Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, functional impairment, and neuropsychiatric symptoms. It represents the most prevalent form of dementia among the elderly population. Accumulating evidence indicates that oxidative stress plays a pivotal role in the pathogenesis of AD. Notably, elevated levels of oxidative stress have been observed in the brains of AD patients, where excessive reactive oxygen species (ROS) can cause extensive damage to lipids, proteins, and DNA, ultimately compromising neuronal structure and function. Amyloid β‑protein (Aβ) has been shown to induce mitochondrial dysfunction and calcium overload, thereby promoting the generation of ROS. This, in turn, exacerbates Aβ aggregation and enhances tau phosphorylation, leading to the formation of two pathological features of AD: extracellular Aβ plaque deposition and intracellular neurofibrillary tangles (NFTs). These events ultimately culminate in neuronal death, forming a vicious cycle. The interplay between oxidative stress and these pathological processes constitutes a core link in the pathogenesis of AD. The signaling pathways mediating oxidative stress in AD include Nrf2, RCAN1, PP2A, CREB, Notch1, NF‑κB, ApoE, and ferroptosis. Nrf2 signaling pathway serves as a key regulator of cellular redox homeostasis, exerts important antioxidant capacity and protective effects in AD. RCAN1 signaling pathway, as a calcineurin inhibitor, and modulates AD progression through multiple mechanisms. PP2A signaling pathway is involved in regulating tau phosphorylation and neuroinflammation processes. CREB signaling pathway contributes to neuroplasticity and memory formation; activation of CREB improves cognitive function and reduce oxidative stress. Notch1 signaling pathway regulates neuronal development and memory, participates in modulation of Aβ production, and interacts with Nrf2 toco-regulate antioxidant activity. NF‑κB signaling pathway governs immune and inflammatory responses; sustained activation of this pathway forms “inflammatory memory”, thereby exacerbating AD pathology. ApoE signaling pathway is associated with lipid metabolism; among its isoforms, ApoE-ε4 significantly increases the risk of AD, leading to elevated oxidative stress, abnormal lipid metabolism, and neuroinflammation. The ferroptosis signaling pathway is driven by iron-dependent lipid peroxidation, and the subsequent release of lipid peroxidation products and ROS exacerbate oxidative stress and neuronal damage. These interconnected pathways form a complex regulatory network that regulates the progression of AD through oxidative stress and related pathological cascades. In terms of therapeutic strategies targeting oxidative stress, among the drugs currently used in clinical practice for AD treatment, memantine and donepezil demonstrate significant therapeutic efficacy and can improve the level of oxidative stress in AD patients. Some compounds with antioxidant effects (such asα-lipoic acid and melatonin) have shown certain potential in AD treatment research and can be used as dietary supplements to ameliorate AD symptoms. In addition, non-drug interventions such as calorie restriction and exercise have been proven to exerted neuroprotective effects and have a positive effect on the treatment of AD. By comprehensively utilizing the therapeutic characteristics of different signaling pathways, it is expected that more comprehensive multi-target combination therapy regimens and combined nanomolecular delivery systems will be developed in the future to bypass the blood-brain barrier, providing more effective therapeutic strategies for AD.

