OBJECTIVE: To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation. METHODS: Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing. RESULTS: APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ _1-42, and Aβ _1-40, were decreased in SV2A-overexpressed cells. CONCLUSION These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics* ; Membrane Glycoproteins/genetics* ; Animals ; Protein Transport ; Nerve Tissue Proteins/genetics* ; Humans ; Mice ; Endosomes/metabolism* ; trans-Golgi Network/metabolism*

OBJECTIVE: We aimed to investigate the patterns of fasting blood glucose (FBG) trajectories and analyze the relationship between various occupational hazard factors and FBG trajectories in male steelworkers. METHODS: The study cohort included 3,728 workers who met the selection criteria for the Tanggang Occupational Cohort (TGOC) between 2017 and 2022. A group-based trajectory model was used to identify the FBG trajectories. Environmental risk scores (ERS) were constructed using regression coefficients from the occupational hazard model as weights. Univariate and multivariate logistic regression analyses were performed to explore the effects of occupational hazard factors using the ERS on FBG trajectories. RESULTS: FBG trajectories were categorized into three groups. An association was observed between high temperature, noise exposure, and FBG trajectory ( P < 0.05). Using the first quartile group of ERS1 as a reference, the fourth quartile group of ERS1 had an increased risk of medium and high FBG by 1.90 and 2.21 times, respectively (odds ratio [ OR] = 1.90, 95% confidence interval [ CI]: 1.17-3.10; OR = 2.21, 95% CI: 1.09-4.45). CONCLUSION An association was observed between occupational hazards based on ERS and FBG trajectories. The risk of FBG trajectory levels increase with an increase in ERS.
Humans ; Male ; Adult ; Blood Glucose/analysis* ; China ; Prospective Studies ; Occupational Exposure/adverse effects* ; Risk Factors ; Middle Aged ; Steel ; Fasting/blood* ; Metal Workers ; East Asian People

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective To investigate the correlation between sleep duration and chest pain in the Chinese population.Methods A cross-sectional analysis was conducted using data on chest pain and sleep duration from 7942 participants in the 2018 China Health and Retirement Longitudinal Study(CHARLS).Among them,1239 had chest pain and 6703 did not;2645 were aged>65 years and 5297 were aged≤65 years.All participants were categorized into three groups based on sleep duration:≤6 h(n=3123),6-8 h(n=2959),and>8 h(n=1860).Differences in characteristics such as gender,age,marital status,education level,diabetes,and hypertension were compared across these groups.Multivariate logistic regression analysis,curve fitting,and threshold effect analysis were further employed to explore the correlation between sleep duration and chest pain.Results A total of 7942 participants were finally included in the study.Among the three groups with sleep duration>8 h,6-8 h and≤6 h,the incidences of chest pain were 12.6%,13.0%,and 19.8%,respectively.Multivariate logistic regression analysis demonstrated that with the increase in sleep duration,the incidence of chest pain showed a decreasing trend[odds ratio(OR)=0.88,95%confidence interval(CI)0.86-0.91,P<0.001].Curve fitting and threshold effect analysis indicated a U-shaped relationship between sleep duration and the risk of chest pain.In the population aged≤65 years,the inflection point for sleep duration was 8.5 h,beyond which the risk of chest pain did not decrease;in the population aged>65 years,the inflection point was 7.7 h,beyond which the risk of chest pain significantly increased(P<0.05).Conclusions There is a U-shape relationship between sleep duration and the risk of chest pain.In the age group≤65 years old,8.5 h is the turning point;in the population>65 years old,7.7 h is the turning point.When the sleep duration is below the turning point,prolonging the sleep time can help reduce the risk of chest pain.It is recommended to maintain an appropriate sleep duration of 6-8 h to reduce the risk of chest pain.

