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08 April 2026, Volume 30 Issue 10 Previous Issue   

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Gut microbiota tryptophan metabolite indole-3-propionic acid alleviates inflammatory bowel disease-related osteoporosis in a mouse model  Qiu Xueli, Cui Hao, Wu Chenyang, Tao Lide, Yao Yuqian, Tian Bo, Bai Jinyu, Zhang Yingzi 2026, 30 (10):  2413-2421.  doi: 10.12307/2026.615 Abstract ( 38 )   PDF (5296KB) ( 1 )   Save BACKGROUND: The gut-bone axis refers to the interaction network through which gut microbiota and its metabolites influence bone development, metabolism, and health by regulating host immune, endocrine, and metabolic pathways. Previous studies have demonstrated that disturbances in gut microbiota have been shown to interact with inflammatory bowel disease-associated osteoporosis. OBJECTIVE: To investigate the protective effects and potential mechanisms of the gut microbiota tryptophan metabolite, indole-3-propionic acid, in inflammatory bowel disease combined with osteoporosis. METHODS: Male Balb/c mice, aged 6-8 weeks, were randomly divided into three groups: control, model, and indole-3-propionic acid groups. In the latter two groups, 1.5% sodium dextran sulfate was added to the drinking water for 12 weeks to induce chronic enteritis, and then in the indole-3-propionic acid group, intraperitoneal injections of indole-3-propionic acid at a dose of 20 mg/kg were administered three times per week, for 4 weeks. Severity of colon inflammation was assessed by hematoxylin-eosin staining, colon length measurement, and ELISA detection of intestinal inflammatory cytokine levels. Bone mass and structure of the femur were analyzed by Micro-CT scanning. Viability of osteoblasts and osteoclasts and bone metabolism were assessed using tartrate-resistant acid phosphatase staining, hematoxylin-eosin staining, calcein double labeling and immunofluorescence staining.  RESULTS AND CONCLUSION: (1) The colon length in the model group was shorter than that in the control group, while indole-3-propionic acid treatment improved the colon length. Hematoxylin-eosin staining of the colon showed that the model group exhibited disrupted colon structure, disordered crypt arrangement, and extensive infiltration of inflammatory cells. After the administration of indole-3-propionic acid, the infiltration of inflammatory cells was significantly reduced, and the colon structure was restored. (2) ELISA results indicated that the levels of intestinal inflammatory cytokines were significantly elevated in the model group compared with the control group (P < 0.000 1). After treatment with indole-3-propionic acid, the levels of intestinal inflammatory cytokines were significantly reduced (P < 0.001). (3) Micro-CT scanning and three-dimensional reconstruction showed that indole-3-propionic acid significantly alleviated bone loss in the mouse model of chronic enteritis. (4) Tartrate-resistant acid phosphatase staining and hematoxylin-eosin staining revealed that indole-3-propionic acid reduced the number of osteoclasts and increased the number of trabeculae. Calcein double labeling experiments showed that indole-3-propionic acid treatment improved bone formation capacity. Immunofluorescence analysis indicated that indole-3-propionic acid promoted the expression of SP7. These findings suggest that indole-3-propionic acid improves bone metabolism by reducing intestinal inflammation, inhibiting osteoclast activity, and upregulating osteoblast function, highlighting its potential application in the treatment of osteoporosis associated with inflammatory bowel disease. Figures and Tables | References | Related Articles | Metrics

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Effects of ankle taping on knee and ankle biomechanics of individuals with chronic ankle instability in the side-cutting and stop-jumping tasks Li Xinke, Feng Ru, Rong Ke, Sun Xiaole, Zhou Zhipeng, Yang Chen 2026, 30 (10):  2422-2429.  doi: 10.12307/2026.638 Abstract ( 41 )   PDF (1332KB) ( 0 )   Save BACKGROUND: Chronic ankle instability occurs mostly during landing and side-cutting tasks. Taping is one of the most commonly used means of ankle sports protection, but the mechanism of action is controversial, and whether taping can limit ankle motion in patients with chronic ankle instability during functional activities and affect the knee joint to compensatory variation still needs further exploration. OBJECTIVE: To determine the effect of ankle taping on knee and ankle biomechanics in patients with chronic ankle instability during the side-cutting and stop-jumping tasks. METHODS: Thirteen patients with chronic ankle instability (trial group) and thirteen healthy male college students (control group) were enrolled. Each participant performed the biomechanical tests with and without the basketweave ankle taping. The kinematic and kinetic data during 45° side-cutting and stop-jumping were synchronously collected by Vicon motion capture system and AMTI forceplates. A two-way repeated measures analysis of differences was performed to determine the effects of taping and group on knee and ankle angles and moments during the stance phase of side-cutting and stop-jumping.  RESULTS AND CONCLUSION: (1) There was an interaction effect between taping and group on the peak ankle valgus angle during stance phase of stop-jumping (P=0.034). The ankle valgus angle in the trial group with taping was significantly lower than that in the trial group without taping (P=0.006), while the ankle valgus angle in the trial group with taping was significantly lower than that in the control group with taping (P=0.024). (2) There was an interaction effect between taping and group on the peak knee valgus moment during the stance phase of stop-jumping (P=0.027). The knee valgus moment in the trial group with taping was significantly lower than that in the trial group without taping (P=0.003). (3) No interaction effect between taping and group on peak ankle plantarflexion moment (P=0.977), peak knee extension moment (P=0.281) during stance phase of stop-jumping, and peak ankle valgus angle (P=0.211) during the stance phase of side-cutting was detected. Taping significantly decreased these three variables (P ≤ 0.019). (4) Taping showed no significant effects on other knee and ankle angles and moments during the stance phase of side-cutting and stop-jumping (P ≥ 0.053). Therefore, ankle taping decreased the peak ankle valgus angle and peak knee valgus moment of patients with chronic ankle instability during the stance phase in stop-jumping task compared with the healthy controls, suggesting that taping may better limit ankle valgus and knee joint loading. Figures and Tables | References | Related Articles | Metrics

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Mechanism by which Maxing Kugan Decoction intervenes in oleic acid-induced acute lung injury in rats Jiao Taiqiang, Han Xingji, Li Xiangyang, Nan Yi, Yuan Ling, Li Jiaqing, Niu Yang 2026, 30 (10):  2430-2439.  doi: 10.12307/2026.643 Abstract ( 37 )   PDF (6210KB) ( 0 )   Save BACKGROUND: Maxing Kugan Decoction is a Chinese medicinal preparation derived from "San Ao Tang," which is effective in relieving cough and asthma, clearing internal heat, nourishing yin and moistening dryness. It has been widely used in the treatment of respiratory tract infectious diseases in Ningxia and neighboring areas, and can effectively prevent and control the occurrence and development of acute lung injury. However, its mechanism of action is still unclear in the treatment of acute lung injury. OBJECTIVE: To explore the dynamic preventive and therapeutic effects of Maxing Kugan Decoction on oleic acid-induced acute lung injury in Sprague-Dawley rats.  METHODS: Forty-five Sprague-Dawley rats were allocated into three groups: control (5 rats), model (20 rats), and Maxing Kugan Decoction (20 rats). The Maxing Kugan Decoction group received daily gavage for 7 days prior to modeling. At 1 hour after final administration, both the model and Maxing Kugan Decoction groups were injected with oleic acid via the tail vein to induce the acute lung injury model. Five rats from each group were sampled at 3, 6, 12, and 24 hours after injection to evaluate lung tissue function through blood gas analysis. Lung tissue edema and damage to the alveolar-capillary barrier were evaluated through the measurement of the lung coefficient, lung wet-to-dry weight ratio, total cell count in bronchoalveolar lavage fluid, total protein concentration, and lung permeability index. The inflammatory response in lung tissue was assessed by quantifying the levels of inflammatory factors and detecting the number and polarization of macrophages using immunofluorescence. The extent of lung tissue injury was determined using hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The progression of pulmonary fibrosis following lung injury was examined using Masson staining. RESULTS AND CONCLUSION: (1) Compared with the control group, the rats in the model group exhibited pronounced symptoms of shortness of breath, reduced activity, and cyanosis of the lips and face immediately following the tail vein injection of oleic acid. After 3 hours, there was a notable decrease in the partial pressure of oxygen (PaO2), blood oxygen saturation (SaO2), and oxygenation index (PaO2/FiO2), the partial pressure of carbon dioxide (PaCO2), lung coefficient, and lung wet-to-dry weight ratio. Additionally, the levels of tumor necrosis factor-α, interleukin-6, and interleukin-1β in bronchoalveolar lavage fluid were significantly elevated, accompanied by an increase in the total cell count and lung permeability index. Histopathological analysis revealed significant inflammatory infiltration, tissue edema, thickening of the alveolar septa, apoptosis of pulmonary cells, and mild collagen fiber hyperplasia and deposition. Additionally, there was a notable polarization of rat lung macrophages towards the M1 phenotype. At 6 hours, all injuries were further exacerbated, and blood gas indices declined to their lowest levels. By 12 hours, although blood gas indices showed recovery, histopathological staining of lung tissues indicated compensatory alveolar enlargement or shrinkage. Concurrently, the levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid reached the peak. At 24 hours, there was an alleviation in the blood gas indices and inflammatory response, but the oxygenation index remained within the range indicative of acute lung injury. Furthermore, lung tissue damage and edema continued to worsen, accompanied by significant collagen fiber hyperplasia and deposition. (2) Compared with the model group during the same period, Maxing Kugan Decoction demonstrated a significant capacity to mitigate the aforementioned pathological alterations, delay the onset of acute lung injury, inhibit the polarization of macrophage, and reduce inflammatory responses, tissue edema, collagen fiber deposition, and apoptosis in lung tissue cells. To conclude, Maxing Kugan Decoction effectively prevents the occurrence of oleic acid-induced acute lung injury, diminishes the severity and duration of acute lung injury, and promotes the recovery from tissue edema and collagen fiber deposition following acute lung injury. Figures and Tables | References | Related Articles | Metrics

