ObjectiveTo explore the effects of different concentrations of oleic acid on human osteosarcoma cell lines 143B and HOS， as well as the impacts of the optimal concentration of oleic acid on cellular lipid droplet synthesis and cell functions. MethodsThe 143B and HOS cells were treated with varying concentrations of oleic acid （0， 25， 50， 100， and 200 µmol/L） for 48 hours. Following treatment， oil red O staining and BODIPY staining were performed to determine the optimal concentration. Subsequently， CCK-8 assays and colony formation experiments were conducted to assess the effect of this optimal concentration of oleic acid on the cell proliferation of both cell lines. Transwell migration assays were utilized to evaluate the influence of the optimal concentration on migratory capacity and Transwell invasion assays were utilized to evaluate the invasive ability. Additionally， Western blot analysis was employed to examine the expression levels of epithelial-mesenchymal transition （EMT） markers Epithelial cadherin （E-cadherin） and Neural cadherin （N-cadherin） in response to treatment with the optimal concentration of oleic acid. ResultsTreatment with oleic acid did not induce significant cell death in either 143B or HOS cells； however， an increase in intracellular lipid droplets was observed alongside enhanced proliferation， migration， invasion capabilities as well as EMT transformation potential （P<0.05）. ConclusionOleic acid induces lipid droplet synthesis in osteosarcoma cells which subsequently promotes their proliferation， migration and invasion abilities along with EMT transformation.

Objective To explore the clinical values of non-invasive myocardial work (MW) and tissue motion annular displacement (TMAD) in evaluation of anthracycline therapy-related cardiac dysfunction in patients with non-Hodgkin lymphoma. Methods A total of 62 patients with non-Hodgkin lymphoma who received standardized chemotherapy based on doxorubicin. Two and three dimensional transthoracic echocardiography, along with two dimensional speckle tracking echocardiography, were performed one day before chemotherapy and at 3, 6, and 9 months after chemotherapy to assess left ventricular ejection fraction, global longitudinal strain (GLS), MW parameters, and TMAD. Logistic regression analysis was used to evaluate the risk factors for cancer therapy-related cardiac dysfunction (CTRCD). The receiver operating characteristic curve was used to assess the diagnostic values of MW- and TMAD-related parameters for CTRCD. Results Compared to baseline, GLS, global work index (GWI), global constructive work (GCW), global work efficiency (GWE), TMAD at midpoint (TMADmid), and TMADmid percentage of left ventricular long-axis diameter (TMADmid%) decreased at 3 months after chemotherapy, while global wasted work (GWW) increased at 6 months after chemotherapy (P＜0.05). Logistic regression analysis showed that the relative reduction in GLS and TMADmid% at 3 months after chemotherapy were independent predictors for CTRCD （P＜0.05), while MW parameters were not independent predictors for CTRCD. GLS reduction≥10.3% and TMADmid% reduction≥15.8% at 3 months after chemotherapy predicted CTRCD with 0.866 and 0.824 of area under the curve (AUC), 92% and 75% of sensitivity, and 74% and 80% of specificity, respectively. AUC of combination of two indexes improved to 0.905, with 75% of sensitivity and 90% of specificity. Conclusions In non-Hodgkin lymphoma patients, the combination of GLS and TMADmid% is helpful of predicting CTRCD early, TMAD may be a novel diagnostic index for CTRCD, and GLS has superior predictive performance than MW for CTRCD.

