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    08 February 2026, Volume 30 Issue 4 Previous Issue    Next Issue
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    Triptolide in the treatment of osteoarthritis: network pharmacology analysis and animal model validation
    Chen Yixian, Chen Chen, Lu Liheng, Tang Jinpeng, Yu Xiaowei
    2026, 30 (4):  805-815.  doi: 10.12307/2026.549
    Abstract ( 84 )   PDF (4054KB) ( 130 )   Save
    BACKGROUND: Osteoarthritis is a chronic degenerative disease of the joints that can lead to disability. Its main pathological features are persistent inflammation and cartilage destruction. Triptolide has been used to treat a variety of chronic joint diseases. However, the mechanism of triptolide in the treatment of osteoarthritis has not been clarified
    OBJECTIVE: To identify the effective targets of triptolide in the treatment of osteoarthritis by network pharmacology, and to investigate the therapeutic effect of triptolide on osteoarthritis in the osteoarthritis model.
    METHODS: Network pharmacology was used to anticipate the potential targets and signaling pathways of triptolide in the treatment of osteoarthritis, and molecular docking technology was used to validate the core targets. A rat osteoarthritis model was established by anterior cruciate ligament transection. Eight weeks after modeling, the rats were administered with triptolide and sodium hyaluronate by intra-articular injection for 6 weeks. After 6 weeks of intervention, the pathological changes in rat knee joints were observed by hematoxylin-eosin staining and safranin O-fast green staining. The levels of inflammatory factors in rat serum were detected by enzyme-linked immunosorbent assay. The expression of aggrecan, type I platelet-responsive protein-containing desmoglein metalloproteinase 5, type II collagen and matrix metalloproteinase 13 proteins in rat articular cartilage was tested by immunohistochemical staining.
    RESULTS AND CONCLUSION: (1) The results of network pharmacology indicated that the target of triptolide may be related to the inhibition of the release of factors such as interleukin 6, tumor necrosis factor ɑ, interleukin 1β, matrix metalloproteinase 9, and the over-activation of the nuclear factor-κB/JAK2-STAT3 signaling pathway. (2) Triptplide could reduce the degree of joint swelling in osteoarthritic rats; pathologically improve the articular cartilage and maintain the cartilage structure; decrease the serum levels of interleukin 6, tumor necrosis factor ɑ, interleukin 1β, matrix metalloproteinase 9, and matrix metalloproteinase 3 in osteoarthritic rats; reduce the protein expression of matrix metalloproteinase 13 and type I platelet-responsive protein-containing desmoglein metalloproteinase 5 in the articular cartilage; and increase the expression of type II collagen and aggrecan in the cartilage, thereby achieving cartilage protection. 
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    Effect and mechanism by which Pterocarya hupehensis skan total flavonoids regulates the proliferation, migration and apoptosis of fibroblast-like synoviocytes
    Bao Zhuoma, Hou Ziming, Jiang Lu, Li Weiyi, Zhang Zongxing, Liu Daozhong, Yuan Lin
    2026, 30 (4):  816-823.  doi: 10.12307/2026.547
    Abstract ( 87 )   PDF (2183KB) ( 8 )   Save
    BACKGROUND: Studies have confirmed that Pterocarya hupehensis skan total flavonoids (PHSTF) can improve the level of collagen-induced arthritis in rats, but there is still a lack of research on the regulation of Wnt/β-catenin signaling pathway in fibroblast-like synoviocytes and its effect on related cell functions.
    OBJECTIVE: To investigate the effect and mechanism of PHSTF on lipopolysaccharide-induced proliferation, migration and apoptosis of fibroblast-like synoviocytes based on the Wnt/β-catenin signaling pathway
    METHODS: Fibroblast-like synoviocytes were divided into control group, lipopolysaccharide group, lipopolysaccharide + low-, medium-, and high-dose PHSTF groups (10, 20, and 40 μg/mL), lipopolysaccharide + Wnt pathway inhibitor DKK1 group, and lipopolysaccharide + Wnt pathway inhibitor DKK1 + high-dose PHSTF group (40 μg/mL). The cell counting kit-8 method was used to detect the effect of PHSTF on the viability of fibroblast-like synoviocytes, and the final drug concentration and time were screened. Flow cytometry was used to detect the apoptosis of fibroblast-like synoviocytes. Cell scratch assay, EDU staining and cell cloning assay were used to detect the migration and proliferation of fibroblast-like synoviocytes. Western blot assay was used to detect the protein expression levels of Wnt3a, β-catenin, tumorigenic genes, matrix metalloproteinase 2, matrix metalloproteinase 9, Bax and Bcl-2 in fibroblast-like synoviocytes.
    RESULTS AND CONCLUSION: (1) Compared with the control group, the cell viability decreased significantly when the concentration of PHSTF was > 40 μg/mL 
    (P < 0.01). Therefore, the drug concentration of ≤ 40 μg/mL was selected for subsequent experiments. (2) Compared with the lipopolysaccharide group, the wound healing rate, cell clone formation rate and the number of EDU-positive cells in the low-, medium- and high-dose PHSTF groups were significantly reduced, while the apoptosis rate was significantly increased (P < 0.05-0.01). (3) Western blot results showed that compared with the lipopolysaccharide group, low-, medium- and high-dose PHSTF significantly inhibited cellular Wnt3a, β-catenin, cellular tumorigenic genes, matrix metalloproteinase 2, matrix metalloproteinase 9, and Bcl-2 protein expression, and promoted the expression of Bax protein (P < 0.01). (4) Compared with the DKK1 group, the combination of DKK1 and high-dose PHSTF significantly inhibited the protein expression of Wnt3a, β-catenin, matrix metalloproteinase 2, matrix metalloproteinase 9 and Bcl-2 protein expression and promoted the protein expression of Bax (P < 0.01). To conclude, PHSTF may inhibit the proliferation and migration of fibroblast-like synoviocytes and promote apoptosis by inhibiting the Wnt/β-catenin signaling pathway. 
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    Effect of type 2 diabetes mellitus on orthodontic tooth movement and bone microstructure parameters on the tension side in rats
    Yan Chengbo, Luo Qiuchi, Fan Jiabing, Gu Yeting, Deng Qian, Zhang Junmei
    2026, 30 (4):  824-831.  doi: 10.12307/2025.994
    Abstract ( 105 )   PDF (1737KB) ( 36 )   Save
    BACKGROUND: Bone remodeling is the biological basis of orthodontic tooth movement. Type 2 diabetes mellitus leads to metabolic changes in the jaw and alveolar bone, so it is hypothesized that tooth mobility characteristics may be altered in a high-sugar environment.
    OBJECTIVE: To explore the impact of type 2 diabetes mellitus on orthodontic tooth movement in rats within one tooth movement cycle.
    METHODS: Seventy-two Sprague-Dawley rats were selected. Forty rats were randomly chosen and fed with a high-fat diet to construct a type 2 diabetes mellitus model. Thirty-two rats that were successfully modeled were randomly divided into a type 2 diabetes mellitus group (n=16) and a diabetic orthodontic group (n=16). The remaining 32 rats were randomly divided into a control group (n=16) and an orthodontic group (n=16). The rats in the orthodontic group and the diabetic orthodontic group were equipped with nickel-titanium coil spring orthodontic force application devices to move the unilateral maxillary first molars mesially with a force of 50 g. The rats were anesthetized and sacrificed on the 3rd, 7th, 14th, and 21st days after orthodontic treatment, and Micro-CT was used to measure the mesial displacement of the first molars and detect the changes in the bone microstructure parameters on the tension side.
    RESULTS AND CONCLUSION: There were significant differences in the tooth movement distances among the four groups of rats on the 3rd, 7th, 14th, and 21st days of orthodontic treatment (P < 0.05). There were significant differences in bone mineral density, bone volume fraction and trabecular bone separation on the tension side among the four groups on the 7th, 14th, and 21st days of orthodontic treatment (P < 0.05). There were differences in the trabecular thickness among the four groups on the 3rd and 14th days of orthodontic treatment (P < 0.05). The diabetic orthodontic group had the smallest tension-side alveolar bone mineral density, bone volume fraction, and trabecular thickness, and the largest tooth movement distance and trabecular separation on the 21st day of orthodontic treatment. The above results indicate that type 2 diabetes mellitus adversely affects bone microstructural parameters on the tension side in orthodontic tooth movement in rats, suggesting the occurrence of an osteoporotic state.
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    Three-dimensional finite element analysis of mandibular second molar mesial movement by clear aligner
    Qiu Shenglei, Li Daokun, Wang Chunjuan, Li Na
    2026, 30 (4):  832-840.  doi: 10.12307/2026.505
    Abstract ( 79 )   PDF (5473KB) ( 13 )   Save
    BACKGROUND: Orthodontic treatment to move the mandibular second molar in place of the missing first molar is a good method for preserving natural teeth. However, molars often exhibit mesial tipping when using clear aligners. The impact of attachments and overcorrection on the molar mesialization with clear aligners is unclear.
    OBJECTIVE: To investigate the effects of attachments and overcorrection on displacement and biomechanics of the mandibular second molar mesialization.
    METHODS: A finite element model with the left mandibular first molar missing was constructed using a volunteer's cone-beam CT and intraoral scan data. The experiment was divided into four groups based on the position of attachments on the left mandibular second molar: without attachment, buccal attachment, lingual attachment, and buccal-lingual attachment, with overcorrection degrees (0°, 1°, 2°, 3°, and 4°) for each group, totaling 20 models. The calculation and analysis of the displacement trends and stress were performed using Abaqus software.