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Dodder intervenes with chronic stress depression in a mouse model: changes in NLRP3 inflammasome Song Andong, , Fu Huiling, , Yuan Bo, Li Guohua, Jia Xusheng, Jia Menghui 2026, 30 (10):  2440-2448.  doi: 10.12307/2026.636 Abstract ( 36 )   PDF (2061KB) ( 0 )   Save BACKGROUND: Dodder, as a traditional tonic herb in Chinese medicine, has anti-inflammatory and antidepressant properties, which may be involved in inhibiting neuroinflammatory cascades. However, whether this effect interferes with the neuroimmune imbalance mechanism of depression by specifically regulating pyroptosis and neuroinflammatory cascades mediated by the NLRP3/ASC/Caspase-1 signaling axis has not yet been systematically elucidated. OBJECTIVE: To explore the therapeutic effect and mechanism of dodder in chronic stress depression mice based on NLRP3 inflammasome.   METHODS: ICR mice were randomly divided into blank group, model group, paroxetine group (2.6 mg/kg) and dodder group (10.2 g/kg). The depression model was induced in the latter three groups by chronic unpredictable mild stress for 4 weeks. Sugar-water preference, forced swimming and tail hanging tests were used to detect depression-like behaviors. The levels of interleukin-1β, interleukin-6, tumor necrosis factor-α and the contents of 5-hydroxytryptamine, dopamine and brain-derived neurotrophic factor in hippocampus were detected by ELISA. Western blot assay was used to analyze NLRP3/ASC/Caspase-1 protein expression. qRT-PCR was used to quantify the mRNA expression of interleukin-1β, NLRP3, ASC, and inducible nitric oxide synthase. The morphological changes of hippocampal neurons were observed by hematoxylin-eosin staining.   RESULTS AND CONCLUSION: (1) Compared with the blank group, the model group showed significant depression-like behavior phenotype: the sugar-water preference rate was decreased to 46.4%, the immobility time of forced swimming was increased by 2.0-fold, and the rest time of tail suspension was increased by 2.9-fold (all P < 0.01). The density of neurons in the hippocampal CA3 region was decreased, and the pathological features included nuclear shrinkage, reduced dendritic branches and enlarged neuronal spaces. The levels of hippocampal inflammatory cytokines, interleukin-1β, interleukin-6, and tumor necrosis factor-α, were significantly increased (P < 0.05), while the levels of neurotransmitters, 5-hydroxytryptamine, dopamine and brain-derived neurotrophic factor, were significantly decreased (P < 0.05). The relative expressions of NLRP3, ASC and Caspase-1 proteins related to inflammasome in the hippocampus of mice were significantly increased (P < 0.05). (2) Treatments with paroxetine and dodder significantly reversed the depression-like phenotype of mice: the sugar-water preference rate increased to 89.2%-95.1% in the blank group, the immobility time of forced swimming decreased to 65.27%, and the rest time of tail suspension decreased to 61.2% (all P < 0.05 vs. the model group). Hippocampal neurons were significantly recovered, and the levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α were significantly decreased (P < 0.05), while the levels of 5-hydroxytryptamine, dopamine and brain-derived neurotrophic factor were significantly increased (P < 0.05). The relative expressions of NLRP3, ASC and Caspase-1 related to inflammasome in the hippocampus of mice were significantly decreased (P < 0.05). There was no significant difference between paroxetine group and dodder group (P > 0.05). In conclusion, dodder can improve depression-like behaviors in mice subjected to chronic unpredictable mild stress by inhibiting the activation of NLRP3 inflammasome, inhibiting hippocampal neuroinflammation, and increasing hippocampal neurotransmitter levels. Figures and Tables | References | Related Articles | Metrics

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Treadmill exercise improves metabolic-cognitive impairment of circadian rhythm disorder in diabetic mice Li Qingxin, Zhang Guodong, Wei Siang, , Xie Yanli 2026, 30 (10):  2449-2458.  doi: 10.12307/2026.646 Abstract ( 35 )   PDF (1944KB) ( 0 )   Save BACKGROUND: Disturbance of circadian rhythm aggravates insulin resistance and abnormal glucose and lipid metabolism, becoming an important inducement for diabetes and its complications. Regular aerobic exercise enhances insulin sensitivity through activation of the AMPK signaling pathway while upregulating silent information regulation 1 (SIRT1) expression to stabilize rhythmic oscillations of core clock genes. OBJECTIVE: To explore the effect of treadmill exercise on metabolic abnormalities and cognitive dysfunction induced by circadian rhythm disturbance in diabetic mice, and analyze its underlying molecular mechanism.  METHODS: The 8-week-old wild-type C57BL/6J and diabetic db/db mice were selected as normal controls and diabetic controls. Circadian rhythm disorder models were established by intermittent light (8-hour light/4-hour dark, lasting for 6 weeks), and divided into model and diabetes+model groups. Based on a 6-week treadmill exercise, mouse models were divided into model+exercise group and diabetes+model+exercise group. The detection indicators include body mass, serum melatonin, fasting blood glucose, homeostatic model assessment of insulin resistance, glucose tolerance test and insulin tolerance test, fat mass, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and Morris water maze behavioral performance, as well as BMAL1, CLOCK, Nrf2, superoxide dismutase 2, and mRNA expression levels of SIRT1 and glycogen synthase kinase 3β (GSK3β) in pancreatic tissues.  RESULTS AND CONCLUSION: (1) Circadian rhythm disruption significantly exacerbated body mass gain, decreased serum melatonin levels, elevated fasting blood glucose, and abnormal lipid metabolism in db/db mice, while exercise intervention reduced these indicators, improved glucose tolerance and insulin sensitivity, significantly reduced the level of interleukin-4 and elevated the level of interferon-γ in mice with circadian rhythm disorders (P < 0.01). (2) Exercise downregulated the expression of the circadian core genes BMAL1 and CLOCK, activated the Nrf2-superoxide dismutase 2 antioxidant pathway, and regulated the SIRT1-GSK3 β signaling axis. (3) Exercise intervention decreased the escape latency and increased crossing platform frequency of db/db mice (P < 0.01). Overall, by regulating SIRT1-GSK3 β signal axis and antioxidant pathway, treadmill exercise can effectively improve metabolic abnormalities, immune imbalance and cognitive damage caused by circadian rhythm disorder in diabetic mice. Figures and Tables | References | Related Articles | Metrics

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Accuracy of a real-time registration system based on orthodontic landmarks Huang Juneng, Zeng Jingjie, Peng Ying, Lu Wenrong, Tang Min, Zhang Xuejun 2026, 30 (10):  2459-2465.  doi: 10.12307/2026.624 Abstract ( 60 )   PDF (1634KB) ( 1 )   Save BACKGROUND: The superimposition of consecutive cephalometric lateral radiographs is commonly used in orthodontics to assess the outcomes of orthodontic/orthopedic treatments and changes in growth and development. The key factors affecting the accuracy of cephalometric superimposition are landmark localization errors and registration methods. Currently, there is no highly accurate registration system.  OBJECTIVE: To study a real-time registration system that guides the adjustment of landmark localization on cephalometric lateral radiographs to assist in improving registration accuracy and evaluate the precision of this registration method.  METHODS: Pre- and post-treatment cephalometric lateral radiographs of 40 adult patients were selected according to the inclusion criteria. Landmark localization on the pre- and post-treatment radiographs was performed using Labelme software. Real-time visualized registration software was developed using Python, Opencv, and PyQT. Registration was performed using the SellaNasion (SN) superimposition method, the Least Squared Averaged 5 Landmarks (LS-5) method, and the Real-time Least Squared Averaged 5 Landmarks (LS-5R) method. The distance errors and the success detection rate of landmarks anterior nasal spine (ANS), posterior nasal spine (PNS), upper alveolar seat point (A), lower alveolar seat point (B), point of anterior chin (Pog) were measured and compared to evaluate the registration accuracy. RESULTS AND CONCLUSION: The LS-5R method exhibited the smallest landmark distance errors. Compared with the SN method, all landmark distance errors showed statistically significant differences (P < 0.05). The distance errors of PNS, A, B, and Pog landmarks with the LS-5R method were statistically different from those with the LS-5 method (P < 0.05), and the differences increased in sequence. The success detection rate of automatic landmark detection within 1mm, 2mm, and 3mm accuracy ranges was higher for the LS-5R method than for the SN superimposition method. The LS-5R method has smaller superimposition errors compared with the traditional SN method, making it a potentially more reliable method for superimposing consecutive cephalometric lateral radiographs in clinical practice. Figures and Tables | References | Related Articles | Metrics