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

Objective:To evaluate the mechanical stability of the bone block after LeFort Ⅰ osteotomy with maxillary advancement using absorbable plates fixed with tenon-and-mortise structures.Methods:This study developed three finite element models: one for the maxillary LeFort Ⅰ osteotomy with anterior advancement fixed with absorbable plates (Model 1); another for the maxillary LeFort Ⅰ osteotomy with anterior advancement fixed with absorbable plates assisted by tenon-and-mortise structures (Model 2); and the last one for the maxillary LeFort Ⅰ osteotomy with anterior advancement fixed with titanium plates and screws (Model 3). Simulated occlusal forces were applied on the anterior and posterior teeth in each model. The displacement changes of the nasal-palatine point (NP) and posterior nasal spine point (PNS) in the finite element coordinate system were compared and analyzed. The Mises equivalent stress distributions of the metal and absorbable plates were also examined to assess the mechanical stability of the three finite element models. Clinical data from 45 patients with dentofacial deformities treated from January 2017 to January 2023 at the Stomatology Hospital of China Medical University were collected. The age of the patients was 21±3 years. Among these, 15 patients had absorbable plates for fixation, 15 had absorbable plates assisted by tenon-and-mortise structures, and 15 had titanium plates and screws fixation after maxillary advancement. All patients underwent preoperative (T0), postoperative 3 days (T1), and 6 months (T2) spiral CT scans. The CT data in DICOM format were input into digital software, which was used to calculate the distances from the NP and PNS points to the horizontal plane (HP), right sagittal plane (FZSR), and coronal plane (CP) at T1 and T2. The distances at T1 and T2 were statistically analyzed using the Wilcoxon signed-rank test with SPSS 20.0, and a P value of<0.05 was considered statistically significant.Results:The finite element analysis showed that in the absorbable plate-only fixation group, the maximum displacement of the NP point (mm) under anterior and posterior tooth force conditions were 0.6 and 0.12, respectively, and for the PNS point, the maximum displacements were 0.5 and 0.11. In the tenon-and-mortise-assisted absorbable plate fixation group, the displacement of the NP point was 0.40 and 0.02 mm, and the displacement of the PNS point was 0.5 and 0.015 mm. In the titanium plate-screw fixation group, the NP point displacement was 0.33 and 0.055 mm, and the PNS point displacement was 0.16 and 0.1 mm. The Mises equivalent stress on the absorbable plates with tenon-and-mortise structure was significantly lower than that in the absorbable plate-only fixation group, while the titanium plate experienced the highest Mises equivalent stress. The clinical data analysis showed that in the horizontal direction, the postoperative stability of the three fixation methods was similar. However, in the vertical and anterior-posterior directions, the absorbable plate-only fixation group showed significant differences in the distances of PNS-HP, PNS-CP, and NP-CP between T1 and T2 ( P=0.018, P=0.009, P=0.017), suggesting significant postoperative bone displacement. In contrast, the tenon-and-mortise-assisted absorbable plate fixation group and the titanium plate-screw fixation group showed no significant differences in displacement during surgery and postoperatively(all P>0.05), demonstrating higher stability. Conclusions:The tenon-and-mortise-assisted absorbable plate fixation provides comparable stability to titanium plate fixation in clinical results, and it is more stable than absorbable plate-only fixation. In the mechanical study, when force was applied on the anterior teeth, the stability of the tenon-and-mortise-assisted absorbable plate fixation was slightly less than that of titanium plate fixation, but when posterior teeth were used, its stability exceeded both titanium plate fixation and absorbable plate-only fixation. The tenon-and-mortise-assisted absorbable plate fixation serves as an effective alternative to titanium plate fixation after LeFort Ⅰ osteotomy.

Objective:To evaluate the mechanical stability of the bone block after LeFort Ⅰ osteotomy with maxillary advancement using absorbable plates fixed with tenon-and-mortise structures.Methods:This study developed three finite element models: one for the maxillary LeFort Ⅰ osteotomy with anterior advancement fixed with absorbable plates (Model 1); another for the maxillary LeFort Ⅰ osteotomy with anterior advancement fixed with absorbable plates assisted by tenon-and-mortise structures (Model 2); and the last one for the maxillary LeFort Ⅰ osteotomy with anterior advancement fixed with titanium plates and screws (Model 3). Simulated occlusal forces were applied on the anterior and posterior teeth in each model. The displacement changes of the nasal-palatine point (NP) and posterior nasal spine point (PNS) in the finite element coordinate system were compared and analyzed. The Mises equivalent stress distributions of the metal and absorbable plates