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:To explore the current status and influencing factors of family resilience in primary caregivers of advanced cancer patients.Methods:A convenience sampling method was used to select the primary caregivers of advanced cancer patients from the Department of Gastrointestinal Oncology at Beijing Cancer Hospital, between July 2023 and March 2024. A questionnaire survey was conducted using a general information survey, the Family Hardiness Index, the General Self-Efficacy Scale, and subscales for intimacy, emotional expression, and conflict in the Family Environment Scale.Results:A total of 130 questionnaires were distributed, and 120 valid questionnaires were returned, resulting in an effective response rate of 92.31%. The family Hardiness Index score of the 120 primary caregivers was (61.03±6.44) , with scores for the responsibility dimension at (29.35±3.32) , the control dimension at (16.97±2.78) , and the challenge dimension at (14.72±2.17) . The General Self-Efficacy Scale score was (2.60±0.57) , and the Family Environment Scale scores were as follows: intimacy (8.13±1.45) , emotional expression (5.40±1.71) , and conflict 2.00 (1.00, 3.00) . Multiple linear regression analysis showed that emotional expression in the family environment ( P=0.001) , self-efficacy ( P<0.001) , and marital status ( P=0.017) were significant factors influencing family resilience in primary caregivers, explaining 27.2% of the total variance. Conclusions:The family resilience of primary caregivers of advanced cancer patients is at a moderate to high level. Caregivers with spouses, better emotional expression among family members, and higher self-efficacy tend to have higher levels of family resilience.

Objective:To explore the effectiveness of digital management platform led by outpatient specialist nurses among patients with type 2 diabetes in outpatient settings.Methods:From March 2024 to March 2025, adult patients with type 2 diabetes who visited the Endocrinology Clinic at Peking Union Medical College Hospital were selected using convenience sampling. Patients were randomly assigned to the control group and intervention group using the random number table method. Patients in control group received routine education on type 2 diabetes during their clinic visits after enrollment. Intervention group was managed by nurses through a digital management platform, establishing long-term connections with patients. Based on the platform, nurses regularly provided patients with knowledge updates, promptly responded to patient inquiries, reviewed daily dietary records, monitored blood glucose data, conducted weekly telephone follow-ups, and scheduled regular clinic visits to precisely intervene in patients' lifestyles. The glycated hemoglobin (HbA1c) and self-management behavior scores were compared between two groups of patients before and after three months of intervention.Results:A total of 46 patients were enrolled and completed the 3-month follow-up, including 25 in control group and 21 in intervention group. There were no statistically significant differences in HbA1c or self-management behavior scores between the two groups of patients before intervention ( P>0.05). At three months of intervention, the HbA1c reduction in intervention group was greater than that in control group, with a statistically significant difference ( P<0.05). There was no statistically significant difference in Summary of Diabetes Self-Care Activities Scale scores between the two groups ( P>0.05). The difference in changes in diabetic foot self-screening scores between intervention group and control group was statistically significant ( P<0.05) . Conclusions:Specialist nurse-led precision health care management utilizing digital platforms can improve HbA1c and enhance self-management behaviors for diabetic foot in patients with type 2 diabetes, which is expected to be promoted and applied in the outpatient management of diabetes patients.

Objective:To explore the effectiveness of digital management platform led by outpatient specialist nurses among patients with type 2 diabetes in outpatient settings.Methods:From March 2024 to March 2025, adult patients with type 2 diabetes who visited the Endocrinology Clinic at Peking Union Medical College Hospital were selected using convenience sampling. Patients were randomly assigned to the control group and intervention group using the random number table method. Patients in control group received routine education on type 2 diabetes during their clinic visits after enrollment. Intervention group was managed by nurses through a digital management platform, establishing long-term connections with patients. Based on the platform, nurses regularly provided patients with knowledge updates, promptly responded to patient inquiries, reviewed daily dietary records, monitored blood glucose data, conducted weekly telephone follow-ups, and scheduled regular clinic visits to precisely intervene in patients' lifestyles. The glycated hemoglobin (HbA1c) and self-management behavior scores were compared between two groups of patients before and after three months of intervention.Results:A total of 46 patients were enrolled and completed the 3-month follow-up, including 25 in control group and 21 in intervention group. There were no statistically significant differences in HbA1c or self-management behavior scores between the two groups of patients before intervention ( P>0.05). At three months of intervention, the HbA1c reduction in intervention group was greater than that in control group, with a statistically significant difference ( P<0.05). There was no statistically significant difference in Summary of Diabetes Self-Care Activities Scale scores between the two groups ( P>0.05). The difference in changes in diabetic foot self-screening scores between intervention group and control group was statistically significant ( P<0.05) . Conclusions:Specialist nurse-led precision health care management utilizing digital platforms can improve HbA1c and enhance self-management behaviors for diabetic foot in patients with type 2 diabetes, which is expected to be promoted and applied in the outpatient management of diabetes patients.

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.

