Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

BACKGROUND:Socket-shield technique can effectively maintain labial soft and hard tissues,but the incidence of postoperative complications such as exposure and displacement of root shield is relatively high.It is speculated that the root shield may be exposed and displaced due to excessive load after long-term function of dental implants. OBJECTIVE:Through three-dimensional finite element analysis,we aim to study the influence of varying root shield thicknesses on the stress distribution,equivalent stress peaks,and displacement in the root shield,periodontal ligaments,implant,and surrounding alveolar bone under normal occlusal loading.We also attempt to analyze the correlation between the thickness of the root shield and occurrence of mechanical events such as root shield exposure,displacement,and fracture. METHODS:Cone-beam CT data of a patient who met the indication standard of socket-shield technique for maxillary central incisor were retrieved from database.Reverse engineering techniques were used to build models of the maxillary bone and root shield,while forward engineering was used to create models for the implant components based on their parameters.Models depicting various root shield thicknesses(0.5,1.0,1.5,and 2.0 mm)were created using Solidworks 2022 software.ANSYS Workbench 2021 software was then used to simulate and analyze the effects of varying root shield thicknesses on stress distribution,equivalent stress peaks,and displacement of the root shields,periodontal ligaments,implants,and surrounding alveolar bone under normal occlusion. RESULTS AND CONCLUSION:(1)In all root shield models,the stress was concentrated on the palatal cervical side,both sides of the edges and the lower edge of the labial side.As the thickness of the root shield increased,the equivalent stress peak and displacement showed a decreasing trend.The 0.5 mm thickness model produced a stress concentration of 176.20 MPa,which exceeded the yield strength(150 MPa)of tooth tissue.(2)The periodontal ligament stress in each group was concentrated in the neck margin and upper region.With the increase of root shield thickness,the equivalent stress peak and displacement of periodontal ligament showed a decreasing trend.(3)Implant stress in all models was concentrated in the neck of the implant and the joint of the implant-repair abutment,and the labial side was more concentrated than the palatal side.With the increase of root shield thickness,the equivalent stress peak of the implant in the model showed an increasing trend.(4)In each group of models,stress of cortical bone concentrated around the neck of the implant and the periphery of the root shield,and the labial side was more concentrated than the palatal side.With the increase of the thickness of the root shield,the equivalent stress peak around the root shield decreased;the peak value of the equivalent stress of the bone around the neck of the implant showed an increasing trend.In the model,the stress of cancellous bone was mainly concentrated around the neck of the lip of the implant,the top of the thread,the root tip and the lower margin of the root shield,and the labial side was more concentrated than the palatal side.With the increase of the thickness of the root shield,the peak value of the equivalent stress of the bone around the root shield in the model showed a decreasing trend.The minimum principal stress of cortical bone in each group of models was concentrated around the neck of the implant,exhibiting a fan-shaped distribution.As the thickness of the root shield increased,the minimum principal stress of cortical bone showed an increasing trend.(5)These results indicate that different thicknesses of the root shield have different biomechanical effects.The root shield with a thickness of 0.5 mm is easy to fracture.For patients with sufficient bone width,the root shield with a thickness of 2.0 mm is an option to reduce the risk of complications such as root shield exposure,fracture,and displacement.Meanwhile,it should be taken into account to protect the periodontal ligament in the preparation process,and rounding treatments ought to be carried out on both sides and the lower edge of the root shield.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Oxidative stress is increasingly recognized as a major contributor to the pathophysiology of Alzheimer's disease(AD),particularly in the early stages of the disease.The multiplicity advantages of stem cell transplantation make it fascinating therapeutic strategy for many neurodegenerative diseases.We herein demonstrated that human dental pulp stem cells(hDPSCs)mediated oxidative stress improvement and neuroreparative effects in in vitro AD models,playing critical roles in regulating the polarization of hyperreactive microglia cells and the recovery of damaged neurons.Importantly,these therapeutic effects were reflected in 10-month-old 3xTg-AD mice after a single transplantation of hDPSCs,with the treated mice showing significant improvement in cognitive function and neuropathological features.Mechanistically,antioxidant and neuroprotective effects,as well as cognitive enhancements elicited by hDPSCs,were at least partially mediated by Nrf2 nuclear accumulation and downstream antioxidant enzymes expression through the activation of the AKT-GSK3β-Nrf2 signaling pathway.In conclusion,our findings corroborated the neuroprotective capacity of hDPSCs to reshape the neuropathological microenvironment in both in vitro and in vivo AD models,which may be a tremendous potential therapeutic candidate for Alzheimer's disease.

Objective:To explore the vigilant attention function and behavioral changes in sleep disordered breathing(SDB) children.Methods:Thirty SDB children (SDB group) and 30 normal children (control group) were selected from June 2022 to August 2023. All participants underwent continuous performance test(CPT-AX) (Go/Nogo) and behavioral test. The latency and amplitude of contingent negative variation(CNV) components under cue/uncue conditions in leads F3, Fz and F4 were measured. The t-test and Mann-Whitney U test were used to conduct statistical analysis by SPSS 25.0 software. Results:(1) There were no statistically significant differences in the number of correct responses, reaction time and number of false alarms between the SDB group and the control group (all P>0.05).(2) The latencies of cue-CNV in the SDB group(F3: 618.00(582.50, 644.50)ms, Fz: 603.00(579.50, 634.00)ms, F4: (606.87±25.07)ms) were longer than those in the control group(F3: (508.47±25.82)ms, Fz: 502.00(470.00, 520.50)ms, F4: 514.00(487.00, 536.50)ms) in leads F3, Fz and F4. The latency of cue-CNV of lead F4 in the SDB group was higher than that in the control group, and the difference was statistically significant ( P<0.05). The latencies of uncue-CNV in lead F3 and Fz in the SDB group were higher than those in the control group, and the differences were statistically significant (both P<0.05). Conclusion:SDB children have shown activation in the right brain area during attentional tasks, and the prolonged CNV latency may be a sensitive neuroelectrophysiological marker for early clinical assessment of vigilant attention dysfunction.