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Constructing a risk prediction nomogram model for cognitive impairment in hypertensive intracerebral hemorrhage Huang Fengqin, Hu Yalin, Yang Boyin, Luo Xingmei 2026, 30 (10):  2466-2474.  doi: 10.12307/2026.642 Abstract ( 71 )   PDF (2355KB) ( 3 )   Save BACKGROUND: Currently, constructing a risk predictive model for post-stroke cognitive impairment mostly depends on logistic regression, with relatively few studies incorporating Lasso regression for variable selection to address collinearity and overfitting. OBJECTIVE: To explore the factors associated with post-stroke cognitive impairment following hypertensive intracerebral hemorrhage and to construct a nomogram prediction model using LASSO regression, followed by model validation. METHODS: A total of 260 intracerebral hemorrhage patients admitted to the Neurology Emergency Department of the Affiliated Hospital of Guizhou Medical University from August 2022 to August 2024 were initially selected, of whom 127 were classified into the post-stroke cognitive impairment group and 133 into the post-stroke non-cognitive impairment group. Feature selection was optimized using Lasso-logistic regression, and all cohorts were randomly divided into a training set (182 cases) and a validation set (78 cases) in a 7:3 ratio using R Studio software. A risk prediction nomogram model was constructed based on independent risk factors identified from the training set. The model’s discriminative ability was evaluated using the receiver operating characteristic curve, calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test and calibration curve, and clinical benefits were evaluated using a decision analysis curve. RESULTS AND CONCLUSION: (1) Lasso-logistic regression analysis identified the following independent risk factors for post-stroke cognitive impairment after hypertensive intracerebral hemorrhage: age [odds ratio (OR)=1.112, 95% confidence interval (CI)=1.068-1.157, P=0.000), hematoma diameter (OR=2.021, 95% CI=1.025-3.983, P=0.042), intraventricular rupture (OR=2.398, 95% CI=1.149-5.006, P=0.020), surgery (OR=2.542, 95% CI=1.278-5.056, P=0.008), and serum creatinine levels (OR=1.017, 95% CI=1.004-1.031, P=0.010). (2) A nomogram prediction model was constructed accordingly. The receiver operating characteristic curve analysis revealed an area under the curve for the training and validation sets to be 0.826 (95% CI=0.765-0.885) and 0.795 (95% CI=0.693-0.898), respectively. (3) The Hosmer-Lemeshow goodness-of-fit test and calibration curve analysis showed a good fit of the nomogram model, with a χ2 value of 12.710 and a P-value of 0.122 (P > 0.05) for the training set (χ2=12.170, P=0.122 > 0.05) and the validation set (χ2=4.328, P=0.826 > 0.05). (4) The clinical decision curve demonstrated considerable clinical net benefit of the model. In conclusion, the nomogram model based on predictive factors such as age, hematoma diameter > 3 cm, intraventricular rupture, surgery, and serum creatinine levels has a significant predictive value for cognitive impairment within 3 months after hypertensive intracerebral hemorrhage. Figures and Tables | References | Related Articles | Metrics

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Regulation of bone metabolism by myokines under resistance exercise intervention Li Xinying, Zhang Wenhua, Li Xun, Zhang Shihua, Wang Xiaoqiang 2026, 30 (10):  2475-2483.  doi: 10.12307/2026.639 Abstract ( 40 )   PDF (1317KB) ( 5 )   Save BACKGROUND:  Resistance exercise not only directly stimulates bone tissue through mechanical stress, but also indirectly regulates bone metabolism by inducing the secretion of various myokines from muscles. OBJECTIVE: To investigate the skeletal regulation mechanism of myokines under resistance exercise from the perspective of the whole “musculoskeletal system.” METHODS: We searched for relevant literature published from database inception to July 2024 in the Web of Science, PubMed, CNKI, WanFang, and VIP databases. The search terms were “resistance exercise, myokines, bone metabolism, osteoporosis, sarcopenia” in English and Chinese. Finally, 59 articles were included for review.  RESULTS AND CONCLUSION: Studies have shown that myostatin plays a negative regulatory role in muscle growth and development, and its reduction can promote muscle growth. Resistance exercise may indirectly promote bone health by reducing myostatin levels, but the specific mechanism needs to be further explored. Irisin, as a newly discovered myokine, has been shown to have a pro-bone formation effect. Resistance exercise can significantly increase the level of irisin, which in turn may promote the proliferation and differentiation of osteoblasts through the activation of Wnt/β-catenin signaling pathway and other mechanisms. Matrix metalloproteinase-2 plays an important role in bone remodeling, degrading bone matrix components and promoting the balance between bone resorption and formation. Resistance exercise may contribute to the maintenance of normal structure and function of bone tissue by regulating matrix metalloproteinase-2 activity. Insulin-like growth factor-1 is an important growth factor that significantly promotes bone growth and development. Resistance exercise can increase the expression and secretion of insulin-like growth factor-1, which in turn promotes the proliferation, differentiation and mineralization of osteoblasts, and improves bone density and strength. To conclude, resistance exercise positively affects bone metabolism by regulating the expression and activity of myostatin, irisin, matrix metalloproteinase-2 and insulin-like growth factor-1, which can help prevent and treat osteoporosis. However, the specific mechanisms still need to be studied, thereby further elucidating the overall regulatory effects of resistance exercise on the musculoskeletal system. Figures and Tables | References | Related Articles | Metrics

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Mechanisms by which macrophage polarization regulates bone destruction in rheumatoid arthritis Shalayiding · Aierxiding, Gao Jian, Alimujiang · Abudourousuli, Kutiluke · Shoukeer, Aikebaierjiang · Aisaiti, Gulimire · Yilihamu, Jiang Kan, Aikeremujiang · Muheremu 2026, 30 (10):  2484-2490.  doi: 10.12307/2026.610 Abstract ( 30 )   PDF (1880KB) ( 0 )   Save BACKGROUND: Rheumatoid arthritis is a chronic autoimmune disorder characterized by persistent synovitis and progressive joint destruction. Macrophages serve as pivotal effector cells, playing a central role in rheumatoid arthritis pathogenesis through their ability to polarize into distinct functional phenotypes. OBJECTIVE: To review the role of macrophage polarization in bone destruction in rheumatoid arthritis, the regulatory mechanisms involved, and the latest therapeutic advancements. METHODS: Relevant literature published between 2005 and 2025 was retrieved using computer-based searches of the Web of Science Core Collection, WanFang Database, and CNKI. The search terms included “macrophages, rheumatoid arthritis, polarization, bone and joints, cartilage, autoimmunity, inflammation, M1 macrophage, M2 macrophage” in English and Chinese. Finally, 53 articles were included for review.  RESULTS AND CONCLUSION: Rheumatoid arthritis is a chronic inflammatory disorder characterized by persistent inflammatory bone destruction. Inadequate treatment can lead to joint deformities and even functional loss. The imbalance in macrophage polarization, specifically the M1/M2 ratio, is a critical factor in disease progression. This underscores the necessity of investigating the role of macrophage polarization in rheumatoid arthritis-induced inflammatory bone and joint destruction, as well as its regulatory mechanisms, as potential targets for novel therapeutic agents. Figures and Tables | References | Related Articles | Metrics

