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.

Objective: To investigate the differences in three-dimensional maxillary and palatal parameters as well as midpalatal suture maturation stages between Skeletal Class I malocclusion patients with maxillary transverse deficiency (MTD) and normal maxillary transverse development, in order to provide clinical guidance for orthodontic diagnosis and treatment Methods: This study was approved by the institutional ethics committee and informed consent was obtained. Cone-bean CT data from 66 Skeletal Class I malocclusion patients [22 males, 44 females; age (14.39 ± 1.68) years] were analyzed. Based on Yonsei University width analysis, participants were divided into two groups: the maxillary transverse deficiency group [n = 33, age (14.34 ± 1.99) years] and the maxillary transverse normal group [n = 33, age (14.43 ± 1.33) years]. Parameters compared included midpalatal suture maturation stages (A-E), maxillary skeletal width on nasal floor (NF) and maxillary skeletal width on hard palate (HP), maxillary arch width on buccal alveolar crest (BAC) and maxillary arch width on lingual alveolar crest (LAC), palatal vault height, palatal bone thickness, palatal length, surface area, and volume Results: The proportion of patients with palatal suture maturity at stages D+E in the maxillary transverse deficiency group (33%, 11/33) was lower than that in the normal maxillary transverse development group (45%, 15/33), showing no statistically significant difference between the two groups. Compared to the maxillary transverse normal group, significant reductions were observed in the maxillary transverse deficiency group for maxillary widths [NF: (67.63 ± 3.74) mm vs. (71.49 ± 5.11) mm; HP: (64.60 ± 3.53) mm vs. (68.40 ± 4.64) mm], dental arch widths [BAC: (56.88 ± 2.25) mm vs. (59.81 ± 2.71) mm; LAC: (33.90 ± 1.89) mm vs. (36.91 ± 2.20) mm], and palatal surface area [(1 170.80 ± 126.48) mm2 vs. (1 264.76 ± 140.10) mm2]. No significant differences were noted in palatal height, bone thickness, length, or volume. Conclusion Skeletal Class I malocclusion patients with MTD have narrowed maxillary and dental arch widths, reduced palatal surface area, and delayed midpalatal suture maturation. Early maxillary expansion is recommended to harmonize jaw relationship.

Glucagon-like peptide-1 （GLP-1） receptor agonists are a novel class of antidiabetic drugs that also possess lipid- lowering and cardiovascular protective effects， with liraglutide and semaglutide being their representative medications. Based on a systematic literature search， this review summarizes the lipid-lowering mechanisms by which liraglutide and semaglutide exert direct effects on the liver and kidney （regulating autophagy， key lipid metabolism pathways， reverse cholesterol transport， etc.）， direct actions on adipose tissue （affecting adipocyte proliferation and differentiation， expression of lipid metabolism proteins， and gene transcription）， activation of sympathetic pathways through the central nervous system， and modulation of the gut microbiota. Additionally， it summarizes the clinical evidence of their lipid-lowering effects in populations with type 2 diabetes mellitus， overweight individuals， and others. These findings indicate that GLP-1 receptor agonists exert lipid-lowering effects by acting on multiple tissues or systems， providing crucial evidence for further elucidating the molecular mechanisms of these drugs in lipid regulation and exploring potential new ideas for their clinical applications.

BACKGROUND: Gout is a chronic disease primarily caused by elevated urate levels, severely affecting joint health. Its global distribution varies, and updated data for China are lacking. This study aimed to analyze the current burden and trends of gout globally and in China, examining the burden by gender, age, and risk factors while providing future predictions. METHODS: This descriptive epidemiological secondary analysis utilized data from the Global Burden of Disease, Injuries, and Risk Factors (GBD) 2021 study. Age-standardized incidence rate (ASIR), prevalence rate (ASPR), and disability-adjusted life years (DALYs) rates (ASDR) were used to assess the gout burden. Trends from 1990 to 2021 were analyzed across global regions, genders, and sociodemographic index (SDI) levels. The burden in China was further examined by gender, age, and associated risk factors. The Bayesian age-period-cohort (BAPC) model was used to predict future trends. Gout burden in China and the United States was compared. RESULTS: In 2021, gout affected 57 million people globally, with 9.4 million new cases and 1.75 million DALYs. From 1990 to 2021, the ASIR, ASPR, and ASDR increased by 17.2%, 21.9%, and 21.3%, respectively. Males experienced a significantly higher burden, with greater ASIR, ASPR, and ASDR increasing with higher SDI levels. In China, male ASIR, ASPR, and ASDR were over 2.8 times those of females, and the burden increased with age. In 2021, 31.4% of gout-related DALYs in China were attributed to high body mass index and 7.6% to kidney dysfunction. Between 1990 and 2021, the high body mass index-related burden of gout rose annually for both genders, while the kidney dysfunction-related gout burden remained stable. By 2050, the burden of gout in China is expected to continue increasing, with a slower rise in females and a decline in males after an initial increase. However, the overall burden will remain substantial. In comparison, the gout burden will be higher in the United States than in China. CONCLUSIONS Gout is becoming a significant health burden globally and in China, particularly among Chinese males and older individuals. With the aging population and lifestyle changes exacerbating the issue, effective strategies and measures are essential to prevent or reduce gout-related health issues.
Humans ; Gout/epidemiology* ; Male ; Female ; Incidence ; Middle Aged ; Prevalence ; China/epidemiology* ; Adult ; Risk Factors ; Aged ; Global Burden of Disease ; Disability-Adjusted Life Years ; Young Adult ; Adolescent ; Quality-Adjusted Life Years

