BACKGROUND:The surgical treatment of severe lumbar fractures is mainly based on posterior short-segment fixation,and different pedicle screw fixation methods have differences in biomechanical properties.OBJECTIVE:To simulate three different screw fixation techniques in the treatment of severe L1 vertebral fractures using three-dimensional finite element technology,and to compare and analyze the biomechanical characteristics of the upper and lower intervertebral discs,fractured vertebrae,and internal fixation devices during the simulated spinal movement.METHODS:A three-dimensional model of the T11-L3 spine was established to simulate severely unstable fracture of the lumbar 1 vertebral body using the designed three pedicle screw fixation methods:Model A with 4 traditional pedicle screws(2 in each T12 and L2),model B with 4 Universal Spine System pedicle screws(2 in each T12 and L2),and Model C were bilateral intermediate fixation with 6 pedicle screws(2 in each of T12,L1,and L2).Restraint and load were applied to simulate the maximum stress and maximum displacement of the internal fixation,the displacement of the L1 vertebral body,and stress on the intervertebral discs superior and inferior to the injured vertebra during the anterior flexion,posterior extension,left-sided bending,right-sided bending and left-right rotation of the lumbar spine.RESULTS AND CONCLUSION:(1)The maximum displacement and motion range of the lumbar 1 vertebra with Model C in flexion and extension,left bending,right bending,left rotation,and right rotation were lowest in the tested motion states;the maximum stress of the screws and connecting rods was the smallest;and the maximum stress of intervertebral discs superior and inferior to the injured vertebra was the smallest.This was followed by the Model B,while the maximum displacement and motion range of the lumbar 1 vertebra and the stress and displacement of the screw connecting rod in the Model A were highest,but it showed the worst biomechanical stability and was more prone to adjacent segment degeneration.(2)These results show that bilateral intermediate fixation with six pedicle screws during the treatment of severe lumbar fractures is more dispersed in internal fixator stress and exhibits the least displacement and motion range of the vertebral pedicle screws and rods compared with four universal spinal system pedicle screws and four traditional pedicle screws.Thus,it can effectively reduce the occurrence of internal fixation failure and the adjacent segment degeneration.

BACKGROUND:The surgical treatment of severe lumbar fractures is mainly based on posterior short-segment fixation,and different pedicle screw fixation methods have differences in biomechanical properties.OBJECTIVE:To simulate three different screw fixation techniques in the treatment of severe L1 vertebral fractures using three-dimensional finite element technology,and to compare and analyze the biomechanical characteristics of the upper and lower intervertebral discs,fractured vertebrae,and internal fixation devices during the simulated spinal movement.METHODS:A three-dimensional model of the T11-L3 spine was established to simulate severely unstable fracture of the lumbar 1 vertebral body using the designed three pedicle screw fixation methods:Model A with 4 traditional pedicle screws(2 in each T12 and L2),model B with 4 Universal Spine System pedicle screws(2 in each T12 and L2),and Model C were bilateral intermediate fixation with 6 pedicle screws(2 in each of T12,L1,and L2).Restraint and load were applied to simulate the maximum stress and maximum displacement of the internal fixation,the displacement of the L1 vertebral body,and stress on the intervertebral discs superior and inferior to the injured vertebra during the anterior flexion,posterior extension,left-sided bending,right-sided bending and left-right rotation of the lumbar spine.RESULTS AND CONCLUSION:(1)The maximum displacement and motion range of the lumbar 1 vertebra with Model C in flexion and extension,left bending,right bending,left rotation,and right rotation were lowest in the tested motion states;the maximum stress of the screws and connecting rods was the smallest;and the maximum stress of intervertebral discs superior and inferior to the injured vertebra was the smallest.This was followed by the Model B,while the maximum displacement and motion range of the lumbar 1 vertebra and the stress and displacement of the screw connecting rod in the Model A were highest,but it showed the worst biomechanical stability and was more prone to adjacent segment degeneration.(2)These results show that bilateral intermediate fixation with six pedicle screws during the treatment of severe lumbar fractures is more dispersed in internal fixator stress and exhibits the least displacement and motion range of the vertebral pedicle screws and rods compared with four universal spinal system pedicle screws and four traditional pedicle screws.Thus,it can effectively reduce the occurrence of internal fixation failure and the adjacent segment degeneration.

ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription （BSTDP）. MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-LIT-Orbitrap-MS）. Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction （PPI） network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg （mpx： GFP）. At three days post-fertilization （3 dpf）， larvae of zebrafish were randomly assigned to blank group， model group， positive drug dexamethasone acetate group （75 μmol·L^-1）， and BSTDP groups with low， medium， and high doses （500， 1 000， and 2 000 mg·L^-1）. The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa-B （NF-κB） signaling pathway and inflammatory factors including interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsA total of 120 chemical components were identified in BSTDP， among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis （RA） and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine， vomicine， sinapine， rehmannioside， cinnamyl alcohol glycoside， and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 （Akt1）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， TLR4， mitogen-activated protein kinase 14 （MAPK14）， and phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit α （PIK3CA）， thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L^-1. Compared to those in the blank group， zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region （P<0.01） and rising mRNA levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β （P<0.01）. Compared to that in the model group， the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses， as well as the dexamethasone acetate group （P<0.05， P<0.01）. There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β were significantly down-regulated （P<0.05， P<0.01）. ConclusionThis paper identifies the material basis of the efficacy of BSTDP， demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.

ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription （BSTDP）. MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-LIT-Orbitrap-MS）. Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction （PPI） network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg （mpx： GFP）. At three days post-fertilization （3 dpf）， larvae of zebrafish were randomly assigned to blank group， model group， positive drug dexamethasone acetate group （75 μmol·L^-1）， and BSTDP groups with low， medium， and high doses （500， 1 000， and 2 000 mg·L^-1）. The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa-B （NF-κB） signaling pathway and inflammatory factors including interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsA total of 120 chemical components were identified in BSTDP， among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis （RA） and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine， vomicine， sinapine， rehmannioside， cinnamyl alcohol glycoside， and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 （Akt1）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， TLR4， mitogen-activated protein kinase 14 （MAPK14）， and phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit α （PIK3CA）， thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L^-1. Compared to those in the blank group， zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region （P<0.01） and rising mRNA levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β （P<0.01）. Compared to that in the model group， the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses， as well as the dexamethasone acetate group （P<0.05， P<0.01）. There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β were significantly down-regulated （P<0.05， P<0.01）. ConclusionThis paper identifies the material basis of the efficacy of BSTDP， demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.

Background: Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder. Cellular drug screening represents a key approach in the preclinical discovery of AD therapeutics. Moreover, selecting an appropriate cellular model is essential for exploring the mechanisms underlying AD pathogenesis. Objective: This study aimed to establish a progressive strategy integrating cell model construction, monomer evaluation, and effective component group-based drug discovery for the development of novel therapeutics targeting AD. Methods: A novel AD12 cell line stably expressing the double-transgenic genes amyloid precursor protein (APP)695/presenilin 1(PS1)-ΔE9 was first constructed and subjected to lipopolysaccharide (LPS) stimulation. The resulting LPS-induced neuroinflammatory response was characterized using metabolomic analysis. Subsequently, 16 alkaloids derived from traditional Chinese medicine(TCM) were screened with the LPS-AD12 cell model. Molecular docking was then performed to assess the binding affinity of benzoylaconitine (BAC) with APP and PS1 proteins. A targeted metabolomics approach focusing on amino acids and the tricarboxylic acid (TCA) cycle was applied to BAC-treated LPS-AD12 cells. Finally, aconite extract was administered to five-familial-AD-mutations(5xFAD) transgenic mice, and therapeutic efficacy was evaluated through phenotypic and metabolomic analyses. Results: LPS stimulation induced neuroinflammation in AD12 cells, characterized by elevated levels of interleukin-6, amyloid-β (Aβ ), and PS1. The primary metabolic pathways affected in AD12 cells included alanine, aspartate, and glutamate metabolism, as well as arginine biosynthesis. Notably, BAC significantly reduced the levels of Aβ and interleukin-6 in LPS-AD12 cells. Furthermore, molecular docking analyses revealed a strong binding affinity of BAC with APP and PS1 proteins. Targeted metabolomics analysis indicated that the pharmacological activity of BAC was primarily associated with its anti-inflammatory effects, modulation of the cholinergic signaling pathway, and regulation of energy metabolism. Behavioral experiments in 5xFAD mice, together with immunofluorescence assessments of brain tissues (amyloid-β, glial fibrillary acidic protein, and ionized calcium-binding adapter molecule 1), demonstrated that aconite extract treatment significantly alleviated AD-related symptoms. In addition, metabolomics-based mechanistic analyses revealed that serine, acetylcholine, ornithine, and gamma-aminobutyric acid exhibited consistent trends in both brain tissue and serum samples from treated mice. Conclusion: This study established a novel AD12 cell model and an effective, reliable LPS-induced cell-based screening system. Additionally, we proposed a new drug discovery strategy integrating cell model construction, monomer evaluation, and effective component group-based drug discovery. This screening system has the potential to accelerate the identification of anti-AD agents and provides a feasible framework for subsequent in-depth investigations into new drug development from TCM, thereby contributing to the modernization of TCM-derived therapeutics.

