Objective: To explore the feasibility, precision, and clinical value of a personalized primary repair approach centered on digital design, integrating 3D printing technology with multiple materials such as titanium mesh, polyetheretherketone (PEEK), and titanium plates, for complex craniofacial bone defects involving the skull, mandible, orbit, and zygoma resulting from traffic accidents, providing a reference for primary repair of clinically complex craniofacial bone defects. Methods: One patient who was admitted in September 2021 with multiple comminuted fractures of the right craniomaxillofacial region and large-area bone defects caused by a traffic accident was selected. Digital design was integrated throughout the entire repair process. First, preoperative computed tomography (CT) data were used for 3D reconstruction of the craniomaxillofacial region; then, based on the model, the anatomical contour of the healthy left side was reproduced via mirroring technology for the defects on the right side. A targeted repair plan was designed: 3D-printed PEEK material was used to reconstruct the right orbital floor and zygomaticomaxillary complex, a 0.6-mm-thick titanium mesh was adopted to repair the right skull defect, and a 2.0-mm-thick titanium plate was applied for rigid internal fixation of the mandibular fracture. A one-stage repair surgery was completed simultaneously. In addition, a literature review was conducted on studies related to the repair of complex combined craniomaxillofacial defects. Results: CT examination at 1 week postoperatively showed that the average fitting gap of the implants was 0.3 mm, and the symmetry difference of the facial contour was less than 5 mm. At 3 months postoperatively, the patient’s maximum mouth opening reached 38 mm, the occlusal relationship returned to normal, and the diplopia symptom completely disappeared. During the 6-month postoperative follow-up, no complications such as implant loosening, infection, or displacement occurred; the FACE-Q scale score was 91, indicating a high level of subjective patient satisfaction. The literature review indicated that digital design combined with 3D printing technology can significantly improve the accuracy of complex craniomaxillofacial bone defect reconstruction. PEEK material is suitable for the reconstruction of the orbital floor and zygomaticomaxillary complex. Titanium mesh and plates can ensure the stability of the reconstruction. Multi-materials combined reconstruction represents an important therapeutic strategy for such defects. Conclusion The individualized one-stage repair scheme, centered on digital design and combined with 3D printing technology and multi-materials (titanium mesh, PEEK, and titanium plates), can achieve precise anatomical reduction and simultaneous functional recovery for complex combined craniomaxillofacial bone defects caused by traffic accidents.

ObjectiveTranscranial magneto-acoustic stimulation (TMAS) is an emerging non-invasive neuromodulation technique that may provide a novel non-pharmacological intervention strategy for Parkinson's disease (PD). PD is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), leading to motor impairments such as bradykinesia, tremor, and rigidity. Increasing evidence indicates that mitochondrial dysfunction and impaired mitochondrial quality control are central mechanisms underlying dopaminergic neuronal loss. In particular, abnormalities in mitophagy and mitochondrial fission-fusion balance contribute substantially to oxidative stress, energy metabolic failure, and neuronal injury. At present, most clinical treatments for PD mainly alleviate symptoms but do not effectively halt disease progression. Therefore, exploring new interventions targeting the core pathological mechanisms is of considerable significance. This study aims to investigate whether TMAS can improve neural damage and motor dysfunction in PD mice by regulating mitophagy and the fission/fusion dynamic balance, thereby providing theoretical and experimental support for its application in PD treatment. MethodsMale C57BL/6 mice were used in this study. A PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days. After model induction, mice in the intervention group received TMAS once daily for 14 consecutive days, whereas the corresponding control group received sham stimulation. The stimulation target was positioned over the primary motor cortex (M1). Motor performance was evaluated using the pole test and the open-field test. To verify the activation effect of TMAS on the target cortical region, c-Fos immunohistochemistry was performed in the M1. To assess nigral dopaminergic neuronal injury, tyrosine hydroxylase (TH) immunohistochemistry