ObjectiveTo explore the mechanism by which Banxia Xiexin Tang （BXT） regulates the advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） signaling pathway to reduce neuroinflammatory responses and ameliorate cognitive dysfunction in the rat model of vascular dementia （VD）. MethodsThe components of BXT were detected by ultra performance liquid chromatography-quadrupole -orbitrap-tandem mass spectrometry（UPLC-Q-Orbitrap-MS/MS）， and the core components and key action pathways were screened out by network pharmacology and molecular docking. Sixty SPF-grade male SD rats were randomly allocated into the sham and modeling groups by the random number table method. The VD model was replicated by the modified bilateral occlusion of the common carotid arteries （2-VO） method. The successfully modeled rats were randomly allocated into the model， low-， medium-， and high-dose （3.748 5， 7.497， 14.994 g·kg^-1） BXT （BXT-L， BXT-M， and BXT-H）， and nimodipine （NMP， 0.002 7 g·kg^-1） groups according to the random number table method. The rats in the drug intervention groups were administrated with corresponding drugs by gavage， and the sham and model groups received the same amount of normal saline for 14 consecutive days. The Morris water maze， Y-maze， and new object recognition experiments were conducted to evaluate the cognitive dysfunction of rats. Hematoxylin-eosin （HE） staining was used to evaluate the histopathological changes of the hippocampal tissue in rats. The mRNA levels of AGE， RAGE， and phosphorylated nuclear factor-kappa B p65 （p-NF-κB p65） in the hippocampal tissue of rats were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expression of related proteins in the AGE/RAGE pathway in the hippocampal tissue of rats was determined by Western blot and immunohistochemistry （IHC）. The levels of neurotransmitters and inflammatory mediators in the rat serum were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe chemical components of BXT were detected by UPLC-Q-Orbitrap-MS/MS. Network pharmacology and molecular docking identified the AGE/RAGE pathway as the key pathway. The results of the water maze， Y maze， and novel object recognition tests showed that compared with the sham group， the model group demonstrated prolonged successful latency and decreases in number of platform crossings， alternation rate， number of entries into the new arm， preference index， and discrimination index （P0.01）. Compared with the model group， the BXT-H and BXT-M groups showed shortened successful latency （P0.01） and increases in number of platform crossings （P0.05）， alternation rate （P0.01）， number of entries into the new arm （P0.05）， preference index （P0.01）， and discrimination index （P0.01）. HE results showed that compared with the sham group， the cells of model rats were loosely and disorderly arranged， and the nuclei were condensed. Compared with the model group， the pathological changes of the hippocampus in the BXT group were mitigated. Real-time PCR results showed that compared with the sham group， the model group presented up-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 in the hippocampus （P0.01）， and compared with the model group， the BXT-H and BXT-M groups showcased down-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 （P0.01）. Western blot results showed that compared with the sham group， the model group presented up-regulated expression of AGE， RAGE， p-NF-κB p65， and tumor necrosis factor-α （TNF-α） （P0.05）， and compared with the model group， the BXT-H group presented down-regulated expression of AGE， RAGE， p-NF-κB p65， and TNF-α （P0.05）. IHC results showed that compared with the sham group， the model group had increased expression of RAGE （P0.01）， and compared with the model group， the BXT-H and BXT-M groups had reduced expression of RAGE （P0.01）. ELISA results showed that compared with the sham group， the model group exhibited elevated levels of TNF-α and Interleukin-1β （IL-1β） and declined levels of acetylcholine （ACh） and dopamine （DA） in the serum （P0.01）. Compared with the model group， the BXT-L， BXT-M， and BXT-H groups showed lowered levels of TNF-α and IL-1β in the serum （P0.05） and elevated levels of ACh and DA （P0.05）. ConclusionBXT may ameliorate cognitive dysfunction in the rat model of VD by down-regulating the AGE/RAGE signaling pathway， reducing neuroinflammatory responses， and regulating neurotransmitter levels.