Objective:To investigate the establishment, staffing, equipment allocation, and technological capabilities of cardiac intensive care units in public secondary and tertiary hospitals in Henan Province, and to provide a reference for promoting the development of nationwide cardiac critical care.Methods:In September 2023, supported by the Henan Provincial Health Commission, Cardiac Critical Care Committee of the Chinese Medical Doctor Association conducted the first comprehensive survey on the construction of cardiac intensive care units in Henan Province. A Chi-square test was used to compare the findings between secondary and tertiary hospitals.Results:A total of 171 hospitals reported 1 602 cardiac intensive care unit beds, 1 091 physicians (physician-to-bed ratio: 0.68), and 2 298 nurses (nurse-to-bed ratio: 1.43). Tertiary hospitals had a significantly higher proportion of full-time physicians and physicians with a master′s degree or above compared to secondary hospitals. Furthermore, tertiary hospitals had more nurses and a higher proportion of nurses with a bachelor′s degree (all P<0.05). Regarding equipment, tertiary hospitals demonstrated higher availability of activated clotting time (ACT) analyzers, temporary pacemakers, extracorporeal membrane oxygenation (ECMO) machines, intra-aortic balloon pumps (IABP), and pulse index continuous cardiac output (Picco) monitors (all P<0.05). Among the hospitals surveyed, 123 could independently perform coronary interventional procedures, 93 could independently use an IABP, 26 could independently perform ECMO, and 53 offered continuous renal replacement therapy at the bedside. Conclusions:This study provides a preliminary understanding of the current state of cardiac critical care in Henan Province. Tertiary hospitals demonstrated advantages over secondary hospitals regarding medical staffing, the proportion of highly educated personnel, the availability of advanced equipment, such as ACT analyzers, temporary pacemakers, IABP, and Picco monitors, as well as in the performance of advanced procedures, including IABP and ECMO.

BACKGROUND:The highest incidence of spinal fracture is in the thoracolumbar segment,and its symptoms are back pain,posterior convexity deformity,activity limitation,or with spinal cord nerve injury causing lower limb pain,numbness,and even paraplegia and other complications.The finite element method is a digital computer modeling technique,which can simulate the physical model and carry out force analysis realistically.OBJECTIVE:To review the application of finite element method in thoracolumbar spine fractures.METHODS:We searched the Chinese and English literature databases PubMed,Web of Science,and CNKI for relevant literature on the application of the finite element analysis method in spinal thoracolumbar fracture published before March 2024.The search terms in Chinese and English were:finite element analysis methods,biomechanical phenomena,stress analysis,thoracolumbar fractures,spinal fractures.Finally,55 papers were included.RESULTS AND CONCLUSION:(1)The exploration of thoracolumbar fractures caused by different etiologies(osteoporotic,traumatic,and pathological)through the finite element method is conducive to a deeper understanding of the biomechanics of various types of thoracolumbar fractures,and to improve the individualized and fine-tuned treatment of thoracolumbar fractures.(2)The finite element analysis of a single sample or a small number of samples has the chance,and a larger number of samples are required for the future finite element analysis to reduce the chance caused by the sample.(3)The rigid structure of bones alone cannot meet the biomechanical working conditions of the integrity of the physical object,and future finite element models need to incorporate all the structures of the physical object(e.g.,soft tissues,such as muscles and ligaments)as far as possible.(4)The finite element method has been used in more studies on osteoporotic and traumatic thoracolumbar spine fractures,which will need to be more in-depth in the future,and less in the field of pathologic thoracolumbar fractures,which has a wider scope for future research.

Objective:To investigate the clinical subtypes of acute aortic dissection (AAD) through latent class analysis.Methods:This study was a multicenter retrospective cohort study. Patients with AAD admitted to five hospitals, including Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Henan Provincial People′s Hospital, Central China Fuwai Hospital of Zhengzhou University (Fuwai Central China Cardiovascular Hospital), the Third Affiliated Hospital of Xinxiang Medical University and the Second Affiliated Hospital of Chongqing Medical University, between August 2010 and December 2021 were enrolled. Based on clinical and biological characteristics, latent class analysis (models with 2 to 5 latent classes) was conducted to classify the enrolled patients. The optimal classification scheme was determined using model fitting evaluations, including log-likelihood (LL), entropy, Lo-Mendell-Rubin adjusted likelihood ratio test and so on. Clinical data of different subtypes were compared, and in-hospital mortality was analyzed across the entire population and among subgroups receiving different treatments.Results:A total of 2 689 AAD patients, aged 54 (46, 63) years were included, with 1 305 (48.5%) having DeBakey type Ⅰ, 156 (5.8%) type Ⅱ, and 1 228 (45. 7%) type Ⅲ dissections. The cohort comprised 2 134 (79.4%) males. The overall in-hospital mortality rate was 22.8% (613/2 689). Latent class analysis indicated that a two-class model was optimal (LL=147 413.242, entropy=0.812, and PLMRT<0.001). Patients were classified into two subtypes, named clinical subtype 1 and clinical subtype 2. Compared to clinical subtype 1, clinical subtype 2 had a higher proportion of females, was older, had more dissections involving the ascending aorta, and exhibited higher rates of organ dysfunction (elevated alanine aminotransferase and creatinine levels) and inflammatory response (neutrophilia) (all P<0.05). Clinical subtype 2 also showed higher in-hospital mortality compared to subtype 1 (26.3% (238/905) vs. 21.0% (375/1 784), P=0.002). Among patients undergoing surgical treatment, clinical subtype 2 had higher mortality than subtype 1 (40.1% (67/167) vs. 30.0% (101/337), P=0.027). However, no significant differences in mortality were observed between the two subtypes among patients receiving medical therapy or endovascular and hybrid procedures (all P>0.05). Conclusions:Comprehensive latent class analysis identifies two subtypes of AAD with distinct clinical characteristics and treatment responses. These findings provide new insights into individualized clinical decision-making and prognostic evaluation for AAD patients.