs targeting mitochondrial metabolism, oxidative stress, and apoptosis pathways can inhibit bladder tissue degeneration, offering novel therapeutic directions for diabetic cystopathy.
    OBJECTIVE: To explore the association between mitochondrial abnormalities and diabetic cystopathy and to summarize the mechanisms of pharmacological interventions targeting mitochondrial function.
    METHODS: The key words are “mitochondria, diabetes, diabetic cystopathy, diabetic bladder dysfunction, detrusor, urothelium, neuron, peripheral nerves” in Chinese and English. Relevant literature was retrieved from CNKI, WanFang, PubMed, and Web of Science. Selected articles were systematically screened and analyzed.
    RESULTS AND CONCLUSION: During the progression of diabetic cystopathy, mitochondria in detrusor muscle, urothelium, and peripheral nerve cells exhibit alterations in characterization, activity, function, and behavior. Under diabetic conditions, mitochondrial damage leads to increased reactive oxygen species production, increased cytochrome C release, reduced Bcl-2/Bax ratio, enhanced nuclear translocation of apoptosis-inducing factors, and activation of the poly(ADP-ribose) polymerase/c-Jun N-terminal kinase/mitochondrial apoptosis pathway. Mitochondria also act as damage-associated molecular patterns to regulate NLRP3, triggering inflammatory responses. Disrupted mitochondrial energy metabolism involves AMP-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator-1α signaling axis-mediated phenotypic changes, decreased levels of respiratory chain complexes I, II, and IV, impaired oxidative phosphorylation, inhibited tricarboxylic acid cycle, and reduced mitochondrial spare respiratory capacity. Novel therapeutic agents or formulations can ameliorate diabetic cystopathy by alleviating oxidative stress, exerting anti-inflammatory effects, and modulating energy-sensing pathways to restore mitochondrial function. Although mitochondrial roles in other diabetic complications have been extensively studied, research on their involvement in diabetic cystopathy remains insufficient and warrants further exploration.

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    Macrophage autophagy in lung diseases: two-sided effects
    You Huijuan, Wu Shuzhen, Rong Rong, Chen Liyuan, Zhao Yuqing, Wang Qinglu, Ou Xiaowei, Yang Fengying
    2026, 30 (6):  1516-1526.  doi: 10.12307/2026.584
    Abstract ( 1 )   PDF (1888KB) ( 1 )   Save
    BACKGROUND: Macrophages play a key role in the occurrence and progression of lung diseases, and autophagy plays an important role in maintaining environmental homeostasis and functional stability in macrophages. It has been suggested that macrophage autophagic activity has two sides in lung inflammatory diseases.
    OBJECTIVE: To summarize the relationship between macrophage autophagy and lung diseases, thereby providing reference for exploring the prevention and treatment strategies of lung inflammatory diseases by targeting macrophage autophagy.
    METHODS: Literature retrieval was performed in CNKI and PubMed for relevant literature published from database inception to September 2024. The search terms were “macrophage autophagy, efferocytosis, macrophage polarization, acute lung injury, pneumonia, chronic obstructive pulmonary disease, pulmonary fibrosis, asthma” in Chinese and English, respectively. The search results were included or excluded based on the selection criteria, and 100 papers that met the criteria were finally included in the review. 
    RESULTS AND CONCLUSION: (1) The obstruction of autophagy flow will induce the polarization imbalance of macrophages and impair their efferocytosis, resulting in the increase of M1 macrophages and aggravating inflammation. (2) The judgment of autophagic activity should be based on whether the autophagy flow is smooth or not, and it is essential to evaluate the degradation ability of autophagy. Some studies failed to comprehensively detect the degradation ability of autophagy lysosomes to assess whether the autophagy flow is unobtrusive. As a result, the so-called two-sided view of pulmonary macrophage autophagy in pulmonary inflammatory diseases in such studies is actually related to the one-sided judgment of autophagy activity. (3) The pathological manifestations vary across different pulmonary diseases and even at different stages of the same disease. Activation of macrophage autophagy plays a positive role in regulating pulmonary inflammatory homeostasis in conditions such as acute lung injury, infectious pneumonia, mild chronic obstructive pulmonary disease, early-stage pulmonary fibrosis, and secondary asthma. However, in the severe fibrotic stage of chronic obstructive pulmonary disease and the progressive stage of pulmonary fibrosis, the activation of pulmonary macrophage autophagy aggravates pulmonary fibrosis, reflecting the dual nature of macrophage autophagy. In allergic asthma, autophagy is activated in lung-resident macrophages but suppressed in infiltrating monocyte-derived macrophages from circulation. The former is closely related to airway stenosis, and the latter aggravates pneumonia disorders. Therefore, identifying the types and progression stages of lung diseases, along with accurately assessing autophagic activity, is crucial for future investigations into the relationship between macrophage autophagy and disease pathogenesis, thereby facilitating the development of therapeutic strategies in the future.