The chemical constituents were systematically separated from the roots of Berberis polyantha by various chromatographic methods, including silica gel column chromatography, HP20 column chromatography, polyamide column chromatography, reversed-phase C_(18) column chromatography, and preparative high-performance liquid chromatography. The structures of the compounds were identified by physicochemical properties and spectroscopic techniques(1D NMR, 2D NMR, UV, MS, and CD). Four phenylpropanoids were isolated from the methanol extract of the roots of B. polyantha, and they were identified as(2R)-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone-O-β-D-glucopyranoside(1), methyl 4-hydroxy-3,5-dimethoxybenzoate(2),(+)-syringaresinol(3), and syringaresinol-4-O-β-D-glucopyranoside(4). Compound 1 was a new compound, and other compounds were isolated from this plant for the first time. The anti-inflammatory activity of these compounds was evaluated based on the release of nitric oxide(NO) in the culture of lipopolysaccharide(LPS)-induced RAW264.7 macrophages. At a concentration of 10 μmol·L~(-1), all the four compounds inhibited the LPS-induced release of NO in RAW264.7 cells, demonstrating potential anti-inflammatory properties.
Plant Roots/chemistry* ; Animals ; Mice ; Berberis/chemistry* ; RAW 264.7 Cells ; Macrophages/immunology* ; Drugs, Chinese Herbal/isolation & purification* ; Nitric Oxide/metabolism* ; Molecular Structure ; Anti-Inflammatory Agents/isolation & purification*

Based on copper death, this study investigates the effect and mechanism of Shenmai Injection on isoproterenol(ISO)-induced myocardial fibrosis(MF) in rats. SPF-grade male SD rats were randomly divided into a normal group, model group, captopril(5 mg·kg~(-1)) positive control group, and Shenmai Injection low(6 mL·kg~(-1)), medium(9 mL·kg~(-1)), and high(12 mL·kg~(-1)) dose groups. Except for the normal group, the rats in the other groups were subcutaneously injected with ISO(5 mg·kg~(-1)) once a day for 10 consecutive days to establish an MF model. Starting from the second day after successful modeling, intraperitoneal injections of the respective treatments were administered for 28 consecutive days. Hematoxylin-eosin(HE) and Masson staining were used to observe pathological changes and fibrosis levels in the myocardial tissue. Colorimetry was employed to detect serum Cu~(2+) concentration in rats. The levels of inflammatory cytokines interleukin-6(IL-6), interleukin-1β(IL-1β), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), as well as mitochondrial energy metabolites adenosine triphosphate(ATP), adenosine diphosphate(ADP), and adenosine monophosphate(AMP) in serum were measured using enzyme-linked immunosorbent assay(ELISA). Western blot was performed to detect the expression of collagen Ⅰ(Col-Ⅰ), collagen Ⅲ(Col-Ⅲ), and copper death-related proteins dihydrolipoamide acetyltransferase(DLAT), ferredoxin 1(FDX1), lipoic acid synthetase(LIAS), and heat shock protein 70(HSP70) in myocardial tissue. Immunofluorescence was used to detect the expression of DLAT, FDX1, and HSP70, while immunohistochemistry was conducted to examine the expressions of DLAT, FDX1, LIAS, and HSP70. The results showed that, compared to the model group, the myocardial structure disorder and collagen fiber deposition in the drug treatment groups were significantly improved, the cardiac index level was reduced, serum Cu~(2+), IL-6, IL-1β, IL-18, TNF-α, ADP, and AMP levels were significantly decreased, ATP levels were significantly increased, and the expressions of Col-Ⅰ, Col-Ⅲ, and HSP70 proteins in myocardial tissue were significantly reduced, while the expressions of DLAT, FDX1, and LIAS proteins were significantly elevated. In conclusion, Shenmai Injection effectively alleviates myocardial structure disorder and interstitial collagen fiber deposition in ISO-induced MF rats, promotes copper excretion, and reduces copper death in the ISO-induced rat MF model.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Myocardium/metabolism* ; Drug Combinations ; Fibrosis/metabolism* ; Copper/blood* ; Cardiomyopathies/genetics* ; Humans

OBJECTIVE: To elucidate the specific mechanisms by which electroacupuncture (EA) alleviates anxiety and fear behaviors associated with posttraumatic stress disorder (PTSD), focusing on the role of lipocalin-2 (Lcn2). METHODS: The PTSD mouse model was subjected to single prolonged stress and shock (SPS&S), and the animals received 15 min sessions of EA at Shenmen acupoint (HT7). Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear. Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex (PFC). Additionally, the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology. RESULTS: Mice subjected to SPS&S presented increased anxiety- and fear-like behaviors. Lcn2 expression in the PFC was significantly upregulated following SPS&S, leading to increased expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and suppression of PFC neuronal activity. However, EA at HT7 inhibited Lcn2 release, reducing neuroinflammation and hypoexcitability in the PFC. Lcn2 overexpression mitigated the effects of EA at HT7, resulting in anxiety- and fear-like behaviors. CONCLUSION EA at HT7 can ameliorate PTSD-associated anxiety and fear, and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC. Please cite this article as: Yang YD, Zhong W, Chen M, Tang QC, Li Y, Yao LL, et al. Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex. J Integr Med. 2025; 23(5):537-547.
Electroacupuncture ; Stress Disorders, Post-Traumatic/metabolism* ; Animals ; Lipocalin-2/metabolism* ; Prefrontal Cortex/physiopathology* ; Male ; Mice ; Neurons/physiology* ; Disease Models, Animal ; Fear ; Behavior, Animal ; Mice, Inbred C57BL ; Neuroinflammatory Diseases/metabolism* ; Anxiety/therapy* ; Acupuncture Points