were also examined to assess the mechanical stability of the three finite element models. Clinical data from 45 patients with dentofacial deformities treated from January 2017 to January 2023 at the Stomatology Hospital of China Medical University were collected. The age of the patients was 21±3 years. Among these, 15 patients had absorbable plates for fixation, 15 had absorbable plates assisted by tenon-and-mortise structures, and 15 had titanium plates and screws fixation after maxillary advancement. All patients underwent preoperative (T0), postoperative 3 days (T1), and 6 months (T2) spiral CT scans. The CT data in DICOM format were input into digital software, which was used to calculate the distances from the NP and PNS points to the horizontal plane (HP), right sagittal plane (FZSR), and coronal plane (CP) at T1 and T2. The distances at T1 and T2 were statistically analyzed using the Wilcoxon signed-rank test with SPSS 20.0, and a P value of<0.05 was considered statistically significant.Results:The finite element analysis showed that in the absorbable plate-only fixation group, the maximum displacement of the NP point (mm) under anterior and posterior tooth force conditions were 0.6 and 0.12, respectively, and for the PNS point, the maximum displacements were 0.5 and 0.11. In the tenon-and-mortise-assisted absorbable plate fixation group, the displacement of the NP point was 0.40 and 0.02 mm, and the displacement of the PNS point was 0.5 and 0.015 mm. In the titanium plate-screw fixation group, the NP point displacement was 0.33 and 0.055 mm, and the PNS point displacement was 0.16 and 0.1 mm. The Mises equivalent stress on the absorbable plates with tenon-and-mortise structure was significantly lower than that in the absorbable plate-only fixation group, while the titanium plate experienced the highest Mises equivalent stress. The clinical data analysis showed that in the horizontal direction, the postoperative stability of the three fixation methods was similar. However, in the vertical and anterior-posterior directions, the absorbable plate-only fixation group showed significant differences in the distances of PNS-HP, PNS-CP, and NP-CP between T1 and T2 ( P=0.018, P=0.009, P=0.017), suggesting significant postoperative bone displacement. In contrast, the tenon-and-mortise-assisted absorbable plate fixation group and the titanium plate-screw fixation group showed no significant differences in displacement during surgery and postoperatively(all P>0.05), demonstrating higher stability. Conclusions:The tenon-and-mortise-assisted absorbable plate fixation provides comparable stability to titanium plate fixation in clinical results, and it is more stable than absorbable plate-only fixation. In the mechanical study, when force was applied on the anterior teeth, the stability of the tenon-and-mortise-assisted absorbable plate fixation was slightly less than that of titanium plate fixation, but when posterior teeth were used, its stability exceeded both titanium plate fixation and absorbable plate-only fixation. The tenon-and-mortise-assisted absorbable plate fixation serves as an effective alternative to titanium plate fixation after LeFort Ⅰ osteotomy.

Background::Magnetic resonance (MR)-guided ultra-hypofractionated radiotherapy with whole-pelvic irradiation (UHF-WPRT) is a novel approach to radiotherapy for patients with high-risk (HR) and very high-risk (VHR) prostate cancer (PCa). However, the inherent complexity of adaptive UHF-WPRT might inevitably result in longer on-couch time. We aimed to estimate the delivered dose, study the feasibility and safety of adaptive UHF-WPRT on a 1.5-Tesla MR-Linac.Methods::Ten patients with clinical stage T3a-4N0-1M0-1c PCa, who consecutively received UHF-WPRT, were enrolled prospectively. The contours of the target and organ-at-risks on the position verification-MR (PV-MR), beam-on 3D-MR(Bn-MR), and post-MR (after radiotherapy delivery) were derived from the pre-MR data by deformable image registration. The physician then manually adjusted them, and dose recalculation was performed accordingly. GraphPad Prism 9 (GraphPad Prism Software Inc.) was utilized for conducting statistical analyses.Results::In total, we collected 188 MR scans (50 pre-MR, 50 PV-MR, 44 Bn-MR, and 44 post-MR scans). With median 59 min, the mean prostate clinical target volume (CTV)-V 100% was 98.59% ± 2.74%, and the mean pelvic CTVp-V 100% relative percentages of all scans was 99.60% ± 1.18%. The median V 29 Gy change in the rectal wall was -2% (-18% to 20%). With a median follow-up of 9 months, no patient had acute Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or more severe genitourinary (GU) or gastrointestinal (GI) toxicities (0%). Conclusion::UHF-RT to the prostate and the whole pelvis with concomitant boost to positive nodes using an Adapt-To-Shape (ATS) workflow was technically feasible for patients with HR and VHR PCa, presenting only mild GU and GI toxicities. The estimated target dose during the beam-on phase was clinically acceptable based on the 3D-MR–based dosimetry analysis.Clinical trial registration::Chinese Clinical Trial Registry ChiCTR2000033382.