was used to quantify TH-positive neurons in the SNc. Mitochondrial function was evaluated by measuring reactive oxygen species (ROS) levels and adenosine triphosphate (ATP) content in the SNc. Western blot was further performed to determine the expression of mitophagy-related proteins, including PINK1, Parkin, LC3-II, and p62, as well as mitochondrial dynamics-related proteins, including Drp1 and Opa1. ResultsTMAS significantly increased the number of c-Fos-positive cells in M1 (P<0.000 1), indicating effective activation of neurons in the targeted cortical region. Compared with the control group, MPTP-treated mice exhibited marked motor dysfunction, including a significant reduction in total distance traveled in the open-field test (P<0.000 1) and mean speed (P=0.000 1), as well as significant prolongation of turn time and total climbing time in the pole test (P<0.000 1). These behavioral impairments were accompanied by a substantial loss of TH-positive dopaminergic neurons in the SNc, whereas TMAS significantly increased TH-positive neuron survival (P<0.000 1). In parallel, MPTP induced a pronounced increase in ROS levels and a significant reduction in ATP content, indicating severe mitochondrial dysfunction and energy metabolism impairment (P<0.01). TMAS treatment significantly improved motor performance, as reflected by the reversal of MPTP-induced impairment in the open-field and pole tests, and significantly reduced ROS accumulation (P<0.01) while restoring ATP production (P<0.001). At the molecular level, MPTP markedly downregulated PINK1 and Parkin, decreased p62 expression, increased LC3-II accumulation, elevated Drp1 expression, and reduced Opa1 expression, whereas TMAS significantly reversed these abnormalities, suggesting restoration of mitophagy-related mitochondrial quality control and re-establishment of mitochondrial fission-fusion balance. Collectively, these findings indicate that TMAS ameliorates MPTP-induced neurotoxicity and restores mitochondrial homeostasis and energy metabolism. ConclusionTMAS effectively attenuates neural damage and improves motor dysfunction in MPTP-induced PD mice. Its neuroprotective effects are closely associated with multidimensional regulation of the mitochondrial quality control system, including restoration of PINK1/Parkin-mediated mitophagy and rebalancing of Drp1/Opa1-related mitochondrial dynamics. Rather than acting only as a symptomatic neuromodulatory intervention, TMAS may influence a key pathological axis of PD by improving mitochondrial homeostasis in SNc and protecting nigral dopaminergic neurons. These findings provide experimental evidence supporting TMAS as a promising non-invasive physical intervention for PD.

ObjectiveTranscranial magneto-acoustic stimulation (TMAS) is an emerging non-invasive neuromodulation technique that may provide a novel non-pharmacological intervention strategy for Parkinson's disease (PD). PD is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), leading to motor impairments such as bradykinesia, tremor, and rigidity. Increasing evidence indicates that mitochondrial dysfunction and impaired mitochondrial quality control are central mechanisms underlying dopaminergic neuronal loss. In particular, abnormalities in mitophagy and mitochondrial fission-fusion balance contribute substantially to oxidative stress, energy metabolic failure, and neuronal injury. At present, most clinical treatments for PD mainly alleviate symptoms but do not effectively halt disease progression. Therefore, exploring new interventions targeting the core pathological mechanisms is of considerable significance. This study aims to investigate whether TMAS can improve neural damage and motor dysfunction in PD mice by regulating mitophagy and the fission/fusion dynamic balance, thereby providing theoretical and experimental support for its application in PD treatment. MethodsMale C57BL/6 mice were used in this study. A PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days. After model induction, mice in the intervention group received TMAS once daily for 14 consecutive days, whereas the corresponding control group received sham stimulation. The stimulation target was positioned over the primary motor cortex (M1). Motor performance was evaluated using the pole test and the open-field test. To verify the activation effect of TMAS on the target cortical region, c-Fos immunohistochemistry was performed in the M1. To assess nigral dopaminergic neuronal injury, tyrosine hydroxylase (TH) immunohistochemistry was used to quantify TH-positive neurons in the SNc. Mitochondrial function was evaluated by measuring reactive oxygen species (ROS) levels and adenosine triphosphate (ATP) content in the SNc. Western blot was further performed to determine the expression of mitophagy-related proteins, including PINK1, Parkin, LC3-II, and p62, as well as mitochondrial dynamics-related proteins, including Drp1 and Opa1. ResultsTMAS significantly increased the number of c-Fos-positive cells in M1 (P<0.000 1), indicating effective activation of neurons in the targeted cortical region. Compared with the control group, MPTP-treated mice exhibited marked motor dysfunction, including a significant reduction in total distance traveled in the open-field test (P<0.000 1) and mean speed (P=0.000 1), as well as significant prolongation of turn time and total climbing time in the pole test (P<0.000 1). These behavioral impairments were accompanied by a substantial loss of TH-positive dopaminergic neurons in the SNc, whereas TMAS significantly increased TH-positive neuron survival (P<0.000 1). In parallel, MPTP induced a pronounced increase in ROS levels and a significant reduction in ATP content, indicating severe mitochondrial dysfunction and energy metabolism impairment (P<0.01). TMAS treatment significantly improved motor performance, as reflected by the reversal of MPTP-induced impairment in the open-field and pole tests, and significantly reduced ROS accumulation (P<0.01) while restoring ATP production (P<0.001). At the molecular level, MPTP markedly downregulated PINK1 and Parkin, decreased p62 expression, increased LC3-II accumulation, elevated Drp1 expression, and reduced Opa1 expression, whereas TMAS significantly reversed these abnormalities, suggesting restoration of mitophagy-related mitochondrial quality control and re-establishment of mitochondrial fission-fusion balance. Collectively, these findings indicate that TMAS ameliorates MPTP-induced neurotoxicity and restores mitochondrial homeostasis and energy metabolism. ConclusionTMAS effectively attenuates neural damage and improves motor dysfunction in MPTP-induced PD mice. Its neuroprotective effects are closely associated with multidimensional regulation of the mitochondrial quality control system, including restoration of PINK1/Parkin-mediated mitophagy and rebalancing of Drp1/Opa1-related mitochondrial dynamics. Rather than acting only as a symptomatic neuromodulatory intervention, TMAS may influence a key pathological axis of PD by improving mitochondrial homeostasis in SNc and protecting nigral dopaminergic neurons. These findings provide experimental evidence supporting TMAS as a promising non-invasive physical intervention for PD.

BACKGROUND:Our previous studies have found that poly(vinylidene fluoride)bionic periosteum prepared by electrospinning has good cytocompatibility,but its biocompatibility is unknown. OBJECTIVE:To evaluate the biocompatibility of poly(vinylidene fluoride)bionic periosteum doped with Zn2+and Mg2+. METHODS:Poly(vinylidene fluoride),poly(vinylidene fluoride)bionic periosteum doped with 1％Zn2+,doped with 1％Mg2+,and doped with 1％(Zn2++Mg2+)were prepared by electrospinning to make bionic periosteum extract.SD rats were selected as the experimental subjects for hemolysis test,short-term systemic toxicity test,and heat source test.Guinea pigs were selected as the experimental subjects for skin sensitization test.The biocompatibility of bionic periosteum of four groups was tested. RESULTS AND CONCLUSION:(1)The hemolysis test results showed that the hemolysis rates of 1％Zn2+poly(vinylidene fluoride),1％Mg2+poly(vinylidene fluoride),1％Zn2++1％Mg2+poly(vinylidene fluoride)bionic periosteum and poly(vinylidene fluoride)extract were(0.130±0.013)％,(0.149±0.020)％,(0.466±0.018)％,and(0.037±0.018)％,respectively,which met the hemocompatibility standard of biomaterials.(2)The results of short-term systemic toxicity test showed that the four groups of bionic periosteal extract had no toxic signs such as body mass reduction,food intake changes,and dyspnea in SD rats,and had no toxic effects on major organs of rats.(3)Heat source test results showed that after intervention with poly(vinylidene fluoride)bionic periosteum doped with 1％Zn2+,doped with 1％Mg2+,and doped with 1％(Zn2++Mg2+),and poly(vinylidene fluoride)bionic periosteum extract,the elevated body temperature values of SD rats were(0.133±0.058),(0.100±0.010),(0.300±0.010),and(0.300±0.017)℃respectively.All were less than 0.6 ℃and the total temperature increase was less than 1.4 ℃.(4)The results of skin sensitization test showed that no erythema or edema was observed under the skin of guinea pigs after the intervention of bionic periosteum extract of four groups.(5)The results showed that poly(vinylidene fluoride)and poly(vinylidene fluoride)bionic periosteum doped with Zn2+and Mg2+had good biocompatibility.