ObjectiveTo explore the mechanism by which Banxia Xiexin Tang （BXT） regulates the advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） signaling pathway to reduce neuroinflammatory responses and ameliorate cognitive dysfunction in the rat model of vascular dementia （VD）. MethodsThe components of BXT were detected by ultra performance liquid chromatography-quadrupole -orbitrap-tandem mass spectrometry（UPLC-Q-Orbitrap-MS/MS）， and the core components and key action pathways were screened out by network pharmacology and molecular docking. Sixty SPF-grade male SD rats were randomly allocated into the sham and modeling groups by the random number table method. The VD model was replicated by the modified bilateral occlusion of the common carotid arteries （2-VO） method. The successfully modeled rats were randomly allocated into the model， low-， medium-， and high-dose （3.748 5， 7.497， 14.994 g·kg^-1） BXT （BXT-L， BXT-M， and BXT-H）， and nimodipine （NMP， 0.002 7 g·kg^-1） groups according to the random number table method. The rats in the drug intervention groups were administrated with corresponding drugs by gavage， and the sham and model groups received the same amount of normal saline for 14 consecutive days. The Morris water maze， Y-maze， and new object recognition experiments were conducted to evaluate the cognitive dysfunction of rats. Hematoxylin-eosin （HE） staining was used to evaluate the histopathological changes of the hippocampal tissue in rats. The mRNA levels of AGE， RAGE， and phosphorylated nuclear factor-kappa B p65 （p-NF-κB p65） in the hippocampal tissue of rats were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expression of related proteins in the AGE/RAGE pathway in the hippocampal tissue of rats was determined by Western blot and immunohistochemistry （IHC）. The levels of neurotransmitters and inflammatory mediators in the rat serum were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe chemical components of BXT were detected by UPLC-Q-Orbitrap-MS/MS. Network pharmacology and molecular docking identified the AGE/RAGE pathway as the key pathway. The results of the water maze， Y maze， and novel object recognition tests showed that compared with the sham group， the model group demonstrated prolonged successful latency and decreases in number of platform crossings， alternation rate， number of entries into the new arm， preference index， and discrimination index （P<0.01）. Compared with the model group， the BXT-H and BXT-M groups showed shortened successful latency （P<0.01） and increases in number of platform crossings （P<0.05）， alternation rate （P<0.01）， number of entries into the new arm （P<0.05）， preference index （P<0.01）， and discrimination index （P<0.01）. HE results showed that compared with the sham group， the cells of model rats were loosely and disorderly arranged， and the nuclei were condensed. Compared with the model group， the pathological changes of the hippocampus in the BXT group were mitigated. Real-time PCR results showed that compared with the sham group， the model group presented up-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 in the hippocampus （P<0.01）， and compared with the model group， the BXT-H and BXT-M groups showcased down-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 （P<0.01）. Western blot results showed that compared with the sham group， the model group presented up-regulated expression of AGE， RAGE， p-NF-κB p65， and tumor necrosis factor-α （TNF-α） （P<0.05）， and compared with the model group， the BXT-H group presented down-regulated expression of AGE， RAGE， p-NF-κB p65， and TNF-α （P<0.05）. IHC results showed that compared with the sham group， the model group had increased expression of RAGE （P<0.01）， and compared with the model group， the BXT-H and BXT-M groups had reduced expression of RAGE （P<0.01）. ELISA results showed that compared with the sham group， the model group exhibited elevated levels of TNF-α and Interleukin-1β （IL-1β） and declined levels of acetylcholine （ACh） and dopamine （DA） in the serum （P<0.01）. Compared with the model group， the BXT-L， BXT-M， and BXT-H groups showed lowered levels of TNF-α and IL-1β in the serum （P<0.05） and elevated levels of ACh and DA （P<0.05）. ConclusionBXT may ameliorate cognitive dysfunction in the rat model of VD by down-regulating the AGE/RAGE signaling pathway， reducing neuroinflammatory responses， and regulating neurotransmitter levels.