    RESULTS AND CONCLUSION: (1) Mesial tipping and intrusion of the molar, distal tipping of the canines and permolars, and linguaing of the incisors occurred during molar mesialization. (2) The displacement of molars increased when attachments were used, with the maximum displacement occurring when buccal-lingual attachments were applied. Molars tended to tip towards the side without attachments when attachments were designed unilaterally. However, the inclination of molars did not decrease when attachments were used. (3) Molars exhibited reduced mesial tipping and intrusion, approaching overall movement, and the stress of periodontal ligament was relieved and more evenly distributed during overcorrection treatment, and this effect became more pronounced with increased degrees of overcorrection. (4) Attachments can enhance the effectiveness of overcorrection, with the best performance observed when buccal-lingual attachments are used. Using attachments and overcorrection together helps control molar mesial tipping and intrusion, but overall molar movement is not achieved.
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    Application of Onlay bone grafts from mandibular lateral oblique line in implant restoration of bone defects in upper anterior teeth
    Xu Shencong, Fang Zifei, Ji Mingyi, Xu Chengrui, Li Binhong, Cao Jiayu, Xu Junfeng
    2026, 30 (4):  841-848.  doi: 10.12307/2025.959
    Abstract ( 71 )   PDF (1683KB) ( 205 )   Save
    BACKGROUND: With the development of oral implantology, implant restoration has gradually become the first choice of restoration after missing teeth, and bone augmentation procedures have led to the expansion of implant indications and the improvement of the success rate of implant restoration. However, the long-term stability of bone height, width and volume after bone augmentation surgery has been one of the clinical difficulties for oral implantologists.
    OBJECTIVE: To measure and analyze the bone width, height, and volume of different sites in the bone augmentation area at different time points using cone-beam CT and an automatic image alignment program.
    METHODS: Seventeen patients with severe bone defects in the upper anterior region who underwent Onlay bone block grafting in the external oblique region were recruited from the Department of Stomatology, Zhejiang Tongde Hospital. There were 10 males and 7 females, with a mean age of (45.88±12.47) years. The cone-beam CT scans of the patients' Onlay bone grafts were taken at five time points: preoperatively, immediately postoperatively, 6 months postoperatively, immediately post implantation, and 6 months post implantation, and then were statistically analyzed for alveolar bone volume, width, and height in the bone augmentation area, as well as for the difference in the alveolar bone volume of the bone incremental area between patients of different sexes and age.
    RESULTS AND CONCLUSION: (1) The alveolar bone volume in the bone augmentation area was higher immediately and 6 months after bone grafting than before bone grafting (P < 0.05) as well as was higher immediately after bone grafting than 6 months after bone grafting (P < 0.05). The alveolar bone height in the bone augmentation area was higher immediately and 6 months after bone grafting than before bone grafting (P < 0.05). The horizontal width of the alveolar bone at various sites in the bone augmentation area immediately and 6 months after bone grafting was higher than that before bone grafting (P < 
    0.05). (2) There was no significant difference in the volume of bone graft resorption at various sites in the bone augmentation area between males and females immediately and 6 months after bone grafting (P > 0.05). Pearson correlation analysis showed a positive correlation between age and the change in bone augmentation area volume immediately and 6 months after bone grafting, but the difference was not statistically significant (P > 0.05). (3) Twenty-five dental implants with completed implant restorations functioned normally, and the survival rate of the implants was 100%. To conclude, Onlay bone graft implant restoration in the upper anterior region can significantly improve insufficient bone with favorable outcomes. However, there is some amount of bone resorption in the bone augmentation area at 6 months after Onlay bone grafting and it is necessary to open up the second surgical area. Clinicians should consider different bone augmentation procedures in accordance with the specific circumstances. 
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    A prediction model for sarcopenia in postmenopausal women: information analysis based on the China Health and Retirement Longitudinal Study database
    Li Guangzheng, Li Wei, Zhang Bochun, Ding Haoqin, Zhou Zhongqi, Li Gang, Liang Xuezhen
    2026, 30 (4):  849-857.  doi: 10.12307/2025.986
    Abstract ( 104 )   PDF (1720KB) ( 105 )   Save
    BACKGROUND: Sarcopenia is an age-related systemic skeletal muscle disease, which is associated with a variety of adverse outcomes such as falls, functional decline, frailty, and death. Postmenopausal women are one of the high-risk groups for sarcopenia. 
    OBJECTIVE: To develop a predictive model for assessing the risk of sarcopenia in Chinese postmenopausal women based on high-quality database.
    METHODS: Data for this study were derived from 2 370 postmenopausal women from the China Health and Retirement Longitudinal Study (CHARLS), and sarcopenia was assessed using the Asian Working Group on Sarcopenia 2019 (AWGS2019) recommended metrics. The study cohort was randomized into a training set (70%) and a validation set (30%). Risk factors for sarcopenia in postmenopausal women were screened using the least absolute shrinkage and selection operator, ten-fold cross-validation, and logistic regression. Nomogram predicting the risk of sarcopenia in postmenopausal women was constructed based on the risk factors, and the model efficacy was evaluated by the receiver operating characteristic curve and area under the curve (AUC), calibration curve, and decision curve analysis.
    RESULTS AND CONCLUSION: The prevalence of sarcopenia in this study was 23.50% and age, place of residence, sleep quality, cognitive function, depression, and the number of chronic diseases were selected as predictors of sarcopenia in postmenopausal women. The nomogram model showed good discrimination between the training and validation sets, with an AUC value of 0.751 (95% confidence interval=0.724-0.778, P < 0.001), a specificity of 72.2%, and a sensitivity of 63.2% in the training set, and an AUC value of 0.763 (95% confidence interval=0.721-0.805, P < 0.001), with a specificity of 69.6% and a sensitivity of 70.8%. The calibration curve showed a relatively significant agreement between the nomogram model and the actual observations, and the decision curve analysis demonstrated broad and good clinical utility. To conclude, the nomogram to assess the risk of sarcopenia constructed based on age, place of residence, sleep quality, cognitive function, depression, and number of chronic diseases, provides an effective tool for identifying and eliminating risk factors for sarcopenia in Chinese postmenopausal women, and helps to reduce the incidence of sarcopenia.
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    Expression and significance of tumor necrosis factor alpha, nuclear factor kappaB and ionized calcium binding adaptor molecule-1 in the hippocampus of mice with aortic dissection
    Ma Hong, Ding Xueling, Wang Qi, Lyu Hui, Asya Albusm, Cheng Xinyi, Ma Xiang
    2026, 30 (4):  858-863.  doi: 10.12307/2025.958
    Abstract ( 72 )   PDF (1783KB) ( 51 )   Save
    BACKGROUND: Hippocampal injury caused by aortic coarctation has been poorly studied, and combined detection of tumor necrosis factor α, nuclear factor κB and ionized calcium binding adaptor molecule-1 expression in aortic dissection has not been reported.
    OBJECTIVE: To observe histomorphologic changes in the hippocampus of a mouse model of aortic dissection and investigate the expression and significance of tumor necrosis factor alpha, nuclear factor kappaB and ionized calcium binding adaptor molecule-1 in the hippocampus of aortic dissection mice.
    METHODS: Sixteen healthy 3-week-old male C57BL/6 mice were randomly divided into two groups: control group and aortic dissection group, with eight mice in each group. In the aortic dissection group, mice were given β-aminopropionitrile monofumarate as drinking water for 4 weeks, and the angiotensin II microinfiltration pump was then implanted to establish an animal model of aortic dissection. Mice in the control group were given normal diet and water. After the model was established, the maximum diameter of the ascending aorta was measured, hematoxylin-eosin staining and EVG staining were performed to evaluate the model formation rate, and the levels of inflammatory factors tumor necrosis factor α and interleukin 6 in serum were detected by enzyme-linked immunosorbent assay. The hippocampus was dissected and stained with hematoxylin-eosin to observe the pathological changes of the hippocampus in brain sections. The protein expression of tumor necrosis factor α, nuclear factor κB and ionized calcium binding adaptor molecule-1 was detected by western blot analysis.
    RESULTS AND CONCLUSION: (1) Compared with the control group, the maximum diameter of the ascending aorta in the aortic dissection group was significantly enlarged. (2) Hematoxylin-eosin staining of the aorta showed obvious thickening of the middle aorta and destruction and disorder of the aortic wall structure in mice. Neurons in the CA1 and CA3 regions of mice were sparsely arranged, reduced in size, and showed pyknosis with deeply stained nuclei. (3) Serum levels of inflammatory factors tumor necrosis factor α and interleukin 6 were increased in the aortic dissection group compared with the control group (P < 0.01). (4) The expression levels of tumor necrosis factor α, nuclear factor κB, phosphorylated nuclear factor κB, and ionized calcium binding adaptor molecule-1 in the hippocampus were increased in the aortic dissection group compared with the control group (P < 0.05). To conclude, microglial activation and increased expression of tumor necrosis factor α and nuclear factor κB may be involved in hippocampal neuron injury in aortic dissection mice. 
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    Constructing a rat animal model of pelvic organ prolapse: a comparison of three modeling methods
    Yang Jing, Wang Houmei, Wang Yi, Song Min, Ren Jie, Dai Lujun, Xiao Ziwen
    2026, 30 (4):  864-872.  doi: 10.12307/2025.987
    Abstract ( 77 )   PDF (3468KB) ( 73 )   Save
    BACKGROUND: Currently, there are many modeling methods for pelvic organ prolapse animal models, and the commonly used methods are vaginal balloon dilatation, oophorectomy and the combination of the two. There is no study comparing the three modeling methods in detail.