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    Aging-related dysregulation of glucose metabolism: crossroads of cancer and neurodegenerative diseases
    Liu Huan, Zeng Shaopeng, Chen Jun, He Linqian, Yang Ying, Zhang Jing
    2026, 30 (6):  1527-1538.  doi: 10.12307/2026.603
    Abstract ( 0 )   PDF (1781KB) ( 0 )   Save
    BACKGROUND: Epidemiological studies indicate that individuals with neurodegenerative diseases exhibit a comparatively lower risk of developing the majority of cancers. Although the precise mechanisms underlying this inverse correlation remain unclear, it is noteworthy that aberrant glucose metabolism, a pathological factor common to both conditions, may significantly contribute to this association.
    OBJECTIVE: To review the potential relationship between cancers and neurodegenerative diseases in glucose metabolism.
    METHODS: PubMed was searched for relevant literature using the search terms of “cancer, neurodegenerative diseases, Alzheimer’s disease, Parkinson’s disease, metabolic reprogramming, glucose metabolism, aerobic glycolysis, neuroprotection, aging,” and 136 articles were finally included for analysis.
    RESULTS AND CONCLUSION: Cancer and neurodegenerative diseases exhibit a profound pathological correlation at the level of glucose metabolism imbalance associated with aging. Cancer cells promote uncontrolled proliferation, invasion, and metastasis through the persistent activation of aerobic glycolysis, whereas neurodegenerative diseases are characterized by a reduction in aerobic glycolysis. Restoring aerobic glycolysis may confer neuroprotective effects and delay disease progression. The key nodes of glucose metabolism demonstrate a bidirectional regulatory pattern: metabolic regulators, which are significantly upregulated or aberrantly activated in cancer, are inhibited or functionally inactivated in neurodegenerative diseases. Mitochondria play a crucial role in mediating the aging process through the regulation of reactive oxygen species homeostasis and mitochondrial autophagy. They establish regulatory networks that connect cancer and neurodegenerative diseases, and maintaining their functional homeostasis is of paramount importance for disease prevention and treatment.
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    Effect of repetitive transcranial magnetic stimulation and transcranial direct current stimulation on motor function and gait in children with cerebral palsy: a network meta-analysis
    Cao Xinyan, Yu Zifu, Leng Xiaoxuan, Gao Shiai, Chen Jinhui, Liu Xihua
    2026, 30 (6):  1539-1548.  doi: 10.12307/2026.574
    Abstract ( 1 )   PDF (2642KB) ( 1 )   Save
    OBJECTIVE: Repetitive transcranial magnetic stimulation and transcranial direct current stimulation have shown positive effects in improving gross motor function in children with cerebral palsy. A network meta-analysis was performed to analyze the clinical efficacy of repetitive transcranial magnetic stimulation and transcranial direct current stimulation on the improvement of lower limb motor function and gait in children with cerebral palsy.
    METHODS: Randomized controlled trials (RCT) about repetitive transcranial magnetic stimulation and transcranial direct current stimulation on lower limb motor function and gait in children with cerebral palsy were collected from CNKI, WanFang, VIP, SinoMed, PubMed, Web of Science, Medline. The search time limit was from the inception to October 5, 2024. After screening literature, extracting data and evaluating the risk of bias of included studies, Stata 15.0 software was used for network meta-analysis, AND GRADE profiler was used for quality evaluation. 
