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.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

To investigate the value of self-developed air-free laparoscopic auxiliary instruments in the clinical application of thyroid diseases.The clinical data of 70 transaxillary and 45 transareolar air-free laparoscopic surgeries for thyroid cancer and 40 conventional open surgeries were retrospectively compared.The transaxillary and transareolar laparoscopic groups had significantly longer operative times than the open group,while the postoperative satisfaction was higher in the endoscopic group than in the open group.This set of instruments has advantage of novel design,scientific structure,safe application.It can be compatible with a variety of thyroid and breast air-free laparoscopic procedures,which can promote the development and popularization of laparoscopic technology.

Objective:To investigate the predictive value of controlling nutritional status (CONUT) score in the prognosis of patients with advanced diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 654 patients newly diagnosed with advanced DLBCL diagnosed in 7 medical centers in Huaihai Lymphoma Working Group from October 2009 to January 2022 were retrospectively collected. All the patients received rituximab-based immune chemotherapy regimens. The patients were randomly assigned to the training set (458 cases) and the validation set (196 cases) in a 7:3 ratio. The clinicopathological data of patients were collected, and the CONUT score was calculated based on albumin, lymphocyte count, and total cholesterol. The optimal critical value of CONUT scote was determined by using MaxStat method. Kaplan-Meier method was used to draw survival curves; Cox proportional hazards model was used to make univariate analysis and multivariate analysis on the factors influencing overall survival (OS). The efficacy of CONUT score in combination with the International prognostic index (IPI) and an enhanced IPI (NCCN-IPI) in predicting OS was evaluated by using receiver operating characteristic (ROC) curves.Results:The median follow-up time of 654 patients was 38.1 months (95% CI: 35.3 months- 40.9 months), and the 5-year OS rate was 49.2%. According to the MaxStat method, the optimal critical value for CONUT score was determined to be 6 points. All the patients were classified into the normal nutritional status group (CONUT score ≤ 6 points, 489 cases) and the poor nutritional status group (CONUT score > 6 points, 165 cases). The results of the multivariate analysis showed that CONUT score > 6 points, male, lactate dehydrogenase >240 U/L, high white blood cell count, low hemoglobin level and age > 60 years were independent risk factors for OS of patients with advanced DLBCL (all P < 0.05). Patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group in the overall cohort of advanced DLBCL. Subgroup analysis revealed that among patients with Eastern Cooperative Oncology Group-performance status (ECOG PS) score < 2 points, IPI low-intermediate risk, IPI intermediate-high risk, NCCN-IPI low-intermediate risk, and NCCN-IPI intermediate-high risk, the patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group (CONUT score ≤ 6 points) (all P < 0.05). Conclusions:CONUT score has a certain value in the assessment of the prognosis of patients with advanced DLBCL, and its predictive efficacy is further improved when combined with IPI and NCCN-IPI.

Objective:To explore the correlation between high cholinergic pathway signaling and cognitive function in patients with Parkinson disease(PD) accompanied with sleep disorder.Methods:PD patients admitted from 2017 to 2022 were divided into PD with sleep disorder group (PD-SD group) ( n=56) and PD without sleep disorder group (PD-NSD group) ( n=41) according to the Parkinson's disease sleep scale (PDSS) score. All participants underwent magnetic resonance imaging examination.All patients were evaluated by the PDSS, Hoehn-Yahr (H-Y), Montreal cognitive assessment scale (MoCA), and cholinergic pathways hyper intensities scale (CHIPS). The difference of cognitive function between the two groups and the correlation between CHIPS and cognitive function were analyzed.Independent sample t-test, Spearman correlation analysis, and binary Logistic regression analysis were performed on the data by SPSS 26.0 statistical software. Results:(1)The MoCA score of the PD-SD group (22.00 (5.00)) was lower than that of the PD-NSD group (26.00 (5.00)) ( Z=-3.830, P<0.05). The total and all aspects scores of CHIPS in PD-SD group were higher than those in PD-NSD group(the total score of the low external capsule: 12.00(8.00), 0(8.00), the total score of the high external capsule: 12.00(2.00), 6.00(9.00), the total score of the radial crown: 8.00(0), 4.00(4.00), the total score of the centrum semiovale: 3.00(4.00), 0(2.00), the total score of the right side: 16.00(9.00), 5.00(10.00), the total score of the left side: 17.00(6.00), 7.00(9.00), the total score of CHIPS: 32.00(14.00), 14.00(20.00))( Z=-5.081, -5.873, -4.933, -3.211, -5.562, -6.232, -5.995, all P<0.05). (2)The correlation analysis between the score of CHIPS and cognitive function in the PD-SD group showed that, the total score of the low external capsule ( r=-0.286), the total score of the centrum semiovale ( r=-0.307), the total score of the right side ( r=-0.376), the total score of the left side ( r=-0.284) and the total score of CHIPS ( r=-0.349) were negatively correlated with MoCA(all P<0.05). (3)Binary Logistic regression analysis showed that white matter lesions in centrum semiovale, low inner capsule, right and left leukodystrophy were not influence factors for cognitive impairment (all P>0.05). Conclusion:PD patients with sleep disorders have lower cognitive function scores, higher CHIPS scores, and significant changes in white matter lesions compared to those without sleep disorders. In PD patients with sleep disorders, the higher the CHIPS score, the lower the cognitive function score, and the more significant the rate of cognitive impairment occurrence and development.

