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    08 June 2026, Volume 30 Issue 16 Previous Issue    Next Issue
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    BTN3A2 is a key target for the development or prevention of new drugs for knee osteoarthritis: a randomization study based on drug targeting
    Wei Bingqi, Sun Jiahui, Chen Liu, Li Yijing, Wan Hejia, Qi Yifan, Wang Shangzeng
    2026, 30 (16):  4021-4029.  doi: 10.12307/2026.703
    Abstract ( 81 )   PDF (18842KB) ( 8 )   Save
    BACKGROUND: Knee osteoarthritis has a high prevalence in China, and current therapeutic drugs are often associated with side effects and adverse reactions.
    OBJECTIVE: To explore the causal relationship between druggable genes and knee osteoarthritis using the Mendelian randomization approach, thereby providing a reference framework for the development of new drugs for knee osteoarthritis.
    METHODS: This study utilized data from 2 941 druggable genes in the FinnGen database and knee osteoarthritis-related data from the Genome-Wide Association Study (GWAS) Catalog database. Drug target mendelian randomization analysis, false discovery rate correction, and co-localization analysis were conducted to identify potential drug targets for knee osteoarthritis. The final results were validated using the eQTLGen Consortium database to enhance the reliability of the identified drug targets.
    RESULTS AND CONCLUSION: A total of 2 941 druggable genes were analyzed using Mendelian randomization and 21 potential drug targets were identified. Following false discovery rate correction and sensitivity analyses, two drug targets were retained: Dipeptidase 1 (DPEP1) and Butyrophilin Subfamily 3 Member A2 (BTN3A2). Further co-localization analysis identified BTN3A2 as the sole key drug target. Validation using the eQTLGen Consortium database, which includes 2 525 drug-target genes, further confirmed the significant causal relationship between BTN3A2 and knee osteoarthritis. To conclude, BTN3A2 is identified as a key therapeutic target for the development of novel drugs or preventive interventions for knee osteoarthritis. This study primarily relied on international genetic databases to identify potential drug targets, providing a reference framework for drug development tailored to the Chinese population. The findings contribute to the establishment of a robust, effective, clearly defined, and low-side-effect framework for the prevention and treatment of knee osteoarthritis in Chinese patients.
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    Cone beam computed tomography of the distance and position of the root apex of the mandibular second molar relative to the mandibular canal
    Weng Zhirong, Gegentana
    2026, 30 (16):  4030-4037.  doi: 10.12307/2026.700
    Abstract ( 81 )   PDF (1807KB) ( 72 )   Save
    BACKGROUND: The root morphology of the mandibular second molar is complex and diverse, making root canal treatment challenging. In addition to the mandibular third molar, the root apex of the mandibular second molar is the closest to the mandibular canal among the mandibular posterior teeth. During root canal treatment and apical surgery on the mandibular second molar, the inferior alveolar nerve is at risk of accidental damage, which can lead to changes in temperature sensation, pain, and mechanical sensitivity in the affected area, ultimately impacting the oral physiological functions of patients.
    OBJECTIVE: To investigate the distance and positional relationship between the root apex of the mandibular second molar and the mandibular canal across various anatomical types, and to evaluate the influence of sex, side, and age on this relationship with the purpose of enhancing the safety of mandibular second molar treatments.
    METHODS: The cone beam computed tomography data of 330 eligible patients were included in the final analysis. A total of 660 mandibular second molars from 164 males and 166 females were analyzed. The cohort included 200 cases in the youth group, 103 cases in the middle-aged group, and 27 cases in the older adult group. The distance and positional relationship between the root apex of the mandibular second molar and the mandibular canal were measured across different subtypes, including conical fused root type, double-rooted type, and C-shaped root type. SPSS 24.0 software was used to compare and analyze the differences across genders, sides, and ages.
    RESULTS AND CONCLUSION: (1) The most common type of double-rooted type was often found in males. This root morphology in female and young individuals was more complex, and the detection rates for conical fused roots and C-shaped roots were higher. (2) The apex of the conical fused root was closest to the mandibular canal, followed by the C-shaped root and then the double-rooted type. The distal root of the double-rooted type was closer to the mandibular canal than the mesial root. In males, the distance from the mandibular canal to the proximal and distal roots of the double-rooted type was greater than in females. Additionally, the distance between the mandibular canal and the root apex of the mandibular second molar increased with age. (3) The positional relationship between the mandibular canal and the mandibular second molar can be classified as buccal lateral, directly below the root apex, lingual lateral, close to the root apex, or through the root tip. Conical fused roots and C-shaped roots in females are more likely to be located directly above the mandibular canal than in males. (4) The results indicated that conical fused roots and C-shaped roots were more common in female and young individuals, with a shorter distance between the root apex and the mandibular canal. Furthermore, the positions of these two root types were closely related, which increases the risk of damage to the inferior alveolar nerve during root canal treatment.
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    Relationship between spatio-temporal gait characteristics and fall risk in stroke patients
    Xu Feng, Gu Dongyang, Zhu Zihao, Li Qiujie, Wan Xianglin
    2026, 30 (16):  4038-4044.  doi: 10.12307/2026.335
    Abstract ( 89 )   PDF (1196KB) ( 66 )   Save
    BACKGROUND: Abnormalities in the spatio-temporal gait characteristics of stroke patients are closely associated with their risk of falling.
    OBJECTIVE: To construct a model for assessing the fall risk of stroke patients based on spatio-temporal gait parameters, thereby providing a foundation for refining the fall risk assessment system and optimizing fall prevention strategies for such patients.
    METHODS: Thirty-four stroke patients with unilateral hemiplegia who were discharged after recovery were recruited. These patients were divided into two groups based on whether they had a history of falls within 6 months prior to testing: the faller group (with a history of falls) and the non-faller group (without a history of falls). The Qualisys infrared motion capture system was employed to collect the coordinates of surface markers on the patients’ bodies during walking, from which temporal-spatial gait parameters were calculated. Univariate analysis was used to compare the spatio-temporal gait parameters between the two groups, and logistic regression analysis was conducted to establish a regression model for assessing the fall risk of patients.
    RESULTS AND CONCLUSION: (1) A total of 34 eligible participants were included in the study, comprising 19 individuals in the faller group and 15 in the non-faller group. (2) The faller group exhibited a significantly higher percentage of stance phase on the unaffected side compared with the non-faller group (P < 0.05). Additionally, the faller group had significantly lower values for the percentage of swing phase on the unaffected side, stride length on the unaffected side, stride length on the affected side, double support time, and walking speed compared with the non-faller group (P < 0.05). (3) The variables ultimately included in the logistic regression model were the percentage of stance phase on the unaffected side and double support time (P < 0.05). The overall accuracy of this model was 79.4%, with a sensitivity of 73.7% and specificity of 86.7%. To conclude, the percentage of stance phase on the unaffected side and double support time during walking in stroke patients can effectively assess fall risks. The fall risk assessment model for stroke patients constructed based on spatio-temporal gait parameters can provide clinicians with a basis for screening patients at high risk of falls and implementing early preventive treatments.
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    Predictive efficacy of machine learning models for postoperative prognosis in older adult patients with acute intracerebral hemorrhage
    Chen Feijun, Chen Yingguo, Li Zhengyang, Hu Yuan, Li Fang
    2026, 30 (16):  4045-4053.  doi: 10.12307/2026.707
    Abstract ( 83 )   Save
    BACKGROUND: Recent studies on the pathological mechanisms of acute intracerebral hemorrhage have shown that the occurrence of poor postoperative prognosis in patients with acute intracerebral hemorrhage is directly related to brain tissue edema caused by intracerebral hemorrhage. The severity of brain tissue edema is closely associated with a cascade reaction of inflammatory factors.
    OBJECTIVE: To investigate the correlation between serum inflammatory factor protein levels and postoperative brain edema volume in older adult patients with acute intracerebral hemorrhage using machine learning algorithms to analyze their impact on the occurrence of poor postoperative prognosis.
    METHODS: A total of 250 older adult patients with acute cerebral hemorrhage who underwent surgery at Yichun People's Hospital between June 2022 and June 2024 were included in this study. They were divided into a poor prognosis group and a good prognosis group based on their postoperative outcomes. Relevant patient data were collected to analyze the correlation between serum levels of matrix metalloproteinase-9, NOD-like receptor protein 3, and angiopoietin-like protein 2 and postoperative brain edema volume. A risk factor analysis was conducted using the occurrence of poor postoperative outcomes as the dependent variable. Risk prediction models for poor postoperative outcomes in older adult patients with acute cerebral hemorrhage were constructed using machine learning algorithms, including Logistic regression, Classification and Regression Tree, Back Propagation Neural Network, and Support Vector Machine. The receiver operating characteristic curve was used to assess the predictive efficacy of the different algorithms.
    RESULTS AND CONCLUSION: (1) Among the 250 patients included in this study, 113 patients (45.20%) were assigned to the poor prognosis group, while 137 patients (54.80%) to the good prognosis group. (2) Multivariate analysis revealed that matrix metalloproteinase-9 (OR = 1.037, 95% CI = 1.010-1.064, P = 0.007), NOD-like receptor protein 3 (OR = 64.050, 95% CI = 5.139-798.325, P = 0.001), angiopoietin-like protein 2 (OR = 82.519, 95% CI = 6.961-978.225, P < 0.001), and brain edema volume (OR = 6.859, 95% CI = 2.109-22.309, P = 0.001) were independent factors associated with poor postoperative outcomes in older adult patients with acute cerebral hemorrhage. (3) The Classification and regression Tree algorithm indicated that NOD-like receptor protein 3, brain edema volume, and matrix metalloproteinase-9 were risk factors associated with poor postoperative outcomes. (4) The Back Propagation Neural Network algorithm ranked the influential factors as follows: Angiopoietin-like protein 2 > NOD-like receptor protein 3 > matrix metalloproteinase-9 > brain edema volume > tumor necrosis factor-alpha > National Institutes of Health Stroke Scale (NIHSS) score > history of alcohol consumption > history of hypertension > amount of blood loss > duration of illness. (5) The Support Vector Machine algorithm identified the top five influential factors as NOD-like receptor protein 3 (predictor importance = 0.25), angiopoietin-like protein 2 (predictor importance = 0.22), amount of blood loss (predictor importance = 0.14), tumor necrosis factor-alpha (predictor importance = 0.12), and brain edema volume (predictor importance = 0.10). (6) Among the four machine learning algorithms evaluated, the Support Vector Machine algorithm demonstrated the best predictive performance. (7) Results from this study suggest that serum levels of matrix metalloproteinase-9, NOD-like receptor protein 3, and angiopoietin-like protein 2 in older adult patients with acute cerebral hemorrhage are correlated with postoperative brain edema volume. These factors can be used to construct a risk prediction model for postoperative outcomes using machine learning algorithms, with the Support Vector Machine algorithm showing the best diagnostic efficacy.