Endotoxins are common exogenous pyrogens. Excessive endotoxins in medical devices and injections can lead to serious consequences such as sepsis, septic shock, and even death. Therefore, endotoxin detection plays a crucial role in medical, pharmaceutical, and food sectors. The wide application of Limulus amebocyte lysate (LAL) has led to a sharp decline in the number of horseshoe crabs. Moreover, the LAL assay has limitations such as interbatch variations and difficulty in quantification. The recombinant factor C (rFC) assay is stable between batches, highly sensitive, and capable of quantitation, and thus it can be used as an alternative for the LAL assay. However, the high cost and complex procedures involved in producing recombinant factor C have limited the widespread application of this method. In order to simplify the preparation and reduce the production cost of recombinant factor C, this study focuses on the production of recombinant factor C based on the baculovirus expression system. Multiple measures such as a high-yield and anti-apoptotic vector qBac-IIIG, the optimal signal peptide, and the optimized codon were used to reach the goal of endotoxin detection with cell supernatant. This method simplifies the steps of protein purification. The sensitivity of the supernatant reached 0.05 EU/mL in a 1-L fermentation system, and 500 000 detecting reactions can be supported per liter of fermentation broth. This study increases the yield and activity of recombinant factor C, simplifies the procedures of protein purification, and reduces the cost, laying a foundation for the promotion and application of recombinant factor C in endotoxin detection.
Animals ; Recombinant Proteins/genetics* ; Horseshoe Crabs/chemistry* ; Baculoviridae/metabolism* ; Endotoxins/analysis* ; Protein C/biosynthesis* ; Genetic Vectors/genetics* ; Arthropod Proteins/genetics* ; Enzyme Precursors ; Serine Endopeptidases

Objective:To analyze the factors associated with non-radiographic bone erosion in gout pa-tients,to improve the understanding of bone erosion in gout,and to promote the early detection of bone erosion.Methods:A retrospective analysis was conducted on the medical records of gout patients treated at Beijing Jishuitan Hospital from January 2018 to January 2022.Bone erosion was detectable by ultra-sound but not detected by X-ray as non-radiographic bone erosion;no bone erosion was detected by both ultrasound and joint X-ray as undetected bone erosion.A case-control study was used,and the two groups were matched 1∶2 according to age and sex.The differences between the two groups were com-pared in terms of general information,joint involvement characteristics,laboratory indicators and compli-cations.In the univariate analysis,P＜0.1 was included in the multivariate analysis,and the conditional Logistic regression was used for the multivariate analysis.P＜0.05 was considered to have statistically significant differences.Results:Among the 41 patients with non-radiographic bone erosion,the top three joints with bone erosion before its occurrence were metatarsophalangeal joint(12 cases),ankle(10 ca-ses),and knee(7 cases).There were 82 patients undetected with bone erosion.There were no signifi-cant differences in general information between the two groups(P＞0.05),including age,gender,body mass index,and alcohol consumption history.The characteristics of affected joints in the non-radio-graphic bone erosion group were compared with those in the no bone erosion detected,and the former had more affected joints(P=0.02),and a higher proportion of patients with at least 3 attacks of gout per year(P＜0.001).There were no significant differences in serum uric acid,fasting blood glucose,cholesterol,triglycerides,low-density lipoprotein,high-density lipoprotein,creatinine,homocysteine,white blood cell count,and urine pH between the two groups(P＞0.05).The results of multivariate analysis showed that at least 3 flares of gout per year was an independent risk factor for radiologically negative bone erosion in patients with gout,with an OR(95％CI)of 5.139(1.529-17.271).Conclusion:At least 3 flares of gout per year predicts the occurrence of radiologically negative bone erosion,and these patients should be given more attention to achieving treatment targets.

Objective:To investigate the relationship between macrophage activation related factors and clini-cal symptoms of schizophrenia(SCZ).Methods:Outpatient or inpatient SCZ patients(n=166)and normal con-trols(n=71)meeting the diagnostic criteria of DSM 4th edition were selected as subjects.The psychopathological symptoms were assessed by the Positive and Negative Syndrome Scale(PANSS),and the concentrations of α-Na-Galases,MAF and IL-18 were determined by enzyme-linked immunosorbent assay(ELISA).The correlation be-tween biological indicators and clinical symptoms was analyzed and the mediation effect was tested.Results:The concentrations of α-NaGalases(P＜0.001)and MAF(P＜0.01)in SCZ group were lower than those in normal control group.In SCZ group,IL-18 was negatively correlated with α-NaGalases concentration(r=-0.24,P＜0.01).α-NaGalases was positively correlated with MAF concentration(r=0.67,P＜0.001),and the total score of PANSS positive symptom scale was positively correlated with IL-18(r=0.21,P＜0.05)and MAF concentration(r=0.22,P＜0.01).The mediating effect of α-NaGalases and MAF was statistically significant,and the relative mediating effect accounted for 25.47％.Conclusion:The increase of IL-18 level may indicate the occurrence of positive symptoms of schizophrenia,and α-NaGalases and MAF may negatively regulate the inflammatory damage effect of IL-18 on SCZ,thereby reducing the positive symptoms.