Background and Aims:Implant-based breast reconstruction is one of the most common reconstructive approaches after mastectomy for breast cancer.However,the incidence of postoperative complications remains significant,and the associated risk factors have not been fully elucidated.This study aimed to analyze the incidence of surgical complications following implant-based breast reconstruction in patients undergoing mastectomy at our center and to identify potential risk factors.Methods:A retrospective analysis was conducted on patients who underwent mastectomy and implant-based breast reconstruction at Sun Yat-sen Memorial Hospital between May 2004 and August 2022.Patients were grouped according to the presence or absence of postoperative surgical complications,and multivariate Logistic regression was used to identify independent risk factors.Results:A total of 545 patients with 602 reconstructed breasts were included.Surgical complications occurred in 13.6%(82/602)of the cases,including infection,wound dehiscence/poor healing,flap or nipple-areola necrosis,and implant leakage/rupture.Multivariate analysis revealed that nipple-areola complex resection(OR=1.934,95%CI=1.056-3.542,P=0.033),postoperative radiotherapy(OR=2.483,95%CI=1.527-4.036,P<0.001),implant volume≥300 mL(OR=1.663,95%CI=1.025-2.696,P=0.039),and surgeon experience with fewer than 10 cases(OR=1.804,95%CI=1.092-2.979,P=0.021)were all independent risk factors for complications.Conclusion:NAC resection,radiotherapy,large implant volume,and limited surgical experience are important independent risk factors for postoperative surgical complications following implant-based breast reconstruction.Thorough preoperative evaluation and appropriate surgical planning are essential to minimize risks.

Objective:To explore the clinical efficacy value of the medical failure mode,and failure mode and effect analysis(FMEA)mode in equipment management of the department of optimizing blood purification equipment.Methods:Based on the management concept of medical FMEA,a FMEA management mode for equipment was constructed to manage the hemodialysis equipment in the blood purification department of the First Affiliated Hospital of Hebei North University.A total of 83 used hemodialysis equipment in the blood purification department of our hospital from October 2022 to September 2024 were selected,and they were managed respectively by using conventional management mode and FMEA management mode.The differences of operation quality of equipment,comprehensive efficiency of equipment and the management capabilities of managers who used the equipment between two kinds of management modes were compared.Results:The average values of failure rate of equipment,self-repair rate,maintenance rate,and standardized operation rate of using FMEA management mode were respectively(4.72±0.11)%,(90.62±3.44)%,(95.42±2.43)%and(96.22±1.48)%.The failure rate of FMEA management mode was lower than that of conventional management mode,while the self-repair rate,maintenance rate,and standardized operation rate were higher than those of conventional management mode,and the differences were statistically significant(t=108.568,13.658,9.318,10.354,P＜0.05).The average values of availability ratio of equipment,ratio of performance index,and ratio of quality index of adopting FMEA management mode were respectively(91.04±2.65)%,(96.94±2.31)%and(97.66±1.19)%,which were higher than those of conventional management mode,and the differences were statistically significant(t=19.330,13.085,14.889,P＜0.05).The scores of job responsibilities,basic knowledge for equipment,guarantee capabilities for operation and management performance of manager were respectively(94.12±2.76),(92.03±2.50),(91.35±2.62)and(93.65±3.28)in using the FMEA management mode,which were all higher than those of the conventional management mode,and the differences were statistically significant(t=7.630,11.027,17.311,11.645,P＜0.05).Conclusion:The application of medical FMEA management mode in the management for hemodialysis equipment in the blood purification department can improve the quality of equipment operation,and reduce the failure frequency of equipment,and enhance the overall utilization efficiency of equipment,and improve the quality of clinical services in the department.