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Functional impacts of bone bruise and combined injuries in anterior cruciate ligament injuries Zhang Shuang, Huang Zishuai, Wang Jian 2026, 30 (10):  2491-2502.  doi: 10.12307/2026.611 Abstract ( 42 )   PDF (1998KB) ( 0 )   Save BACKGROUND: Anterior cruciate ligament injury, one of the most prevalent sports-related injuries, is often accompanied by bone bruises, meniscal tears, and medial collateral ligament damage. Bone bruises, caused by high-energy loading-induced microstructural damage to trabecular bone, exhibit specific distribution patterns that are correlated with anterior cruciate ligament tear locations and knee injury mechanisms. However, further exploration is required to elucidate the distribution patterns, biomechanical mechanisms of bone bruises, and their associations with combined injuries. OBJECTIVE: To investigate the distribution patterns and characteristics of bone bruises in anterior cruciate ligament injuries, their relationship with injury mechanisms, and their correlations with combined injuries and functional outcomes, thereby providing evidence-based insights to formulate clinical treatment and rehabilitation strategies. METHODS: The first author conducted an initial literature search in March 2024, supplemented by additional searches from August 2024 to October 2024. Databases including PubMed, Embase, and CNKI were queried for studies on knee bone bruises using a combination of subject headings and free-text terms. The search terms included “bone bruise, bone contusion, anterior cruciate ligament, ACL, cartilage damage, meniscus injury, medial collateral ligament, MRI” in English as well as “bone contusion, bone injury, anterior cruciate ligament, cartilage damage, meniscus injury, medial collateral ligament, magnetic resonance imaging, MRI” in Chinese. The search timeframe spanned from January 1, 2000, to October 1, 2024. RESULTS AND CONCLUSION: Based on the inclusion and exclusion criteria, 88 articles were selected for analysis. Bone bruises are common concomitant injuries following anterior cruciate ligament damage, predominantly localized in the lateral tibial plateau and lateral femoral condyle. Their distribution patterns are closely linked to anterior cruciate ligament injury mechanisms, with valgus stress, anterior tibial translation, and internal rotation identified as primary contributors. The severity of bone bruises reflects the mechanical load sustained during injury and correlates significantly with knee laxity and functional impairment. Additionally, bone bruises are strongly associated with combined injuries, including meniscal tears, cartilage damage, and medial collateral ligament injuries. Increased bone bruise severity and the presence of combined injuries may markedly reduce functional scores, delay rehabilitation, and adversely affect long-term patient outcomes. Bone bruises serve not only as critical imaging markers of anterior cruciate ligament injuries but also as key indicators for evaluating injury mechanisms, predicting combined injuries, and assessing long-term knee prognosis. These findings provide multifaceted biomechanical evidence to support precise injury severity assessments and individualized clinical management strategies. Figures and Tables | References | Related Articles | Metrics

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The role of p53 in musculoskeletal diseases Du Yanli, , Wang Yi, , Wang Zhenyu, Wang Xuanhui, , Li Xinye, , Xiong Xifeng, Miao Haixiong, 2026, 30 (10):  2503-2514.  doi: 10.12307/2026.612 Abstract ( 44 )   PDF (1672KB) ( 2 )   Save BACKGROUND: The p53 gene is a key tumor suppressor gene that was initially extensively studied for its central roles in cell cycle regulation, DNA repair, and apoptosis. In recent years, studies have shown that p53 also plays important roles in the pathogenesis of musculoskeletal diseases. Abnormal expression and dysfunction of p53 are considered important factors in the development and progression of these diseases. However, the specific mechanisms and clinical translation potential of p53 have not yet been systematically elucidated. OBJECTIVE: To comprehensively summarize the multiple roles of p53 in musculoskeletal diseases, analyze the molecular mechanisms by which p53 influences disease progression, and evaluate its potential as a therapeutic target across these diseases. METHODS: PubMed was searched for literature published from January 2004 to December 2024 using the keywords of “P53, osteoporosis, post-menopausal osteoporosis, osteoarthritis, degenerative arthritis, rheumatoid arthritis, gout, low back pains, low back ache, back pain, scoliosis” in English. We included original studies, reviews, and clinical trials while excluding non-English articles and studies unrelated to the mechanisms of interest. A total of 81 articles were ultimately selected for comprehensive analysis. RESULTS AND CONCLUSION: p53 is involved in the occurrence and development of musculoskeletal diseases through mechanisms such as regulating the balance of bone formation and resorption (e.g., the p53-Nedd4-Runx2 axis), chondrocyte apoptosis (e.g., the miR-34a-SIRT1-p53 pathway), inflammatory mediators (e.g., tumor necrosis factor-α/interleukin-6), and oxidative stress (e.g., the p53-SLC2A9 axis). Its dual roles (pro-apoptotic and anti-inflammatory) suggest the need for precise regulation of p53 activity. Intervention strategies based on gene editing (e.g., CRISPR/Cas9), small-molecule inhibitors (e.g., PFT-α), and natural products (e.g., naringin) show therapeutic potential, but further clinical validation is needed. In the future, it is necessary to combine multidisciplinary approaches to deepen p53 mechanism research and clinical practice. Figures and Tables | References | Related Articles | Metrics

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Fatigue induction protocols for the lumbar extensor muscles Xing Cong 2026, 30 (10):  2515-2524.  doi: 10.12307/2026.608 Abstract ( 48 )   PDF (1732KB) ( 1 )   Save BACKGROUND:  Fatigue of the lumbar extensor muscle group is an important factor causing symptoms of low back pain. It is also an important cause of the change in posture control strategy during exercise, the reduction in exercise efficiency and the increase in the risk of fall or local joint injury. Therefore, accurate and effective induction of lumbar extensor fatigue in laboratory or clinical conditions can help researchers better understand the body’s neuromuscular control status after lumbar extensor fatigue and explore the causes of related symptoms such as low back pain. OBJECTIVE: To summarize the action form, load setting, fatigue determination method and influencing factors that induce lumbar extensor fatigue, and to summarize the development of fatigue induction protocols for the lumbar extensor muscles. METHODS: The first author selected “lumbar extensor group fatigue, low back pain, lumbar back muscle fatigue, lumbar back muscle endurance, muscle fatigue” as the Chinese search terms and “lumbar extensor muscles, trunk extensor muscles, spinal muscles, muscle endurance, muscles fatigue, muscles fatigue protocol and Sorensen test” as the English search terms. After searching in CNKI, PubMed and Web of Science databases, 68 relevant articles were finally included, including 4 Chinese and 64 English articles. RESULTS AND CONCLUSION: There are mainly three regimens of laboratory-induced lumbar extensor fatigue: Sorensen propulsive stretching activity, sitting stretching activity and standing lifting activity. The fatigue activity of the lumbar extensor group is affected by the properties of muscle fatigue. The intensity of fatigue activities can be adjusted according to the relationship between the actual value and the expected value of the decrease in the maximum voluntary contraction force of the lumbar extensor muscle group. The fatigue status of the lumbar extensor muscle group can be determined quantitatively by combining the change inmyoelectric index with the decline in maximum voluntary contraction force of the muscle group. The individual differences among participants and the internode compensation characteristics of the human movement link are the primary factors influencing the fatigue effects of lumbar extensor muscles. Figures and Tables | References | Related Articles | Metrics

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The relationship between gout and some lifestyles, cardiovascular disease, bone disease, and psychiatric disease Liu Shuhong, Xie Yuhan, Huang Chengcheng, Yang Zhenguo, Li Yang 2026, 30 (10):  2525-2535.  doi: 10.12307/2026.618 Abstract ( 38 )   PDF (1639KB) ( 1 )   Save BACKGROUND: The onset of gout is directly associated with disorders of purine metabolism and/or reduced uric acid excretion. Currently, the etiological factors of gout and its relationship with other diseases are not fully understood. Mendelian randomization studies can effectively mitigate confounding factors and reverse causality, thereby providing novel perspectives and approaches for investigating the associations between gout and various risk factors/diseases. OBJECTIVE: To summarize currently published Mendelian randomization studies related to gout, focusing on the causal relationship between lifestyles, various diseases and metabolites and the development of gout. METHODS: A computerized search was conducted to identify relevant literature published in CNKI and PubMed databases from 2014 to 2024. The search terms were “gout, Mendelian randomization, causality, lifestyle, drinking, alcohol, tea, coffee, mental illness, Alzheimer’s disease, cardiovascular disease, bone disease, osteoarthritis, hypertension, angina, obesity” in Chinese and English, respectively. A total of 88 papers were finally included for review. RESULTS AND CONCLUSION: Current Mendelian randomization studies predominantly support causal relationships between gout and various factors including lifestyles (e.g., tea/coffee consumption), metabolic products, endocrine disorders, obesity, cardiovascular diseases, gut microbiota, micronutrients, novel COVID-19 infection, skeletal disorders, and psychiatric diseases. However, some Mendelian randomization findings do not confirm a causal relationship between gout and some lifestyle conditions (e.g., alcohol consumption), cardiovascular diseases, skeletal disorders, or psychiatric diseases. Although there are some limitations and deficiencies in Mendelian randomization studies, the current conclusions still help us to have a more comprehensive understanding of the pathogenesis of gout and its relationship with other diseases. Figures and Tables | References | Related Articles | Metrics