    OBJECTIVE: To construct and validate a rat animal model of pelvic organ prolapse using three different methods and to identify the advantages and disadvantages of various models.
    METHODS: Seventy-two 8-week SPF-grade female Sprague-Dawley rats were selected and randomly divided into four groups, namely, vaginal balloon dilatation group, ovariectomy group, ovariectomy combined with vaginal balloon dilatation group (the combined group), and the sham-operated group (no ovariectomy and no vaginal dilatation). The vaginal wall tissues of rats were collected at 4, 8 and 12 weeks after the operation for hematoxylin-eosin staining, Masson staining, EVG staining and immunohistochemical staining of α-smooth muscle actin, Vimentin and matrix metalloproteinase 9 detection, and the pelvic floor muscle tissues were taken at 4, 8 and 12 weeks after the operation for hematoxylin-eosin staining, Masson staining and EVG staining.
    RESULTS AND CONCLUSION: (1) Hematoxylin-eosi staining showed that there was no significant difference in the decrease of vaginal epithelial layer thickness in the vaginal balloon dilatation group compared with the sham-operated group,  (P > 0.05), while the thickness of the vaginal epithelial layer was significantly reduced in the ovariectomy group and the ovariectomy combined with vaginal balloon dilation group (P < 0.001), and the reduction was more significant in the ovariectomy combined with vaginal balloon dilation group, remained stable at 8 weeks after surgery and lasted until 12 weeks.  (2) The changes in the content of collagen fibers and elastic fibers in the vaginal wall stained by Masson and EVG staining were the same as the changes in the thickness of the vaginal epithelial layer stained by hematoxylin-eosin, and there were no changes in collagen fibers and elastic fibers in the pelvic floor muscle tissues of the treatment groups. (3) At 4, 8 and 12 weeks after treatment, there was no significant difference in the expression levels of α-smooth muscle actin, Vimentin and matrix metalloproteinase 9 in the vaginal wall tissue of the balloon dilation group compared with the control group (P > 0.05), whereas the expression levels of α-smooth muscle actin and Vimentin were significantly decreased in the ovariectomy group and ovariectomy combined with vaginal balloon dilation group (P < 0.01) and the expression of matrix metalloproteinase 9 showed a significant increase (P < 0.01), with a more pronounced increase in the ovariectomy combined with vaginal balloon dilation group, and the increase reached a stable state at 8 weeks after surgery and could persist up to 12 weeks. To conclude, vaginal balloon dilatation could not maintain the degeneration of pelvic organ prolapse formed by the vaginal wall for a long period, and both ovariectomy and the combined method can be used. Ovariectomy combined with vaginal balloon dilatation can significantly accelerate and aggravate the formation of typical histological features of pelvic organ prolapse in vaginal wall tissues, effectively shorten the experimental period, and improve the efficiency. These effects reach a stable state at 8 weeks after surgery and can be sustained up to 12 weeks, which is practical and convenient for the study of pelvic organ prolapse animal models. 
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    Triptolide inhibits ferroptosis and improves cerebral ischemia-reperfusion injury in a rat model of cerebral artery occlusion/reperfusion
    Zou Rongji, Yu Fangfang, Wang Maolin, Jia Zhuopeng
    2026, 30 (4):  873-881.  doi: 10.12307/2025.992
    Abstract ( 82 )   PDF (2502KB) ( 80 )   Save
    BACKGROUND: Triptolide, a bioactive component of the traditional Chinese medicine Tripterygium wilfordii, has a certain protective effect on neurons. 
    OBJECTIVE: To investigate the effect of triptolide on cerebral ischemia/reperfusion injury. 
    METHODS: (1) Cell experiment: Hippocampal neurons (HT22 cells) were randomly divided into control group, glucose oxygen deprivation/reoxygenation (OGD/R) group, OGD/R+triptolide group, OGD/R+triptolide+si-TIGAR group, OGD/R+si-TIGAR group, and OGD/R+triptolide+rapamycin group. HT22 cell viability was detected by cell counting kit 8. Tp53-induced glycolysis and apoptosis factors, glutathione peroxidase 4, 7 members of the solsolic vector family 11, sphingosine kinase 1 (SPHK1) and (mTOR) were detected by western blot assay. Glutathione, malondialdehyde and iron level were detected using the biochemical kit. (2) Animal experiment: Rats were randomly divided into sham surgery group, model group, and triptolide group. Cerebral artery occlusion/reperfusion rat models were prepared in the latter two groups. Rats in the triptolide group were orally administered 50 mg/kg triptolide for 7 days. Twenty-four hours after administration, LONGA method was used to evaluate the neurological impairment of rats, TTC method was used to observe the conditions of cerebral infarction, TUNEL staining was used to detect cell apoptosis, and western blot was performed to detect the expression level of related proteins. 
    RESULTS AND CONCLUSION: (1) At the cellular level, triptolide promoted cell viability and inhibited apoptosis in HT22 cells treated with OGD/R. Triptolide also increased the expression levels of Tp53-induced glycolysis and apoptosis factors, glutathione peroxidase 4, and 7 members of the solsolic vector family 11, activated the SPHK1/mTOR pathway, increased glutathione content, inhibited malondialdehyde content and iron levels. Rapamycin treatment counteracted the protective effect of triptolide on HT22 cells. (2) At the animal level, triptolide significantly reduced neurological deficits, infarct volume, and cell apoptosis, and inhibited neuronal ferroptosis in brain tissue of rats. To conclude, triptolide can inhibit ferroptosis by upregulating the expression level of Tp53-induced glycolysis and apoptosis factors and activating the SPHK1/mTOR signaling, and thereby reduced cerebral ischemia/reperfusion injury. These findings suggest that triptolide may be a candidate drug for the treatment of cerebral ischemia/reperfusion injury.
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    Thread embedding pretreatment at Xinshu (BL 15) improves cardiac function of acute myocardial ischemia rats
    Chen Xiaoqing, Bian Luyao, Lu Xingyu, Yang Tao, Li Xiang Hai
    2026, 30 (4):  882-891.  doi: 10.12307/2026.550
    Abstract ( 117 )   PDF (3214KB) ( 383 )   Save
    BACKGROUND: Acupuncture at Xinshu (BL 15) can significantly improve cardiac function and protect myocardial cells in acute myocardial ischemia, but the effect and mechanism of thread embedding treatment at Xinshu (BL 15) on cardiac function in acute myocardial ischemia are yet unclear. Nuclear factor κB activation often appears as an intranuclear translocation of the P65 isoform, and activation of the nuclear factor κB signaling pathway is marked by elevated P65 levels.
    OBJECTIVE: To explore the effects of thread embedding pretreatment at Xinshu (BL 15) on cardiac function and the expression levels of interleukin-10, tumor necrosis factor-α, P65 genes and proteins in rats with acute myocardial ischemia.
    METHODS: Thirty-two male Sprague-Dawley rats were randomly divided into a blank group, a model group, a Xinshu (BL 15) acupoint group, and a non-meridian/non-acupoint group using a random number table method, with eight rats in each group. Rat models of acute myocardial ischemia were established in the latter three groups. The Xinshu (BL 15) acupoint group had thread embedding at Xinshu (BL 15) for 14 days, followed by subcutaneous injection of isoproterenol hydrochloride into the back to establish an acute myocardial ischemia rat model. The non-meridian/non-acupoint group had local thread embedding for 14 days, and the rest procedures were the same as above. In the model group, Xinshu (BL 15) was only marked, and the rest procedures were the same as above. In the blank group, Xinshu (BL 15) was only marked, and then an equal amount of physiological saline was injected subcutaneously into the back. After 24 hours of modeling, electrocardiogram and cardiac ultrasound were performed. Abdominal aorta blood was extracted for detection of serum creatine kinase and creatine kinase isoenzyme levels using enzyme-linked immunosorbent assay. Subsequently, the rats were euthanized and samples were collected. Hematoxylin-eosin and TUNEL staining were used to observe the pathological changes of myocardial tissue and the apoptosis of myocardial cells. Real-time fluorescence quantitative PCR (RT-qPCR) and western blot were used to detect the mRNA and protein expression of tumor necrosis factor-α, interleukin-10, and P65 in myocardial tissue respectively.
    RESULTS AND CONCLUSION: (1) Electrocardiogram: Compared with the blank group, the model group, non-meridian/non-acupoint group, and Xinshu (BL 15) acupoint group had significantly elevated ST segment in lead II of the electrocardiogram. (2) Cardiac ultrasound: Compared with the model group, the Left ventricular end-systolic dimension in the Xinshu (BL 15) acupoint group were significantly reduced (P < 0.05), while left ventricular ejection fraction and left ventricular fractional shortening rate were significantly increased (P < 0.05). (4) Serum creatine kinase and creatine kinase isoenzyme: Compared with the model group, the Xinshu (BL 15) acupoint group showed a significant decrease in serum creatine kinase and creatine kinase isoenzyme levels (P < 0.05). (4) Hematoxylin-eosin staining: Compared with the model group, the arrangement of myocardial fibers in the Xinshu (BL 15) acupoint group was basically neat, with less edema and a small amount of inflammatory cell infiltration. (5) TUNEL staining: Compared with the model group, the fluorescence intensity of myocardial cell apoptosis in the Xinshu (BL 15) acupoint group was significantly reduced, and its apoptosis rate was significantly reduced (P < 0.05). (6) RT-qPCR and western blot: Compared with the model group, the myocardial tissue interleukin-10 level in the Xinshu (BL 15) acupoint group was significantly increased (P < 0.05), while tumor necrosis factor-α and P65 levels were significantly decreased (P < 0.05). These findings indicate that thread embedding pretreatment at Xinshu (BL 15) can improve cardiac function in rats with acute myocardial ischemia, and its mechanism of action may be related to the inhibition of the activation of the nuclear factor-κB signaling pathway.