Objective:To explore the clinical efficacy value of the medical failure mode,and failure mode and effect analysis(FMEA)mode in equipment management of the department of optimizing blood purification equipment.Methods:Based on the management concept of medical FMEA,a FMEA management mode for equipment was constructed to manage the hemodialysis equipment in the blood purification department of the First Affiliated Hospital of Hebei North University.A total of 83 used hemodialysis equipment in the blood purification department of our hospital from October 2022 to September 2024 were selected,and they were managed respectively by using conventional management mode and FMEA management mode.The differences of operation quality of equipment,comprehensive efficiency of equipment and the management capabilities of managers who used the equipment between two kinds of management modes were compared.Results:The average values of failure rate of equipment,self-repair rate,maintenance rate,and standardized operation rate of using FMEA management mode were respectively(4.72±0.11)%,(90.62±3.44)%,(95.42±2.43)%and(96.22±1.48)%.The failure rate of FMEA management mode was lower than that of conventional management mode,while the self-repair rate,maintenance rate,and standardized operation rate were higher than those of conventional management mode,and the differences were statistically significant(t=108.568,13.658,9.318,10.354,P＜0.05).The average values of availability ratio of equipment,ratio of performance index,and ratio of quality index of adopting FMEA management mode were respectively(91.04±2.65)%,(96.94±2.31)%and(97.66±1.19)%,which were higher than those of conventional management mode,and the differences were statistically significant(t=19.330,13.085,14.889,P＜0.05).The scores of job responsibilities,basic knowledge for equipment,guarantee capabilities for operation and management performance of manager were respectively(94.12±2.76),(92.03±2.50),(91.35±2.62)and(93.65±3.28)in using the FMEA management mode,which were all higher than those of the conventional management mode,and the differences were statistically significant(t=7.630,11.027,17.311,11.645,P＜0.05).Conclusion:The application of medical FMEA management mode in the management for hemodialysis equipment in the blood purification department can improve the quality of equipment operation,and reduce the failure frequency of equipment,and enhance the overall utilization efficiency of equipment,and improve the quality of clinical services in the department.

Allergen-specific immunotherapy（AIT） remains the only therapeutic approach with the potential to modify the natural course of allergic rhinitis（AR）. Nevertheless, considerable inter-individual variability exists in patients'responses to AIT. To facilitate more reliable assessment of treatment efficacy, the China Rhinopathy Research Cooperation Group（CRRCG） convened young and middle-aged nasal experts in China to formulate the present consensus. The recommended subjective outcome measures for AIT comprise symptom scores, medication scores, combined symptom and medication scores, quality-of-life assessments, evaluation of disease control, and assessment of comorbidities. Objective indicators may supplement these measures. Currently available objective approaches include skin prick testing, nasal provocation testing, and allergen exposure chambers. However, these methods remain constrained by practical limitations and are not yet appropriate for routine implementation in clinical efficacy evaluation. In addition, several biomarkers, including sIgE and the sIgE/tIgE ratio, sIgG4, serum IgE-blocking activity, IgA, cytokines and chemokines, as well as immune cell surface molecules and their functional activity, have been shown to have associations with AIT outcomes. While these biomarkers may complement subjective assessments, they are subject to significant limitations. Consequently, large-scale multicenter trials and real-world evidence are required to strengthen the evidence base. The present consensus underscores the necessity of integrating patients'subjective experiences with objective testing throughout the treatment process, thereby providing a more comprehensive and accurate framework for efficacy evaluation. Looking forward, future investigations should prioritize the incorporation of multi-omics data and artificial intelligence methodologies, which hold promise for overcoming current limitations in assessment strategies and for advancing both the standardization and personalization of AIT.
Humans ; Allergens/immunology* ; China ; Consensus ; Desensitization, Immunologic ; Immunoglobulin E ; Quality of Life ; Rhinitis, Allergic/therapy* ; Treatment Outcome ; East Asian People