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    Cerebral palsy decoction improves cerebral palsy in male and female young rats: mechanisms based on the “gut-brain-muscle” axis
    Zou Yuxiong, Liu Xiaomeng, Liu Ying, Zhu Yue, Li Shuming, Guo Fangyang, Yu Xinyu, Nie Heyun, Liu Qian, Ao Meiying
    2026, 30 (16):  4054-4066.  doi: 10.12307/2026.715
    Abstract ( 94 )   PDF (17660KB) ( 8 )   Save
    BACKGROUND: Based on over 20 years of clinical experience with cerebral palsy decoction at Jiangxi Provincial Hospital of Traditional Chinese Medicine, its efficacy and safety have been confirmed in the treatment of cerebral palsy, but the underlying mechanisms remain unclear.
    OBJECTIVE: To investigate the effects and correlations of cerebral palsy decoction on gut microbiota, neural cells and neurotransmitters, as well as motor dysfunction in both female and male young rats with cerebral palsy.
    METHODS: The cerebral palsy model was prepared in Sprague-Dawley young rats subjected to intrauterine infection and hypoxia combined with postnatal movement restriction. After modeling, the model group and the administration group were administered normal saline and cerebral palsy decoction via gavage, respectively. Administration in each group lasted 15 days. Behavioral performance was assessed using the suspension test and slope test. Pathological changes in brain tissue were observed through hematoxylin-eosin staining and Nissl staining. Neurotransmitter levels were measured using ELISA, and gut microbiota was analyzed by 16S rDNA high-throughput sequencing.
    RESULTS AND CONCLUSION: (1) Compared with the model group, the administration group showed enhanced behavioral abilities in slope and suspension tests (P < 0.01). (2) Compared with the model group, the number of neuronal cells and Nissl bodies in the hippocampus and cerebral cortex increased in the administration group. (3) In the hippocampus, compared with the model group, the administration group exhibited elevated acetylcholine levels (male: P < 0.05; female: P > 0.05), decreased acetylcholinesterase levels (male: P < 0.01; female: P < 0.01), increased norepinephrine levels (male: P < 0.05; female: P < 0.001), and elevated serotonin levels (male: P < 0.05; female: P > 0.05). (4) In the cerebral cortex, compared with the model group, the administration group showed increased acetylcholine levels (male: P < 0.05; female: P > 0.05), decreased acetylcholinesterase levels (male: P < 0.05; female: P > 0.05), elevated norepinephrine levels (male: P < 0.01; female: P < 0.05), and increased serotonin levels (male: P < 0.01; female: P < 0.01). (5) Compared with the model group, the administration group demonstrated significant improvements in the diversity and abundance of gut microbiota, including the genera norank_f__Oscillospiraceae, Escherichia, norank_f__Muribaculaceae, and Lactobacillus. The improvements in gut microbiota diversity and abundance showed significant differences between male and female rats. These findings indicate that the clinical empirical formula, cerebral palsy decoction, can effectively improve motor dysfunction in young rats with cerebral palsy by modulating the structure and abundance of gut microbiota, promoting the development of neurons and Nissl bodies in brain tissues, and influencing neurotransmitter levels. This establishes a “gut-brain-muscle” axis association.

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    Role and mechanism by which acupuncture regulates autophagy in a rat model of cerebral hemorrhage
    Ji Dejiang, Zhang Xiaojing, Ye Gaxi
    2026, 30 (16):  4067-4076.  doi: 10.12307/2026.705
    Abstract ( 70 )   PDF (2922KB) ( 19 )   Save
    BACKGROUND: Research has found that cellular autophagy is an important target for treating cerebral hemorrhage. Acupuncture improves cerebral blood flow, alleviates inflammatory responses, and promotes nerve regeneration by regulating neuronal apoptosis, pyroptosis, autophagy, and other processes, thereby protecting against nerve injury induced by cerebral hemorrhage.
    OBJECTIVE: To explore the potential regulatory mechanism of acupuncture at both Baihui and Xuanli on autophagy response caused by cerebral hemorrhage in rats and the recovery of neural function after cerebral hemorrhage. 
    METHODS: Sixty-three male Sprague-Dawley rats were randomly divided into seven groups. (1) Except for the sham operation group, a cerebral hemorrhage model was prepared based on autologous blood injection. (2) In the acupuncture group, acupuncture at both Baihui and Xuanli was initiated on the second day post-modeling, administered twice daily. In the 3-methyladenine group, the autophagy inhibitor 3-methyladenine was injected into the lateral ventricle 15 minutes prior to modeling. (4) In the 3-methyladenine+acupuncture group, the same acupuncture treatment as the acupuncture group was given based on the treatment in the 3-methyladenine group. (5) In the rapamycin group, the autophagy activator rapamycin was injected into the lateral ventricle 15 minutes before modeling. (6) In the rapamycin+acupuncture group, based on the treatment in the rapamycin group, the same acupuncture treatment as the acupuncture group was performed. Neurological dysfunction in rats was assessed using the Longa score at 1, 3, and 7 days after acupuncture. Hematoxylin-eosin staining was used to observe pathological changes in rat brain tissue. Immunohistochemistry was used to detect the expression of the autophagy protein LC3. RT-qPCR was used to detect the expression of autophagy genes. Western blot was used to detect the expression of related proteins in rat brain tissue.
    RESULTS AND CONCLUSION: (1) Longa score results showed that acupuncture reduced nerve injury caused by cerebral hemorrhage in rats. (2) In the sham operation group, the structural layers of the rat brain were clear, and cells were arranged regularly; in the model group, there was infiltration of inflammatory cells and microglia; in the acupuncture group, inflammatory injury and cellular swelling decreased over time; in the 3-methyladenine group, inflammatory cell infiltration increased over time, and microglia proliferated freely; in the 3-methyladenine+acupuncture group and the rapamycin group, inflammatory cell infiltration gradually decreased, and neuronal cells gradually arranged in an orderly manner; in the rapamycin+acupuncture group, inflammatory cell infiltration decreased with increasing acupuncture time, and neurons remained normal and arranged regularly. (3) On day 7 of acupuncture, compared with the sham operation group, the model group showed significantly increased LC3 expression (P < 0.05), significantly decreased p62 expression (P < 0.05), and significantly increased p-mTOR and p-p70S6K expression (P < 0.05). Compared with the model group, the acupuncture group showed significantly increased LC3 expression, while p62, p-mTOR, and p-p70S6K expressions were significantly reduced (P < 0.05). Compared with the 3-methyladenine group, LC3 expression was significantly increased, and p62, p-mTOR, and p-p70S6K expressions were significantly reduced (P < 0.05) in the 3-methyladenine+acupuncture group. Compared with the rapamycin group, the rapamycin+acupuncture group showed significantly reduced LC3 expression (P < 0.05), significantly increased p62 expression (P < 0.05), and no significant difference in p-mTOR and p-p70S6K expression (P > 0.05). In conclusion, acupuncture at both Baihui and Xuanli can promote the recovery of neurological function in rats with cerebral hemorrhage and promote autophagy by activating the mTOR/p70S6K signaling pathway.

