Aim To explore the protective effect of the isochroman compound Asperisochroman B(AB)on oxygen-glucose deprivation/reoxygenation(OGD/R)injury of neurons based on the PI3K/AKT/Foxo1 path-way and to reveal the related mechanism.Methods Primary neurons were cultured and the OGD/R model was constructed.The primary neurons were divided in-to the blank control group,OGD/R group,and AB low,medium,and high concentration(3,10,30 μmol·L-1)groups.The effects of AB on primary neurons were determined by CCK-8 assay,lactate dehydrogen-ase(LDH)release assay,and Hoechst 33342 stai-ning.The expression levels of PI3K,AKT,and Foxo1-related proteins were detected by Western blot.After intervention with the PI3K inhibitor(LY294002)and re-modeling and intervention with high concentra-tion of AB(30 μmol·L-1),the expression of PI3K/Foxo1 pathway-related proteins was detected by West-ern blot.Results Compared with the OGD/R group,AB could significantly increase the cell survival rate of primary neurons and reduce the release of LDH.The results of Hoechst 33342 and immunofluorescence stai-ning showed that AB reduced apoptosis after OGD/R injury.Western blot results showed that compared with the OGD/R group,after AB intervention,the expres-sion levels of Bcl-2 and NeuN proteins in neurons sig-nificantly increased(P＜0.01),and the expression level of Bax protein significantly decreased(P＜0.01).At the same time,it upregulated the expres-sion levels of p-AKT and PI3K proteins,promoted Foxo1 phosphorylation,and downregulated the expres-sion of Foxo1.Compared with the high-dose AB group,LY294002 could inhibit the changes of the a-bove indicators and reverse the protective effect of AB on OGD/R-injured primary neurons.Conclusions AB can alleviate oxygen-glucose deprivation/reoxygen-ation-induced neuronal injury,and its mechanism may be related to the activation of the PI3K/AKT/Foxo1 signaling pathway.

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

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Aim To investigate the protective effect of Gualou Guizhi granules(GLGZG)on neuronal injury induced by LPS-activated microglia based on Notch signaling pathway.Methods LPS-activated microglia were co-cultured with neurons to construct neuron inju-ry models,and the cells were divided into the control group,model group,Notch inhibitor(DAPT)group,GLGZG(50,100,200 mg·L-1)group,DAPT+100 mg·L-1GLGZG group.After intervention,the activity of HT22 cells was detected by CCK-8 method,and rel-ative mRNA expression was detected by real-time PCR.The relative protein expression was detected by Western blot.Results Compared with the model group,after GLGZG intervention,the cell activity was significantly improved,GLGZG decreased IL-6,IL-12,Bax,Notch 1,caspase-3,Delta-1,NICD,RBPSUH,HES1 expression,and increased Bcl-2 expression(P＜0.05).Compared with the model group,the NICD,RBPSUH and HES1 mRNA and protein expressions significantly decreased after DAPT treatment(P＜0.05),and there was no superposition effect with GLG-ZG.Conclusion GLGZG may play a neuroprotective role by inhibiting inflammatory factors and apoptosis,and inhibiting Notch signaling pathway.

Objective To explore the relationship between thyroid function and hyperactivity behavior(HB)in children with attention deficit hyperactivity disorder(ADHD),and further understand the potential factors contributing to increased risk of ADHD,and provide references for the treatment of ADHD in children.Methods A total of 134 pediatric ADHD patients who were treated and followed up at Huzhou Central Hospital from February 2018 to August 2023 were selected as the research subjects.According to the hyperactivity index(HI),they were divided into non HB group(n=71)and HB group(n=63).General information and routine laboratory parameters were compared between two groups.HB-related factors were evaluated by using binary Logistic regression analysis.Finally,Pearson linear correlation analysis and receiver operating characteristic curve were used to study the relationship between HB and thyroid stimulating hormone(TSH)and the potential diagnostic value of TSH levels in distinguishing ADHD children with HB.Results The differences in lactic acid and TSH levels between two groups of cases were statistically significant,with HB group significantly higher compared to non HB group(P＜0.05).Among them,TSH level was independently associated with HB and positively correlated with HI score(r=0.668,P＜0.00 1).Additionally,TSH level had a certain value in distinguishing ADHD children with HB,with a cut-off point of 2.57 μIU/ml(sensitivity was 65.1％,specificity was 74.7％).Conclusion This study revealed a positive correlation between serum TSH level and HB in children with ADHD,and it can be used to differentiate ADHD children with HB.