BACKGROUND:The pelvis has abundant trabecular bone content,but the ability of conventional sacroiliac percutaneous fixation to control trabecular bone is limited,leading to fixation failure.Therefore,the development of devices that can more effectively control trabecular bone tension is of significant importance.OBJECTIVE:The mechanical properties of a novel sacroiliac tension screw were investigated using biomechanical testing and numerical modeling analysis,along with an assessment of the reliability of the pull-out force numerical model.METHODS:A mechanical model was established based on the working principle of the novel sacroiliac tension screw.Numerical methods were employed to analyze its pull-out performance,validated through mechanical testing with polyurethane material to assess the reliability of the pull-out force numerical model.Using pelvic specimens,the mechanical effectiveness of the novel sacroiliac tension screw in repairing sacroiliac joint injuries was analyzed under normal standing posture,along with an evaluation of the load stiffness of different pelvic models in the standing position.RESULTS AND CONCLUSION:(1)The average error between the computed values of the numerical model and the measured values was 13.19％,indicating a certain level of validity for the numerical model.(2)The damage to the polyurethane material after the extraction of the screw was less pronounced in the novel screw group.(3)The average effective holding displacement for the novel screw was approximately(9.24±0.27)mm,significantly greater than the average displacement of(1.71±0.57)mm observed with the lag screws.However,the maximum resistance to pullout for the lag screws was significantly higher than that for the novel screws.(4)The novel screw effectively repaired sacroiliac joint injuries.(5)The stiffness after repair of sacroiliac joint injuries was equivalent when using a single novel screw compared to using two lag screws.(6)These results prove that the theoretical model for the maximum resistance to pullout of the screws established in this study has a certain level of validity and can guide the design of them with improved mechanical performance.The novel sacroiliac spiral blade screw can effectively hold trabecular bone and has practical clinical utility.

To investigate the pharmacological activities and potential mechanisms of action of the active components in Artemisia argyi with artificial intelligence technology, a search was conducted in the HIT, TCMSP, and TCMIO databases, obtaining 199 active components of A. argyi. A comprehensive set of algorithms, including KNN, MLP, RF, SVM, and models based on Lipinski’s and Veber’s rules, was employed to predict the toxicity and oral bioavailability of A. argyi compounds, identifying 14 components that are non-toxic and have good oral bioavailability. The synthetic accessibility score (SAscore) model was used to analyze the synthetic accessibility of the 14 components mentioned above, and molecular segments were fragmented using BRICS and RECAP algorithms. Mining of the STP and PM databases yielded 406 target proteins for the core components of A. argyi, and Cytoscape was used to screen out 5 core targets: SRC, EGFR, PTPN11, HRAS, and PDGFRB. GO and KEGG enrichment analyses indicated that the core targets were involved in 808 GO enrichment analysis entries and 71 signaling pathways, including EGFR tyrosine kinase inhibitor resistance, gap junction, phospholipase D, and JAK/STAT. Molecular docking results showed that active compounds of A. argyi have a good binding affinity with proteins SRC, EGFR, PTPN11, and HRAS. Cellular experiments have confirmed that ledol, an active component of A. argyi, can promote the proliferation of HUVEC cells within a certain concentration range and can increase the expression of EGFR protein. This study reveals the pharmacological characteristics and potential molecular mechanisms of the active components of A. argyi and lays a solid scientific foundation for its medicinal development.

BACKGROUND:The plantarflexor weakness is a common muscle defect in patients with spastic cerebral palsy and Charcot-Marie-Tooth,which clinically manifests abnormal gaits,and the relationship between plantarflexor weakness and abnormal gaits is unclear. OBJECTIVE:To explore the biomechanical behavior of the lower limb under the action of a single factor of plantarflexor weakness to reveal the mechanism of abnormal gait induced by plantarflexor weakness and to provide guidance for the rehabilitation training of patients with plantarflexor weakness. METHODS:A predictive framework of musculoskeletal multibody dynamics in the sagittal plane was established based on OpenSim Moco to predict lower limb joint angles and muscle activation changes during walking in normal subjects.The validity of the framework was verified by combining the inverse kinematics and electromyogram activation time of the experimental data.Reduced isometric muscle forces were used to model plantarflexor weakness and to compare predicted lower extremity joint angles,joint moments,and muscle energy expenditure with normal subjects to analyze the effects of plantarflexor weakness on lower extremity biomechanics. RESULTS AND CONCLUSION:(1)The Moco-based prediction framework realistically predicted the biomechanical changes of the lower limbs during walking in normal subjects(joint angles:normalized correlation coefficient≥0.73,root mean square error≤7.10°).(2)The musculoskeletal model used a small stride support phase to increase the"heel-walking"gait during plantarflexor weakness.When the plantarflexor weakness reached 80%,the muscle energy expenditure was 5.691 4 J/kg/m,and the maximum activation levels of the gastrocnemius and soleus muscles were 0.72 and 0.53,which might cause the plantarflexor weakness patients to be more prone to fatigue when walking.(3)Muscle energy expenditure was significantly higher when the weakness of plantarflexors exceeded 40%,and the joint angles and moments of the lower limbs deteriorated significantly when the weakness of plantarflexors exceeded 60%,suggesting that there may be a"threshold"for the effect of plantarflexor weakness on gait,which may correspond to the point at which health care professionals should intervene in the clinical setting.