    RESULTS: A total of 19 studies were included, involving 4 treatment measures: conventional therapy, high-frequency repetitive transcranial magnetic stimulation, low-frequency repetitive transcranial magnetic stimulation and anodic transcranial direct current stimulation. The results of network meta-analysis showed that in terms of improving gross motor function, low-frequency repetitive transcranial magnetic stimulation [mean difference (MD)=9.48, 95% confidence interval (CI) (6.61,12.34), P < 0.05] was the most effective. In terms of alleviating spasticity, high-frequency repetitive transcranial magnetic stimulation [MD =-0.63, 95% CI (-1.72, 0.45), P < 0.05] had the best efficacy. In terms of improving ankle joint range of motion and step speed, transcranial direct current stimulation [MD=2.27, 95% CI (1.37, 3.17), P < 0.05; MD=0.11, 95% CI (0.05, 0.17), P < 0.05] was the most effective. 
    CONCLUSION: Existing clinical evidence suggests that low-frequency repetitive transcranial magnetic stimulation has the best therapeutic effect compared with other intervention measures in terms of improving lower limb gross motor function. In terms of reducing spasticity, high-frequency repetitive transcranial magnetic stimulation has a more significant effect. In terms of improving gait, transcranial direct current stimulation has more advantages.
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    Potential drug targets for the treatment of rheumatoid arthritis: large sample analysis from European databases
    Guo Ying, Tian Feng, Wang Chunfang
    2026, 30 (6):  1549-1557.  doi: 10.12307/2026.575
    Abstract ( 1 )   PDF (1515KB) ( 4 )   Save
    BACKGROUND: Rheumatoid arthritis is influenced by complex genetic and environmental factors. Although observational studies have found some correlation between plasma proteins and rheumatoid arthritis, the susceptibility to confounding and reverse causation makes it difficult to clarify whether these proteins are pathogenic factors of rheumatoid arthritis.
    OBJECTIVE: To explore the potential of plasma proteins as biomarkers and therapeutic targets in rheumatoid arthritis through Mendelian randomization analysis of plasma proteins in the onset and progression of rheumatoid arthritis.
    METHODS: A large-scale two-sample Mendelian randomization analysis was conducted to comprehensively assess the causal relationships between 1 553 circulating proteins and rheumatoid arthritis based on the Decode database (developed by Decode Genetics in Iceland, which contains genomic data from the Icelandic population), the MR-Base platform (developed by a team of researchers at the University of Oxford in the United Kingdom, specifically designed to provide genetic and phenotypic data for Mendelian randomization analyses), and the GWAS Catalog platform (developed by the European Institute of Bioinformatics, which provides data for genome wide association studies worldwide). The causal effects were estimated using the Wald ratio and inverse variance weighting methods, with Bonferroni correction applied to control for false positives caused by multiple testing. To ensure the robustness of the results, sensitivity analyses were performed to validate the positive causal relationship between circulating proteins and rheumatoid arthritis, and Bayesian colocalization and phenome scanning were used to exclude confounding effects and horizontal pleiotropy. Additionally, external validation was carried out using new plasma protein datasets to reduce the likelihood of false discoveries. Finally, small-molecule compounds associated with candidate proteins were identified using the Drug Signatures Database (DsigDB), and molecular docking was performed to predict the binding patterns and energies between proteins and compounds, identifying the most stable and likely binding molecules and mechanisms.