Aim To investigate the protective effect of Gualou Guizhi granules(GLGZG)on neuronal injury induced by LPS-activated microglia based on Notch signaling pathway.Methods LPS-activated microglia were co-cultured with neurons to construct neuron inju-ry models,and the cells were divided into the control group,model group,Notch inhibitor(DAPT)group,GLGZG(50,100,200 mg·L-1)group,DAPT+100 mg·L-1GLGZG group.After intervention,the activity of HT22 cells was detected by CCK-8 method,and rel-ative mRNA expression was detected by real-time PCR.The relative protein expression was detected by Western blot.Results Compared with the model group,after GLGZG intervention,the cell activity was significantly improved,GLGZG decreased IL-6,IL-12,Bax,Notch 1,caspase-3,Delta-1,NICD,RBPSUH,HES1 expression,and increased Bcl-2 expression(P＜0.05).Compared with the model group,the NICD,RBPSUH and HES1 mRNA and protein expressions significantly decreased after DAPT treatment(P＜0.05),and there was no superposition effect with GLG-ZG.Conclusion GLGZG may play a neuroprotective role by inhibiting inflammatory factors and apoptosis,and inhibiting Notch signaling pathway.

Objective To explore the relationship between thyroid function and hyperactivity behavior(HB)in children with attention deficit hyperactivity disorder(ADHD),and further understand the potential factors contributing to increased risk of ADHD,and provide references for the treatment of ADHD in children.Methods A total of 134 pediatric ADHD patients who were treated and followed up at Huzhou Central Hospital from February 2018 to August 2023 were selected as the research subjects.According to the hyperactivity index(HI),they were divided into non HB group(n=71)and HB group(n=63).General information and routine laboratory parameters were compared between two groups.HB-related factors were evaluated by using binary Logistic regression analysis.Finally,Pearson linear correlation analysis and receiver operating characteristic curve were used to study the relationship between HB and thyroid stimulating hormone(TSH)and the potential diagnostic value of TSH levels in distinguishing ADHD children with HB.Results The differences in lactic acid and TSH levels between two groups of cases were statistically significant,with HB group significantly higher compared to non HB group(P＜0.05).Among them,TSH level was independently associated with HB and positively correlated with HI score(r=0.668,P＜0.00 1).Additionally,TSH level had a certain value in distinguishing ADHD children with HB,with a cut-off point of 2.57 μIU/ml(sensitivity was 65.1％,specificity was 74.7％).Conclusion This study revealed a positive correlation between serum TSH level and HB in children with ADHD,and it can be used to differentiate ADHD children with HB.

Aim To explore the protective effect of the isochroman compound Asperisochroman B(AB)on oxygen-glucose deprivation/reoxygenation(OGD/R)injury of neurons based on the PI3K/AKT/Foxo1 path-way and to reveal the related mechanism.Methods Primary neurons were cultured and the OGD/R model was constructed.The primary neurons were divided in-to the blank control group,OGD/R group,and AB low,medium,and high concentration(3,10,30 μmol·L-1)groups.The effects of AB on primary neurons were determined by CCK-8 assay,lactate dehydrogen-ase(LDH)release assay,and Hoechst 33342 stai-ning.The expression levels of PI3K,AKT,and Foxo1-related proteins were detected by Western blot.After intervention with the PI3K inhibitor(LY294002)and re-modeling and intervention with high concentra-tion of AB(30 μmol·L-1),the expression of PI3K/Foxo1 pathway-related proteins was detected by West-ern blot.Results Compared with the OGD/R group,AB could significantly increase the cell survival rate of primary neurons and reduce the release of LDH.The results of Hoechst 33342 and immunofluorescence stai-ning showed that AB reduced apoptosis after OGD/R injury.Western blot results showed that compared with the OGD/R group,after AB intervention,the expres-sion levels of Bcl-2 and NeuN proteins in neurons sig-nificantly increased(P＜0.01),and the expression level of Bax protein significantly decreased(P＜0.01).At the same time,it upregulated the expres-sion levels of p-AKT and PI3K proteins,promoted Foxo1 phosphorylation,and downregulated the expres-sion of Foxo1.Compared with the high-dose AB group,LY294002 could inhibit the changes of the a-bove indicators and reverse the protective effect of AB on OGD/R-injured primary neurons.Conclusions AB can alleviate oxygen-glucose deprivation/reoxygen-ation-induced neuronal injury,and its mechanism may be related to the activation of the PI3K/AKT/Foxo1 signaling pathway.

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

Humans ; Vascular Stiffness ; Coal Mining ; Occupational Diseases/epidemiology* ; Risk Factors ; Coal ; Miners