BACKGROUND: Chronic kidney disease (CKD) poses a major global health challenge, often foreshadowing poor patient outcomes. The C-reactive protein to albumin ratio (CAR) serves as a pivotal biomarker, demonstrating a strong correlation with adverse outcomes in cardiovascular disease (CVD). This study sought to examine the correlation between CAR and the risk of all-cause and cardiovascular mortality in patients with CKD stages 3-5. METHODS: This study utilized data of CKD patients from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010, with follow-up to December 31, 2019. The optimal CAR cutoff value was identified utilizing the method of maximally selected rank statistics. Multivariable Cox proportional hazards regression model, restricted cubic splines (RCS) model, and subgroup analysis were employed to assess the association between CAR and mortality among CKD patients. RESULTS: During a median (with interquartile range) follow-up period of 115 (112,117) months among 2,841 CKD individuals, 1,893 deaths were observed, including 692 deaths due to CVD events. Based on the RCS analysis, a non-linear correlation was observed between CAR and mortality. Using 0.3 as the optimal CAR cutoff value, the cohort was divided into high and low groups. In the fully adjusted model, CKD patients with high CAR values exhibited an elevated risk of all-cause mortality (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.28-1.83, P < 0.001) and cardiovascular mortality (HR 1.48, 95% CI 1.08-2.02, P = 0.014). Compared to the population aged >65 years (HR 1.32, 95% CI 0.99-1.76, P = 0.064), the risk of cardiovascular mortality was significantly higher in those aged ≤65 years (HR 2.19, 95% CI 1.18-4.09, P = 0.014) with elevated CAR levels. CONCLUSIONS A notable correlation exists between the elevation of CAR and increased all-cause and cardiovascular mortality, suggesting its potential as an independent indicator for evaluating the prognosis of patients with CKD stages 3-5.
Humans ; Renal Insufficiency, Chronic/epidemiology* ; Cardiovascular Diseases/blood* ; Male ; Female ; Middle Aged ; C-Reactive Protein/metabolism* ; Aged ; Biomarkers/blood* ; Nutrition Surveys ; Adult ; United States/epidemiology* ; Serum Albumin/analysis*

Our research reveals the critical role of the suprachiasmatic nucleus (SCN) vasoactive intestinal peptide (VIP) neurons in mediating light-induced transient forgetting. Acute exposure to bright light selectively impairs trace fear memory by activating VIP neurons in the SCN, as demonstrated by increased c-Fos expression and Ca²⁺ recording. This effect can be replicated and reversed through optogenetic and chemogenetic manipulations of SCN VIP neurons. Furthermore, we identify the SCN → PVT (paraventricular nucleus of the thalamus) VIP neuronal circuitry as essential in this process. These findings establish a novel role for SCN VIP neurons in modulating memory accessibility in response to environmental light cues, extending their known function beyond circadian regulation and revealing a mechanism for transient forgetting.
Animals ; Vasoactive Intestinal Peptide/metabolism* ; Male ; Mice ; Neurons/metabolism* ; Suprachiasmatic Nucleus/physiology* ; Light ; Mice, Inbred C57BL ; Memory/physiology* ; Fear/physiology* ; Suprachiasmatic Nucleus Neurons/metabolism* ; Optogenetics ; Proto-Oncogene Proteins c-fos/metabolism*