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    Construction and evaluation of a neuralized intestinal mucosal tissue engineering model in vitro
    Wang Mingqi, Feng Shiya, Han Yinhe, Yu Pengxin, Guo Lina, Jia Zixuan, Wang Xiuli
    2026, 30 (4):  892-900.  doi: 10.12307/2025.960
    Abstract ( 98 )   PDF (2896KB) ( 95 )   Save
    BACKGROUND: In vitro construction of tissue-engineered intestinal models plays an important role in intestinal regeneration and intestinal disease research. The interaction of intestinal nervous system and intestinal epithelial barrier to maintain body homeostasis is a hot topic in the bionic construction of tissue-engineered intestinal tract. 
    OBJECTIVE: To construct a bionic model that can mimic the enteric nervous system in vivo. 
    METHODS: Using fibroin protein with villus structure as scaffold, human induced neural stem cells solidified with collagen were added to intestinal epithelial cells (Caco-2 and HT29-MTX-E12) for 3-day culture to construct a co-culture system of intestinal epithelial cells and nerve cells (co-culture group). Human induced neural stem cells or intestinal epithelial cells cultured alone that were inoculated with fibroin scaffolds were set as controls. Cell morphology was observed by scanning electron microscopy and hematoxylin-eosin staining. Cell activity was detected by Live/Dead cell staining. Human induced neural stem cell differentiation was detected by β-microtubulin immunofluorescence staining. Intestinal epithelial histological properties and barrier function were detected by microvillin, sucrase-isomaltase, tight junction protein 1, E-calmodulin, and mucin-2 immunofluorescence staining. The function of mucus secretion from intestinal epithelial cells was detected by Alcian blue staining. Alkaline phosphatase staining was performed to detect differentiation of intestinal epithelial cells, at the same time, sucrase-isomaltase, tight junction protein 1, and alkaline phosphatase mRNAs were detected by RT-qRCR.
    RESULTS AND CONCLUSION: The neuralized intestinal mucosal co-culture model with villi structure was successfully constructed, and neural stem cells and intestinal epithelial cells on the fibroin scaffold showed good cellular activities. After neuralization, the activity of alkaline phosphatase and sucrase-isomaltase in intestinal epithelial cells was enhanced, while the expression level of tight junction protein 1 was up-regulated. To conclude, the neuralized bionic intestinal epithelial model is beneficial to the maturation of intestinal mucosal epithelial cells and the formation of barrier function. 
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    Role and mechanism of probiotics in peri-implantitis
    Wang Jie, Huang Rui, Zhang Ye, Shou Zhaoxi, Yao Jie, Liu Chenxi, Liao Jian
    2026, 30 (4):  901-907.  doi: 10.12307/2026.504
    Abstract ( 86 )   PDF (1123KB) ( 86 )   Save
    BACKGROUND: Studies have found that probiotics have a certain preventive and therapeutic effect on peri-implantitis, and there are further explorations in the mechanism against peri-implantitis. 
    OBJECTIVE: To review the mechanism and clinical application of probiotics in the treatment of peri-implantitis.
    METHODS: Relevant literature was searched on PubMed, Web of Science, CNKI, and WanFang Data, using the search terms of “probiotics, peri-implantitis, flora imbalance, immunoregulation, inflammatory reaction, mechanism of action” in Chinese and English. A total of 90 articles were finally included.
    RESULTS AND CONCLUSION: Probiotics have the following mechanisms. They can activate the anti-inflammatory mechanism by inhibiting the secretion of inflammatory factors and promoting the production of anti-inflammatory factors. They can destroy the cell wall of pathogenic bacteria by secreting microbial complexes and bacteriocins, reduce the pH value of biofilms, improve the composition of microorganisms in microecology, induce the change of bacterial community structure, and restore the balance of microbial population around implants. They have immunomodulatory effects and can enhance the resistance of the host oral mucosa to pathogenic bacteria in the surrounding area of the implant. In addition, probiotics can produce antibacterial compounds, offset the adhesion of pathogenic microorganisms, and regulate immune function. Through the above mechanisms, probiotics have certain potential in the adjuvant treatment of peri-implantitis, which can improve the clinical parameters of peri-implantitis and affect the microbiota. Probiotic therapy provides a new treatment option, but more long-term prospective studies are needed to further verify its effect.
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    Effect of compressive stress microenvironment on cytokines during fracture healing
    Guo Jiachen, Gao Jun, Dai Wenhao, Liao Huayuan, Jiang You, Zhang Xi
    2026, 30 (4):  908-916.  doi: 10.12307/2025.978
    Abstract ( 90 )   PDF (1589KB) ( 16 )   Save
    BACKGROUND: Fracture healing is a very complex physiological process, which is influenced by many factors. In recent years, the use of biomechanical factors in fracture healing has been a major focus in the field of orthopedics, and the mechanical stress environment around the fracture end has an important role in regulating fracture healing. Among them, the study of the mechanism of compressive mechanics on the cytokines of fracture ends is a hot spot for bone-related researchers.
    OBJECTIVE: To summarize the current status and recent advances in the study of the mechanism of action of compressive stress on cytokines in fracture healing in recent years.
    METHODS: A search with the keywords of “compressive stress, fracture healing, cytokine, bone morphogenetic protein, fibroblast growth factor, platelet-derived growth factor, vascular endothelial growth factor, interleukin, tumor necrosis factor-α” in Chinese and English was conducted in the CNKI, WanFang, PubMed, and Web of Science. Initially 506 articles were retrieved, and 94 eligible articles that met the criteria were screened and finally summarized.
    RESULTS AND CONCLUSION: Current studies have found that compressive stress has different effects on different cytokines during fracture healing, which can be achieved mainly by influencing cell signaling, gene expression regulation, and modulation of cell behavior. Among them, compressive stress can be linked to cytokines such as bone morphogenetic protein, fibroblast growth factor, platelet-derived growth factor, vascular endothelial growth factor, interleukin, and tumor necrosis factor-α. This process involves cell proliferation, differentiation and migration, inflammatory response, and changes in the environmental and nutritional conditions of the fracture end, which are key factors affecting fracture healing. The whole paper summarizes the complexity of cytokine action mechanism, the mechanism of compressive stress on its regulation needs to be further carried out in-depth research, and the problems and limitations in the research are considered and future prospects.
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    Effect of macrophage polarization on osteogenesis-angiogenesis coupling in type 2 diabetic osteoporosis
    Cao Wenqi, Feng Xiuzhi, Zhao Yi, Wang Zhimin, Chen Yiran, Yang Xiao, Ren Yanling
    2026, 30 (4):  917-925.  doi: 10.12307/2026.530
    Abstract ( 99 )   PDF (1653KB) ( 127 )   Save
    BACKGROUND: Type 2 diabetes mellitus is a secondary causative factor for osteoporosis. As highly heterogeneous innate immune cells, macrophages may be polarized in a hyperglycemic environment, which affects osteogenesis-angiogenesis coupling. This may be a research target for improving bone quality in patients with type 2 diabetic osteoporosis.
    OBJECTIVE: To explore the role of modulating macrophage M1/M2 polarization to influence osteogenesis-angiogenesis coupling in type 2 diabetic osteoporosis and to summarize the effects of commonly used anti-glucose and anti-osteoporosis drugs and bone biorepair materials on bone osteogenesis-angiogenesis coupling by regulating macrophage M1/M2 polarization.
    METHODS: The keywords of “macrophage polarization, type 2 diabetes, osteoporosis, osteogenesis-angiogenesis coupling” in Chinese and “macrophages, macrophage polarization, osteogenesis-angiogenesis coupling” in English were used to search for relevant literature in CNKI and PubMed, respectively. Seventy-nine pieces of literature were screened and analyzed.  
    RESULTS AND CONCLUSION: (1) Type 2 diabetes mellitus causes the body to be in a hyperglycemic environment and increases the secretion of inflammatory-related factors in the body, which promotes macrophage polarization towards M1 and decreases the number of M2 macrophages. (2) In type 2 diabetes, promoting M2 macrophage polarization is beneficial for osteogenesis-angiogenesis coupling. (3) Some anti-glycemic drugs, active ingredients in traditional Chinese medicine and bone biorepair materials can improve type 2 diabetic osteoporosis by regulating macrophage M1/M2 polarization, reducing M1/M2 ratio, and promoting osteogenesis-angiogenesis coupling.
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    Cartilage degeneration in temporomandibular joint osteoarthritis: mechanisms and regenerative challenges
    Yang Xiao, Bai Yuehui, Zhao Tiantian, Wang Donghao, Zhao Chen, Yuan Shuo
    2026, 30 (4):  926-935.  doi: 10.12307/2026.532
    Abstract ( 78 )   PDF (1314KB) ( 142 )   Save
    BACKGROUND: The exact pathogenesis of temporomandibular joint osteoarthritis is currently unclear. Traditional clinical treatment strategies for temporomandibular joint osteoarthritis are symptomatic treatments such as pain relief and reduction of inflammation, which can stop the progression of the disease to a certain degree but cannot reverse the destruction of the cartilage. Cartilage degeneration, as one of the most prominent pathologic features in the development of temporomandibular joint osteoarthritis, has been the subject of an increasing number of studies that focus on its pathogenesis. Consequently, we hope to provide an ideal radical solution for the regeneration of the temporomandibular joint.