Objective:To analyze the health responsibilities of both the supply and demand sides in the process of community chronic disease management for the elderly,as well as to provide a reference for the fulfillment of the health responsibilities of both the supply and demand sides in the process of chronic disease management.Methods:Elderly people were extracted as research subjects from communities,that were under the jurisdiction of the 27 community health service centers we selected.By using the method of questionnaire surveys and in-depth interviews,this paper analyzed the health responsibilities of both the supply and demand sides from the perspective of chronic diseases and health awareness among the elderly,self-management responsibilities of the elderly,and the health responsibility of community health service institutions.Results:There was still room for improvement in the fulfillment of health responsibilities by both the supply and demand sides,and the ability of elderly people to fulfill self-management responsibilities needs to be improved.Under the guidance of the three-level prevention theory,there were varying degrees of deficiencies in the fulfillment of health responsibilities by community health service institutions in all dimensions.Conclusion:It is suggested to clarify the health responsibilities of both the supply and demand sides for chronic disease management,with the goal of achieving the health of the elderly population,to complete both the supply and demand sides to jointly build an interactive model of health responsibility of chronic disease management in the elderly community,and to realize the health co-construction and sharing.

Objective:To carry out a scoping review on characteristics and effects of intervention program for promoting motor behavior among older adults in the community based on transtheoretical model (TTM), so as to explore the mechanism and connotation of TTM guiding strategy selection in the intervention program.Methods:The literature on the intervention program for promoting motor behavior among older adults in the community based on TTM was systematically searched in PubMed, Embase, CINAHL, Cochrane Library, PsycINFO, China National Knowledge Infrastructure and Wanfang Data. The search period was from database establishment to October 11, 2023. Two researchers conducted a summary and data analysis of the included literature.Results:A total of 15 articles were included, and the intervention framework included two types according to behavior change stages and behavior change patterns. The intervention strategy mainly included 17 items, such as emphasizing the benefits of exercise and drawbacks of no-exercise, establishing family support relationships, sharing exemplary experiences, rewarding, setting reminders, and signing commitments. The intervention strategies mainly involved 14 forms such as health lectures, one-on-one communication, exercise commitment letters, exercise logs, group communication meetings, and material/honor. The outcome measures consisted of feasibility (safety, retention, attendance, satisfaction) and effectiveness (exercise compliance, behavioral stage changes, physical function, self-efficacy, decision balance and so on) .Conclusions:The stages of change in TTM can guide the design of intervention frameworks for promoting motor behavior among older adults in the community, and the change program can guide the intervention strategies and design of application forms. The characteristic of the TTM based intervention program for promoting motor behavior among older adults in the community is that it contains intervention strategies that are suitable for each stage of behavior, and has short-term effectiveness and feasibility in terms of results. It is necessary to further clarify the details of the intervention program to explore its long-term effectiveness, and conduct follow-up.

Objective:To conduct a scoping review on gamified exercise interventions for elderly patients with cognitive impairment to provide insights for the application of gamification design in exercise programs for this population.Methods:Guided by the scoping review framework proposed by Arksey and O'Malley, a systematic search was conducted in databases including China National Knowledge Infrastructure, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, CINAHL, Web of Science, Scopus, ProQuest, and Wiley Online Library. The search covered the period from the establishment of the databases to June 12, 2024. An integrative analysis was performed on the included literature.Results:A total of 12 studies were included. The most commonly used gamification elements were achievement- and progress-oriented features, while the most frequently applied behavior change theories were behavior change techniques and social cognitive theory.Conclusions:Gamification-based exercise interventions can improve adherence to exercise programs in elderly patients with cognitive impairment, promote physical activity, and enhance cognitive function. Future research should focus on combining various theories with different gamification elements to encourage proactive exercise behavior in elderly individuals with cognitive impairment.

