BACKGROUND:Degenerative scoliosis is defined as a condition that occurs in adulthood with a coronal cobb angle of the spine>10° accompanied by sagittal deformity and rotational subluxation,which often produces symptoms of spinal cord and nerve compression,such as lumbar pain,lower limb pain,numbness,weakness,and neurogenic claudication.The finite element method is a mechanical analysis technique for computer modelling,which can be used for spinal mechanics research by building digital models that can realistically restore the human spine model and design modifications. OBJECTIVE:To review the application of finite element method in the etiology and treatment of degenerative scoliosis. METHODS:The literature databases CNKI,PubMed,and Web of Science were searched for articles on the application of finite element method in degenerative scoliosis published before October 2023.Search terms were"finite element analysis,biomechanics,stress analysis,degenerative scoliosis,adult spinal deformity"in Chinese and English.Fifty-four papers were finally included. RESULTS AND CONCLUSION:(1)The biomechanical findings from the degenerative scoliosis model constructed using the finite element method were identical to those from the in vivo experimental studies,which proves that the finite element method has a high practical value in degenerative scoliosis.(2)The study of the etiology and treatment of degenerative scoliosis by the finite element method is conducive to the prevention of the occurrence of the scoliosis,slowing down the progress of the scoliosis,the development of a more appropriate treatment plan,the reduction of complications,and the promotion of the patients'surgical operation.(3)The finite element method has gradually evolved from a single bony structure to the inclusion of soft tissues such as muscle ligaments,and the small sample content is increasingly unable to meet the research needs.(4)The finite element method has much room for exploration in degenerative scoliosis.

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

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.

Objective:Studying the effect of PRDX4 on esophageal squamous cell carcinoma cells(esophageal carcinoma,ESCC)proliferation and apoptosis as well as its potential mechanism.Methods:The University of Alabama at Birmingham cancer data analysis portal(UALCAN),gene expression profiling interactive analysis(GEPIA)and the Cancer Genome Atlas(TCGA)databases were used to predict PRDX4 expres-sion in ESCC and its relationship with pathological features and prognosis.The cancer and adjacent tissues of 60 patients with ESCC who un-derwent radical resection in the Affiliated Hospital of Weifang Medical College from August 2010 to August 2023 were selected as research samples.The expression level of PRDX4 in the patients was detected by immunohistochemistry(IHC).The extracted cancer and adjacent tis-sues were homogenized to analyze its mRNA expression.The expression levels of PRDX4 mRNA and related signaling proteins in ESCC cells were analyzed by real-time quantitative PCR and Western blot.Cell Counting Kit-8(CCK-8)assay and flow cytometry were used to analyze the effect of PRDX4 on cell proliferation and apoptosis.Finally,a subcutaneous tumor model in nude mice was constructed to validate the in vitro experimental results.Results:The data from the GEPIA and UALCAN showed that PRDX4 expression was abnormally increased and re-lated to the pathology stage,grade,and survival rate of patients.After knockdown and overexpression of PRDX4 in an ESCC cell line,the ex-pression of PRDX4,phos-phosphatidylinositol 3-kinase(p-PI3K),phos-protein kinase B(p-AKT),cyclinD1,and survivin protein decreased and increased,respectively;cell proliferation and apoptosis were positively regulated.Compared with the sh-NC group,tumor volume and weight in the sh-PRDX4 group were decreased.Conclusions:PRDX4 regulates the proliferation and apoptosis of ESCC cells by activating the PI3K/AKT signaling pathway.