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Glial-neuronal interactions in basal ganglia neurodegenerative diseases: regulatory mechanisms and potential therapeutic targets Li Minghui, Zhang Yingbi, Zhang Xiaorui, Yin Jihong, Wang Peng 2026, 30 (10):  2536-2549.  doi: 10.12307/2026.644 Abstract ( 29 )   PDF (2768KB) ( 0 )   Save BACKGROUND: Glial-neuronal interactions play a crucial role in maintaining central nervous system homeostasis through metabolic support, immune regulation, and synaptic pruning. Dysfunction in these interactions is closely associated with the pathological progression of basal ganglia neurodegenerative diseases. OBJECTIVE: To summarize the regulatory mechanisms and roles of glial-neuronal interactions in basal ganglia neurodegenerative diseases and to explore their potential therapeutic targets. METHODS: Relevant literature published from January 2020 to November 2024 was retrieved from the CNKI, PubMed, and Web of Science databases. Search terms included “basal ganglia, striatum, substantia nigra, globus pallidus; glial cells, astrocytes, microglia, oligodendrocytes; neurons, neurodegeneration, synaptic dysfunction; Parkinson’s disease, Huntington’s disease, multiple system atrophy, neurodegenerative diseases; metabolic coupling, neuroinflammation, synaptic pruning, oxidative stress, organoid model, single-cell sequencing; therapeutic targets, glial modulation, neuroprotection, blood-brain barrier, off-target effect” in Chinese and English. Based on the inclusion and exclusion criteria, 113 articles were ultimately selected for review and summarization. RESULTS AND CONCLUSION: (1) Dysregulation of glial-neuronal interactions leads to metabolic imbalance, neuroinflammation, and synaptic dysfunction, thereby exacerbating the degeneration of basal ganglia neurons. (2) In Parkinson’s disease, impaired glutamate transporter function in astrocytes leads to decreased glutamate clearance and triggers neuronal toxicity. (3) In multiple system atrophy, oligodendrocyte dysfunction leads to neuronal demyelination and axonal damage. (4) In Huntington’s disease, microglia exacerbate neuroinflammation by mediating cytokine release via Toll-like receptor 4. (5) Therapeutic strategies targeting glial-neuronal interactions (e.g., cannabinoid-2 receptor agonists, nucleotide-binding oligomerization structural domain-like receptor protein 3 inhibitors, etc.) have demonstrated potential in both animal experiments and clinical trials. In conclusion, glial-neuronal interactions play a significant role in the pathological progression of basal ganglia neurodegenerative diseases. Therapeutic strategies targeting this mechanism demonstrate promising potential for treating these diseases. Figures and Tables | References | Related Articles | Metrics

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Efficacy of non-invasive neuromodulation techniques on autism spectrum disorder: a network meta-analysis Gao Shiai, Yu Zifu, Chen Jinhui, Cao Xinyan, Leng Xiaoxuan, Liu Xihua 2026, 30 (10):  2550-2559.  doi: 10.12307/2026.649 Abstract ( 34 )   PDF (2349KB) ( 1 )   Save OBJECTIVE: To systematically evaluate the rehabilitation efficacy of different non-invasive neuromodulation techniques in children with autism spectrum disorder by network meta-analysis.  METHODS: A literature search was conducted in CNKI, VIP, WanFang, China Biomedical Literature Database, PubMed, Web of Science, Cochrane Library, and Embase for randomized controlled trials of different non-invasive neuromodulation techniques to improve autism spectrum disorders. The search time was from database inception to January 2025, and two reviewers independently screened the literature, extracted the data, and evaluated the quality of the included studies, and used Stata 18.0 to perform a network meta-analysis of the data.  RESULTS: A total of 32 randomized controlled trials involving 8 intervention modalities were included. The results of network meta-analysis showed that based on the application of conventional rehabilitation training, virtual reality technology had the best effect in improving the score of the Autism Behavior Scale [standardized mean difference (SMD)=-12.55, 95% confidence interval (CI) (-20.85, -4.25), P < 0.05], followed by Theta burst magnetic stimulation [SMD=-11.34, 95% CI (-20.94, -1.74), P < 0.05], repetitive transcranial magnetic stimulation [SMD=-9.28, 95% CI (-12.80, -5.77), P < 0.05], and neurofeedback technology [SMD=-8.75, 95% CI (-15.26, -2.23), P < 0.05]. In terms of the Childhood Autism Rating Scale score, virtual reality technology had the most significant improvement effect [SMD=-6.36, 95% CI (-9.61, -3.11), P < 0.05], followed by repetitive transcranial magnetic stimulation [SMD=-5.98, 95% CI (-9.46, -2.51), P < 0.05], neurofeedback technology [SMD=-4.63, 95% CI (-9.14, -0.13), P < 0.05], and transcutaneous electrical nerve stimulation [SMD=-4.14, 95% CI (-5.73, -2.55), P < 0.05]. In terms of Autism Treatment Assessment Scale score, neurofeedback technology had the most significant improvement effect [SMD=-16.44, 95% CI (-24.10, -8.78), P < 0.05], followed by virtual reality technology [SMD=-14.09, 95% CI (-22.45, -5.73), P < 0.05], repetitive transcranial magnetic stimulation [SMD=-12.06, 95% CI (-16.45, -7.68), P < 0.05], transcutaneous electrical nerve stimulation [SMD=-10.58, 95% CI (-20.44, -0.72), P < 0.05], and transcranial direct current stimulation [SMD=-9.75, 95% CI (-18.62, -0.88), P < 0.05]. CONCLUSION: The current evidence suggests that different non-invasive neuromodulation techniques have different effects on the improvement of autism spectrum disorder on the basis of conventional rehabilitation training. Virtual reality shows the best effect in improving Autism Behavior Scale and Child Autism Rating Scale scores, while neurofeedback technology shows the most significant improvement in Autism Treatment Assessment Scale scores. Due to the limitations of the number and quality of included studies, these conclusions need to be validated by more high-quality studies. Figures and Tables | References | Related Articles | Metrics

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Meta-analysis of the effects of aquatic exercise on balance function and motor ability in elderly patients with Parkinson’s disease Li Tingwen, , Zhang Jianhua 2026, 30 (10):  2560-2568.  doi: 10.12307/2026.647 Abstract ( 44 )   PDF (2991KB) ( 0 )   Save OBJECTIVE: To systematically evaluate the effects of aquatic exercise on balance function and motor ability in elderly patients with Parkinson’s disease. METHODS: A comprehensive search for randomized controlled trial studies of aquatic exercise interventions for elderly patients with Parkinson’s disease was conducted in Chinese databases such as CNKI, WanFang, and VIP, as well as English databases including Web of Science, PubMed, EMBASE, ScienceDirect, and the Cochrane Library. The search period ranged from January 2000 to March 2024. The intervention group received aquatic exercise or combined aquatic and terrestrial exercise modalities, while the control group engaged in routine rehabilitation or land-based exercises. Outcome measures included the score of Part III of the Unified Parkinson’s Disease Rating Scale, the Berg Balance Scale score, the Timed Up and Go test, the Parkinson’s Disease Questionnaire-39 score, and the results of the 5-Minute Sit-to-Stand test. Two researchers independently extracted the data and assessed the risk of bias for each included study according to the Cochrane Handbook 5.3 criteria. Meta-analysis was performed using RevMan 5.3 statistical software. RESULTS: A total of 7 high-quality randomized controlled trials, involving 241 patients, were included in this meta-analysis. The results indicated that, compared with the control group, the intervention group showed significantly higher scores on the Berg Balance Scale [mean difference (MD)=5.30, 95% confidence interval (CI): 2.55-8.06, P=0.000 2] and the 5-Minute Sit-to-Stand test [MD=3.79, 95% CI: 1.84-5.75, P=0.0001] after the intervention. Additionally, the Timed Up and Go test time was significantly shorter in the intervention group [MD=-1.93, 95% CI: -2.64 to -1.22, P < 0.000 01]. However, there were no statistically significant differences between the two groups in the Part III of the Unified Parkinson’s Disease Rating Scale scores [MD=-1.31, 95% CI: -3.90-1.28, P=0.32] or the Parkinson’s Disease Questionnaire-39 scores [MD=-3.64, 95% CI: -9.77-2.49, P=0.24] after the intervention.  CONCLUSION: Aquatic exercise significantly improves balance function, lower limb muscle strength, gait speed, and mobility in elderly patients with Parkinson’s disease. However, its effects on overall motor functions such as upper limb coordination and fine motor skills, as well as on quality of life, remain unclear. Further studies with rigorous methodologies and longer intervention periods are warranted to validate these findings. Figures and Tables | References | Related Articles | Metrics