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    Sonic hedgehog signaling pathway regulates the formation and septation of the outflow tract in the embryoic mouse heart
    Yao Kaining, Yan Yunan, Zhou Yifan, Shi Liang, Cao Ximei, Zeeshan Rahim, Yang Yanping
    2026, 30 (16):  4077-4087.  doi: 10.12307/2026.679
    Abstract ( 57 )   PDF (22204KB) ( 4 )   Save
    BACKGROUND: Second heart field and cardiac neural crest are involved in the formation and septation of the outflow tract. However, the exact regulatory mechanism of the Sonic hedgehog (Shh) signaling pathway in this process have not been clarified.
    OBJECTIVE: To explore the regulatory role of the components of the Shh signaling pathway in the formation and septation of outflow tract.
    METHODS: Mouse embryos at embryonic 10-15 days were obtained from pregnant ICR mice, and serial section samples were prepared after paraffin embedding to observe the spatiotemporal expression patterns of insulin gene enhancer binding protein-1 (isl-1), sonic hedgehog (Shh), Ptch1, Ptch2, Smoothened, Gli3, and bone morphogenetic protein 2 by immunohistochemical staining and double immunofluorescence staining. The foregut and adjacent mesoderm mesenchyme of mouse embryos at embryonic 10.5 days were dissected and the relationship between the Shh signaling pathway and bone morphogenetic proteins and cells in the second heart field and cardiac neural crest was explored by western blot and co-immunoprecipitation.
    RESULTS AND CONCLUSION: (1) On embryonic 10-11.5 days, the expression of Shh and Gli3 was seen in the pharyngeal endoderm, whereas the expression of Ptch1, Ptch2, and Smoothened was coupled to the development of respiratory endoderm. The respiratory endoderm formation resulted in an increase in isl-1-
    positive progenitors in the second heart field and was involved in the development of the outflow tract. Components of the Shh signaling pathway were not expressed in the core mesenchyme of the branchial arch, but appeared in the dorsal wall of the pericardial cavity. (2) During the formation and fusion of the outflow tract endocardial cushion, Ptch1, Ptch2, and Smoothened were expressed in the myocardium, and Gli3 was expressed in the mesenchymal cells of the myocardium and endocardial cushion, as well as in the walls of the aortic and pulmonary trunk. (3) On embryonic 10-11.5 days, isl-1 and bone morphogenetic protein 2 were co-expressed in the foregut endoderm and second heart field. Activating protein 2α-positive cardiac neural crest cells surrounding the aortic arch arteries co-expressed either Gli3 or bone morphogenetic protein 2. Co-immunoprecipitation result showed that activating protein 2α interacted with Gli3 or bone morphogenetic protein 2. These findings indicate that the Shh signaling pathway contributes to second heart field development, and plays variant roles in the formation, migration, and differentiation of the second heart field subpopulations. The Shh signaling pathway has a sustained role in endocardial cushion formation and fusion of the outflow tract. Gli3 and bone morphogenetic protein 2 cooperatively regulate the migration of cardiac neural crest cells.

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    Treatment of acute myeloid leukemia with corynoline: network pharmacology analysis of potential mechanisms and experimental validation
    Zhou Wu, Zhang Jingxin, Liu Yuancheng, Hu Chenglong, Wang Siqi, Xu Jianxia, Huang Hai, Wei Sixi
    2026, 30 (16):  4088-4104.  doi: 10.12307/2026.706
    Abstract ( 86 )   PDF (11133KB) ( 15 )   Save
    BACKGROUND: Corynoline has been shown to possess pharmacological activity against tumors such as esophageal squamous cell carcinoma and triple-negative breast cancer. However, its pharmacological effects and molecular mechanisms in treating acute myeloid leukemia remain poorly understood.
    OBJECTIVE: To investigate the therapeutic effects of corynoline on acute myeloid leukemia and its underlying molecular mechanisms.
    METHODS: Human acute myeloid leukemia cell lines Kasumi-1 and MOLM-13 were cultured in vitro and treated with varying concentrations of corynoline (4, 6, and 8 μmol/L), with dimethyl sulfoxide used as a control. The cell viability was detected using CCK-8 assay for 24, 48, and 72 hours, and the pharmacological activity of corynoline was assessed by flow cytometry. The target genes for corynoline treatment of acute myeloid leukemia were predicted using network pharmacology. Potential mechanisms were analyzed through GO and KEGG analysis. A protein interaction network was constructed, and core targets were identified using clinical correlation analysis. The binding affinity to these core targets was assessed through molecular docking and molecular dynamics simulations. Finally, the molecular mechanisms by which corynoline treats acute myeloid leukemia were evaluated using quantitative reverse transcription-polymerase chain reaction and Western blot assays.
    RESULTS AND CONCLUSION: (1) Corynoline inhibited the proliferation of acute myeloid leukemia cells, induced apoptosis, and caused G2/M cell cycle arrest. (2) Network pharmacology identified 102 intersecting target genes associated with corynoline and acute myeloid leukemia. (3) GO and KEGG analyses revealed that corynoline treated acute myeloid leukemia by regulating protein phosphorylation, inducing apoptosis, and targeting the phosphoinositide 3-kinase/protein kinase B signaling pathway. (4) The protein-protein interaction network and clinical correlation analysis identified retinoic acid receptor beta, prostaglandin-endoperoxide synthase 2, mouse double minute 2, and mitogen-activated protein kinase 14 as core targets. Molecular docking and dynamics simulations demonstrated strong interactions between corynoline and these targets. (5) Results from quantitative reverse transcription-polymerase chain reaction and Western blot assays indicated that corynoline exerted effects against acute myeloid leukemia by inhibiting the activation of phosphoinositide 3-kinase/protein kinase B signaling pathway and promoting the degradation of mouse double minute 2, which in turn activates p53 transcriptional function. (6) This study elucidates the in vitro pharmacological role of corynoline in acute myeloid leukemia treatment and the underlying mechanism, providing additional theoretical foundations for the application of natural compounds in the treatment of acute myeloid leukemia.