    OBJECTIVE: To review the progress of research on cartilage degeneration in temporomandibular joint osteoarthritis.
    METHODS: The search terms were “temporomandibular joint osteoarthritis, degradation of cartilage matrix, synovitis, oxidative stress, chondrocyte hypertrophy, chondrocyte apoptosis, ferroptosis, autophagy, angiogenesis, extracellular vesicles” in Chinese and English. Literature search was conducted in PubMed database and CNKI, and the time limit for the search was from January 2004 to October 2024. Screening was performed by analyzing and reading the literature, and according to the inclusion and exclusion criteria, 81 papers were finally included for review. 
    RESULTS AND CONCLUSION: (1) Increased secretion of cartilage matrix degrading enzymes causes degradation of the cartilage matrix, leading to cartilage degeneration. (2) Synovitis promotes cartilage degeneration through macrophage M1-type polarization and production of inflammatory mediators. (3) Oxidative stress promotes cartilage degeneration by exacerbating the inflammatory response through overproduction of reactive oxygen species. (4) Chondrocyte phenotypic changes and death lead to the decrease of cartilage matrix synthesis, resulting in cartilage degeneration. (5) Blood vessels of subchondral bone penetrate the calcified cartilage layer to reach the superficial cartilage layer, which destroys the cartilage structure and leads to cartilage degeneration. (6) Bioactive substances carried by serum-derived extracellular vesicles in inflammatory states also promote cartilage degeneration in temporomandibular joint osteoarthritis.
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    Advances in research and application of tissue engineering therapeutic strategies in oral submucous fibrosis
    Yu Shiyu, Yu Sutong, Xu Yang, Zhen Xiangyan, Han Fengxuan
    2026, 30 (4):  936-948.  doi: 10.12307/2025.963
    Abstract ( 113 )   PDF (2215KB) ( 129 )   Save
    BACKGROUND: Oral submucous fibrosis is a chronic progressive disease that is prone to malignant transformation. Traditional treatment methods are not ideal and have limitations. As an emerging discipline, tissue engineering has opened up a new path for the treatment of oral submucous fibrosis.
    OBJECTIVE: To review the latest progress in the pathogenesis and treatment of oral submucous fibrosis, and to summarize and analyze the role and research progress of mesenchymal stem cells, bioscaffold materials, and tissue-engineered oral mucosa in oral submucous fibrosis, thereby providing ideas for the research and clinical application of tissue engineering in the treatment of oral submucous fibrosis.
    METHODS: In October 2024, the first author used computers to search for relevant literature from January 1970 to October 2024 in PubMed and CNKI databases. The search terms were “oral submucous fibrosis, tissue engineering, mesenchymal stem cells, bioscaffold materials” in English and Chinese, respectively. A total of 166 articles were finally included for analysis.
    RESULTS AND CONCLUSION: (1) The pathogenesis of oral submucous fibrosis is complex, and many factors are closely related to oral submucous fibrosis, but ultimately they promote the development of oral submucous fibrosis by promoting collagen deposition and accelerating fibroblast proliferation. (2) Traditional treatment methods for oral submucous fibrosis have problems such as low patient compliance and unsatisfactory results, and new treatment strategies are urgently needed. (3) Mesenchymal stem cells regulate the pathological microenvironment, reduce inflammation and inhibit the process of fibrosis due to their immunomodulatory and antioxidant properties, providing a new idea for the treatment of oral submucous fibrosis. (4) Biomass materials, as drug and cell delivery carriers, regulate the pathological microenvironment and are used in various fibrotic diseases, providing a new solution for the treatment of oral submucous fibrosis. (5) Tissue-engineered oral mucosa can be used as an autologous mucosa substitute to promote tissue repair, and also provides a basis for the establishment of disease models. (6) Tissue engineering treatment strategy has great potential for achieving comprehensive treatment of oral submucous fibrosis, but its role in the treatment of oral submucous fibrosis has not yet been verified. It is of great significance to explore tissue engineering-based treatment strategies for oral submucous fibrosis in the future.
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    Effects of inter-limb asymmetry on athletic performance from the perspective of bilateral limb control strategy
    Jin Zhiyong, Wang Yufeng, Zhao Binjie, Xiong Minquan, Yan Li
    2026, 30 (4):  949-963.  doi: 10.12307/2026.523
    Abstract ( 118 )   PDF (1927KB) ( 140 )   Save
    BACKGROUND: Inter-limb asymmetry is a common phenomenon observed during human growth and development. Prolonged specialized training can lead to specific adaptations in inter-limb asymmetry among athletes.
    OBJECTIVE: To review the formation causes, manifestations, and impacts of inter-limb asymmetry on sports performance, and provide an overview of the relevant assessment methods and intervention strategies.
    METHODS: A literature search was conducted in the CNKI, WanFang, PubMed, and Web of Science databases from their inception to September 2024. The search terms included “asymmetry, asymmetries, asymmetric, asymmetrical, imbalance, strength, power, force, jump, sprint, athletic performance, anthropometry, injury” in English and Chinese. After excluding duplicate publications, irrelevant content, and conference papers, a total of 131 articles were finally included for analysis.
    RESULTS AND CONCLUSION: (1) Inter-limb asymmetry can be influenced by various factors including genetics, task demands, training regimens, injuries, fatigue, and limb preference. These factors lead to being primarily manifested in anatomical structure, strength performance, and task-specific asymmetry. (2) An increase in inter-limb asymmetry can result in impaired performance in bilateral in-phase symmetric movements. However, the relationship between increased inter-limb asymmetry and bilateral out-of-phase symmetric movements remains unclear and requires further investigation. (3) Training interventions have been shown to effectively mitigate inter-limb asymmetry, with unilateral training demonstrating superior outcomes compared with bilateral training. The choice of training methods and content should be tailored to meet the specific demands of the sport. (4) To further clarify the relationship between inter-limb asymmetry and athletic performance, it is recommended that future research adopt the concept of “task specificity” in inter-limb asymmetry. This includes standardizing study designs, selecting sensitive testing methods and indicators, unifying calculation methods to provide more high-quality evidence, and establishing categorized warning threshold standards for inter-limb asymmetry in different sports.
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    Double lactate threshold exercise training: development context, basic connotation, application effect and mechanism of action
    Wei Bo, Qiu Jiangang
    2026, 30 (4):  964-974.  doi: 10.12307/2026.531
    Abstract ( 195 )   PDF (4464KB) ( 317 )   Save
    BACKGROUND: The lactate threshold is a crucial physiological indicator for assessing the aerobic metabolic capacity and training level of endurance athletes, representing the intensity point at which lactate production and clearance reach a dynamic equilibrium within the organism. The traditional lactate threshold training, which is a prolonged and stable-intensity training, aims to enhance the aerobic endurance and lactate clearance efficiency of athletes. In recent years, with the advancement of exercise physiology, double lactate threshold training has emerged as an innovative training modality, drawing extensive attention from both the academic circle and practitioners. Nevertheless, current systematic research on double lactate threshold training remains limited, particularly in aspects such as its physiological mechanisms, optimal implementation plans, and long-term effects.
    OBJECTIVE: To systematically sort out the development course of double lactate threshold training, deeply analyze its fundamental connotations, objectively assess its application effects, and investigate its physiological action mechanisms, with the expectation of providing scientific basis and guidance for the improvement and optimization of endurance sports training theories and practices.
    METHODS: With the search terms of “lactate threshold training, double lactate threshold training, lactate training, threshold training, endurance training, Norwegian training method, Norwegian training mode, Norwegian training experience,” a systematic search was conducted in databases, including PubMed, Web of Science, Embase, Medline, Cochrane Library, CNKI, WanFang, and VIP. After screening, 8articles met the requirements, involving 8 training cases, and 14 top international athletes, and sports events include 800 m, 1 500 m, 5 000 m, 10 000 m, and cross-country running (9.5 km for men and 4.5 km for women).
    RESULTS AND CONCLUSION: (1) For the first time, double lactate threshold training was defined as a training strategy aimed at improving aerobic and speed capabilities, involving separate aerobic and anaerobic threshold training sessions within a single training day (aerobic training load intensity requirement of 0.7 -2.0 mmol/L, anaerobic training load intensity requirement of 2.0-4.5 mmol/L), with a training frequency of ≥ 2 times per week and a training volume of 120-160 km per week. (2) Double lactate threshold training has positive effects on muscle adaptability and plasticity (dimension and elasticity), increasing aerobic and anaerobic capabilities, and alleviating central neural fatigue and peripheral fatigue. (3) The main mechanisms by which double lactate threshold training yields effects may include hormone secretion, protein synthesis and inhibitory regulation, muscle fiber recruitment and cell swelling, mitochondrial biosynthesis and improvement in the chain of respiratory function, and neurotransmitter regulation. (4) In the practical application of double lactate threshold training, factors such as individualized training plans, load intensity design and monitoring for threshold training days, and applicable sports events should be fully considered. For the systematic improvement of double lactate threshold training, further exploration is still needed in terms of application subjects, training plans, action mechanisms, effect evaluation, and safe application.
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    Isometric exercise reduces resting blood pressure: a meta-analysis of moderating factors and dose effects
    Jiang Yang, Peng Hao, Song Yanping, Yao Na, Song Yueyu, Yin Xingxiao, Li Yanqi, Chen Qigang
    2026, 30 (4):  975-986.  doi: 10.12307/2025.913
    Abstract ( 81 )   PDF (5008KB) ( 6 )   Save
    OBJECTIVE: Elevated blood pressure increases the risk of cardiovascular diseases. Isometric exercise training has been shown to significantly reduce resting blood pressure, but the factors influencing its effectiveness remain unclear, and specific application guidelines are yet to be established. This study aims to evaluate the impact of isometric exercise training on resting blood pressure through meta-analysis, explore its moderating factors, and provide evidence-based recommendations based on its dose-response relationship. 