OBJECTIVE: To evaluate the analgesic efficacy of ultrasound-guided high fascia iliaca compartment block (HFICB) in managing tourniquet-related pain following total knee arthroplasty (TKA). METHODS: A prospective randomized controlled trial was conducted involving 84 patients with severe knee osteoarthritis or rheumatoid arthritis who underwent unilateral TKA between March 2024 and December 2024. Patients were randomly assigned to two groups ( n=42) using a random number table. In the trial group, ultrasound-guided HFICB was performed preoperatively, with 0.2% ropivacaine injected into the fascia iliaca compartment. No intervention was administered in the control group. Baseline characteristics, including gender, age, surgical side, body mass index, and preoperative visual analogue scale (VAS) scores at rest and during movement, showed no significant difference between the two groups ( P>0.05). In both groups, a tourniquet was applied after osteotomy and before pulsed lavage, and removed after the closure of the first layer of the joint capsule. Postoperative assessments were conducted at 6, 12, 24, and 48 hours, including VAS scores at the tourniquet site (at rest and during movement), Bromage motor block scores, Ramsay sedation scores, and Bruggrmann comfort scale (BCS) scores to evaluate patient comfort. Additionally, the average tramadol consumption and incidence of nausea and vomiting within 48 hours postoperatively were recorded and compared. RESULTS: In the trial group and control group, VAS scores during movement at the tourniquet site significantly improved at all postoperative time points compared to preoperative levels ( P<0.05). VAS scores at rest increased transiently at 6 hours after operation in both groups, and then gradually decreased to the preoperative level. Except that there was no significant difference at 48 hours after operation in the trial group ( P>0.05), there were significant differences at other time points of two groups compared to preoperative score ( P<0.05). Except for VAS score at rest at 6 hours, VAS score during movement at 48 hours, and BCS comfort score at 48 hours ( P>0.05), the trial group showed significantly better outcomes than the control group in terms of VAS score at rest, VAS score during movement, Ramsay sedation scores, and BCS comfort scores at all other time points ( P<0.05). No significant difference was found in Bromage motor block scores between the groups ( P>0.05). Tramadol was used in 3 patients in the trial group and 7 patients in the control group within 48 hours after operation, the dosage was (133.30±14.19) mg and (172.40±22.29) mg, showing significant difference ( P<0.05). Nausea and vomiting occurred in 4 patients (9.5%) in the trial group and 3 patients (7.1%) in the control group, with no significant difference in incidence between groups ( P>0.05). CONCLUSION Ultrasound-guided HFICB provides effective analgesia for tourniquet-related pain following TKA, facilitates early postoperative functional recovery of the knee joint, and may serve as a valuable clinical option for postoperative pain management in TKA patients.
Humans ; Arthroplasty, Replacement, Knee/adverse effects* ; Nerve Block/methods* ; Male ; Female ; Pain, Postoperative/etiology* ; Tourniquets/adverse effects* ; Prospective Studies ; Middle Aged ; Ropivacaine/administration & dosage* ; Aged ; Ultrasonography, Interventional ; Anesthetics, Local/administration & dosage* ; Pain Measurement ; Fascia ; Osteoarthritis, Knee/surgery* ; Treatment Outcome ; Arthritis, Rheumatoid/surgery*