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Meta-analysis of lumbar bone mineral density, pain score and fall incidence in middle-aged and elderly osteoporosis patients undergoing whole-body vibration training Ren Pengbo, Li Tingwen, Cai Feng, Zhang Jian 2026, 30 (10):  2569-2575.  doi: 10.12307/2026.634 Abstract ( 47 )   PDF (1932KB) ( 0 )   Save OBJECTIVE: Numerous studies have confirmed that whole-body vibration training has a definite therapeutic effect on osteoporosis, effectively improving balance function and enhancing prognostic quality in such patients. Herein, we systematically evaluate the effects of whole-body vibration training on lumbar bone density, pain scores, and fall incidence rates in patients with osteoporosis. METHODS: The databases of PubMed, EMBASE, ScienceDirect, Cochrane Library, CNKI, VIP and WanFang Data, and China Biology Medicine (CBM) were searched by computer to screen out randomized controlled trials of middle-aged and elderly patients with osteoporosis who underwent whole-body vibration training. The trial group received whole-body vibration training, and the control group received only additional treatment or no intervention. The literature search was conducted using a combination of free terms and subject headings, and the search terms included “whole-body vibration training,” “middle-aged and elderly,” “quinquagenarian,” “osteoporosis,” “vibration therapy,” “mechanical vibration,” “visual analogue scale score,” and “fall incidence rates.” The retrieval period covered from the inception of each database to December 2024. Meta-analysis was performed using RevMan 5.3 statistical software. RESULTS: This meta-analysis included 10 randomized controlled trials with a total of 656 patients. The analysis results showed no statistically significant differences in lumbar bone mineral density [mean difference (MD)=0.01, 95% confidence interval (CI): -0.01 to 0.04, P=0.22], radial trabecular volumetric bone mineral density [MD=-0.87, 95% CI: -2.93 to 1.20, P=0.41], and tibial trabecular volumetric bone mineral density [MD=0.34, 95% CI: -0.69 to 1.38, P=0.52] between the two groups. However, the whole-body vibration training group had a significantly lower visual analog scale score [MD=-1.48, 95% CI: -2.91 to -0.05, P=0.04] and a lower fall incidence rate compared to the control group [odds ratio=0.52, 95% CI: 0.29 to 0.92, P=0.03]. CONCLUSION: Whole-body vibration training can significantly alleviate pain and reduce the incidence of falls in middle-aged and elderly patients, but the effect of improving lumbar bone mineral density is not obvious, and more research and follow-up with higher quality and longer intervention time are needed to further verify the conclusion. Figures and Tables | References | Related Articles | Metrics

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Theta-stimulation for the treatment of motor function and daily activity ability in the lower extremities of stroke patients: a meta-analysis Hu Xin, Wan Haili, Du Liang, Li Yongjie, Xia Yuan 2026, 30 (10):  2576-2583.  doi: 10.12307/2026.616 Abstract ( 43 )   PDF (2635KB) ( 0 )   Save OBJECTIVE: A meta-analysis was conducted to systematically evaluate the effect of intermittent theta-burst stimulation on improving lower limb motor function, balance function, and daily activity ability in stroke patients. METHODS: A comprehensive search was conducted on randomized controlled trials on intermittent theta-burst stimulation for stroke treatment, with a cutoff date of November 2024, from major bibliographic databases including Cochrane Library, Scopus, PubMed, Embase, ProQuest, Web of Science, CNKI, China Biomedical Literature Database, VIP, and WanFang databases. The inclusion criteria were met by trials that administered intermittent theta stimulation to the cerebellum/M1, with the experimental group receiving this stimulation and the control group receiving routine rehabilitation treatment. The meta-analysis was conducted using RevMan 5.3 and Stata 16.0. RESULTS: A total of 12 articles with 444 patients were included in the meta-analysis, which demonstrated that intermittent theta-burst stimulation can enhance the Fugl-Meyer score of the lower extremities in patients following stroke [WMD=2.87, 95% confidence interval (CI) (1.77, 3.98), P < 0.000 01] and the Berg Balance Scale score [WMD=5.79, 95% CI (3.80, 7.79), P < 0.000 01] and Modified Barthel Index [WMD=6.32, 95% CI (4.02, 8.44), P < 0.000 01]. Subgroup analysis revealed that when compared with 600 pulses, 1 200 stimulation pulses yielded a more pronounced enhancement in lower limb Fugl-Meyer scores [WMD=4.31, 95% CI (2.91, 5.71), P < 0.000 01], the Berg Balance Scale score [WMD =8.12, 95% CI (5.27, 10.98), P < 0.000 01] and the Modified Barthel Index [WMD=8.50, 95% CI (6.55, 10.45), P < 0.000 01]. CONCLUSION: Intermittent theta-burst stimulation has been demonstrated to enhance lower limb motor ability, balance function, and daily living ability scores in patients who have experienced a stroke. Among the various forms of intermittent theta stimulation, 1 200-pulse intermittent theta stimulation has been shown to yield the most significant improvements in lower limb motor ability, balance function, and daily living ability. Figures and Tables | References | Related Articles | Metrics

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Meta-analysis of the clinical efficacy of high-intensity interval exercise and middle-intensity continuous training in patients with coronary heart disease Hu Yujie, Xie Ping, , Lu Weijie, Yang Kang, Deng Yaoting, Liu Mengyang 2026, 30 (10):  2584-2593.  doi: 10.12307/2026.625 Abstract ( 26 )   PDF (2679KB) ( 0 )   Save OBJECTIVE: Although existing studies have suggested that high-intensity interval training may be more effective than moderate-intensity continuous training in improving cardiopulmonary function in patients with coronary heart disease, its clinical efficacy remains controversial. Therefore, this meta-analysis aims to systematically evaluate the clinical efficacy of high-intensity interval training versus moderate-intensity continuous training in patients with coronary heart disease.  METHODS: Randomized controlled trials of high-intensity interval training and moderate-intensity continuous training in cardiac rehabilitation of coronary heart disease were included by searching Chinese and English databases such as CNKI, WanFang Database, Wipro, PubMed, Cochrane Library, Embase, and Web of science. Meta-analysis of the final included literature was performed using Review Manager 5.3 and StataMP 17.  RESULTS: A total of 10 studies met the study criteria and included 773 patients. Compared with moderate-intensity continuous training, high-intensity interval training resulted in higher peak oxygen uptake and oxygen uptake at the first ventilatory threshold were higher [mean difference=1.30, 95% confidence interval (0.71, 1.89), P < 0.000 1; mean difference=1.54, 95% confidence interval (0.56, 2.53), P=0.002]. Both groups showed no significant difference in resting systolic blood pressure, resting diastolic blood pressure, resting heart rate and peak heart rate (P > 0.05).  CONCLUSION: Compared with moderate-intensity continuous training, high-intensity interval training is more advantageous in improving peak oxygen uptake and oxygen uptake at the first ventilation threshold in coronary artery disease, while has no significant effects on resting heart rate, peak heart rate, resting systolic blood pressure, and resting diastolic blood pressure. Figures and Tables | References | Related Articles | Metrics

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Effects of high-intensity interval training and moderate-intensity continuous training on cognitive function in patients with neurodegenerative diseases: a meta-analysis Tang Zhuolin, Yin Mingyue, Bai Mingyang, Zheng Huakun, Yan Henghao, Xu Kai, Liu Qian 2026, 30 (10):  2594-2607.  doi: 10.12307/2026.626 Abstract ( 38 )   PDF (5728KB) ( 0 )   Save OBJECTIVE: Cognitive impairment associated with neurodegenerative diseases seriously affects the quality of life of patients. High-intensity interval training and moderate-intensity continuous training can improve cognitive function by inducing the production of brain-derived neurotrophic factor and enhancing synaptic plasticity, but the advantages and disadvantages of the two are inconclusive. Therefore, the purpose of this study is to evaluate the difference between high-intensity interval training and moderate-intensity continuous training in improving cognitive function in patients with neurodegenerative diseases. METHODS: The Web of Science core collection, Medline (EBSCO Host), PubMed and Cochrane Library databases were searched to include randomized controlled trials on high-intensity interval training and moderate-intensity continuous training to improve cognitive function in neurodegenerative diseases patients. The search time was from the establishment of each database to July 25, 2024. The PEDro scale was used for quality evaluation, and R Studio (version 4.4.1) was used for meta-analysis. RESULTS: A total of 27 randomized controlled trials were included, with a total of 1 613 subjects (592 in the high-intensity interval training group; 405 cases in the moderate-intensity continuous training group; 616 cases in the control group). Compared with the control group (no or low-intensity exercise), both high-intensity interval training and moderate-intensity continuous training could significantly improve the cognitive function of patients with neurodegenerative diseases [Hedges’g=0.15, 95% confidence interval (0.02, 0.29), P=0.02; Hedges’g=0.74, 95% confidence interval (0.01, 1.47), P=0.04]. Subgroup analyses showed that different types of neurodegenerative diseases and different cognitive function assessment scales could significantly affect the interventional effect of moderate-intensity continuous training, and patients with Alzheimer’s disease could achieve greater cognitive improvement than those with Parkinson’s disease (Hedges’g = 2.24 vs. 0.15, P=0.02), The Mini-Mental State Examination could better capture the cognitive changes before and after intervention than the Unified Parkinson’s Disease Rating Scale (Hedges’g=4.21 vs. 0.25, P < 0.01). In addition, age has a significant impact on the effect of moderate-intensity continuous training intervention (P=0.08), and patients ≥ 65 years can achieve greater cognitive benefits than those under 65 years of age (Hedges’g=0.99 vs. 0.22). There was no significant difference in the improvement of cognitive function between high-intensity interval training and moderate-intensity continuous training [Hedges’g=-0.02, 95% confidence interval (-0.30, 0.26), P = 0.88]. CONCLUSION: Both high-intensity interval training and moderate-intensity continuous training can significantly improve the cognitive function of neurodegenerative diseases patients and are equally effective, but people of different ages may have different optimal training types: patients < 65 years old may have greater cognitive benefits through high-intensity interval training intervention, while patients ≥ 65 years old may have better cognitive function through moderate-intensity continuous training. It is worth noting that the interventional effect of moderate-intensity continuous training is subjected to multiple adjustments of disease type, evaluation tool and age, suggesting that a differentiated exercise prescription and evaluation system should be formulated according to the characteristics of patients in clinical practice. Figures and Tables | References | Related Articles | Metrics