    RESULTS AND CONCLUSION: (1) Sensitivity analyses, including Bayesian colocalization and phenome scanning, identified four plasma proteins with reliable causal relationships with rheumatoid arthritis: FCRL3, IL6R, ICOSLG, and TNFAIP3. Their genetic effects were estimated as follows: FCRL3 [odds ratio (OR)=1.12, 95% confidence interval (CI): 1.07–1.17], IL6R (OR=0.94, 95% CI: 0.91–0.96), ICOSLG (OR=2.42, 95% CI: 1.67–3.52), and TNFAIP3 (OR=2.19, 95% CI: 1.88–2.56). Furthermore, molecular docking analysis revealed that the small-molecule compound benzo[a]pyrene exhibited favorable binding with these candidate proteins, suggesting its potential as a therapeutic agent for rheumatoid arthritis. (2) This study provides a comprehensive analysis of the genetic causal relationships of FCRL3, IL6R, ICOSLG, and TNFAIP3 in rheumatoid arthritis. These proteins not only serve as potential molecular biomarkers for rheumatoid arthritis risk screening and disease prevention, but also offer key candidate targets for further understanding the pathogenic mechanisms of rheumatoid arthritis and developing targeted therapies. Although the study is based on European populations, its findings offer important insights for biomedical research in China. By incorporating Mendelian randomization methods to analyze genetic causality, future research on rheumatoid arthritis in the Chinese population could provide more accurate causal inferences, offering theoretical support for localized risk assessment and treatment strategies.
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    Visualization analysis of literature on the effect of lipid metabolism on osteoporosis
    Huang Jie, Zeng Hao, Wang Wenchi, Lyu Zhucheng, Cui Wei
    2026, 30 (6):  1558-1568.  doi: 10.12307/2026.593
    Abstract ( 2 )   PDF (4087KB) ( 43 )   Save
    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.
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    DYRK2: a novel therapeutic target for rheumatoid arthritis combined with osteoporosis based on East Asian and European populations
    Wu Zhilin, , He Qin, Wang Pingxi, Shi Xian, Yuan Song, Zhang Jun, Wang Hao
    2026, 30 (6):  1569-1579.  doi: 10.12307/2026.609
    Abstract ( 0 )   PDF (7793KB) ( 0 )   Save
    BACKGROUND: Studies have shown that rheumatoid arthritis and osteoporosis are positively correlated, but the causal relationship and related mechanisms have not yet been confirmed. With the cross-fertilization of computer science and life sciences, Mendelian randomization and bioinformatics analyses based on genome-wide association study (GWAS) and transcriptome sequencing data can assess the causal relationship between two diseases, explore the related mechanisms, and mine the therapeutic targets, which will be beneficial to the precision treatment of rheumatoid arthritis combined with osteoporosis. 
    OBJECTIVE: To explore the causal relationship between rheumatoid arthritis and osteoporosis using two-sample Mendelian randomization and to mine potential co-morbid targets and potential targeted drugs through summary-data-based Mendelian randomization and bioinformatics analyses, aiming to provide theoretical basis for mechanism exploration and precision treatment in the field of rheumatoid arthritis combined with osteoporosis. 
    METHODS: (1) Firstly, GWAS data of rheumatoid arthritis, osteoporosis, and cis-expression quantitative trait locus (cis-eQTL) in Asian and European populations were downloaded from the GWAS Catalog, IEU Open GWAS, FinnGen, and eQTLGen databases, and were used for two-sample Mendelian randomization analysis and summary-data-based Mendelian randomization analysis. (2) Transcriptome sequencing data of rheumatoid arthritis (GSE93272 and GSE15573) were downloaded from the GEO database for bioinformatics analysis. (3) Subsequently, forward and inverse Mendelian randomization analyses between rheumatoid arthritis and osteoporosis were performed, and inverse variance weighted was used as the main metric for the analyses, and the results were corroborated with MR Egger, simple mode, weighted median and weighted mode. (4) Then, the genes closely related to rheumatoid arthritis and osteoporosis were identified based on the summary-data-based Mendelian randomization analysis, and the co-disease targets of rheumatoid arthritis and osteoporosis were mined based on cross-analysis. Meanwhile, the biological functions of the co-morbid targets were verified based on bioinformatics analysis and cellular experiments. (5) In addition, a rheumatoid arthritis risk prediction nomogram was constructed based on DYRK2, and its prediction performance was verified by receiver operating characteristic curve, correction curve and decision curve. Finally, the target potential drugs were mined based on Enrichr database and molecular docking was performed. 