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    Effect of swimming exercise combined with probiotic intervention on anti-inflammatory and apoptotic gene expression in renal tissue of type 2 diabetic rats
    Niu Qi, Chen Junji, Tu Haining, Mo Weibin, Zhong Yujin, Li Mingliang
    2026, 30 (16):  4105-4114.  doi: 10.12307/2026.714
    Abstract ( 59 )   PDF (1841KB) ( 4 )   Save
    ACKGROUND: Type 2 diabetes mellitus is often accompanied by renal inflammation and cellular apoptosis, contributing to diabetic nephropathy. However, the mechanistic interplay of combined swimming exercise and probiotic intervention in this context remains to be fully elucidated.
    OBJECTIVE: To investigate the effects of swimming exercise and probiotics on renal function level, renal tissue apoptosis and inflammatory factors in type 2 diabetic rats.
    METHODS: There were 60 SPF grade male Sprague-Dawley rats at 8 weeks of age. Ten rats were randomly selected as the normal group, and 50 rats in the modeling group were injected intraperitoneally with streptozotocin to establish a rat model of type 2 diabetes mellitus. Forty rats successfully molded were selected and randomly divided into the diabetic group, the swimming exercise group, the probiotic group, the swimming exercise + probiotics group (combined intervention group), with 10 animals in each group. The rats in the swimming exercise and combined intervention groups were subjected to weightless swimming exercise once a day for 6 days per week, with swimming times of 15, 25 and 40 minutes in the first 3 days of the first week, and 60 minutes per day starting from the 4th day, for a total of 6 weeks of training. The rats in the probiotic and combined intervention groups were gavaged with a solution of 10.0 mL/kg/d PiLeJe probiotic bacteria (at a concentration of 107 CFU/mL) for 1 hour prior to the training. Kidney function indexes, apoptotic gene expression, inflammatory factor indexes and protein expression were measured.
    RESULTS AND CONCLUSION: (1) The fasting blood glucose levels of rats in the combined intervention group were lower than those in the diabetic group (P < 0.01). The urinary microalbumin levels of rats in the swimming exercise group, probiotic group, and combined intervention group were all lower than those in the diabetic group (P < 0.01). The serum urea nitrogen levels of rats in the swimming exercise group and combined intervention group were both lower than those in the diabetic group (P < 0.01). The serum creatinine and cystatin C levels of rats in the combined intervention group were both lower than those in the diabetic group (P < 0.01). (2) The levels of tumor necrosis factor α, interleukin 6, interleukin 1β, nuclear factor κB inhibitory protein α, and ultrasensitive C-reactive protein were lower in the swimming exercise, probiotic, and combined intervention groups than in the diabetic group (P < 0.05 or P < 0.01). In addition, the level of interleukin 6 was lower in the combined intervention group than the diabetic, swimming exercise and probiotic groups (P < 0.01). (3) The expression of Bax, Caspase-3 and P53 was lower in the swimming exercise, probiotic and combined intervention groups than the diabetic group (P < 0.05 or P < 0.01). The expression of Bcl-2 was higher in the swimming exercise, probiotic and combined intervention groups than the diabetic group (P < 0.05 or P < 0.01). (4) The protein expression of nuclear transcription factor κB was lower in the probiotic and combined intervention groups than in the diabetic group (P < 0.05). Toll-like receptor 4 protein expression was lower in the combined intervention group than in the diabetic group (P < 0.05). The protein expression of interleukin 17 was lower in the probiotic and combined intervention groups than in the diabetic group (P < 0.05 or P < 0.01). To conclude, swimming exercise and probiotic intervention could reduce blood glucose, improve renal function indexes and inhibit renal inflammatory response, so as to achieve the protection of renal function. The protective effect of the combined intervention may be related to the involvement of inflammatory factors nuclear transcription factor κB, Toll-like receptor 4 and interleukin 17 in the regulation of cellular inflammation and inhibition of apoptotic factors Bax, Bcl-2, Caspase-3 and P53. And the effect of swimming exercise combined with probiotic intervention is superior to that of swimming exercise or probiotics alone.
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    Joint analysis of electromyography spectrum and amplitude of the interactive effects of work posture and load combinations on upper limb fatigue
    Xue Enkai, Xu Hongqi
    2026, 30 (16):  4115-4124.  doi: 10.12307/2026.747
    Abstract ( 84 )   PDF (112988KB) ( 23 )   Save
    BACKGROUND: Upper limb work-related musculoskeletal disorders warrant attention due to their adverse impacts on an individual’s health and socioeconomic well-being, with muscle fatigue being a primary contributing factor.
    Objective: To investigate the interaction effects of work posture and load combinations on muscle fatigue characteristics during static upper limb tasks using joint analysis of electromyography  spectrum and amplitude, aiming to provide multidimensional biomechanical evidence for preventing upper limb work-related musculoskeletal disorders.
    Methods: Fourteen healthy subjects performed static tasks of shoulder flexion and abduction at 20°, 40°, and 60° angles with loads set at 10%, 30%, and 50% of their one-repetition maximum. Surface electromyography signals and Borg CR-10 scale data were simultaneously recorded. Muscle fatigue was quantified using joint analysis of electromyography spectrum and amplitude-derived metrics, including root mean square slope and median frequency slope. Paired samples t-tests were used to analyze the proportion of fatigue states before and after fatigue. Analysis of variance was used to assess the effects of postures, loads, and their interaction on fatigue state proportions.
    Results and Conclusion: (1) The posture-load combination significantly influenced task tolerance (P < 0.05), with the 60°-50% one-repetition maximum combination yielding the shortest maximum endurance time (P < 0.001). (2) Changes in muscle fatigue states before and after fatigue under specific combinations: fatigue state proportions in the supraspinatus and upper trapezius significantly decreased under the 20° 10% one-repetition maximum combination (P < 0.05). Fatigue state proportions in the upper trapezius showed an extremely significant difference under the 40° 10% one-repetition maximum combination (P < 0.01). (3) The effects of postures and loads on muscle fatigue were independent of each other. At 20°flexion, the proportion of fatigue in the anterior deltoid muscle showed significant differences (P < 0.05) when comparing loads of 10% one-repetition maximum versus 30% one-repetition maximum, and 10% one-repetition maximum versus 50% one-repetition maximum (P < 0.05); however, under the load condition of 10% one-repetition maximum, the fatigue proportions between the anterior and the anterior and middle deltoids showed significant differences (P < 0.05) only between the 20° and 60° angles, specifically during the pre-fatigue and full-range phases (P < 0.05).(4) No significant interaction effects between postures and loads were detected (P > 0.05). These finding indicate that high-load and high-angle tasks markedly accelerate muscle fatigue; postures and loads independently influence fatigue progression without observable synergistic effects. Joint analysis of electromyography spectrum and amplitude shows limited sensitivity to muscle fatigue characteristics in capturing posture-load interactions.

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    A Transformer-based convolutional neural network fusion approach for single inertial recognition of lumbar rehabilitation exercises
    Yu Shenghan, Cheng Xiankai, Zheng Yue, Yang Ying
    2026, 30 (16):  4125-4136.  doi: 10.12307/2026.685
    Abstract ( 102 )   PDF (6160KB) ( 66 )   Save
    BACKGROUND: Inertial measurement units are widely used for human posture perception and dynamic capture. Deep learning has gradually replaced traditional rules and feature engineering, and is commonly used in action recognition tasks. Convolutional neural networks perform well in extracting local dynamic features, while Transformer-based convolutional neural networks approach demonstrates strong capabilities in modeling long-term dependencies.
    OBJECTIVE: To develop a recognition method based on a Transformer-convolutional neural networks-based fusion model to classify lumbar rehabilitation exercises using data from a single inertial measurement unit.
    METHODS: A dataset was constructed by collecting tri-axial accelerometer and gyroscope signals from six healthy participants performing standardized lumbar rehabilitation movements with a single waist-mounted inertial measurement unit. Each trial was labeled according to the exercise type. Transformer-based convolutional neural network fusion model was trained using this dataset to construct a motion classification system. Model performance was evaluated using leave-one-out cross-validation and compared against baseline models, including  linear discriminant analysis, support vector machine, multi-layer perception, and the standard Transformer. 
    RESULTS AND CONCLUSION: Experimental results show that the proposed Transformer-based convolutional neural network fusion model achieved a classification accuracy of 96.67% and an F1-score of 0.966 9 across five exercise categories. Compared with conventional algorithms, it demonstrated superior accuracy and generalizability under the single-sensor constraint. These findings validate the practicality of deep learning models using single inertial measurement unit data for lumbar rehabilitation monitoring and provide a foundation for developing lightweight, highly deployable home-based rehabilitation systems.