Objective:Based on a single-center retrospective study,to explore the efficacy of intervertebral fusion through different approaches combined with pedicle screw internal fixation in the treatment of single-segment low-grade lumbar spondylolisthesis.Methods:This study retrospectively analyzed the clinical data of 87 patients with single-segment low-grade lumbar spondylolisthesis who were treated in our hospital from January 2021 to August 2022,the cases were divided into Group A(41 cases)and Group B(46 cases)according to the differences in surgical methods.Group A received treatment with posterior lumbar interbody fusion(PLIF)combined with pedicle screw internal fixation,while Group B received treatment with percutaneous endoscopic posterior lumbar interbody fusion(PE-PLIF)combined with pedicle screw internal fixation.Both groups were followed up for two years.The Visual Analogue Scale(VAS)scores of the waist and legs,perioperative indicators,recovery of lumbar function[Japanese Orthopaedic Association(JOA)score,Oswestry Disability Index(ODI)score],and serum inflammatory mediators levels[interleukin-1α(IL-1α),transforming growth factor β1(TGF-β1),interleukin-6(IL-6)],the rate of lumbar interbody fusion,the rate of lumbar spondylolisthesis and the incidence of postoperative complications of the two groups were compared.Results:The operation time and the number of intraoperative X-ray fluoroscopy sessions in group B were both more than those in group A,while the hospital stay,the intraoperative blood loss and total incision length in Group B were all shorter than those in group A(P＜0.05).The VAS scores of the waist and legs in both groups decreased at 3 d after operation and the last follow-up(P＜0.05),and the VAS scores of the waist and legs in group B were lower than those in group A(P＜0.05).The ODI scores of both groups decreased at 3 d after operation and the last follow-up,and the ODI scores of group B were lower than those in group A;The JOA score increased,and the JOA scores of group B were all higher than those in group A(P＜0.05).Serum IL-1α,TGF-β1 and IL-6 levels in both groups decreased at 3 d and 7 d after operation,and serum IL-1α,TGF-β1 and IL-6 levels in group B were all lower than those in group A(P＜0.05).There was no statistically significant difference in the incidence of complications,the rate of lumbar interbody fusion,and the rate of lumbar spondylolisthesis between the two groups(P＞0.05).Conclusion:Compared with PLIF,PE-PLIF combined with pedicle screw internal fixation in the treatment of single-segment low-grade lumbar.spondylolisthesis,can better relieve the degree of pain of the waist and legs,improve lumbar dysfunction,regulate serum inflammatory mediators levels more effectively,and has higher safety and significant therapeutic efficacy.

Objective To investigate the predictive value of matrix γ-carboxyglutamic acid protein(matrix GLA protein)expression in patients with acute myocardial infarction(AMI)for major adverse cardiovascular events(MACE)after percutaneous coronary intervention(PCI).Methods A total of 157 AMI patients undergoing PCI in our department from November 2021 to Septem-ber 2023 were recruited,and divided into a MACE group(43 cases)and a non-MACE group(114 cases)based on the occurrence of MACE over a 12-month follow-up period post-surgery.Multiva-riate logistic regression analysis was used to screen the predictors of MACE and to verify their predictive value.Results The MACE group had significantly older age,larger proportion of diabe-tes,and higher low-density lipoprotein cholesterol(LDL-C)level,but lower matrix GLA protein level than the non-MACE group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that age(OR=1.168,95％CI:1.004-1.358,P=0.044),diabetes(OR=3.085,95％CI:1.024-9.301,P=0.045)and LDL-C(OR=2.473,95％CI:1.185-5.163,P=0.016)were risk factors,and matrix GLA protein(OR=0.527,95％CI:0.426-0.653,P=0.001)was a protective factor for MACE in AMI patients after PCI.ROC curve analysis indicated that matrix GLA pro-tein had the highest predictive value of MACE in AMI patients after PCI,with an AUC value of 0.838(95％CI:0.770-0.892).After adjusting for age,diabetes,and LDL C,the restricted cubic spline revealed that matrix GLA protein level was in a nonlinear negative correlation with MACE risk(x2=30.260,P＜0.05).Conclusion Matrix GLA protein can predict the occurrence of MACE in AMI patients after PCI.