Objective To report a case of tibial synovial sarcoma and review relevant literature to enhance understanding of this disease.Methods The clinical data of a patient with tibial synovial sarcoma treated at Kaifeng Central Hospital were retrospectively analyzed.A literature search was conducted in domestic and international databases,including China National Knowledge Infrastructure(CNKI),Wanfang Data,PubMed,Web of Science,and Embase,up to July 2024.Relevant literature was comprehensively reviewed to summarize the imaging and pathological characteristics,treatment,and prognosis of synovial sarcoma.Results A 29-year-old female patient was admitted with left lower extremity pain.X-ray examination revealed a proximal tibia space-occupying lesion suggestive of malignancy,and a mid-tibial space-occupying lesion considered benign.Contrast-enhanced computed tomography(CT)and plain magnetic resonance imaging(MRI)of the proximal tibial lesion also suggested malignancy.Ultrasound-guided biopsy of the proximal tibial tumor revealed a poorly differentiated malignant tumor.Immunohistochemistry results indicated monophasic synovial sarcoma,requiring genetic testing for definitive diagnosis.The patient underwent wide resection of the proximal left tibial malignancy with tumor-type artificial joint replacement,combined with curettage and bone cement filling for the left mid-tibial lesion under anesthesia.Postoperative pathology of space-occupying lesions in the proximal tibia confirmed monophasic synovial sarcoma,and fluorescence in situ hybridization(FISH)demonstrated a rupture of the synovial sarcoma translocation gene(SYT)(i.e.,SS18 positive).There was no recurrence or metastasis found in the patient during the reexamination 6 months after postoperative chemotherapy.As of July 2024,15 cases of genetically confirmed primary intraosseous synovial sarcoma have been reported internationally.Symptoms included pain and swelling,with a medical history of 1-2 years.The X-ray and CT findings showed osteolytic destruction with bone cortical discontinuity.In 13 cases,the intraosseous masses extended to the extraosseous area;in 2 cases,punctate calcifications were detected within the masses.Plain MRI scan showed iso-signal or hypo-signal on T1WI and hyper-signal,iso-signal,and hypo-signal on fat-suppressed T2WI,and enhanced MRI scan demonstrated heterogeneous enhancement.Pathological examination showed spindle-shaped cells under microscopy.Immunohistochemistry results showed positive epithelial membrane antigen(EMA),broad-spectrum cytokeratin(AE1/AE3),Ewing's sarcoma marker(CD99),and transducin-like enhancer of Split 1(TLE1).Twelve patients underwent surgical treatment;6 patients received adjuvant chemotherapy after surgery,of whom 4 developed local recurrence or distant metastasis at initial diagnosis,and 3 died during follow-up.Among the 6 patients who did not receive adjuvant chemotherapy,3 suffered from recurrence or distant metastasis.Conclusions Primary intraosseous synovial sarcoma is a rare malignant tumor with non-specific clinical manifestations.Imaging features typically include osteolytic destruction and intraosseous masses extending extraosseously,suggesting an intraosseous origin.Pathology and immunohistochemistry aid diagnosis,but definitive confirmation relies on further genetic testing.At present,the main treatment regimens for synovial sarcoma involve comprehensive therapies such as surgery and adjuvant chemotherapy,and the prognosis of patients is poor.

OBJECTIVES: To study the clinical and genetic characteristics of osteopetrosis (OPT) in children. METHODS: A retrospective analysis was performed on the clinical data of 14 children with OPT. Whole-exome sequencing was used to detect pathogenic genes, and clinical phenotypes and genotypic features were summarized. RESULTS: Among the 14 children (10 males and 4 females), the median age at diagnosis was 8 months. Clinical manifestations included systemic osteosclerosis (14 cases, 100%), anemia (12 cases, 86%), infections (10 cases, 71%), thrombocytopenia (9 cases, 64%), hepatosplenomegaly (8 cases, 57%), and developmental delay (5 cases, 36%). Malignant osteopetrosis (MOP) cases had lower platelet counts, creatine kinase isoenzyme, and serum calcium levels, but higher white blood cell counts, lactate dehydrogenase, and alkaline phosphatase levels compared to non-MOP cases (P<0.05). Genetic testing identified 15 variants in 12 patients, including 8 variants in the CLCN7 gene (53%), 6 in the TCIRG1 gene (40%), and 1 in the TNFRSF11A gene (7%). Three novel CLCN7 variants were identified: c.2351G>C, c.1215-43C>T, and c.1534G>A. All four patients with TCIRG1 variants exhibited MOP clinical phenotypes. Of the seven patients with CLCN7 variants, 4 presented with intermediate OPT, 2 with benign OPT, and 1 with MOP. CONCLUSIONS Clinical phenotypes of OPT in children are heterogeneous, predominantly involving CLCN7 and TCIRG1 gene variants, with a correlation between clinical phenotypes and genotypes.
Humans ; Osteopetrosis/genetics* ; Male ; Female ; Infant ; Child, Preschool ; Retrospective Studies ; Vacuolar Proton-Translocating ATPases/genetics* ; Child ; Chloride Channels/genetics* ; Mutation ; Receptor Activator of Nuclear Factor-kappa B