Objective:To investigate the differences in acoustic characteristics between older patients with dysarthria resulting from anterior and posterior circulation cerebral infarctions.Methods:A case-control study was conducted.Sixty hospitalized older patients with dysarthria were selected and divided into two groups: the anterior circulation cerebral infarction group and the posterior circulation cerebral infarction group, each comprising 30 cases.Additionally, thirty healthy individuals aged 65 and above were included as a control group.The subjective evaluation of the patients' overall phonetic function was conducted using the GRBAS scale.Objective parameters, including fundamental frequency(F0), Jitter, Shimmer, maximum phonation time(MPT), maximum sound pressure level(SPLmax), minimum sound pressure level(SPLmin), and the dysphonia severity index(DSI), were collected using the DIVAS2.5 voice analysis system.We analyzed the acoustic characteristics across the three groups: patients with dysarthria and healthy subjects.Results:The grade(G), roughness(R), breathiness(B), asthenia(A), and strain(S)scores of patients in both the anterior and posterior circulation cerebral infarction groups were significantly higher than those of the healthy control group( F=16.574, 39.793, 46.309, 52.154, 25.603; all P<0.001).Furthermore, the roughness(R)and strain(S)of the voice in the anterior circulation cerebral infarction group were significantly elevated compared to the posterior circulation cerebral infarction group, whereas the breathiness(B), asthenia(A), and grade(G)scores in the posterior circulation cerebral infarction group were significantly higher than those in the anterior circulation cerebral infarction group(all P<0.001).The fundamental frequency value(F0)of the voice in patients with anterior circulation cerebral infarction was significantly greater than that of both the posterior circulation cerebral infarction group and the healthy control group( F=39.050, P<0.001).In contrast, the fundamental frequency value(F0)of patients with posterior circulation cerebral infarction was lower than that of the healthy control group( P=0.003).Additionally, the Jitter value in the anterior circulation cerebral infarction group was higher than in both the posterior circulation cerebral infarction group and the healthy control group( F=64.976, P<0.001).The Shimmer value in the anterior circulation cerebral infarction group was lower than that in the posterior circulation cerebral infarction group but higher than that in the healthy control group(both P<0.001).Finally, the values of MPT, SPLmin and SPL max, DSI in the anterior circulation cerebral infarction group were higher than those in the posterior circulation cerebral infarction group and lower than those in the healthy control group( F=90.406, 24.003, 16.164; all P<0.001); the value of DSI in the anterior circulation cerebral infarction group was lower than in both the posterior circulation cerebral infarction group and the healthy control group( F=87.921, P<0.001). Conclusions:There are notable differences in the acoustic characteristic parameters of dysarthria resulting from injuries at various anatomical sites in older patients with cerebral infarction.In practical clinical settings, a comprehensive evaluation of dysarthria in these patients should integrate the anatomical location of the injury, subjective symptom assessment, and objective analysis of acoustic characteristics to inform precise and personalized rehabilitation strategies.

Objective To explore the biological function and downstream mechanism of ETS1 in glioma.Methods Bioinformatics and immunohistochemistry were used to analyze the differential expression characteristics of ETS1 in gliomas;qRT-PCR was employed to detect the expression level of ETS1 mRNA and lncRNA X-inactive specific transcript(XIST).CCK-8 and 5-ethyl-2′-deoxyuridine experiments were conducted to detect cell growth.Western blot was used to detect the expression of apoptosis-related proteins(Bax,Bak,Bcl-2).PROMO database was utilized to predict the binding sites between ETS1 and XIST promoter.Dual-luciferase reporter gene assay and chromatin immunoprecipitation-quantitative polymerase chain reaction assays were performed to verify the binding relationship between ETS1 and the XIST promoter region.cBioPortal database was used to analyze the correlation between the expression of ETS1 mRNA and XIST in glioma tissues.Results The expression levels of ETS1 mRNA and protein were significantly upregulated in glioma(P<0.05).The depletion of ETS1 significantly inhibited the proliferation of glioma cells and promoted cell apoptosis(P<0.05).ETS1 could target and bind with the XIST promoter and promote the expression of XIST(P<0.05).The overexpression of XIST reversed the effects of ETS1 on the proliferation of glioma cells and the promotion of cell apoptosis(P<0.05).Conclusion ETS1 is highly expressed in glioma tissues.It could promote the expression of lncRNA XIST,boost the proliferation of glioma cells,and inhibit cell apoptosis.