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    Association between triglyceride-glucose-body mass index and the risk of hypertension in middle-aged and elderly Chinese population
    Zhou Zigui, Liu Jingjing
    2026, 30 (16):  4137-4145.  doi: 10.12307/2026.688
    Abstract ( 68 )   PDF (2451KB) ( 6 )   Save
    BACKGROUND: The current prevention and control system of hypertension is facing the dilemma of "three lows" in awareness, treatment, and control rates; therefore, there is an urgent need to develop precise screening tools based on metabolic comprehensive indicators. The association between triglyceride-glucose-body mass index, as a novel biomarker of metabolic obesity, and the risk of hypertension in middle-aged and elderly Chinese population has not been fully validated.
    OBJECTIVE: To validate the association between triglyceride-glucose-body mass index and the risk of hypertension in the middle-aged and elderly Chinese population based on the database of the China Health and Retirement Longitudinal Study (CHARLS).
    METHODS: A total of 4 743 adults aged ≥ 45 years without hypertension were included. Using the quartile grouping method, the baseline triglyceride-glucose-body mass index was sorted in ascending order and divided into four equally sized intervals: the first quartile group (Q1, with the index < 170), the second quartile group (Q2, with the index between 170.38 and 191.176), the third quartile group (Q3, with the index between 191.179 and 216.82), and the fourth quartile group (Q4, with the index between 216.85 and 553.39). The Cox proportional hazards model was used to evaluate the association between triglyceride-glucose-body mass index and the risk of hypertension. Nonlinear relationships were identified using restricted cubic spline analysis, and robustness was validated through multiple sensitivity analysis.
    RESULTS AND CONCLUSION: During the median follow-up period of 6.42 years, 1 975 hypertension patients were newly diagnosed, with an incidence rate of 648.80 cases per 10 000 person-year. For every 10 units increase in the triglyceride-glucose-body mass index, the risk of hypertension increased by 6% (hazard ratio: 1.06, 95% confidence interval [CI]: 1.05-1.08) in the first quartile group; the hazard ratios for the second quartile group, the third quartile group, and the fourth quartile group were 1.20 (95% CI: 1.02-1.40), 1.38 (95% CI: 1.17-1.62), and 1.97 (95% CI: 1.56-2.25), respectively. Using restricted cubic splines, a nonlinear correlation was identified between the triglyceride-glucose-body mass index and the risk of hypertension (P < 0.001), with an inflection point value of 146.1 (hazard ratio before the inflection point: 0.99, P > 0.05; and hazard ratio after the inflection point: 1.14, P < 0.001). The results showed that there was a significant positive correlation and nonlinear threshold effect between triglyceride-glucose-body mass index and the risk of hypertension in middle-aged and elderly population. It is recommended to use the triglyceride-glucose-body mass index < 146.1 as a cut-off point for preventing metabolic-related hypertension; therefore, the risk management of hypertension can be achieved through the control of weight, blood glucose and lipid.

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    Plantar pressure characteristics and gait analysis of outdoor workers
    Liu Zixuan, Wei Dehua, Zheng Hailiang, Wang Jiangning, Gao Lei
    2026, 30 (16):  4146-4153.  doi: 10.12307/2026.748
    Abstract ( 90 )   PDF (1427KB) ( 7 )   Save
    BACKGROUND: Outdoor workers frequently walk on uneven surfaces, which exposes them to abnormal foot biomechanics and makes them high-risk individuals for plantar fasciitis and Achilles tendinopathy.
    OBJECTIVE: To analyze the plantar pressure distribution and gait characteristics of outdoor workers under natural walking conditions, in order to provide a basis for high-risk foot monitoring and the design of protective footwear. 
    METHODS: This study included 24 outdoor workers as the experimental group and 12 healthy individuals as the control group. Both groups underwent natural gait testing using the PRESSUREPLATE-SCIENTIC pressure plate. The PODOMED gait analysis system was used to collect plantar pressure parameters across the full gait cycle, including peak plantar pressure, foot load distribution ratios, cadence, walking speed, stance phase, swing phase, and center of pressure displacement. Differences between the two groups in terms of plantar pressure and gait parameters were analyzed.
    RESULTS AND CONCLUSION: (1) Compared with the control group, the experimental group showed significantly higher peak pressures in the medial heel (left), lateral heel (left), third to fifth metatarsal regions (left), medial heel (right), lateral heel (right), midfoot (right), and first to third metatarsal regions (right) (P < 0.05). (2) Compared with the control group, in the experimental group, the forefoot load ratios (left and right) were significantly greater, while the rearfoot load ratios (left and right) were significantly smaller (P < 0.05). (3) The experimental group also exhibited higher cadence and walking speed (P < 0.05), longer stance phase duration, shorter swing phase duration (P < 0.05), and greater anterior-posterior center of pressure displacement on both feet (P < 0.05). Given the specific environmental conditions of outdoor workers, targeted attention should be paid to the pressure borne by the heel, forefoot, and arch regions to ensure appropriate foot care and prevent foot disorders.

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    H-type angiogenesis and its role in various skeletal disease animal models
    Peng Hao, Jiang Yang, Song Yanping, Wu Quan, Yao Na, Chen Qigang, Shen Zhen
    2026, 30 (16):  4154-4165.  doi: 10.12307/2026.658
    Abstract ( 72 )   PDF (2321KB) ( 54 )   Save
    BACKGROUND: H-type blood vessels provide new perspectives and entry points for a deeper understanding of the regulatory mechanisms of vascular-mediated bone metabolism due to their unique functions. 
    OBJECTIVE: To explore the generation mechanisms of H-type blood vessels in various animal models of skeletal diseases and their effects on bone metabolism.
    METHODS: A systematic search was conducted for H-type blood vessel-related literature in both Chinese and English from January 2014 to February 2025 across databases including CNKI, VIP, WanFang, PubMed, Scopus, and Web of Science. Duplicate and non-qualifying studies were excluded, and a systematic analysis was performed on 141 selected articles addressing H-type blood vessels in different skeletal disease animal models. 
    RESULTS AND CONCLUSION: H-type blood vessels exhibit specific generation mechanisms and biological functions across various skeletal disease models. These vessels play a crucial role in intra-bone angiogenesis and are closely associated with bone metabolism, potentially serving as early biomarkers for assessing bone mass levels. The formation and function of H-type blood vessels differ in different animal models of skeletal diseases. In conditions such as osteoporosis, fractures, and osteonecrosis, promoting the expression of H-type blood vessels can significantly enhance vascular remodeling and improve bone regeneration capabilities. Conversely, in malignant skeletal diseases such as osteoarthritis and bone tumors, selectively inhibiting the expression of H-type blood vessels emerges as a potential therapeutic intervention strategy. Furthermore, several key signaling pathways, including hypoxia-inducible factor 1α/vascular endothelial growth factor, platelet-derived growth factor BB, and Wnt/β-catenin, have been identified as playing important roles in the generation of H-type blood vessels. This provides new scientific insights into understanding the vessel-mediated regulatory mechanisms of bone metabolism and establishes an important theoretical foundation for the clinical application value of H-type blood vessels as potential therapeutic targets. By analyzing the role of H-type blood vessels in various animal models of skeletal diseases, this study offers critical evidence for further exploration of the mechanisms and therapeutic targets of human musculoskeletal diseases.

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    Ferroptosis inhibitors in the treatment of osteoarthritis: diversity and multitarget characteristics
    Chen Xinlong, Meng Tao, Wang Yaomin, Zhang Kefan, Li Jian, Shi Hui, Zhang Chenchen
    2026, 30 (16):  4166-4179.  doi: 10.12307/2026.351
    Abstract ( 90 )   PDF (1709KB) ( 151 )   Save
    BACKGROUND: Recent studies have shown that ferroptosis, a novel iron-dependent form of cell death, plays an important role in the progression of osteoarthritis.
    OBJECTIVE: To introduce the mechanisms of ferroptosis, including iron homeostasis imbalance, lipid peroxidation, and weakened antioxidant systems, and to summarize the potential applications of various ferroptosis inhibitors in the treatment of osteoarthritis.
    METHODS: Literature retrieval was conducted in the CNKI and PubMed databases using the keywords of “osteoarthritis, ferroptosis, lipid peroxidation, ferroptosis inhibitors, chondrocytes, reactive oxygen species, glutathione peroxidase 4” in Chinese and English, respectively. Retrieval time was from January 2012 to January 2025. A total of 90 articles were systematically reviewed and summarized.
    RESULTS AND CONCLUSION: (1) Ferroptosis, as an iron-dependent form of cell death, involves the following core mechanisms: (i) Iron homeostasis imbalance: Excess iron generates reactive oxygen species through the Fenton reaction, leading to lipid peroxidation and cell death; (ii) Lipid peroxidation: Reactive oxygen species attack polyunsaturated fatty acids in the cell membrane, causing membrane degradation and ferroptosis; (iii) Weakened antioxidant systems: Intracellular antioxidant systems (such as Xc- system/glutathione/glutathione peroxidase 4, nuclear factor E2-related factor 2, mitogen-activated protein kinase/nuclear factor κB signaling pathways) play a key role in ferroptosis. When the antioxidant capacity is insufficient to counteract lipid peroxidation, cells undergo ferroptosis. (2) In the context of osteoarthritis, various ferroptosis inhibitors have shown therapeutic potential. Iron chelators reduce Fenton reactions and lipid peroxidation by chelating excess iron, thereby inhibiting chondrocyte ferroptosis. Antioxidants alleviate chondrocyte damage by inhibiting lipid peroxidation and enhancing antioxidant capacity. Natural compounds modulate signaling pathways such as nuclear factor E2-related factor 2 and mitogen-activated protein kinase/nuclear factor κB to inhibit ferroptosis and slow osteoarthritis progression. (3) Additionally, inhibitors of acyl-CoA synthetase long-chain family member 4 exert chondroprotective effects by inhibiting lipid peroxidation and correcting iron metabolism disorders. (4) Although ferroptosis inhibitors show promising potential in the treatment of osteoarthritis, most current studies are still at the cellular and animal experimental stages, with a lack of large-scale clinical trials to verify their safety and efficacy. Future research should further explore the specific mechanisms of ferroptosis and promote the clinical application of ferroptosis inhibitors, providing new strategies for the treatment of osteoarthritis.