Objective To conduct the biomechanical analysis on a new power-assisted knee orthosis.Methods A self-force source power-assisted knee orthosis was used,and four motions(level walking,sitting and standing,ascending and descending stairs)were measured before and after wearing the orthosis.A musculoskeletal multibody dynamic model was adopted to calculate the joint angles and pressures at the knee,patellofemoral and hip joints.The effects of power-assisted knee orthosis on biomechanical changes of lower limbs were investigated by comparing the joint angles and pressures before and after wearing this orthosis.Results The orthosis would reduce the knee angles during level walking,as well as the knee pressures during sitting and standing on the wearing side.Wearing the orthosis did not significantly affect the joint angles during sitting and standing;however,it led to a significant decrease in joint pressures at both bilateral knee joints and patellofemoral joints.During ascending and descending stairs,the knee angle change on the wearing side was opposite to that on the non-wearing side.The increase of the peak knee angle was(14.3±3.6)%on the non-wearing side during ascending stairs.Conclusions The power-assisted knee orthosis can offer a conservative treatment for individuals with various knee diseases by reducing joint angles and pressures in daily motions.

Objective:To evaluate the clinical efficacy of minimally invasive Chevron-Akin osteotomy (MICA) in the treatment of mild to moderate hallux valgus without addressing the proximal projection.Methods:A retrospective analysis was conducted on 31 patients with unilateral mild to moderate hallux valgus who underwent third-generation MICA surgery at Shanghai Sixth People's Hospital from January 2019 to June 2020. Among these patients, 2 were male and 29 were female, with an average age of 41.13±7.8 years (range: 21-64 years). A total of 12 patients had mild hallux valgus, while 19 patients had moderate hallux valgus. The average body mass index (BMI) was 24.37±1.28 kg/m 2 (range: 22.06-26.13 kg/m 2). Preoperative and postoperative foot X-rays were taken at multiple time points, including 1 day, 1.5 months, 3 months, 12 months, and 24 months after surgery. These X-rays were used to assess the medial eminence width (MEW) of the first metatarsal head, the proximal medial projection width (PMRW) of the first metatarsal, the hallux valgus angle (HVA), the intermetatarsal angle (IMA), and the distal metatarsal articular angle (DMAA). Functional improvements and pain relief were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) forefoot score and the visual analogue scale (VAS). Results:All 31 patients completed an average follow-up period of 25.67±2.35 months (range: 24-31 months). The average operation time was 39.55±7.31 minutes (range: 32-46 minutes). The number of intraoperative fluoroscopy exposures averaged 16.23±2.38 times (range: 13-21 times). At the two-year follow-up, significant improvements were observed in all measured parameters when compared to preoperative values ( P<0.05). The HVA decreased from 35.18°±3.59° before surgery to 10.93°±0.90° after surgery. The IMA was reduced from 11.47°±0.85° to 6.94°±0.65°, and the DMAA decreased from 15.24°±1.13° to 4.31°±0.56°. The MEW decreased from 4.07±0.70 mm to 0.13±0.11 mm. The PMRW, which was measured at one day postoperatively and at the two-year follow-up, decreased from 3.44±0.66 mm to 0.19±0.11 mm. Functional assessments also showed significant improvements ( P<0.05). The AOFAS forefoot score increased from 57.42±3.93 before surgery to 89.52±3.46 at the two-year follow-up. Pain levels, as assessed by the VAS, decreased from 5.68±1.11 preoperatively to 0.77±0.50 postoperatively. At the two-year follow-up, 97% of patients reported excellent satisfaction with the surgical outcome. During the follow-up period, complications included mild numbness around the wound in two cases, metatarsophalangeal joint stiffness in one case, and hallux valgus recurrence in one case, accounting for 3% of the cohort. Conclusion:Third-generation MICA without addressing the proximal projection is an effective procedure for correcting mild to moderate hallux valgus. This technique significantly improves foot function, reduces pain, and leads to high levels of patient satisfaction.