Ulcerative colitis (UC) is a chronic inflammatory disorder with a complex etiology, characterized by intestinal inflammation and barrier dysfunction. Platycodon grandiflorus polysaccharides (PGP), the primary component of Platycodon grandiflorus, and hesperidin (Hesp), a prominent active component in Citrus aurantium L. (CAL), have both demonstrated anti-inflammatory properties. This study aims to elucidate the underlying mechanism of the synergistic effect of PGP combined with Hesp on UC, focusing on the coordinated interaction between the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways. A mouse model of UC induced by dextran sulfate sodium (DSS) and a cell model using lipopolysaccharide (LPS)-induced RAW264.7/IEC6 cells were employed to investigate the in vitro and in vivo anti-inflammatory effects of PGP combined with Hesp on UC and its potential mechanism of action. The results indicated that compared to the effects of either drug alone, the combination of PGP and Hesp significantly modulated inflammatory factor levels, inhibited oxidative stress, regulated colonic mucosal immunity, suppressed apoptosis, and restored intestinal barrier function in vitro and in vivo. Further in vitro studies revealed that PGP significantly inhibited the PI3K/AKT signaling pathway, while Hesp significantly inhibited the JAK2/STAT3 signaling pathway. The use of inhibitors and activators targeting both pathways validated the synergistic effects of PGP combined with Hesp on the PI3K/AKT and JAK2/STAT3 signaling pathways. These findings suggest that PGP combined with Hesp exhibits a synergistic effect on DSS-induced colitis, potentially mediated through the phosphatase and tensin homolog (PTEN)/PI3K/AKT and interleukin-6 (IL-6)/JAK2/STAT3 signaling pathways.
Animals ; STAT3 Transcription Factor/genetics* ; Janus Kinase 2/genetics* ; Polysaccharides/administration & dosage* ; Colitis, Ulcerative/chemically induced* ; Mice ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Drug Synergism ; Male ; Hesperidin/administration & dosage* ; Platycodon/chemistry* ; Phosphatidylinositol 3-Kinases/genetics* ; Disease Models, Animal ; RAW 264.7 Cells ; Mice, Inbred C57BL

Objective:To analyze the mediating effect of cardiovascular health status (CVH) on the association between educational level and cardiovascular disease (CVD).Methods:The participants were from Shanghai Suburban Adult Cohort and Biobank, and questionnaire survey, physical examination, blood biochemistry were conducted from 2016 to 2020 for baseline information collection, and follow up was conducted until March 31, 2024 based on the medical data, CVD incidence data and death surveillance data at different levels. The associations of educational level, CVH and time to CVD onset of the study population were analyzed using the accelerated failure time model to analyze the mediating effects of CVH, health behaviors, and health factors in the association of educational level and time to CVD onset. The mediating effects of educational level, gender, and age moderated associations were also analyzed.Results:A total of 57 312 participants were included, with 2 780 new cases of CVD during a median follow-up of 6.71 (6.71-6.72) years, and a mean incidence density of 7.77/1 000 person-years (95% CI: 7.48/1 000 person-years -8.06/1 000 person-years). In total, the less educational level and the lower CVH, the higher CVD incidence density ( P<0.05). The results of accelerated failure time models showed that the time ratio for CVD-free survival was 1.15 (95% CI: 1.06-1.24) and 1.33 (95% CI: 1.10-1.60) for moderate and high educational level, respectively. The results of the mediation effect analysis showed that the association between moderate and high educational level and time to CVD onset was 29.60% (20.50%-50.00%) and 36.10% (23.80%-59.00%), 9.97% (5.07%-20.00%) and 13.84% (6.84%-29.00%), 15.24% (9.64%-27.00%) and 17.55% (11.58%-33.00%) of mediators mediated by CVH, health behaviors, health factors, respectively. Among them, there was an exposure-mediated interaction of educational level and a positive moderating effect of age. Conclusion:CVH, health behaviors and health factors had a proportionate mediating effect in the association between educational level and risk of CVD development.

This paper reviews the main contents, characteristics, applications, advantages and limitations of self-management assessment tools for hypertension patients, comparatively analyzes the basic conditions and applications of the existing assessment tools and makes suggestions, with a view to providing references for healthcare professionals in China to select, develop and apply self-management assessment tools for hypertension patients.