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    Traditional Chinese medicine effective ingredients for the treatment of rheumatoid arthritis: mechanism based on nuclear factor kappaB signaling pathway
    Fu Xiao, Li Jigao, Yan Xiaonan, Song Zhe, Guo Yuejun, Li Hanbing, Zhou Quan
    2026, 30 (16):  4180-4192.  doi: 10.12307/2026.716
    Abstract ( 131 )   PDF (1949KB) ( 430 )   Save
    BACKGROUND: Previous studies have shown that the nuclear factor κB signaling pathway is highly expressed in rheumatoid arthritis and promotes the progression of rheumatoid arthritis by regulating cytokines, vascular endothelial growth factor, endogenous antioxidant enzymes, and etc.
    OBJECTIVE: To summarize and analyze the mechanism of the nuclear factor κB signaling pathway on rheumatoid arthritis, and to review the relevant literature on the treatment of rheumatoid arthritis with traditional Chinese medicine in the past 5 years, in order to provide new reference for the clinical treatment of rheumatoid arthritis.
    METHODS: Using “NF-κB, rheumatoid arthritis, traditional Chinese medicine, bone injury, TCM monomeric compounds, TCM herb pairs, TCM compound formulations, research progress” as Chinese and English search terms, we searched for literature on the relationship between nuclear factor κB and rheumatoid arthritis, as well as the intervention and regulation with traditional Chinese medicine monomers, drug pairs, and compound formulas published in CNKI and PubMed databases from March 2016 to March 2025. Finally, 87 articles were included for review.
    RESULTS AND CONCLUSION: (1) Nuclear factor κB plays a crucial role in the pathogenesis of rheumatoid arthritis. (2) The nuclear factor κB signaling pathway leads to rheumatoid arthritis by inducing inflammatory cell aggregation, producing reactive oxygen species, regulating osteoclast formation, and mediating vascular dysplasia. (3) Chinese herbal monomers such as baicalein, traditional Chinese medicine such as Radix Polygoni multiflori Preparata (Zhichuanwu)-White Peony Root (Baishao), and traditional Chinese medicine compound Yiyifuzi Baijiang powder inhibit the progression of rheumatoid arthritis by regulating nuclear factor κB-related signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B/nuclear factor κB, mitogen activated protein kinase/nuclear factor κB, and Toll-like receptor 4/nuclear factor κB.
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    Multidimensional target regulation of vascular endothelial growth factor A in articular cartilage development
    Wang Zhengye, Liu Wanlin, Zhao Zhenqun
    2026, 30 (16):  4193-4203.  doi: 10.12307/2026.720
    Abstract ( 67 )   PDF (1375KB) ( 12 )   Save
    BACKGROUND: The health and functional maintenance of articular cartilage are hot topics in the field of orthopedics. Vascular endothelial growth factor A, as a key regulator of angiogenesis, has long been a subject of debate regarding its role in cartilage development.
    OBJECTIVE: To systematically summarize the multidimensional regulatory mechanisms of vascular endothelial growth factor A in articular cartilage development and its role in diseases, explore its feasibility as a therapeutic target, and analyze the current technical bottlenecks and potential breakthroughs in treatment strategies.
    METHODS: A comprehensive literature search was conducted in PubMed, CNKI, WanFang Data, and VIP databases (from database inception to May 2025), supplemented by manual retrieval of relevant books. High-quality studies focusing on the regulatory mechanisms of vascular endothelial growth factor A in articular cartilage development and diseases were selected. A total of 117 articles (112 in English and 5 in Chinese) were included for systematic analysis and synthesis.
    RESULTS AND CONCLUSION: Vascular endothelial growth factor A spatiotemporally modulates chondrocyte differentiation and metabolism via interactions with its receptors; its splice isoforms exhibit distinct roles in cartilage development and diseases; the coupling of mechanical and biochemical signals further enhances regulatory complexity. In osteoarthritis, the expression of vascular endothelial growth factor A is concentration-dependent, with low levels promoting cartilage repair and high levels exacerbating cartilage degradation. In rheumatoid arthritis, vascular endothelial growth factor A aggravates disease progression by promoting synovial angiogenesis and inflammatory cell infiltration. In developmental dysplasia of the hip, vascular endothelial growth factor A significantly promotes joint cartilage development. Vascular endothelial growth factor A shows promise for early disease intervention, but major bottlenecks remain, including inadequate spatiotemporal precision in delivery systems, off-target risks of gene editing, and the lack of molecular subtyping for personalized treatment. In conclusion, vascular endothelial growth factor A exerts complex and pleiotropic effects in articular cartilage development and disease, necessitating precise modulation for therapeutic applications. Current research faces bottlenecks in delivery system precision, gene editing safety, and the absence of personalized treatment strategies. Future work should focus on optimizing delivery systems, integrating single-cell multi-omics for personalized therapy, and exploring vascular endothelial growth factor A crosstalk with other signaling pathways. Additionally, there is an urgent need to shift the research paradigm from “single-target inhibition” to “microenvironment remodeling,” relying on interdisciplinary technical integration and precise design of preclinical models. Comprehensive efforts are required to overcome challenges and promote clinical translation, including single-cell sequencing to elucidate chondrocyte subpopulation responses, CRISPR-Cas9 screening for stage-specific regulatory elements, development of intelligent controlled-release systems, interaction models, engineered carriers, integration of multi-omics, construction of organoid models, and the use of artificial intelligence for prediction, bringing new hope for the treatment of articular cartilage-related diseases.