Mesenchymal stem cells(MSCs) are multipotent stem cells with the ability to self-renew and differentiate into multiple lineages. In recent years, MSCs have been increasingly used as a therapeutic strategy in orthopedic diseases such as osteoarthritis, rheumatoid arthritis, cartilage damage, tendon bone damage, bone defects, and degenerative bone diseases. Compared with cell-free therapy, MSCs have achieved better results. However, due to their widespread sources, complex action mechanisms, and diverse product types, there are certain limitations and controversies in their clinical application in orthopedics. This article will discuss the current main applications and future trends of MSCs in the field of orthopedics, looking forward to the prospects of MSCs application in orthopedics.

Objective:To evaluate the safety and efficacy of early precise lower limb weight-bearing functional rehabilitation after open reduction and internal fixation of ankle fractures.Methods:A restropective multi-center study was conducted to enroll the eligible 120 patients with malleolar fracture who received the same surgical treatment from March 2023 to December 2023 at the trauma centers in 7 tertiary hospitals according to the inclusion criteria. They were assigned into a study group ( n=60) for precise lower limb weight-bearing functional rehabilitation with the assistance of intelligent lower limb walking rehabilitation crutches and a control group ( n=60) for conventional weight-bearing functional rehabilitation which was gradually increased according to their own feelings under the protection of a walking boot. All the 60 patients in the study group completed their final follow-ups. They were 25 males and 35 females, with an age of (43.8±16.6) years and a body mass index of (25.3±2.3) kg/m 2. Only 51 patients in the control group completed their final follow-ups. They were 27 males and 24 females, with an age of (45.1±16.4) years and a body mass index of (24.7±2.3) kg/m 2. When their incisions healed and their sutures were removed 2 weeks after operation, the patients were guided to start lower limb weight-bearing functional rehabilitation, and exercises for foot and ankle joint mobility and lower limb muscles. The end point of follow-up was 12 weeks after operation. The 2 groups were compared in terms of the crutch-off rates, thigh circumferences, calf circumferences, dorsiflexions, plantarflexions, ankle swellings, American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scores, and visual analog scale (VAS) pain scores at 6 and 12 weeks after operation. The complications were also recorded in the 2 groups. Results:No statistically significant differences were observed in the baseline characteristics between the 2 groups, indicating comparability ( P>0.05). At 6 and 12 weeks after operation, the crutch-off rates [41.7% (25/60) and 100.0% (60/60)], dorsiflexions (69.3%±21.6% and 82.9%±26.3%) and AOFAS ankle-hindfoot scores [(68.5±7.6) points and (96.9±3.7) points] in the study group were significantly better than those in the control group [13.7% (7/51) and 39.2% (20/51), 61.5%±16.5% and 72.0%±14.3%, (61.9±9.3) points and (90.1±7.2) points] ( P<0.05). At 6 weeks after operation, the thigh circumference (97.4%±1.9%), calf circumference (97.3%±1.9%), and plantarflexion (76.6%±19.8%) in the study group were significantly higher than those in the control group (95.9%±2.5%, 94.6%±3.2%, and 63.9%±16.9%) ( P<0.05). There were no significant differences between the 2 groups in ankle swelling at 6 or 12 weeks after operation, or thigh or calf circumference, plantarflexion, or VAS pain score at 12 weeks after operation ( P>0.05). No wound complications, secondary fracture displacement, or loosening of internal fixation occurred in either group during the follow-up period. There were no cases of nonunion or delayed union. Conclusions:Early lower limb weight-bearing functional rehabilitation after open reduction and internal fixation of ankle fractures demonstrates good safety. Precise weight-bearing rehabilitation accelerates functional recovery of the ankle, enabling earlier return to normal daily activities.