    METHODS: Following the PRISMA guidelines, a systematic search was conducted in PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases using keywords “Isometric exercise training,” “Systolic blood pressure,” and “Diastolic blood pressure,” covering literature up to September 2024. Randomized controlled trials involving isometric exercise training and resting blood pressure were included. Three independent researchers performed literature screening and data extraction, assessing bias risk and quality grades using the Risk of Bias 2.0 tool and GRADE framework. Main effect pooling, publication bias assessment, subgroup, and regression analysis were conducted using R software (version 4.3.4). 
    RESULTS: A total of 28 articles (comprising 32 randomized controlled trials) involving 977 participants were included. (1) Meta-analysis results indicated that isometric exercise training significantly reduced resting systolic blood pressure (MD=-8.01, 95%CI=-9.22 to -6.80, P < 0.01, I²=18.20%, low evidence grade) and diastolic blood pressure (MD=-3.46, 95%CI=-4.64 to -2.28, P < 0.01, I²=0%, moderate evidence grade) compared to no exercise. (2) Subgroup analysis results revealed significant influences of gender, health status, exercise modality, frequency, intensity, duration, sets per session, rest duration, and baseline blood pressure on the main effects for both systolic (P < 0.01) and diastolic blood pressure (P < 0.05). (3) Regression analysis results did not show any significant influencing factors, but body mass index (β=-4.11, P=0.091) showed a significant negative trend on the main effect for systolic blood pressure. (4) No significant publication bias was observed in the meta-analysis results (P > 0.05). 
    CONCLUSION: (1) Isometric exercise training significantly lowers systolic (low evidence grade) and diastolic (moderate evidence grade) blood pressure with clinically meaningful thresholds. (2) Participant characteristics (gender, health status, baseline blood pressure, and body mass index) and isometric exercise training protocols (modality, frequency, intensity, duration, cycle, sets per session, and rest duration) influence its antihypertensive effects. (3) The article recommends the optimal blood pressure management prescription: three sessions per week, with four sets per session, each set lasting 2 minutes with a 2-minute rest, at an intensity of 95% HRpeak using isometric wall squat exercises; the intervention period can be adjusted around a 6-week node. Future high-quality research is urgently needed to further validate and support these conclusions.
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    Effects of resistance exercise therapy on pain and function in patients with cervical spondylotic radiculopathy: a meta-analysis
    Li Hanyue, Li Yini, Xiang Linmei, Li Sen
    2026, 30 (4):  987-996.  doi: 10.12307/2026.529
    Abstract ( 102 )   PDF (3717KB) ( 33 )   Save
    OBJECTIVE: In recent years, resistance exercise therapy as a means of rehabilitation has attracted much attention, but its therapeutic effect on cervical radiculopathy is still controversial. This study evaluated the clinical efficacy of resistance exercise in the treatment of cervical radiculopathy through a systematic meta-analysis. 
    METHODS: A comprehensive search was conducted in CNKI, VIP, WanFang, Chinese Biomedical Literature Database, PubMed, Web of Science, Cochrane Library and Embase for clinical randomized controlled trials related to resistance exercise in the treatment of cervical radiculopathy. The search time was from the establishment of each database to November 30, 2024. The resistance training group (experimental group) used resistance exercise or resistance exercise as the main intervention method. The control group received other rehabilitation therapy except resistance exercise. Outcome measures included total effective rate, visual analog scale score, Neck Disability Index, Tanaka Symptom Scale for Cervical Spondylosis, cervical joint motion, and recurrence rate. Cochrane bias risk assessment tool and physical therapy evidence database scale were used to determine the quality of the included references. Meta-analysis was performed using RevMan 5.4 software and Stata 17.0. 
    RESULTS: (1) Finally, 9 RCTs were included, including a sample size of 673 cases. GRADE evidence quality evaluation showed that the total effective rate was medium level of evidence, while visual analog scale score, Neck Disability Index, Tanaka Symptom Scale for Cervical Spondylosis score, joint motion, and recurrence rate were low level of evidence. (2) The results of meta-analysis showed that the total effective rate in the experimental group was higher than that in the control group (RR=1.22, 95% confidence interval [CI]=1.06-1.41, P=0.005). (3) The visual analog scale score in the experimental group was better than that in the control group (mean difference [MD]=-0.72, 95% CI=-0.98 to -0.46, P < 0.000 01). The Neck Disability Index in the experimental group was better than that in the control group (MD=-2.57, 95% CI=-4.13 to -1.02, P=0.001). The Tanaka Symptom Scale for Cervical Spondylosis score in the experimental group was better than that in the control group (MD=3.83, 95% CI=3.55-4.10, P < 0.000 01). Cervical joint motion: the anterior flexion joint motion of the experimental group was better than that of the control group (MD=2.86, 95% CI=2.30-3.43, P < 0.000 01); the posterior extension joint motion of the experimental group was better than that of the control group (MD=5.23, 95% CI=3.81-6.64, P < 0.000 01). The range of motion of the left rotator joint in the experimental group was better than that in the control group (MD=7.15, 95% CI=5.43-8.87, P < 0.000 01); the range of motion of the right rotator joint in the experimental group was better than that in the control group (MD=5.45, 95% CI=3.59-7.31, P < 0.000 01). The range of motion of the left flexion joint in the experimental group was better than that in the control group (MD=3.35, 95% CI=1.98-4.72, P < 0.000 01); the range of motion of the right flexion joint in the experimental group was better than that in the control group (MD=3.91, 95% CI=2.65-5.17, P < 0.000 01). The recurrence rate in the experimental group was lower than that in the control group (RR=0.22, 95% CI=0.06-0.80, P=0.02).
    CONCLUSION: Resistance exercise can effectively improve the pain of patients with cervical radiculopathy, promote the recovery of cervical vertebra function and reduce the recurrence rate. However, the evidence level of the methodological quality and outcome indicators of the included studies is low, and more high-quality and large-sample randomized controlled trials are needed for further research and confirmation in the future.
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    Effect of exercise intervention in elderly individuals with sarcopenia and its comorbidities: a meta-analysis
    Sun Jiahe, Shi Jipeng, Zhu Tianrui, Quan Helong, Xu Hongqi
    2026, 30 (4):  997-1007.  doi: 10.12307/2026.019
    Abstract ( 105 )   PDF (2940KB) ( 74 )   Save
    OBJECTIVE: A great deal of evidence indicates that regular exercise can improve the health status of elderly individuals, including reducing overall and abdominal fat levels, increasing muscle mass and bone mineral density of the limbs, thereby preventing or delaying the onset of sarcopenia and its comorbidities. This study aims to determine the most reliable type, duration, and intensity of exercise interventions through meta-analysis to prevent, delay, and alleviate sarcopenia and its comorbidities in elderly individuals.
    METHODS: Randomized controlled trials examining the effects of exercise interventions on elderly individuals with sarcopenia and its comorbidities were searched in the PubMed, Embase, Web of Science, Cochrane Library, CNKI, and WanFang databases. The Cochrane Risk of Bias Tool was used to assess the quality of the included studies, and RevMan 5.3 software was employed for meta-analysis. Subgroup analyses were conducted to explore the effects of different exercise intervention protocols on various outcome measures. In addition, Stata 16.0 software was used to perform sensitivity analysis to assess the stability of the results, and funnel plots and Egger’s test were employed to evaluate publication bias, ensuring the comprehensiveness and reliability of the results.
    RESULTS: (1) Sixteen studies involving 861 patients with sarcopenia and its comorbidities were included. (2) The meta-analysis results indicated that, compared with the control group, exercise significantly improved grip strength, knee muscle strength, appendicular skeletal muscle mass, skeletal muscle index, Timed Up and Go test results, gait speed, and insulin-like growth factor 1 levels (P < 0.05). However, the effect of exercise intervention on the sit-to-stand test was not significantly improved (P > 0.05). (3) Based on the results of subgroup analysis, it is recommended that elderly patients with sarcopenia and its comorbidities engage in exercise at least three times per week, with each session lasting no more than 30 minutes or exceeding 45 minutes, for at least 12 weeks. The exercise protocol should be flexibly adjusted according to the patient’s health status and individual needs.
    CONCLUSION: Exercise interventions significantly improve muscle mass, muscle strength, physical function, and insulin-like growth factor 1 levels in elderly individuals with sarcopenia and its comorbidities, thereby enhancing their quality of life. However, further research is needed to validate these findings and optimize specific intervention protocols.
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    Network meta-analysis of non-invasive brain stimulation in the treatment of lower limb motor dysfunction after stroke
    Yang Yuanyuan, Zhou Shanshan, Cheng Xiaofei, Feng Luye, Tang Jiqin
    2026, 30 (4):  1008-1018.  doi: 10.12307/2025.967
    Abstract ( 98 )   PDF (3663KB) ( 114 )   Save
    OBJECTIVE: Most of the existing studies are based on traditional Meta-analysis to study the efficacy of single stimulation protocols such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation on lower limb motor dysfunction in stroke patients, and it is not possible to clarify which stimulation protocol is the optimal choice. This study used network meta-analysis to systematically evaluate the clinical efficacy of different regimens of non-invasive brain stimulation in the treatment of lower limb motor dysfunction after stroke.