    RESULTS AND CONCLUSION: (1) Forward Mendelian randomization analysis of rheumatoid arthritis and osteoporosis showed statistically significant results except for GCST90044540 and GCST90086118, and all other results indicated a significant causal relationship and positive correlation between rheumatoid arthritis and osteoporosis. (2) Inverse Mendelian randomization analysis suggested that no significant causal relationship was seen between osteoporosis and rheumatoid arthritis. (3) Summary-data-based Mendelian randomization analysis identified a total of 412 and 344 genes positively associated with rheumatoid arthritis and osteoporosis, and 421 and 347 genes negatively associated. Based on the cross-analysis, 26 co-morbid genes were subsequently obtained. Among them, DYRK2 was a potential therapeutic target, and subsequent bioinformatics analysis and cellular experiments confirmed its important role in the progression of rheumatoid arthritis and osteoporosis. (4) Furthermore, the constructed nomogram has excellent predictive performance. Finally, four potential DYRK2-targeting drugs (undecanoic acid, metyrapone, JNJ-38877605, and ACA) were discovered and molecular docking also demonstrated reliable targeting ability. (5) In conclusion, based on GWAS data from Asian and European populations, we successfully demonstrated that rheumatoid arthritis and osteoporosis are causally related at the genetic level, DYRK2 is a potential therapeutic target, and four small molecules are potential target drugs.
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    Bibliometric and visual analysis of the research status and trends of senescence in osteoporosis
    Zhang Haiwen, Zhang Xian, Xu Taichuan, Li Chao
    2026, 30 (6):  1580-1591.  doi: 10.12307/2026.594
    Abstract ( 0 )   PDF (4446KB) ( 10 )   Save
    BACKGROUND: Cellular senescence, which triggers the aging process of physiological decline in the body, is closely related to osteoporosis. With the development of aging research, significant progress has been made in the study of targeted clearance of senescent cells. Accordingly, senolytic cell therapy for osteoporosis based on this has attracted increasing attention. Current research on the association between aging and osteoporosis shows the characteristic of multidisciplinary intersection. However, existing reviews are mostly based on a single database (such as PubMed) and lack a systematic comparative analysis of Chinese and English literature. Therefore, it is of great academic value to integrate resources from multiple databases and systematically reveal the research status and hot trends of aging in the field of osteoporosis research.
    OBJECTIVE: To summarize the development, current status, hotspots, and future trends of research on aging in the field of osteoporosis over the past 20 years, so as to provide references for future related research.
    METHODS: We searched for research literature on the correlation between aging and osteoporosis in CNKI, WanFang, VIP and Web of Science Core Database. The search time span was from August 1, 2004 to September 24, 2024. Then, we used NoteExpress 4.0 for data cleaning and CiteSpace 6.3R1 (Advanced) and Excel (2024) for literature analysis.
    RESULTS AND CONCLUSION: Since 2004, research on the correlation between aging and osteoporosis has shown a significant growth trend. Bibliometric analysis shows that (as of September 2024), and 1 275 English documents and 151 Chinese documents have been published, with the highest number of publications in China and the United States. In terms of publishing institutions, the Mayo Clinic ranked first, followed by Shanghai Jiao Tong University and the University of California system. As for core authors, Sundeep Khosla and Joshua Nicholas Farr were the authors with the most publications and citations, while Pei Lingpeng and Hui Bodi were the most worthy of attention in Chinese literature. After the keywords “aging” and “osteoporosis” and their synonyms were excluded, it was found that cellular senescence, senescence-associated secretory phenotype, signaling pathways, and targeted senolytic cell clearance therapy haven been the current research hotspots and theoretical frontiers.
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    Potential target genes for spondylolisthesis: drugable genome analysis based on the European population-based biodatabase
    Zhang Qingfeng, Wang Chaoyi, Yang Jingyan, Li Hanyu, Zhao Yuyang, Hao Huatao, Yu Dong
    2026, 30 (6):  1592-1601.  doi: 10.12307/2026.595
    Abstract ( 0 )   PDF (4395KB) ( 7 )   Save
    BACKGROUND: Spondylolisthesis is a common disease, and there is a lack of effective drugs to treat it. There is still a need to further define the pathogenesis and screen out more suitable therapeutic targets for spondylolisthesis. Mendelian randomization analysis can be used to explore the drugable genes associated with spondylolisthesis and provide valuable guidance for the development of more effective and targeted therapeutic drugs.
