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.

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.

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 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.

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.

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 explore the predictive value of serum angiopoietin-like protein 4(ANGPTL4)and C-X3-C motif chemokine ligand 1(CX3CL1)for poor prognosis in patients with acute cerebral infarction(ACI)undergoing intravascular intervention therapy.Methods A total of 180 ACI patients undergoing endovascular intervention in our department from January 2021 to February 2024 were prospectively recruited and served as the study group,and according to the prognosis,they were divided into a good prognosis group(97 cases)and a poor prognosis group(83 cases).Another 180 individuals who taking healthy checkup in the same period served as the control group.The levels of ANGPTL4 and CX3CL1 were measured by ELISA.Results The ser-um ANGPTL4 level was significantly lower while that of CX3CL1 was obviously higher in the study group than the control group(P＜0.01).The poor prognosis group had notably longer time from onset to admission and larger proportions of having NIHSS score at admission≥15 and an-terior circulation cerebral infarction,lower serum ANGPTL4 level and higher CX3CL1 level when compared with the good prognosis group(P＜0.01).Multivariate logistic regression analysis showed that time from onset to admission,NIHSS score at admission,location of cerebral infarc-tion,and CX3CL1 were risk factors,and ANGPTL4 was a protective factor for poor prognosis in ACI patients(P＜0.05,P＜0.01).ROC curve analysis showed that the AUC value of serum ANGPTL4,CX3CL1 and their combinzation in predicting poor prognosis in ACI patients was 0.816(95％CI:0.755-0.877),0.860(95％CI:0.791-0.930),and 0.901(95％CI:0.846-0.956),respectively,and the combined indicators showed better predictive value than each indicator alone(Z=2.716,Z=2.732,P＜0.05).Conclusion Serum ANGPTL4 and CX3CL1 levels are abnormal-ly expressed in ACI patients after intravascular intervention therapy,and are related to prognosis.Their combined detection can improve the predictive value for poor prognosis.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.