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Current status and hotspot analysis of experimental research on electroacupuncture intervention for peripheral nerve regeneration: electroacupuncture parameters, acupuncture effects and molecular mechanisms Liu Tongyan, Li Yuan, Sun Wei, Yao Bing, Fang Shanshan, Zhou Lingyun 2026, 30 (10):  2608-2617.  doi: 10.12307/2026.637 Abstract ( 38 )   PDF (3410KB) ( 6 )   Save BACKGROUND: Currently, experimental research on electroacupuncture intervention for peripheral nerve injury is rapidly developing, involving various nerves and disease types. A bibliometric analysis of this field holds significant value. OBJECTIVE: To summarize the development history, current research status, hotspots and future trends in the field of experimental research on electroacupuncture intervention in peripheral nerve injury. METHODS: Literature related to electroacupuncture intervention for peripheral nerve regeneration was retrieved from CNKI, CBM, and Web of Science Core Collection databases up to December 2024. After screening, deduplication, and data cleaning, CiteSpace and VOSviewer were used to analyze the data and generate visual knowledge maps. RESULTS AND CONCLUSION: A total of 432 articles were included (181 from CNKI, 186 from CBM, and 65 from the Web of Science Core Collection). The annual publication count showed a fluctuating upward trend, with a number of core authors identified, but author and institutional distributions remained scattered without forming a cohesive core group. Chinese-language articles contained 599 keyword nodes, while English-language articles had 364. The main disease focuses were mononeuropathy, neuropathic pain, and diabetic peripheral neuropathy. Research depth has progressively increased, with current studies concentrating on optimal electroacupuncture parameters, acupuncture effects, and molecular mechanisms for these conditions. Astrocytes and microglia emerged as burst terms in Chinese and English literature, respectively. Future efforts should intensify experimental research on electroacupuncture intervention for peripheral nerve injury by enhancing collaboration among authors and institutions, integrating advanced technologies such as materials science and high-throughput sequencing, to identify new breakthroughs. These measures will collectively promote high-quality research output and advance the field. Figures and Tables | References | Related Articles | Metrics

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Visualization analysis of lumbar spondylolisthesis treatment research from a bibliometric perspective Huang Hailun, Wei Yatao, Liu Yongai, Wu Junzhe, Gao Heng, Sun Kui, Cao Zhenwen 2026, 30 (10):  2618-2628.  doi: 10.12307/2026.627 Abstract ( 34 )   PDF (5171KB) ( 2 )   Save BACKGROUND: Although treatment strategies for lumbar spondylolisthesis have diversified, existing studies mainly focus on single techniques or short-term outcomes, lacking systematic integration of global research trends and core hotspots. OBJECTIVE: To analyze the global research status, knowledge structure, core hotspots, and future directions in lumbar spondylolisthesis treatment through bibliometric and visualization tools. METHODS: Literature related to lumbar spondylolisthesis treatment was retrieved from the Web of Science database (2010–2025). Multi-dimensional analyses were conducted using CiteSpace, VOSviewer, and Excel, including annual publication volume, country/region contributions, institutional collaboration, author influence, journal distribution, co-cited references, and keyword co-occurrence/burst analysis. RESULTS AND CONCLUSION: A total of 367 publications were included, showing an overall upward trend (annual average: 26.5 papers) from 2010 to 2024, with 5 new studies published in early 2025. China led in publication output (130 papers), while the United States dominated academic influence with 3 072 total citations and an H-index of 32, acting as the hub of international collaboration networks. Key institutions included the University of California, San Francisco, and Mayo Clinic. World Neurosurgery had the highest number of publications and citations and the Journal of Neurosurgery-Spine ha the highest citation frequency. Notable authors included American scholar Mummaneni, pv (H-index 60) and Chinese scholar Tian Wei (7 papers). High-frequency keywords included “lumbar spondylolisthesis” (128 occurrences), “surgery” (104), “fusion” (75), and “minimally invasive surgery.” Burst keywords indicated shifts toward minimally invasive techniques, complication management, and interdisciplinary integration. Figures and Tables | References | Related Articles | Metrics

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Relationship between inflammatory factors and rheumatoid arthritis: a large-sample analysis based on the FinnGen R10 database and genome-wide association studies Jiang Kai, Rong Yifa, Jia Haifeng, Li Hanzheng, Lu Bowen, Liang Xuezhen, Li Gang 2026, 30 (10):  2629-2640.  doi: 10.12307/2026.617 Abstract ( 29 )   PDF (6621KB) ( 0 )   Save BACKGROUND: Rheumatoid arthritis is a chronic, systemic autoimmune disease, and its pathogenesis involves multiple inflammatory factors and metabolites. However, the causal relationships are not yet clear. In China, although the diagnosis and treatment of rheumatoid arthritis have improved in recent years, some patients still suffer from disabilities due to a lack of early diagnosis and standardized treatment. OBJECTIVE: To assess the potential causal relationships between inflammatory factors and rheumatoid arthritis using Mendelian randomization methods, providing new support and perspectives for clinical research in order to fill the gap in the understanding of the relationship between the pathogenesis of rheumatoid arthritis and inflammatory factors, thereby providing new potential targets and guidance for the treatment and prevention of rheumatoid arthritis. METHODS: The disease data were obtained from a genome-wide association study in the FinnGen R10 database, including genetic data from 13 621 patients with rheumatoid arthritis and 262 844 healthy controls. The 91 inflammatory factors were derived from a meta-analysis of 11 cohorts, involving 14 824 participants of European descent. For the forward Mendelian randomization analysis, a P-value of < 5 × 10−6 was used to identify instrumental variables related to inflammatory factors and rheumatoid arthritis. For the reverse Mendelian randomization analysis, a P-value of < 5 × 10−8 was used to identify instrumental variables related to rheumatoid arthritis and inflammatory factors. The linkage disequilibrium parameters for both forward and reverse analyses were set at 0.001, and the genetic distance was set at 10 000 kb. Only instrumental variables with an F-statistic greater than 10 were considered, and confounding factors were removed. The causal relationships between the 91 inflammatory factors and rheumatoid arthritis were studied using methods such as inverse variance weighting, MR-Egger, weighted median, simple mode, and weighted mode, with inverse variance weighting being the primary method. A P-value of < 0.05 was considered significant. Heterogeneity and horizontal pleiotropy were excluded if their P-values were > 0.05. Reverse Mendelian randomization analysis was also conducted to exclude reverse causality. RESULTS AND CONCLUSION: (1) C-C motif chemokine 23 [odds ratio (OR): 0.921, P=0.006], fibroblast growth factor 19 (OR=0.906, P=0.046), interleukin-12 subunit beta (OR=0.899, P=0.009), interleukin-2 (OR=0.889, P=0.024), and leukemia inhibitory factor receptor (OR=0.876, P=0.047) have protective effects on rheumatoid arthritis. (2) In contrast, C-C motif chemokine 19 (OR=1.118, P=0.032), C-C motif chemokine 4 (OR=1.107, P=0.004), interleukin-7 (OR=1.211, P=0.018), and tumor necrosis factor (OR=1.119, P=0.040) have detrimental effects on rheumatoid arthritis. These findings provide new insights and evidence for the role of inflammatory factors in rheumatoid arthritis, filling the gap in this field and potentially leading to new strategies for the prevention and treatment of rheumatoid arthritis. Figures and Tables | References | Related Articles | Metrics