Objective To analyze the correlations of serum homocysteine (Hcy), lactate dehydrogenase (LDH) and interleukin-17 (IL-17) levels with the clinical characteristics and short-term efficacy of acute leukemia (AL). Methods Ninety-five AL patients were selected as study group, and another 95 healthy volunteers during the same period were chosen as control group. The general information and levels of Hcy, LDH and IL-17 were compared between the two groups. The serum levels of Hcy, LDH and IL-17 were compared among patients with different clinical characteristics in the study group. The relationship between serum Hcy, LDH and IL-17 levels and the clinical features of AL was analyzed. The serum levels of Hcy, LDH and IL-17 before and after treatment, as well as their change values (△indicating the absolute value of the change in the corresponding indicator before and after treatment) were compared among AL patients. The correlation of the changes in serum Hcy, LDH and IL-17 levels with the short-term efficacy of AL was analyzed. Results The serum levels of Hcy, LDH, and IL-17 in the study group[(14.36±3.24) μmol/L, (591.42±113.85) U/L and (9.64±3.01) pg/mL, respectively]were significantly higher than those in the control group [(9.75±2.08) μmol/L, (120.81±20.64) U/L and (4.08±1.25) pg/mL, respectively](P < 0.05). In the study group, patients at high risk of stratification had significantly higher serum levels of Hcy, LDH and IL-17 [(15.83±3.10) μmol/L, (636.19±110.54) U/L and (10.62±2.96) pg/mL, respectively] compared to patients at low and medium risk[(12.58±2.71) μmol/L, (537.28±95.68) U/L and (8.45±2.29) pg/mL, respectively]. Patients with extramedullary infiltration had significantly higher serum levels of Hcy, LDH, and IL-17[(16.12±3.15) μmol/L, (647.59±115.46) U/L and (11.05±3.04) pg/mL, respectively]compared to patients without extramedullary infiltration[(13.38±2.89) μmol/L, (560.11±97.25) U/L and (8.85±2.65) pg/mL, respectively](P < 0.05). There was a positive correlation of serum levels of Hcy, LDH, and IL-17 with the risk stratification and extramedullary infiltration of AL in the study group (P < 0.05). Patients with poor treatment response in the study group had significantly higher serum levels of Hcy, LDH and IL-17 before and after treatment compared to patients with a good treatment response, and △Hcy, △LDH and △IL-17 were significantly smaller than those of patients with a good treatment response (P < 0.05). There were positive correlations between △Hcy, △LDH and △IL-17 and the short-term efficacy of AL in the study group (P < 0.05). Conclusion The serum levels of Hcy, LDH and IL-17 are positively correlated with the risk stratification and extramedullary infiltration of AL, and the changes in these indicators before and after treatment are positively correlated with the short-term efficacy of AL.

Objective:To investigate the significance of B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation in the prediction of response to apatinib treatment in advanced radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC). Methods:Twenty patients (10 males, 10 females, age: 51.5(46.3, 65.0) years) with advanced RAIR-DTC from Peking Union Medical College Hospital between March 2016 and March 2023 were retrospectively enrolled, and all patients were treated with apatinib and underwent genetic sequencing (including BRAF V600E and telomerase reverse transcriptase (TERT) promoter). The serological and imaging data, progression-free survival (PFS) and overall survival (OS) data were collected during apatinib treatment. The Kaplan-Meier survival analysis (log-rank test) was performed, and Mann-Whitney U test were used to analyze the differences of duration of response (DOR) between mutation group and wild-type group. Then univariate and multivariate Cox regression analyses were conducted. Results:The PFS (35.3 vs 9.2 months, χ2=7.53, P=0.006) and DOR (25.8(7.4, 35.2) vs 8.2(2.5, 13.4) months, U=23.00, P=0.046) of the BRAF V600E mutation group were longer than those of the wild-type group. Univariate Cox regression analysis showed that the BRAF V600E mutation group had better PFS benefit (hazard ratio ( HR)=0.22 (95% CI: 0.06-0.72), P=0.013), and the risk of disease progression or death in patients with lung metastasis and bone or brain metastasis was 3.06(95% CI: 1.10-8.54, P=0.033) times higher than that in patients with lung metastasis alone. Further, multivariate cox regression analysis showed that only BRAF V600E mutation was an independent predictor of PFS ( HR=0.23 (95% CI: 0.07-0.80), P=0.021), suggesting that RAIR-DTC patients with BRAF V600E mutation might have better efficacy of apatinib. There was no significant difference in PFS ( χ2=1.34, P=0.247) and OS ( χ2=0.19, P=0.664) between TERT promoter mutation group and wild-type group. Conclusion:RAIR-DTC patients with BRAF V600E mutation have longer PFS and DOR after apatinib treatment than those with BRAF V600E wild-type, suggesting that BRAF V600E may be a potential biomarker to guide tyrosine kinase inhibitor (TKI) therapy and help to refine TKI treatment indications.