Objective:To evaluate the correlation between the degree of posterior longitudinal ligament (PLL) injury and various parameters of vertebral body injury in patients with thoracolumbar burst fractures.Methods:A total of 48 patients with thoracolumbar burst fractures were admitted to the Spine Surgery Center of the Second Affiliated Hospital of Inner Mongolia Medical University between December 2022 and January 2024. The cohort consisted of 31 males and 17 females, with a mean age of 44.1±11.8 years (range, 18-65 years). Based on the PLL injury grading method proposed by Sun Zhaoyun, patients were classified into three groups: mild, moderate, and severe. However, due to an insufficient number of patients in the severe group ( n=3), the moderate and severe groups were combined for statistical analysis, resulting in two groups: mild, and moderate-to-severe. Patient demographic and clinical data were collected. Local kyphosis (LK), inversion angle (IA), horizontal rotation angle (HRA), increased interspinous distance (IISD), anterior vertebral body compression ratio (AVBCR), posterior vertebral body compression ratio (PVBCR), middle vertebral body compression ratio (MVBCR), the ratio of height of bone fragment (RHBF), the ratio of width of bone fragment (RWBF), and mid-sagittal canal diameter compression ratio (MSDCR) were measured. Statistical analyses were performed using SPSS 25.0. Categorical variables were expressed as frequency (percentage) and analyzed using chi-square and Fisher exact tests. Continuous variables were tested for normality, with non-normally distributed data analyzed using the rank-sum test and expressed as median (interquartile range). Multivariate logistic regression analysis was performed to identify independent risk factors, and receiver operating characteristic (ROC) curves were plotted to calculate the area under the curve (AUC) to evaluate predictive performance. Results:Among the 48 patients, only 3 were found to have severe PLL injury, necessitating the combination of the moderate and severe groups for statistical purposes. Patients in the moderate-to-severe group demonstrated significantly higher AVBCR, PVBCR, RHBF, MVBCR, MSDCR, and IA compared to the mild group ( P<0.05). Multivariate logistic regression identified AVBCR, PVBCR, MSDCR, and IA as independent risk factors for moderate-to-severe PLL injury ( OR>1, P<0.05). ROC curve analysis revealed that AVBCR, PVBCR, MSDCR, IA, and their combined index could effectively predict moderate-to-severe PLL injury ( P<0.05). Notably, the combined index showed superior predictive performance (AUC=0.970) compared to individual parameters. Threshold values were determined as follows: AVBCR>45.30%, PVBCR>12.17%, MSDCR>27.13%, IA>5.90°, and the combined index >0.61, indicating PLL damage. Conclusion:AVBCR, PVBCR, MSDCR, IA, and their combined index are significantly associated with moderate-to-severe PLL injury in thoracolumbar burst fractures. The combined index demonstrates superior predictive ability compared to single parameters, providing a reliable tool for assessing PLL integrity.

Objective:Cardiac arrest (CA) represents a significant public health challenge, posing a substantial threat to individual health and survival. To enhance the survival rates of patients experiencing out-of-hospital cardiac arrest (OHCA), Baoan District in Shenzhen City has undertaken exploratory initiatives and practical interventions, yielding promising preliminary outcomes.Methods:1.Innovate emergency medical services by developing a "four-circle integration" system that connects to the hospital. This system encompasses the social emergency medical system, the out-of-hospital emergency medical system, the in-hospital emergency medical service system, and the intensive care treatment system. 2.Develop a comprehensive model for the construction of a social emergency medical training system, characterized by party leadership, government oversight, departmental coordination, professional guidance, technological support, and community involvement, termed the "Baonan Model." Additionally, establish evaluation criteria to assess the effectiveness of the social emergency medical training system in Baonan District; 3. Develop a cardiac arrest registration system and a social emergency medical training management system for Baonan District; 4. Enhance the proficiency in treatment techniques and the quality of cardiopulmonary resuscitation among emergency medical professionals; 5. Strengthen and advance the development of a "five-minute social rescue network" to address the critical "emergency window period." .Result:In Baonan District, 9.18% of the public is trained in emergency medical skills. The bystander CPR rate for OHCA is 26.11%, AED use is at 4.78%, the 30-day survival rate is 6.31%, and the discharge survival rate is 4.44%.Conclusion:The implementation of the aforementioned measures can substantially enhance the survival rate of patients experiencing OHCA at the time of discharge.