Objective:To explore the cognitive function characteristics of children with primary snoring (PS) and obstructive sleep apnea-hypopnea syndrome (OSAHS) using event-related potentials.Methods:From October 2020 to October 2022, 20 children with OSAHS, 20 children with PS, and 22 normal children were recruited for continuous performance task (CPT) and behavioral assessments. ERP and behavioral data were meticulously recorded, with measurements of N1, P2, N2, and P3 wave amplitudes and latencies at F3, Fz, and F4 electrode sites. Statistical analyses were conducted using one-way ANOVA and Kruskal-Wallis test via SPSS 25.0 software.Results:(1) Behavioural test: There was no statistically significant difference in terms of correct responses, response times, and false alarms among the three groups (all P>0.05). (2) F3 Lead: There were statistically significant differences in Go-P2 amplitude, Nogo-P2 amplitude, Nogo-P2 latency, Go-P3 amplitude, and Nogo-P3 latency among the three groups (all P<0.05). Specifically, the OSAHS group exhibited higher Go-P2 amplitude((15.03±5.12) μV vs (10.97±5.50)μV), Nogo-P2 amplitude((14.80±5.84) μV vs (9.67±4.79)μV), and Go-P3 amplitude((11.58±6.02) μV vs (7.49±4.89) μV) compared to the normal group. Additionally, the OSAHS and PS groups exhibited longer Nogo-P2 latency compared to the normal group((223.10±20.61) ms vs (208.00±23.09) ms, (230.60±13.61) ms vs (208.00±23.09) ms), as well as prolonged Nogo-P3 latency((459.20±34.26) ms vs (460.40±24.52) ms and (429.91±31.49) ms) (all P<0.05). Fz Lead: There were statistically significant differences in Go-N1, Go-P2, Nogo-P2, Go-P3, Nogo-N2 wave amplitudes, and Nogo-P3 latency among the three groups (all P<0.05). Compared to the normal group, the OSAHS group exhibited increased Go-P3 amplitude((9.07±5.68) μV vs (5.10±3.51) μV) and decreased Nogo-N2 amplitude((-8.80±5.97) μV vs (-12.84±4.86) μV). Moreover, both the OSAHS and PS groups had prolonged Nogo-P3 latency compared to the normal group((481.60±45.16) ms vs (435.13±28.17) ms and 484.00(443.50, 525.00) ms vs (435.13±28.17) ms) (both P<0.05). F4 Lead: There were statistically significant differences in Go-P2 and Nogo-P2 wave amplitudes among the three groups (all P<0.05). Compared to the normal group, the OSAHS group demonstrated increased Go-P2 amplitude((13.72±5.64) μV vs (9.70±4.59) μV) and Nogo-P2 amplitude((13.90±5.35) μV vs (9.64±3.74) μV) (both P<0.05). Conclusions:Both children with OSAHS and PS exhibit attentional cognitive impairments. However, children with OSAHS demonstrate more pronounced deficits in conflict monitoring, response inhibition, and executive functioning. The prolonged latency of the P3 wave serves as a sensitive electrophysiological marker for the early detection of neurocognitive impairment in children with sleep disordered breathing.

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]

Objective To evaluate the direct economic burden caused by surgical site infection(SSI)in patients with orthopaedic trauma under the payment management of disease diagnosis-related groups(DRG).Methods Clinical data of patients with orthopaedic trauma in a tertiary first-class hospital from May 1,2022 to May 30,2023 were surveyed retrospectively.Patients were grouped based on whether SSI occurred.Differences in average length of hospital stay,average hospitalization expense,and other indicators between SSI patients and non-SSI patients in the same DRG subgroup were compared,and the direct economic burden caused by SSI was analyzed.Results A total of 435 patients who paid according to the DRG payment management were included in the study.Twenty-two pa-tients had SSI,with an SSI incidence of 5.06％.Both the average length of hospital stay and average hospitalization expense of patients in the SSI group were higher than those in the non-SSI group,with statistically significant differ-ences(P＜0.05).The DRG subgroups of SSI patients were mainly four groups:IF45,IF15,IJ13,and ZC13.Among them,the average length of hospital stay of SSI patients in the IF45,IF15,and ZC13 groups increased sig-nificantly(P＜0.05),and the average hospitalization expense of SSI patients in the IJ13 group increased significantly(P＜0.05).Conclusion Under the DRG payment management,the direct economic burden of orthopaedic trauma patients with SSI increases significantly.It is necessary to periodically evaluate and identify high-risk DRG subgroup patients,so as to adopt precise infection control interventions and reduce SSI incidence.