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    Different exercise modalities improve health gains in vascular function in overweight or obese children and adolescents: a Bayesian meta-analysis
    Xu Yang, Li Xiupeng, Yang Bing, Yang Chunbaixue, Zhao Zhongwei
    2026, 30 (16):  4204-4218.  doi: 10.12307/2026.729
    Abstract ( 126 )   PDF (4543KB) ( 16 )   Save
    OBJECTIVE: In recent years, exercise has been widely recognized as an effective non-pharmacological intervention for improving vascular health. This study conducted a systematic review of the effects of different exercise modalities on the prevention and improvement of cardiovascular disease in overweight or obese children and adolescents.
    METHODS: Randomized controlled trials (RCTs) investigating the effects of different exercise modalities on vascular function in overweight or obese children and adolescents were retrieved from PubMed, Web of Science, Cochrane Library, and EBSCO-SPORTD. The control group continued their normal lifestyle, while the experimental group underwent continuous traditional aerobic training, resistance training, traditional interval training, or combined training. The search period ranged from the inception of each database to February 17, 2025. Two researchers independently screened the studies, assessed their quality, and extracted data. Bayesian meta-analysis was performed using RevMan 5.4 and R software to evaluate outcome measures, including pooled effect sizes, subgroup analysis, Markov chain convergence diagnostics, and funnel plot construction.
    RESULTS: (1) A total of 15 randomized controlled trials that met the requirements were finally included, involving 767 subjects. The overall quality of the included literature was high. (2) Bayesian meta-analysis results revealed that compared with the control group, different exercise interventions had an improvement effect on three indices in overweight or obese children and adolescents, namely pulse wave conduction velocity [standardized mean difference (SMD)=-0.72, 95% confidence interval (CI): -1.30 to -0.15], flow-mediated dilation (SMD=0.91, 95% CI: 0.38 to 1.40) and carotid intima-media thickness (SMD=-0.28, 95% CI: -0.51 to -0.06). (3) The results of subgroup analysis further showed that compared with the control group, high-intensity interval training was effective in improving pulse wave conduction velocity (SMD=-1.13, 95% CI: -1.76 to -0.51, P < 0.05), flow-mediated dilation (SMD=0.74, 95% CI: 0.15 to 1.34, P < 0.05) and carotid intima-media thickness (SMD=-0.80, 95% CI: -1.40 to -0.20, P < 0.05); and aerobic training had a statistically significant improvement in blood flow-mediated vasodilatory function (SMD=1.37, 95% CI: 0.97 to 1.77, P < 0.05) in overweight or obese children and adolescents.
    CONCLUSION: Current evidence suggests that exercise interventions have a significant beneficial effect on vascular function in overweight or obese children and adolescents. High-intensity interval training has the most prominent effect on improving functional vascular health in children and adolescents who are overweight or obese, with conventional aerobic training having the second most significant improvement. It is recommended that more research be conducted in the future to determine the optimal exercise training prescription for children and adolescents who are overweight or obese.
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    Network meta-analysis of robot-assisted gait training interventions on lower limb motor function in stroke patients
    Gao Zan, Liu Yixuan, Zhang Lichen, Hou Bing, Tang Yalei, Li Shumei, Che Pengcheng, Dou Na
    2026, 30 (16):  4219-4228.  doi: 10.12307/2026.710
    Abstract ( 96 )   PDF (20697KB) ( 14 )   Save
    OBJECTIVE: To conduct a network meta-analysis to systematically evaluate the rehabilitation effects of robot-assisted gait training on lower limb motor function in stroke patients, and to optimize exercise prescriptions based on research evidence regarding exercise time, frequency, cycle, and weight loss plan.
    METHODS: A computerized literature search was conducted using the PubMed, Web of Science, Cochrane Library, Embase, CNKI, VIP, Wanfang, and SinoMed databases to identify randomized controlled trials published from inception until January 2025. The intervention effects of robot assisted gait training (robot group) and traditional rehabilitation training (control group) on lower limb function in stroke patients were compared, and the exercise prescription parameters for single training duration, weekly training frequency, and total intervention period were optimized based on evidence-based medicine. Data integration and analysis were performed using Review Manager 5.4.1 software, and related charts were created with Stata 17.0 software to visually present the results of the study. 
    RESULTS: (1) A total of 22 articles were finally included, with a total of 998 patients, including 492 in the control group and 506 in the robot group. (2) The meta-analysis results showed that compared with conventional rehabilitation training, robot assisted gait training effectively improved the lower limb motor function in stroke patients, as measured by the Fugl-Meyer Assessment of Lower Extremity score, Berg Balance Scale score, Functional Ambulation Category Scale score, and 6-minute walk test score (P < 0.05). (3) The results from the cumulative ranking probability curve analysis showed that the optimal exercise prescription for improving lower limb motor function based on Fugl-Meyer Assessment of Lower Extremity score was single training duration of 40-60 minutes, weekly training frequency of 6-10 times, and continuous intervention period of 8-12 weeks. 
    CONCLUSION: The meta-analysis shows that robot assisted gait training effectively promotes the improvement of lower limb motor function, walking ability, balance function, and walking endurance in stroke patients. The most significant improvement in the Fugl-Meyer Assessment of Lower Extremity score of lower limb motor function in stroke patients occurs when an exercise prescription of 40-60 minutes per session, 6-10 times per week, and lasting 8-12 weeks is used.

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    Postmenopausal osteoporosis: visualization analysis of related signaling pathways
    Zou Shunyi, Yi Jin, Zeng Hao, Li Jianqi, Wu Zhongping
    2026, 30 (16):  4229-4239.  doi: 10.12307/2026.724
    Abstract ( 112 )   PDF (8293KB) ( 19 )   Save
    BACKGROUND: Signaling pathways are important factors affecting bone metabolic stability and play an indispensable role in the onset and progression of postmenopausal osteoporosis.
    OBJECTIVE: To perform a visual analysis of literature published over the past 20 years on signaling pathways related to postmenopausal osteoporosis and to explore the current state of development and research hotspots in this field.
    METHODS: We retrieved the Web of Science Core Collection database for English-language literature on signaling pathways related to postmenopausal osteoporosis. The search period was from January 1, 2004 to October 20, 2024. Utilizing CiteSpace 6.3.R1 and R4.4.1 software, we conducted comprehensive statistical analyses of authors, countries, institutions, journals, cited references, and keywords, subsequently generating corresponding visualization maps.
    RESULTS AND CONCLUSION: According to the inclusion and exclusion criteria, 853 articles were selected for analysis. The author with the highest number of publications was Xu Jiake, while China emerged as the leading country in publication output. Shanghai Jiao Tong University ranked as the institution with the highest number of publications. Among journals, Frontiers in Pharmacology demonstrated the highest publication volume, whereas Journal of Bone and Mineral Research received the most citations. Knowledge exchange occurred across molecular science, biology, genetics, and immunology disciplines. In recent years, “fracture prevention” and “bone resorption” become relatively stable research directions, while “network pharmacology” and “model” emerges as prominent keywords. Over the past two decades, publications on signaling pathways related to postmenopausal osteoporosis have shown an overall upward trend in the number of publications, reflecting increasing interdisciplinary integration. Among the top 10 most co-cited references, 5 studies validated the safety and efficacy of sclerostin monoclonal antibody through different approaches; 4 reviews summarized the diagnosis and treatment of osteoporosis or postmenopausal osteoporosis; and 1 study explored the role and mechanism of the Wnt signaling pathway in bone homeostasis and related diseases. Research hotspots in this field focus on elucidating signaling pathway mechanisms, particularly their associated cytokines and gene expression patterns in complex biological processes. Currently, the most prominent pathways under investigation include nuclear factor kappa B, phosphatase and tensin homolog, and nuclear factor of activated T-cells, cytoplasmic 1 pathways. In terms of treatments, the development of drugs targeting signaling pathway represents a promising direction for future treatment of postmenopausal osteoporosis, with traditional Chinese medicine applications gaining notable attention. Moreover, the combination of network pharmacology and animal models has emerged as a popular research approach in recent years.
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    Potential effects of cuproptosis-related genes in the onset of ankylosing spondylitis: a multi-omics Mendelian randomization study
    Song Zhichao, Qi Wenrong, Meng Peng, Zhang Yanyan
    2026, 30 (16):  4240-4252.  doi: 10.12307/2026.734
    Abstract ( 74 )   PDF (24572KB) ( 7 )   Save
    BACKGROUND: Cuproptosis may be involved in the pathogenesis of ankylosing spondylitis, but there is a lack of direct genetic evidence.
    OBJECTIVE: To investigate the genetic relationship between cuproptosis-related genes and ankylosing spondylitis using multi-omics Mendelian randomization analysis, heterogeneity testing, and colocalization methods. 
    METHODS: The genome-wide association study (GWAS) data related to ankylosing spondylitis were obtained from the FinnGen database (jointly developed by Finland and the University of Helsinki), the UK Biobank (UKB) database (jointly established by the UK Medical Research Council and the UK government), and the GWAS Catalog database (developed by the European Molecular Biology Laboratory and the European Bioinformatics Institute). All these databases are open access, and the studies involved have been approved by the relevant institutional review boards. We acquired quantitative trait loci data related to ankylosing spondylitis, specifically focusing on blood methylation, gene expression, and protein abundance. We used data from FinnGen as the primary discovery set, further validating our findings with supplementary data from the UK Biobank and the GWAS Catalog. The multi-omics Mendelian randomization method helped us assess the potential molecular links between the molecular features of cuproptosis-related genes and ankylosing spondylitis. Finally, we employed colocalization analysis to determine if the detected genetic signals shared common causal variants.  
    RESULTS AND CONCLUSION: Our analysis revealed potential genetic causal links between ankylosing spondylitis and several genes and loci, including carcinoembryonic antigen-related cell adhesion molecule 8 (cg09422614), ferric chelate reductase 1 (cg09370016), galactose-3-O sulfotransferase 1 (cg04030848), sideroflexin 5 (cg03344820), sulfite oxidase (cg06495347, cg22580629), thymidine phosphorylase (cg11654620, cg16367976). These genes and loci showed significant associations in multi-omics Mendelian randomization analyses involving both blood mQTLs and eQTLs. Colocalization analysis further strengthened the evidence for an association between the methylation loci of galactose-3-O sulfotransferase 1, sulfite oxidase, and thymidine phosphorylase and the risk of ankylosing spondylitis (PP.H4 > 0.5). Our investigation into methylation regulatory mechanisms indicated that increased methylation levels at cg09422614, cg09370016, and cg03344820 were positively correlated with the risk of ankylosing spondylitis. The risk of ankylosing spondylitis was increased by positively regulating the expression levels of these genes. Conversely, while methylation levels at cg04030848, cg06495347, and cg22580629 also showed a positive correlation with the risk of ankylosing spondylitis, and they appeared to increase the risk of ankylosing spondylitis by positively regulating the expression levels of their respective genes. Interestingly, thymidine phosphorylase gene expression levels showed a negative correlation with the risk of ankylosing spondylitis, with methylation at cg11654620 and cg16367976 positively regulating thymidine phosphorylase gene expression. The GSE25101 dataset blood sample analysis indicated that carcinoembryonic antigen-related cell adhesion molecule 8, ferric chelate reductase 1, galactose-3-O sulfotransferase 1, sideroflexin 5, sulfite oxidase, and thymidine phosphorylase exert regulatory effects in the pathogenesis of ankylosing spondylitis and may participate in its pathological progression. This study not only sheds light on the potential pathogenic role of cuproptosis mechanisms in ankylosing spondylitis but also offers a theoretical basis for future multi-omics functional mechanism research and precision diagnosis and individualized treatment of ankylosing spondylitis, particularly within the Chinese population.