Aim To explore the effect of succinate/G protein coupled receptor 91(GPR91)on mitochondria in vascular endothelial cells and its regulatory mechanisms.Methods Transmission electron microscopy,Western blot and fluorescence microscopy were used to observe the effects of succinate analogues diethyl succinate(DS),GPR91 agonist and inhibitor on the mitochondrial morphology,cristae,cristate homeostasis related proteins reactive oxygen species(ROS)content,Ca2+concentration,mitochondrial membrane potential,the expression of dihydroorotate dehydrogenase(DHODH)and oxidized coenzyme Q10(CoQlO).Fluorescence probes were used to observe the effect of DHODH inhib-itor and CoQ10 on ROS level and Ca2+concentration of endothelial cells.Results After DS treatment,the mitochon-dria showed pyknosis and mitochondrial volume significantly decreased,electron density of the mitochondrial membrane in-creased,and the number of cristae decreased in endothelial cells;the expression of cristae homeostasis related proteins MIC60 decreased by 23％,while cellular ROS level and Ca2+concentration increased;mitochondrial membrane potential decreased(P＜0.05 or P＜0.01).After GPR91 agonist treatment,the expression of cristae homeostasis related proteins MIC60 decreased by 31％,meanwhile,cellular ROS level increased by 27％and Ca2+concentration increased by 36％;mitochondrial membrane potential decreased(P＜0.05 or P＜0.01).After GPR91 inhibitor treatment,the expression of cristae homeostasis related proteins MIC60 increased by 22％and ATP5I increased by 40％;the levels of ROS decreased by 41％and Ca2+concentration decreased by 67％;and the mitochondrial membrane potential was restored to normal(P＜0.05 or P＜0.01).After DS treatment,the expression of DHODH decreased by 43％and the level of oxidized CoQ10 in-creased by 120％(P＜0.05 or P＜0.01).After GPR91 agonist treatment,the expression of DHODH decreased by 22％and the level of oxidized CoQ10 increased by 36％(P＜0.05 or P＜0.01).After GPR91 inhibitor treatment,the expres-sion of DHODH increased by 40％and the level of oxidized CoQ10 decreased by 39％(P＜0.01).After DHODH inhibi-tor treatment,the ROS level increased by 20％and Ca2+concentration increased by 28％,and mitochondrial membrane po-tential reduced at same time(P＜0.05 or P＜0.01).Exogenous oxidized CoQ10 inhibited ROS production by 30％and decreased Ca2+concentration by 20％(P＜0.05 or P＜0.01).Conclusion Succinate/GPR91 promotes mitochondrial damage in endothelial cells,and its mechanism may relate to down-regulating the expression of DHODH and inhibiting the reduction of CoQ10 by affecting the mitochondrial cristae homeostasis.

Objective:To construct a core competency indicator system for oncology advanced practice nurses.Methods:This study is a cross-sectional study. A preliminary draft of the core competency indicator system for oncology advanced practice nurses was developed through literature review and expert group coordination from June to November 2022. The core competency indicator system for oncology advanced practice nurses was established using the Delphi method for expert consultation and the analytic hierarchy process.Results:A total of 54 experts from 11 hospitals and four medical schools in 10 provinces and municipalities directly under the central government across the country were included in two rounds of expert consultation. The effective response rates of the questionnaire were all 100%, with an expert authority coefficient of 0.90, Kendall coordination coefficients of 0.089 to 0.179 and 0.101 to 0.176 ( P<0.01). The final established core competency indicator system for oncology advanced practice nurses included seven primary indicators and 69 secondary indicators. Conclusions:The core competency indicator system for oncology advanced practice nurses is comprehensive and has the characteristics of specialized oncology nursing, and the construction process is scientific and reliable, laying the foundation for future training of oncology advanced practice nurses.

Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.