Objective To compare the application value of direct arteriovenous fistula(AVF),after ultrasound-guided percutaneous transluminal angioplasty(PTA)dilation of radial artery AVF formation and reverse"J"arteriovenous graft(AVG)in hemodialysis patients with small diameter vessels.Methods Totally 96 end-stage renal disease patients with distal radial artery＜1.5 mm and cephalic vein≥2.0 mm who planning to receive hemodialysis were retrospectively enrolled.The patients were divided into AVF group(n=30),PTA+AVF group(n=34)and AVG group(n=32)according to fistulization methods.The technical success rate,clinical success rate,primary patency rate and secondary patency rate were compared among groups.Results The technical success rate of AVF group,PTA+AVF group and AVG group was 80.00%,94.12%and 100%,respectively,and the clinical success rate was 30.00%,82.35%and 93.75%,respectively,with significant differences among 3 groups(both P＜0.05).The primary patency rate 1,3,6,9 and 12 months after fistulization in AVF group was 80.00%,30.00%,27.59%,27.59%and 24.14%,respectively,in PTA+AVF group was 94.12%,82.35%,78.79%,68.75%and 62.50%,respectively,while in AVG group was 100%,93.33%,83.33%,76.67%and 66.67%,respectively,all being significant different among 3 groups(all P＜0.05).The secondary patency rate 1,3,6,9 and 12 months after fistulization in AVF group was 83.33%,75.00%,75.00%,70.83%and 58.33%,respectively,in PTA+AVF group was 93.33%,93.33%,83.33%,83.33%and 80.00%,respectively,while in AVG group was 100%,100%,93.33%,90.00%and 80.00%,respectively,also being significant different among 3 groups(all P＜0.05).Conclusion Compared with direct and after ultrasound-guided PTA dilation of radial artery AVF formation,AVG formation was more valuable for hemodialysis patients with small diameter vessels.

Objective To investigate the impact and underlying mechanism of curcumin(Cur)on the aberrant proliferation and migration of VSMC.Methods VSMC was treated with Ang Ⅱ to establish a cell proliferation model.The experiment included blank control group,model group,and low-,medium-and high-dose Cur treatment groups(1.5,3.0 and 4.5 pmol/L,n=11).To explore the effect of Cur on the AMPK/mTOR signaling pathway,VSMC was also assigned into blank control,Ang Ⅱ(10-6 mol/L),Cur(3.0 μmol/L)and Ang Ⅱ+Cur groups(n=3).Western blotting was employed to detect the expression of VSMC differentiation markers(α-SMA),dedif-ferentiation marker(OPN),autophagy-related proteins(P62 and Beclin-1),and proteins involved in the AMPK/mTOR pathway(AMPK,p-AMPK,mTOR,p-mTOR,p70S6K,p-p70S6K).Results Exposure to Ang Ⅱ enhanced the proliferation and migration of VSMC when compared with the blank control group(155％vs 100％,66％vs 48％,P＜0.05).When compared with the model group,the proliferative rate was significantly lower in the medium-and high-dose Cur groups,and the migratory rate was obviously decreased in the three Cur groups(P＜0.05).The α-SMA expression was increased in the medium-and high-dose Cur groups,and that of OPN was decreased in the three Cur groups when compared with the model group(P＜0.05).Enhanced Be-clin-1 and p-AMPK/AMPK and down-regulated P62,p-mTOR/mTOR,and p-p70S6K/p70S6K were observed in the Ang Ⅱ and Cur groups than the blank control group(P＜0.05).The Cur Ang Ⅱ and Cur+AngⅡ groups had notably higher Beclin-1 and p-AMPK/AMPK but lower P62,p-mTOR/mTOR,and p-p70S6K/p70S6K than the Ang Ⅱ group(P＜0.05).Conclusion Cur in-hibits the proliferation and migration of VSMC induced by Ang Ⅱ,potentially through its activa-ting the AMPK/mTOR signaling pathway and enhancing autophagy in VSMC.