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    Bioinformatics-based analysis of shared genes and associations in immune mechanisms between rheumatoid arthritis and Crohn’s disease
    Lu Liwei, Huang Keqi, Chen Yueping, Zhuo Yinghong, Zhu Naihui, Wei Peng
    2026, 30 (16):  4253-4264.  doi: 10.12307/2026.731
    Abstract ( 98 )   PDF (16173KB) ( 11 )   Save
    BACKGROUND: Rheumatoid arthritis and Crohn’s disease are common autoimmune diseases. Clinical studies have found that these two diseases can coexist and may be related, but there is currently no research to prove that there are common pathogenic genes and immune mechanisms between them.
    OBJECTIVE: To identify the shared genes and immune mechanisms between rheumatoid arthritis and Crohn’s disease through bioinformatics and two machine learning methods.
    METHODS: Training and validation datasets for rheumatoid arthritis and Crohn’s disease were retrieved from the GEO database (an open database developed by the United States National Library of Medicine) and uniformly organized. The “limma” package was used to perform differentially expressed genes of rheumatoid arthritis and Crohn’s disease. Weighted gene co-expression network analysis was applied to the training sets of rheumatoid arthritis and Crohn’s disease to identify disease-related modules, and the intersection was taken to preliminarily screen gene sets, while GO and KEGG analyses were conducted. Twenty gene sets were identified through the protein-protein interaction network and MCODE algorithm. Two machine learning algorithms, LASSO regression and random forest, were independently applied to the training sets of rheumatoid arthritis and Crohn’s disease to screen key characteristic genes for each disease. Subsequently, the intersection of the screening results of rheumatoid arthritis and Crohn’s disease was taken to obtain shared potential key genes, and the accuracy was verified through the validation set to determine the core genes. Finally, CIBERSORT immune infiltration and other functional analyses were performed to confirm the correlation between core genes and rheumatoid arthritis as well as Crohn’s disease.
    RESULTS AND CONCLUSION: A total of 2 516 differentially expressed genes were obtained for rheumatoid arthritis, and 281 differentially expressed genes for Crohn’s disease. Following intersection analysis using WGCNA, protein-protein interaction network, and two machine learning algorithms, three core genes were identified: CASP1, TRIM21, and PSMB10. Enrichment analysis showed that the two diseases were associated with antigen processing and presentation, luminal side of endoplasmic reticulum membrane, and binding to multiple immunoglobulins. The expression trends of three core genes in the validation sets of the two diseases were consistent with those in the training set. Immune cell infiltration analysis revealed significantly increased expression of M0 macrophages, M1 macrophages, and neutrophils in both rheumatoid arthritis and Crohn’s disease. This indicates that neutrophils may play an important role in the pathogenesis of rheumatoid arthritis and Crohn’s disease. This study not only enhances our understanding of the commonalities between two important autoimmune diseases, but more importantly, it provides valuable insights and specific guidance for Chinese researchers in the discovery and validation of new targets, the development of novel diagnostic and therapeutic technologies, and the application of translational medicine research models.

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    Application trends of eye-tracking technology in rehabilitation: a visualization analysis based on CiteSpace and VOSviewer
    Wei Jingyi, Wang Xiaojing, Liu Xihua
    2026, 30 (16):  4265-4277.  doi: 10.12307/2026.689
    Abstract ( 123 )   PDF (12243KB) ( 21 )   Save
    BACKGROUND: The use of eye-tracking technology and oculometry in clinical rehabilitation assessment and training is gradually increasing, making it particularly important to understand the practical value of eye-tracking technology; however, no studies have been conducted to analyze this area bibliometrically.
    OBJECTIVE: To study the current situation and frontier trends of the research on eye-tracking technology in the field of rehabilitation. 
    METHODS: A subject-word combination was used to search for relevant literature on the application of eye-tracking technology in rehabilitation from January 1, 2014 to February 5, 2025, in the CNKI, WanFang Database, and Web of Science Database. CiteSpace 6.4.R1 was used for publication volume, country, institution, author, and keyword co-occurrence, clustering, bursting, and timeline analysis; VOSviewer 1.6.20 was used for journal co-occurrence analysis, cited literature co-occurrence analysis, and reference co-citation analysis.
    RESULTS AND CONCLUSION: (1) A total of 491 papers were included, including 44 in Chinese and 447 in English. The number of publications in both Chinese and English generally showed an upward trend. The authors with the most publications in Chinese and English were Zhang Yifan and Ciuffreda Kenneth Joseph respectively. The institutions with the most publications in Chinese and English were Shandong University of Traditional Chinese Medicine and Centre National de la Recherche Scientifique (CNRS) respectively. (2) The results of keyword co-occurrence and clustering of eye-tracking technology applied in rehabilitation showed that Chinese keywords were cognitive function, autism spectrum disorders, attention, stroke, and unilateral spatial neglect; and English keywords were attention, homonymous hemianopia, children, visual neglect, and deficit disorder. The keywords with higher bursting intensity in Chinese included cognitive function, eye movement, and review, while those in English included stroke, dynamic visual acuity, attention, and virtual reality. (3) As a technology that can recognize and track the vision of people, eye-tracking technology is gradually becoming a research hot spot in the field of rehabilitation medicine, mainly focusing on cognitive rehabilitation of stroke patients, unilateral neglect rehabilitation, attention rehabilitation for children with autism spectrum disorder and attention deficit hyperactivity disorder, study of eye movement patterns in patients with brain injury. (4) The use of eye-tracking technology in combination with conventional rehabilitation therapy can be more efficient in diagnosing and treating patients with dysfunction. In the future, eye-tracking technology may be further combined with new technologies, such as virtual reality and brain-computer interfaces, to improve the level of clinical rehabilitation medicine. 


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    Bibliometric analysis of ferroptosis and Alzheimer’s disease
    Liu Annan, Li Jianhui, Gao Wei, Li Xue, Song Jing, Xing Liping, Li Honglin
    2026, 30 (16):  4278-4288.  doi: 10.12307/2026.730
    Abstract ( 101 )   PDF (4412KB) ( 21 )   Save
    BACKGROUND: With the rapid development of Alzheimer’s disease research in recent years, ferroptosis and Alzheimer’s disease have gradually become hot topics in academia. However, there is no systematic bibliometric analysis in this field.
    OBJECTIVE: To analyze research hotspots and future trends of ferroptosis and Alzheimer’s disease using bibliometric methods.
    METHODS: The Web of Science Core Collection database was searched for relevant literature on ferroptosis and Alzheimer’s disease from January 2015 to January 2025. CiteSpace 6.3.R1 and VOSviewer 1.6.19 were used to conduct a visual analysis of annual publication volume, countries, institutions, authors, co-cited literature and journals, keywords, etc. of the included literature and draw a knowledge map.
    RESULTS AND CONCLUSION: A total of 411 articles were included. The number of articles on ferroptosis and Alzheimer’s disease has been increasing year by year. China has the largest number of publications (249 articles), and the University of Melbourne is the most productive institution in this field. Scott Ayton has published the most articles, and Cell is the journal with the highest citation frequency. The co-occurrence analysis of keywords showed that the main research hotspots in this field include oxidative stress, cell death and lipid peroxidation, etc. Cluster analysis indicated that the current research in this field mainly focuses on the pathogenesis of Alzheimer’s disease, disease prevention and treatment. The burst words that emerged in the past 2 years mainly include amyloid precursor protein, iron accumulation, brain iron concentration and central nervous system.

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