Objective To investigate the mechanism by which Colony Stimulating Factor-1(CSF1)inhibits apoptosis in neurons subjected to oxygen-glucose deprivation(OGD).Methods Primary rat cortical neurons were divided into the OGD damaged neuron model group(OGD group),the rh-CSF1 intervention group(rh-CSF1 group),and control group.The sample size for each group was 3.After intervention with recombinant human CSF1(rh-CSF1),neuronal apoptosis rate and intracellular ATP content,reactive oxygen species levels,mitochondrial membrane potential,and mitochondrial DNA copy number were measured.The content of malondialdehyde within mitochondria and the activity of superoxide dismutase were also assessed.Results Intervention with rh-CSF1 increased mitochondrial membrane potential(0.55±0.03 vs.0.43±0.06,P<0.01),mitochondrial DNA copy number(0.88±0.05 vs.0.72±0.06,P<0.05),ATP content[(15.70±0.99)mmol/mg vs.(11.70±1.00)mmol/mg,P<0.01)],and superoxide dismutase[(18.47±1.38)U/mg vs.(14.78±1.81)U/mg,P<0.05)]activity in neurons injured by OGD.It also reduced levels of rectivereactive oxygen species(3.64±0.21 vs.4.45±0.33,P<0.05)and malondialdehyde within mitochondria[(2.13±0.19)mmol/mg vs.(2.78±0.20)mmol/mg,P<0.05)],and inhibited neuronal apoptosis(10.12±0.78 vs.17.04±1.23,P<0.01)Conclusion rh-CSF1 may alleviate the damage in neurons induced by OGD by improving mitochondrial function,reducing oxidative stress,and inhibiting cell apoptosis.

Objective To observe the value of CT radiomics for differentiating spinal bone islands(BI)and osteoblastic metastases(OBM).Methods Data of 109 BI lesions in 98 patients and 282 OBM lesions in 158 patients(including 103 OBM in 48 lung cancer cases,86 OBM in 52 breast cancer cases and 93 OBM in 58 prostate cancer cases)from 3 medical institutions were retrospectively analyzed.Data obtained from institution 1 were used as the internal dataset and divided into internal training set and internal validation set at a ratio of 7∶3,from institution 2 and 3 were used as external dataset.All datasets were divided into female data subset(including OBM of female lung cancer and breast cancer)and male data subset(including OBM of male lung cancer and prostate cancer).Radiomics features were extracted and screened to construct 3 different support vector machine(SVM)models,including model1 for distinguishing BI and OBM,model2 for differentiating OBM of female lung cancer and breast cancer,and model3 for differentiating OBM of male lung cancer and prostate cancer.Diagnostic efficacy of model1,CT value alone and 3 physicians(A,B,C)for distinguishing BI and OBM were assessed,as well as differentiating efficacy for different OBM of model2 and model3.Receiver operating characteristic(ROC)curves were drawn,and area under the curves(AUC)were calculated and compared.The differential diagnostic efficacy of model2 and model3 were also assessed with ROC analysis and AUC.Results AUC of model1 for distinguishing spinal OBM from BI in internal training set,internal validation set and external dataset was 0.99,0.98 and 0.86,respectively.In internal training set,model1 had higher AUC for distinguishing BI and OBM than that of physician A(AUC=0.78),B(AUC=0.87)and C(AUC=0.93)as well as that of mean CT value(AUC=0.78,all P＜0.05).AUC in internal training set,internal validation set and external dataset of model2 for identifying female lung cancer and breast cancer OBM was 0.79,0.75 and 0.73,respectively,of model3 for discriminating male lung cancer from prostate cancer OBM was 0.77,0.74 and 0.77,respectively.Conclusion CT radiomics SVM model might reliablely distinguish OBM and BI.