Objective:To explore associated factors of post-discharge depressive symptom severity in patients with bipolar disorder.Methods:A longitudinal follow-up was conducted to investigate the demographic,behavioral,and clinical characteristics,and social function among discharged patients with bipolar disorder who met the DSM-5 diagnostic criteria.Clinical characteristics were assessed with the Hamilton Depression Scale(HAMD)and Brief Psychiatric Rating Scale(BPRS).Single factor and multivariate regression were carried out to explore the associat-ed factors of depressive symptom severity in patients with bipolar disorder.Results:A total of 298 discharged pa-tients with bipolar disorder were face-to-face interviewed to complete the follow-up survey.At follow-up time,psy-chotic symptoms(standardized(β)=0.18),housework((β)=0.23),social interaction((β)=0.17)and BPRS total score((β)=0.46)were positively associated with HAMD total score.Productive labor and work((β)=-0.27)and person-al life management((β)=-0.15)were negatively associated with HAMD total scores.Conclusion:Post-discharge depressive symptom severity in bipolar disorder patients is influenced by multiple factors.Effective management of psychotic symptoms,combined with enhanced community-based social rehabilitation and functional recovery,may help reduce the persistence or worsening of depressive symptoms and improve prognosis.

Aim To identify the underlying target of bullatine A(BA)against rheumatoid arthritis(RA)u-sing limited proteolysis-small molecule mapping(LiP-SMap)drug target proteomics and to provide a scientif-ic basis for clinical application of Aconiti brachypodi Radix in the treatment of RA.Methods LiP-SMap drug target proteomics was employed to perform bioin-formatics analysis for comparing and validating the dif-ferential protein expression after BA intervention.A collagen-induced arthritis(CIA)model was estab-lished in DBA/1 mice using bovine type Ⅱ collagen.The mice were then divided into the CIA model group,methotrexate-positive control group(MTX group),and BA groups(10 mg·kg-1 and 20 mg·kg-1)based on their clinical scores.After drug intervention,the thera-peutic efficacy against RA was assessed by joint index scores and foot thickness measurements.Histopatholog-ical changes in the arthritic joints of CIA mice were e-valuated using hematoxylin and eosin(HE)staining.Enzyme-linked immunosorbent assay(ELISA)was employed to detect inflammatory cytokines interleukin-17(IL-17)and total IgG and IgG3 anti-collagen-spe-cific antibodies levels from the serum of CIA mice.Flow cytometry was used to detect the expression levels of intracellular Th17 cells(IL-17+CD4+T cells)and Th1 cells(IFN-γ+CD4+T cells).Fluorescent quanti-tative PCR was performed to detect the expression of genes related to differential proteins.Results The proteomic analysis identified Serpinb1a as a protein with strong binding affinity to BA,and KEGG enrich-ment analysis indicated IL-17 signaling pathway was a crucial pathway of BA in against RA.BA treatment significantly reduced clinical scores and foot thickness,improved local arthritis symptoms in CIA mice,and al-leviated inflammatory cell infiltration into arthritic joints(P＜0.05).Differential protein validation re-sults showed that BA had strong affinity with Serpinb1a(-5.92 kJ·mol-1)and downregulated the expres-sion of Serpinb1a mRNA.Furthermore,the administra-tion of BA markedly reduced serum IL-17 A levels from CIA mice,inhibited the expression of intracellular IL-17 A and IFN-γ cytokines in splenic CD4+T cells(P＜0.05),and significantly downregulated the transcrip-tional expression of IL-17F(P＜0.05).Conclusion BA exhibits therapeutic effects on collagen-induced arthritis,and its mechanism of action may involve the regulation of Serpinb1a and the IL-17 signaling path-way.