    METHODS: CNKI, WanFang, VIP, CBM, PubMed, Medline and Web of Science databases were searched to collect randomized controlled trials on different regimens of non-invasive brain stimulation for lower limb motor dysfunction after stroke from inception to October 1, 2024. Data extraction was performed on the included studies. RevMan 5.4.1 software was used for traditional meta-analysis and the quality of the included studies was evaluated. Stata 17.0 software was used for network meta-analysis. 
    RESULTS: (1) A total of 39 studies involving 2 920 patients were included, involving 6 treatment methods: conventional rehabilitation training, high-frequency repetitive transcranial magnetic stimulation, low-frequency repetitive transcranial magnetic stimulation, intermittent theta burst stimulation, continuous theta burst stimulation, and transcranial direct current stimulation. (2) The results of network meta-analysis showed that high-frequency repetitive transcranial magnetic stimulation, low-frequency repetitive transcranial magnetic stimulation, intermittent theta burst stimulation, and transcranial direct current stimulation were superior to conventional rehabilitation training in the Fugl-Meyer assessment for lower extremity motor function. (3) In terms of improving Berg balance scale score, high-frequency repetitive transcranial magnetic stimulation, low-frequency repetitive transcranial magnetic stimulation, and intermittent theta burst stimulation were significantly different from conventional rehabilitation training (P < 0.05), and there was a significant difference between high-frequency repetitive transcranial magnetic stimulation and intermittent theta burst stimulation (P < 0.05). (4) In improving modified Barthel index and Barthel index, high-frequency repetitive transcranial magnetic stimulation, low-frequency repetitive transcranial magnetic stimulation, intermittent theta burst stimulation, and transcranial direct current stimulation were superior to conventional rehabilitation training. (5) Under the cumulative ranking chart, high-frequency repetitive transcranial magnetic stimulation showed the best efficacy in Fugl-Meyer assessment for lower extremity motor function, Berg balance scale score, modified Barthel index and Barthel index, followed by low-frequency repetitive transcranial magnetic stimulation. 
    CONCLUSION: Both high- and low-frequency repetitive transcranial magnetic stimulation can improve the lower limb motor function and balance function of patients with stroke, and can improve the activities of daily living of patients to varying degrees. Moreover, the effect of high-frequency repetitive transcranial magnetic stimulation is better than that of low-frequency repetitive transcranial magnetic stimulation.
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    Association between thyroid function and osteoporosis: genome-wide data analysis of European populations
    Zeng Hao, Sun Pengcheng, Chai Yuan, Huang Yourong, Zhang Chi, Zhang Xiaoyun
    2026, 30 (4):  1019-1027.  doi: 10.12307/2026.548
    Abstract ( 79 )   PDF (4563KB) ( 70 )   Save
    BACKGROUND: Several observational studies have found a strong association between thyroid function and its related disorders and osteoporosis, but the causal relationship is unclear.
    OBJECTIVE: To ascertain the causal relationship between genetically predicted thyroid function and its associated disorders, as well as osteoporosis, through the Mendelian randomization analysis with extensive pooled genetic data.
    METHODS: Pooled data from genome-wide association studies were employed to investigate the causal relationship between thyroid function and its associated disorders and osteoporosis. This was achieved through the utilization of the inverse variance weighting method as the primary Mendelian randomization analysis method, in conjunction with the MR-Egger method, weighted median method, simple model method, and weighted model method. A two-step mediated Mendelian randomization analysis was used to calculate the mediating effect of drug-mediated thyroid dysfunction on osteoporosis and the mediating proportion. Subsequently, sensitivity analyses were conducted using the MR-Egger intercept test and MR-PRESSO to detect multiplicity, Cochran’s Q test to detect heterogeneity, and leave-one-out to perform sensitivity analyses.
    RESULTS AND CONCLUSION: (1) The results of the inverse variance weighting method showed that thyroid function had an effect on bone mineral density, and that thyrotropin, free triiodothyronine on bone mineral density, free thyroxine, and subclinical hyperthyroidism all had a causal effect on bone mineral density. (2) In addition, mediation analyses revealed a potential mediating effect of carbimazole in the causal relationship between hyperthyroidism and the risk of developing osteoporosis, as well as a potential mediating effect of levothyroxine sodium in the causal relationship between hypothyroidism and the risk of developing osteoporosis. (3) In conclusion, thyrotropin, which is high in the normal range, has been demonstrated to increase bone mineral density. Conversely, free triiodothyronine and free thyroxine, which are also high within the normal range, as well as subclinical hyperthyroidism, have been shown to decrease bone mineral density. The risk of developing osteoporosis is partially mediated by the pathway of taking the therapeutic medication in the context of pharmacologic treatment of thyroid dysfunction. (4) The present study primarily focuses on European population data. However, given the commonality of the genetic background and the generalizability of genome-wide data analysis methods, it is of significant importance to explore the pathogenesis of osteoporosis in the Chinese population, develop effective interventions, and provide genetic counseling.

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    Plasma metabolites, immune cells, and hip osteoarthritis: causal inference based on GWAS data from European populations
    Rong Xiangbin, , Zheng Haibo, Mo Xueshen, Hou Kun, Zeng Ping,
    2026, 30 (4):  1028-1035.  doi: 10.12307/2025.972
    Abstract ( 68 )   PDF (2151KB) ( 96 )   Save
    BACKGROUND: Some studies have confirmed the changes in the function of immune cell subsets such as monocytes, T cells, B cells, and natural killer cells (NK cells) in patients with osteoarthritis, but the specific regulatory mechanisms are unclear.
    Objective: To explore the causal relationship between plasma metabolite-mediated immune cells and hip osteoarthritis. 
    METHODS: The Genome-Wide Association Studies (GWAS) data of 731 immune cells were used as the exposure, the GWAS data of hip osteoarthritis were used as the outcome, and 1 400 plasma metabolites were selected as mediating factors. The GWAS database is an important database for genetic association studies, maintained by international organizations with no country-specific affiliation. The inverse variance weighting method in the two-sample Mendelian randomization method was the main method, and the Bayesian weighted Mendelian randomization method was used to analyze the prior distribution, sample data and weights, which were then used to calculate the posterior distribution. The accuracy and reliability of the inverse variance weighting results were evaluated according to the posterior distribution, supplemented by MR-Egger, weighted median, simple model, and weighted mode methods. The pliotropy test and heterogeneity test were used to ensure the robustness of the process. The results of the inverse variance weighting method were used for subsequent mediating effect analysis. 
    RESULTS AND CONCLUSION: (1) The inverse variance weighting method identified 4 immune cells strongly correlated with hip osteoarthritis, and 20 metabolites strongly associated with hip osteoarthritis, all of which had no reverse causal relationship. At the same time, the validation results of Bayesian weighted Mendelian randomization method showed that the posterior mean value was similar to the estimated value of the inverse variance weighting, and the posterior variance was relatively lower. One monocyte subtype (PDL-1 on CD14-CD16+) was finally screened out to have a causal relationship with hip osteoarthritis, with a total effect of -0.047 (odds ratio=0.954, 95% confidence interval: 0.926-0.983), and a mediating effect of -0.004 (odds ratio=0.939, 95% confidence interval: 0.902-0.978) mediated by alliin levels, accounting for 8.5% of the total effect. It was concluded that alliin is a protective factor in the progression of hip osteoarthritis, in which this metabolite plays a mediating role. (2) The large amount of data from international databases and European population analysis is of great significance to Chinese biomedicine, which can provide clues for research on the genetic susceptibility to similar diseases in the Chinese population, aiding in discovering the unique associations. The pharmacogenomic approaches used can be adapted to screen for drug response genes in the Chinese population, enhancing the precision of personalized medicine. Additionally, the advanced high-throughput technologies and statistical methods employed can be learned and applied to disease prevention and treatment research.
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    Relationship between Alzheimer’s disease and sarcopenia and body mass index: analysis of GWAS datasets for European populations
    He Qiwang, , , Chen Bo, Liang Fuchao, Kang Zewei, Zhou Yuan, Ji Anxu, Tang Xialin,
    2026, 30 (4):  1036-1046.  doi: 10.12307/2025.969
    Abstract ( 80 )   PDF (5059KB) ( 219 )   Save
    BACKGROUND: Alzheimer’s disease has been associated with sarcopenia, but a causal relationship has not been established. Exploring the causal relationship between the two most common disability-burdening diseases in the aging population - Alzheimer’s disease and sarcopenia - and their potential mediating factors holds certain implications for further alleviating the healthcare costs and socioeconomic burden for older adults in China.
    OBJECTIVE: To explore the potential causal relationship between Alzheimer’s disease and sarcopenia in the general population using a Mendelian randomization study and to explore the role of body mass index in this context.
    METHODS: Two-sample Mendelian randomization analysis based on published genome-wide association studies (GWAS) were used to infer causality, and univariate Mendelian randomization and mediation analyses were used in the study design. Through the Integrative Epidemiology Unit (IEU) database, ieu-b-2 was selected as the Alzheimer’s disease dataset (sample size: 63 926), ieu-b-4816 as the body mass index dataset (99 998), ebi-a-GCST90000027 as the appendicular lean mass dataset (244 730), ukb-b-7478 as the left hand grip strength dataset (461 026), ukb-b-10215 as the right hand grip strength dataset (461 089) and ukb-b-4711 as the walking pace dataset (459 915). Inverse-variance weighting was used as the primary analysis method, and the results were validated by pleiotropy and heterogeneity analysis. The Steiger Directionality Test was performed to validate the reasonableness of the causal direction. 