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Screening of genes related to mitochondrial dysfunction and ferroptosis in atherosclerosis and target prediction of regulatory traditional Chinese medicine Qi Xiang, Cao Shan, Chen Jian, Zhang Yijia, Liu Keke, Xu Zifu, Liu Wang, Fu Xiaoxiao, Yin Xiaolei 2026, 30 (10):  2641-2652.  doi: 10.12307/2026.635 Abstract ( 33 )   PDF (12598KB) ( 1 )   Save BACKGROUND: Mitochondrial dysfunction and ferroptosis are widely involved in the development of atherosclerosis. Research on biomarkers related to mitochondrial dysfunction and ferroptosis in atherosclerosis is important for disease diagnosis and treatment.  OBJECTIVE: To investigate mitochondrial dysfunction- and ferroptosis-related biomarkers in the pathogenesis of atherosclerosis using bioinformatics and machine learning algorithms, and to predict potential regulatory traditional Chinese medicines (TCMs).  METHODS: The atherosclerosis dataset GSE100927 was obtained from the GEO database (which is the gene expression database, developed by the National Center for Biotechnology Information in 2000, collects and organizes gene expression data submitted by research institutions and scientists worldwide), and differentially expressed genes were identified, followed by immune infiltration analysis. Weighted correlation network analysis (WGCNA) identified atherosclerosis-related module genes. These module genes were intersected with mitochondrial dysfunction genes, ferroptosis genes, and differentially expressed genes. Consensus clustering analysis was performed on the disease group data based on the intersected genes, and differentially expressed genes between the clusters were identified. Enrichment analysis of the differentially expressed genes was conducted. Hub genes were screened using machine learning algorithms, including the least absolute shrinkage and selection operator (LASSO) and random forest. An atherosclerosis cell model was constructed using RAW264.7 cells, and hub genes were validated through qPCR. Finally, databases were used to predict TCMs regulating the Hub genes. RESULTS AND CONCLUSION: Five intersected genes were identified by intersecting differentially expressed genes, WGCNA module genes, and mitochondrial dysfunction- and ferroptosis-related genes. Consensus clustering analysis based on these five genes identified two subtypes. Differential analysis between the subtypes revealed 994 subtype-specific differentially expressed genes related to mitochondrial dysfunction and ferroptosis. Three hub genes, dematin actin binding protein (DMTN), Fc gamma receptor IIIa (FCGR3A), and microsomal glutathione S-transferase 1 (MGST1), were predicted using two machine learning algorithms. Experimental validation suggested that DMTN and MGST1 have significant diagnostic values. TCM prediction results indicated that Angelica sinensis and cinnamon may regulate DMTN and MGST1. To conclude, DMTN and MGST1 have diagnostic values and can serve as characteristic genes related to mitochondrial dysfunction and ferroptosis in atherosclerosis. TCMs such as Angelica sinensis and cinnamon have potential as regulators of these genes and warrant further research. Figures and Tables | References | Related Articles | Metrics

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Analysis of thematic evolution pathways in the field of physical activity and neurogenesis Jiao Jingya, Zhang Yeting 2026, 30 (10):  2653-2661.  doi: 10.12307/2026.628 Abstract ( 32 )   PDF (2518KB) ( 3 )   Save BACKGROUND: Neurogenesis is the ability of neural stem cells, or neural progenitors, to generate new nerve cell types. Exercise has been shown to promote neurogenesis; however, the underlying mechanisms involved remain unclear. In recent years, research on the relationship between physical activity and neurogenesis has been increasing, with evolving research hotspots and trends in this field. Therefore, it is necessary to conduct a comprehensive review of the literature in this field. OBJECTIVE: To explore the dynamic evolution of research topics in the field of physical activity and neurogenesis using bibliometric methods, and to clarify its developmental status and changes in knowledge structure, thereby providing guidance for future research directions. METHODS: Based on the Web of Science Core Collection database, the search strategy for the topic terms was defined as: TS=(“physical exercise” AND neurogenesis) OR TS=(“physical activity” AND neurogenesis) OR TS=(“exercise” AND neurogenesis), with the document types limited to (Article OR Review). Following the inclusion and exclusion criteria, 2 469 relevant documents were selected as the research dataset, and SciMAT software was employed for visualization analysis. RESULTS AND CONCLUSION: The field of “physical activity and neurogenesis” can be categorized into seven major evolutionary directions: “progenitor cells,” “neurotrophic factors,” “dementia,” “neural progenitor cells,” “neural precursor cells,” “exercise interventions,” and “antioxidants,” which collectively form 25 sub-evolutionary pathways. Topics such as “enriched environment,” “neurotrophic factors,” and “cognitive function” are likely to become future research focuses. This field primarily targets populations such as older adults, children, and adolescents, with a specific emphasis on diseases like dementia. Moreover, exploring the molecular biological mechanisms through which physical activity promotes neurogenesis has significantly advanced research in this field. Figures and Tables | References | Related Articles | Metrics

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Cathepsin F as a potential serum biomarker for stroke risk prediction: GWAS database data analysis Tian Meng, Lou Tianwei, Zhang Yongchen, Jia Hongling 2026, 30 (10):  2662-2670.  doi: 10.12307/2026.606 Abstract ( 34 )   PDF (2863KB) ( 0 )   Save BACKGROUND: Prior research has indicated a correlation between cathepsins and stroke, but the nature of this relationship—whether causal—has yet to be established.  OBJECTIVE: To scrutinize the potential causal links between cathepsins and stroke using the Mendelian randomization method.  METHODS: Leveraging summary statistics from genome-wide association studies (GWAS, developed jointly by the U.S. National Human Genome Research Institute and the European Bioinformatics Institute), we performed Mendelian randomization analyses using both univariable and multivariable approaches to investigate the causal associations of various cathepsin types with stroke risk and its specific subtypes. The inverse variance weighting method was used as the main method to assess the causal association effect, and the weighted median method and MR-Egger regression were used to assess the reliability and stability of the results. RESULTS AND CONCLUSION: (1) The univariable Mendelian randomization analysis revealed that elevated Cathepsin S levels were associated with a reduced likelihood of cardioembolic stroke (odds ratio [OR]=0.901, 95% confidence interval [CI]: 0.832-0.976, P=0.010). However, this causal effect was not corroborated in the reverse Mendelian randomization analysis. The reverse Mendelian randomization analysis suggested that Cathepsin E Subtype (CES) could contribute to lower Cathepsin L2 levels (P=0.020, OR = 0.984, 95% CI=0.972-0.998), yet this finding lacked statistical significance in the multivariable context. A multivariable analysis, incorporating nine cathepsin types, indicated that elevated Cathepsin F levels were associated with an increased risk of all-cause stroke and ischemic stroke (OR=4.667, 95% CI=1.000-21.782, P=0.050, OR=4.771, 95% CI=1.044-21.804, P=0.044). Even after accounting for potential confounding factors, the Mendelian randomization analysis indicated that Cathepsin F holds promise as a serum biomarker for predicting stroke risk. (2) This study is primarily based on the analyses of international databases and European population data, which can serve as a reference for large-scale cohort studies in China and provide technical insights for the development of precision medicine research in China. However, it is essential to consider the differences in genetic background, environmental factors, and lifestyle among the Chinese population, and to conduct biomedical research that aligns with the unique characteristics of Chinese individuals. Figures and Tables | References | Related Articles | Metrics

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Immune cells synergistically regulate inflammatory response, muscle regeneration and metabolic homeostasis in training-induced stress responses Mao Sujie, Gao Jie, Pan Zhuangli 2026, 30 (10):  2671-2680.  doi: 10.12307/2026.648 Abstract ( 18 )   PDF (2651KB) ( 0 )   Save BACKGROUND: Regular physical training modulates immune activity and contributes to improved health and physical performance. However, how immune cells enhance athletic performance through inflammatory regulation, metabolic synergy, and other mechanisms has not been systematically theoretically reported. OBJECTIVE: To sort out the roles of immune cells in muscle repair, energy metabolism and fatigue recovery, and to construct a theoretical framework of “immune regulation-athletic performance.” METHODS: PubMed, Web of Science, Embase and CNKI were searched for literature related to athletic performance and immunity. The search date was until March 1, 2025. Research and review literature related to immune regulation for athletic performance published in recent years was screened, and the synergistic mechanism of immune exercise was explored by combining literature topic summary and mechanism analysis.   RESULTS AND CONCLUSION: In the stress stage caused by sports training, immune cells promote muscle fiber recovery and maintain a stable metabolic state by regulating inflammatory response. The timing, tissue specificity and matching of immune responses with training load are key factors affecting the improvement of athletic performance. The immune system not only plays a role in health defense during exercise adaptation, but also plays a key role in regulating athletic performance. Future research should strengthen causal verification of the mechanism chain and promote multi-omics foundations. Figures and Tables | References | Related Articles | Metrics