    OBJECTIVE: To explore potential therapeutic targets and effective drugs for spondylolisthesis by means of pharmaceutically available genome-wide Mendelian randomization analysis.
    METHODS: Using the Finnish database, eQTLGen consortium, drug signature database, drug-gene interaction database, protein-protein interaction database, organic small molecule biological activity database and protein structure database, which contains genome and health information of half a million Finns, data on druggable genes were subjected to two-sample Mendelian randomization analysis and co-localization analysis with data from genome-wide association studies of spondylolisthesis to identify genes highly associated with spondylolisthesis. In addition, GO and KEGG enrichment analysis, protein network construction, drug prediction and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic agents. 
    RESULTS AND CONCLUSION: In this study, we identified 34 potential drug target genes that were significantly associated with spondylolisthesis, particularly the gene APOBEC3G. This gene showed a significant association with spondylolisthesis outcomes through Mendelian analysis and co-localization analysis, suggesting that APOBEC3G may be a priority therapeutic target. As for other potential mechanisms and drugs, we still need to conduct more in-depth research to determine their roles. This study used a database from a European population, which can be used as a reference for the study of population genetics in China.
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    Causal relationship between age-related macular degeneration and deep vein thrombosis: analysis based on genome-wide association study data
    Liu Hongtao, Wu Xin, Jiang Xinyu, Sha Fei, An Qi, Li Gaobiao
    2026, 30 (6):  1602-1608.  doi: 10.12307/2026.596
    Abstract ( 1 )   PDF (1517KB) ( 2 )   Save
    BACKGROUND: Age-related macular degeneration and deep vein thrombosis may share common pathophysiological mechanisms, but there is a lack of direct evidence regarding their relationship. Traditional studies are confounded by confounding factors and reverse causation.
    OBJECTIVE: To investigate the causal relationship between age-related macular degeneration and deep vein thrombosis based on Mendelian randomization design. 
    METHODS: Through a two-way Mendelian randomization analysis, single nucleotide polymorphisms of exposure and outcomes were obtained from publicly available genome-wide association studies, with deep vein thrombosis data from the FinnGen database in a European population with a sample size of 363 612 and 1 048 575 single nucleotide polymorphisms. In addition, we obtained data on age-related macular degeneration from the IEUOpenGWAS project, also from a European population sample of 105 248 cases covering 11 304 110 single nucleotide polymorphisms. In R4.4.1, we used the TwoSampleMR package (version 0.6.8) to explore the causal effects of exposure factors on outcomes. At the same time, we also conducted a sensitivity analysis via MR-Egger regression, weighted median, weighted model and simple model methods to ensure that the assessment results were robust and reliable. In addition, we used the “heterogeneity” function to test for heterogeneity, and the “horizontal pleiotropy” function and the MR-PRESSO test to further assess horizontal pleotropy. The Cochran’s Q test was used to determine whether there was statistical heterogeneity between single nucleotide polymorphisms, and the leave-one-out method was used to assess whether single nucleotide polymorphisms would significantly interfere with Mendelian randomization analysis. Funnel plots were drawn to assess the potential bias of single nucleotide polymorphisms. Forest plots were plotted to show the effect estimates of single nucleotide polymorphisms on exposure and outcomes, and their confidence intervals were plotted. Scatter plots were plotted to evaluate the relationship between the potency of single nucleotide polymorphisms and their causal effect size on outcome estimates. 
    RESULTS AND CONCLUSION: Both forward and reverse studies showed that there was no causal association between age-related macular degeneration and the occurrence of deep vein thrombosis (P > 0.05). Sensitivity analysis showed that the main analysis results were reliable and robust, with no outliers, heterogeneity, and horizontal pleiotropy, and no single nucleotide polymorphism significantly affected the overall effect estimate. Although it is based on European population data, it has methodological reference value for Chinese biomedical research on complex disease associations. In this field, China can carry out multi-center large-sample studies, accurately analyze the internal links between Chinese population-related diseases, and provide a basis for prevention and treatment strategies and clinical practice.
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