    RESULTS AND CONCLUSION: (1) The Mendelian randomization analyses provided evidence that Alzheimer’s disease predicted the risk of appendicular lean mass [odds ratio (OR)=1.009; 95% confidence interval (CI), 1.001-1.017; P=0.023), and walking pace (OR=1.010; 95% CI, 1.003-1.017; P=0.008). No correlation with hand grip strength was observed. (2) Alzheimer’s disease was negatively correlated with body mass index (OR=0.893; 95% CI, 0.811-0.984; P=0.022); body mass index was positively correlated with appendicular lean mass (OR=1.084; 95% CI, 1.031-1.141; P=0.002) and negatively correlated with walking pace (OR=0.975; 95% CI, 0.969-0.980; P < 0.001). (3) Mediation analyses showed that the causal relationship between Alzheimer’s disease and appendicular lean mass and walking pace was partially mediated by body mass index, with the proportion of mediations being 50.25% and 32.11%, respectively. (4) The results of this study suggest that based on large-scale population studies, genetic prediction of Alzheimer’s disease is a potential risk factor for sarcopenia, in which body mass index plays an important mediating role. This suggests that in clinical practice, attention should be paid to the muscle condition of patients with Alzheimer’s disease, and weight management should be implemented, as maintaining a body mass index within the normal high range may have a preventive effect on the occurrence of sarcopenia in patients with Alzheimer’s disease. However, further research is needed to verify the applicability of this conclusion to other ethnic groups. This study utilized an international public database for analysis, providing a reference for research on the correlation between Alzheimer’s disease and sarcopenia in the Chinese population. It also highlights the significant mediating role of body mass index, offering insights for further prevention and treatment of sarcopenia among Chinese individuals.
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    Circulating inflammatory proteins and myocardial hypertrophy: large sample analysis of European populations from GWAS Catalog and FinnGen databases
    Ding Yu, Chen Jingwen, Chen Xiuyan, Shi Huimin, Yang Yudie, Zhou Meiqi, Cui Shuai,
    2026, 30 (4):  1047-1057.  doi: 10.12307/2025.944
    Abstract ( 87 )   PDF (2854KB) ( 61 )   Save
    BACKGROUND: Myocardial hypertrophy often leads to severe cardiovascular diseases and is difficult to diagnose due to its early stages being hard to detect. Circulating inflammatory proteins have been found to be significantly associated with cardiovascular diseases, yet the specific mechanisms linking them to myocardial hypertrophy remain unclear. 
    OBJECTIVE: To investigate the relationship between circulating proteins and myocardial hypertrophy using multiple Mendelian randomization approaches.
    METHODS: Utilizing data from 91 circulating inflammatory proteins in the GWAS Catalog database and the latest myocardial hypertrophy data from the R11 FinnGen database, we employed bidirectional two-sample Mendelian randomization, multivariate Mendelian randomization, and Genome-Wide Association Studies co-localization to investigate the causal relationship between circulating inflammatory proteins and myocardial hypertrophy. The accuracy of the results was verified through sensitivity tests including MR-PRESSO, Cochran’s Q test, MR-Egger intercept assessment, leave-one-out analysis, and funnel plot analysis.
    RESULTS AND CONCLUSION: In the results of two-sample Mendelian randomization, the primary method used for evaluation was the Inverse Variance Weighting (IVW) approach. It was found that the level of T-cell surface glycoprotein CD6 isoform (IVW: P=0.046, OR=0.74, 95% CI: 0.66-1.00), level of slit chemokine (IVW: P=2.1×10-2, OR=0.74, 95%CI: 0.556-0.95), level of Delta and Notch-like epidermal growth factor-related receptor (IVW: P=3.7×10-4, OR=0.66, 95% CI: 0.49-0.87), level of interleukin-2 (IVW: P=3.8×10-3, OR=0.667, 95%CI: 0.50-0.88), and sulfotransferase 1A1 (IVW: P=1.42×10-2, OR=0.80, 95% CI: 0.67-0.96) had a unidirectional causal effect on cardiac hypertrophy. (2) Among the findings in multivariate Mendelian randomization, the levels of the CD6 isoform of T-cell surface glycoprotein (IVW: P=1.39×10-2, OR=0.81, 95%CI: 0.69-0.96) and the levels of Delta and Notch-like epidermal growth factor-related receptor (IVW: P=3.7×10-2, OR=0.73, 95%CI: 0.55-0.98) were positive, indicating that the results remained significant after excluding the effects of other circulating inflammatory proteins that had an impact on myocardial hypertrophy. (3) In colocalization, T-cell surface glycoprotein CD6 isoform levels had H3+H4=0.96, with the most significant single nucleotide polymorphism being rs59570070, suggesting an intrinsic link between T-cell surface glycoprotein CD6 isoform levels and myocardial hypertrophy. (4) Sensitivity results showed no abnormalities, indicating no heterogeneity or pleiotropic effects influencing the results. (5) These results verified that T cell surface glycoprotein CD6 isoforms, Slit chemokine, Delta and Notch-like epidermal growth factor-related receptors, interleukin-2, and sulfotransferase 1A1 had a unidirectional causal effect on myocardial hypertrophy. T cell surface glycoprotein CD6 isoforms and Delta and Notch-like epidermal growth factor-related receptors had the deepest impact, suggesting that there may be related pathways between T cell surface glycoprotein CD6 isoforms and myocardial hypertrophy. Mendelian randomization studies require large amounts of clinical data and therefore often use European samples from international databases for analysis. Since this analytical method has significant advantages in causal inference, precision medicine, and cross-population validation, its research results still hold great significance for the medical development in China. As Mendelian randomization research deepens, it also promotes the collection and analysis of clinical data in China to some extent. In the future, we can further analyze key protein mechanisms, combine multiomics and clinical validation, develop an inflammatory marker monitoring system and novel anti-inflammatory therapies, thereby promoting the prevention and control of cardiovascular diseases and the development of personalized medicine.
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    Effects of Guilu Erxian Glue on gut microbiota in rats with knee osteoarthritis: machine learning and 16S rDNA analysis
    Gu Fucheng, Yang Meixin, Wu Weixin, Cai Weijun, Qin Yangyi, Sun Mingyi, Sun Jian, Geng Qiudong, Li Nan
    2026, 30 (4):  1058-1072.  doi: 10.12307/2025.933
    Abstract ( 92 )   PDF (4499KB) ( 180 )   Save
    BACKGROUND: The Guilu Erxian Glue consists of Testudinis Plastrum, Cornu Cervi, Lycii Fructus, and Ginseng Radix. In earlier clinical observations, it is discovered that using Guilu Erxian Glue to treat patients with liver-kidney deficiency type knee osteoarthritis effectively alleviated knee pain, increased the range of motion, and improved walking ability. However, the exact mechanism by which oral administration of Guilu Erxian Glue can produce local therapeutic effects on the knee joint is still unclear.  
    OBJECTIVE: To investigate the effects of Guilu Erxian Glue on gut microbiota in rats with knee osteoarthritis and to evaluate its mechanism using 16S rDNA sequencing and machine learning analysis. 
    METHODS: Totally 18 female SD rats were randomly divided into three groups: blank group, model group, and Guilu Erxian Glue group, with 6 rats in each group. A knee osteoarthritis model was prepared using the destabilization of the medial meniscus surgical method. After successful modeling, the Guilu Erxian Glue group was given a decoction of Guilu Erxian Glue by gavage, while the blank and model groups were given an equal amount of distilled water. After 28 days of continuous intervention, high performance liquid chromatography was used to detect the active ingredients of Guilu Erxian Glue. MRI imaging was used to observe the condition of rat knee articular cartilage. Fecal samples were collected; DNA was extracted using a kit, amplified and purified by PCR, and an Illumina sequencing library was constructed. The Illumina MiSeq platform was used for high-throughput sequencing to generate raw sequence data. After obtaining the raw data, QIIME2 software was used to process the data. Linear Discriminant Analysis Effect Size analysis and random forest algorithm were used to screen for differential species in microbial data. KEGG and MetaCyc functional pathway analyses were used to explore the association between key microbial communities and experimental groups. Linear discriminant analysis effect values and random forest algorithm were used to screen for differential species. Association networks were used to analyze the interactions between microbial communities, and machine learning methods were used to analyze the composition and changes of gut microbiota.
    RESULTS AND CONCLUSION: (1) LC-MS component identification was conducted on the traditional Chinese medicine formula of Guilu Erxian Glue, and a total of 7 effective ingredients were identified. (2) MRI imaging showed that synovitis scope of high-density shadows in rats of the Guilu Erxian Glue group was reduced, and the degeneration of medial femoral condyle cartilage was less than that in the model group. (3) 16S rDNA sequencing showed that the model group rats exhibited significant microbial imbalance, with a significant decrease in the abundance of Firmicutes and Bacteroidetes at the phylum level, while the proportion of Proteobacteria increased significantly (P < 0.05). The gut microbiota structure of rats in the Guilu Erxian Glue group was significantly improved, and the proportion of Firmicutes and Bacteroidetes increased, restoring a more diverse microbiota composition, approaching that of the blank group (P < 0.05). (4) KEGG and MetaCyc functional pathway analysis showed that the Guilu Erxian Glue group significantly activated multiple metabolic pathways, including amino acid metabolism, lipid metabolism, and biotin synthesis pathways (P < 0.05). (5) The results indicate that Guilu Erxian Glue contains seven active ingredients, and the changes in gut microbiota of knee osteoarthritis rats were analyzed using 16S rDNA sequencing. Guilu Erxian Glue can significantly improve the imbalance of gut microbiota, restore the abundance of beneficial bacteria, and have a significant impact on the composition of gut microbiota, providing scientific basis for the efficacy and mechanism of Guilu Erxian Glue. 
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