Aim To investigate the effect of triptolide(TP)on corticosterone(CORT)-induced depression-like behaviors in mice and explore the antidepressant mechanism of TP based on the CREB/BDNF/TrkB sig-naling pathway.Methods Sixty 8-week-old male C57BL/6J mice were randomly divided into five groups:control group,CORT group,TP groups of low and high doses(10,30 μg·kg-1),and fluoxetine(FLU)group(10 mg·kg-1).Except for the control group,the other groups received subcutaneous injec-tions of CORT for three consecutive weeks to establish the model of depression.During the last two weeks of modeling,normal saline,TP and FLU were adminis-tered via intraperitoneal injection respectively.After the administration,depression-like behaviors in mice were assessed using forced swimming test,tail suspen-sion test,and sucrose preference test.Biochemical methods were used to measure the levels of SOD and MDA in the hippocampus and prefrontal cortex(PFC).Cell apoptosis was detected by TUNEL meth-od.Immunohistochemistry,immunofluorescence,and Western blotting were employed to detect the expres-sion of apoptosis/autophagy-related proteins,synaptic structure markers,and proteins related to the CREB/BDNF/TrkB signaling pathway.Results TP signifi-cantly ameliorated CORT-induced depression-like be-haviors in mice,mainly manifested by reduced immo-bility time in the tail suspension test and forced swim-ming test,and increased sucrose preference rate.TP alleviated CORT-induced oxidative stress by increasing SOD levels and reducing MDA production in brain tis-sue.Additionally,TP also inhibited apoptosis and ex-cessive autophagy of neurons in the hippocampus and prefrontal cortex,maintained synaptic plasticity,and significantly upregulated the expression of p-CREB,BDNF,and TrkB.Conclusions TP exhibits potential antidepressant effect in mice by upregulating the CREB/BDNF/TrkB signaling pathway,reducing oxida-tive stress,inhibiting excessive neuronal apoptosis and autophagy,and improving synaptic plasticity.

Objective:To investigate clinical application effect of 5E rehabilitation management combined with health education knowledge in elderly patients with acute myocardial infarction(AMI).Methods:This randomized con-trolled study enrolled 98 elderly AMI patients admitted in Department of Cardiology,Hefei Eighth People's Hospital between July 2020 and February 2023.They were divided into control group(n=49,routine health education knowl-edge mode nursing)and intervention group(n=49,additional 5E rehabilitation management).Both groups were intervened for 2 months.Cardiac function indexes,mental state,scores of disease cognition,Pittsburgh Sleep Qual-ity Index(PSQI),Medical Outcomes Study 36-Item Short-Form Health Survey(SF-36)and incidence of com-plications were compared between two groups.Results:After 2-month intervention,compared with patients in control group,those in intervention group had significant higher left ventricular ejection fraction(LVEF)[(51.66±2.01)％vs.(45.88±1.51)％],scores of disease cognition[(89.43±2.38)points vs.(81.13±1.16)points]and SF-36[(645.58±26.00)points vs.(432.72±18.50)points],and significant lower left ventricular end-dias-tolic diameter(LVEDd)[(47.74±0.86)mm vs.(51.20±1.36)mm],creatine kinase(CK)[(140.89±5.15)U/L vs.(154.32±2.61)U/L],scores of Self-Rating Depression Scale(SDS)[(31.88±1.16)points vs.(41.06±1.22)points],Self-Rating Anxiety Scale(SAS)[(31.09±1.12)points vs.(40.47±0.87)points]and PSQI[(5.54±0.64)points vs.(7.70±0.85)points](P＜0.001 all).Incidence of complications in intervention group was significantly lower than that of control group(4.08％vs.18.36％,P=0.025).Conclusion:5E rehabilitation management combined with health education knowledge mode could significantly improve cardiac function,negative emotions and sleep quality,improve disease cognition and quality of life,and reduce incidence of complications in elderly AMI patients.

Objective:To assess the relationship between basophil levels and mortality in patients with intra-abdominal infection.Methods:Information on patients with intraperitoneal infection admitted to the intensive care unit were extracted from the MIMIC database.A time-dependent Cox regression model was used to adjust for confounders associated with 28-day mortality.Propensity score matching(PSM)was used to balance the baseline differences be-tween groups with different basophil levels,and a restricted cube chart(RCS)was used to show the relationship between basophil count and 28-day mortality in patients with intra-abdominal infection.Results:A total of 4403 patients with intra-abdominal infection were enrolled in the MIMIC database.Patients with high basophil levels have lower mortality than those with low basophil levels.There was an L-shaped curve between basophil level and 28-day mortality,with a cut-off value of 0.47×109/L.Cox regression analysis showed that basophil levels were an independent protective factor for mortal-ity in patients with intra-abdominal infection after adjusting for potential confounders(HR=0.586,95%CI:0.443-0.769).Protective factors for death at basophil levels remained after PSM adjusted for potential confounders(HR=0.628,95%CI:0.470-0.832).Conclusion:Basophil level is an independent protective factor for mortality in patients with intra-abdominal infection,and basophil levels should be dynamically monitored to better evaluate the prognosis of patients.