Adjuvants as essential ingredients amplify the magnitude and durability of immune responses in various vaccine strategies. Polysaccharides with potent immunoenhancing effects are widely applied as promising vaccine adjuvants, however, they have rarely been licensed for use in human vaccines due to the limitation of their efficacy and safety. Moreover, nanoparticles not only act as antigen drug delivery vectors but also possess intrinsic adjuvant functions, revealing the dual effects of nanoparticles in augmenting antigen-specific immune responses. Intriguingly, nanoparticle forms can enhance the immunostimulatory potency of polysaccharide adjuvants, since polysaccharide nanoparticles exert more excellent adjuvant effects than polysaccharides in initiating humoral, cellular and mucosal immune responses. Emerging evidence has also suggested that multiple immune-related signaling pathways including cGAS-STING, NLRP3, TLRs, cell death or metabolism signaling probably participate in the immunomodulation of polysaccharide nanoparticles, but systemic investigations into the adjuvant mechanism are still inadequate. This review aims to give an updated summary and discussion on the adjuvant function and mechanism of polysaccharide nanoparticles for understanding their superior adjuvant property and effectively utilizing them as potent immune adjuvants in vaccine development.

Organ fibrosis is a chronic tissue injury caused by multiple causes,and the continuous dynamic progression will lead to abnormal organ structure and function.Recent studies have shown that Chinese materia medica can inhibit organ fibrosis by regulating the PI3K/Akt pathway,which holds potential significance for developing anti-fibrosis strategies.This article systematically reviewed the role of the PI3K/Akt signaling pathway in the entire process of fibrosis,and summarized the potential mechanisms of Chinese materia medica monomers,drug pairs and compounds that can target and intervene in PI3K/Akt signaling transduction in preventing and treating organ fibrosis,in order to provide reference for the intervention of Chinese materia medica in the PI3K/Akt pathway for the treatment of organ fibrosis.

Objective:To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and 24-h urinary calcium excretion (24-h UCaE) and hypercalciuria in Chinese adults.Methods:This cross-sectional study was conducted from March 2022 to March 2023 in nine cities in China and included 1 239 residents. Demographic characteristics were collected through questionnaires and physical examinations, fasting blood samples were assessed for bone metabolism indicators, and 24-h urine samples were used to determine the 24-h UCaE. Multiple linear regression analysis was used to explore the relationship between serum 25(OH)D and 24-h UCaE and bone metabolism indexes. The relationship between serum 25(OH)D and hypercalciuria was analyzed using a multiple logistic regression model combined with restricted cubic spline modeling.Results:The mean participant age was (47.9±18.1) years, of which 453 (36.6%) were male. The percentages of vitamin D sufficiency, insufficiency, and deficiency were 7.6% (94/1 239), 29.0% (359/1 239), and 63.4% (786/1 239), respectively. The multiple linear regression model showed that after adjusting for the covariates the 24-h UCaE gradually increased with higher levels of 25(OH)D ( P overall <0.001, P nonlinear <0.001). The logistic regression analysis revealed that compared with the vitamin D deficient group, the OR for the prevalence of hypercalciuria in the vitamin D sufficient and vitamin D insufficient groups were 3.290 (95% CI 1.745 to 6.202) and 3.742 (95% CI 2.458 to 5.697), respectively. The results of the restricted cubic spline modeling showed a positive nonlinear relationship between 25(OH)D and the prevalence of hypercalciuria ( P overall <0.001, P nonlinear <0.001). The prevalence of hypercalciuria increased when 25(OH)D was >17.00 μg/L and peaked at 26.71 μg/L, after which there was a decreasing trend in the prevalence of hypercalciuria with increasing 25(OH)D. Conclusion:Associations between serum 25(OH)D levels and urinary calcium excretion and the prevalence of hypercalciuria were observed in the Chinese adult population.

Objective:To investigate the longitudinal stability of the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the Activity of Daily Living Scale (ADL).Methods:The longitudinal cognitive assessment results of 68 dementia patients admitted to the Dementia and Leukoencephalopathy Outpatient Clinic, Department of Neurology, Peking Union Medical College Hospital, from January 2021 to January 2024, were retrospectively analyzed, including the total and sub-items scores of the MMSE, MoCA, and ADL. Two different rules were applied to analyze the abnormality rates: rule 1, where the current test result being better than the previous one was considered an abnormality; rule 2, where the current test result being better than the previous average score was considered an abnormality (If a patient had only 2 cognitive assessments, rule 2 was considered the same as rule 1). Two rules were used to analyze the abnormality rates of the scales. The statistical analyses were repeated after excluding patients with possible anxiety and depression status.Results:In assessing the total score stability, MMSE showed the lowest abnormality rates [27.2% (31/114) under rule 1 and 29.8% (34/114) under rule 2], while MoCA had the highest abnormality rates [41.3% (26/63) and 46.0% (29/63), respectively]. The ADL abnormality rates were 27.7% (23/83) and 33.7% (28/83), respectively. Among MoCA sub-items, category cue, multiple choice cue, second memory trial, orientation, and clock showed higher abnormality rates [31.7%(20/63), 30.2%(19/63), 23.8%(15/63), 22.2%(14/63), 22.2%(14/63), respectively]. After excluding population with possible anxiety and depression status, the relative abnormality rates of MMSE and ADL sub-items did not significantly change, while the abnormality rate of orientation in MoCA sub-items decreased relatively.Conclusion:The MMSE and ADL exhibit good stability in long-term monitoring of dementia patients, serving as essential tools for assessing and following up cognitive changes.

OBJECTIVES: This study aimed to investigate the potential mediating role of plasma phosphorylated tau217 (p-tau217) in the association between periodontitis and mild cognitive impairment (MCI). METHODS: In this case-control study, patients diagnosed with MCI in the Neurology Department of the First Affiliated Hospital of Shandong Second Medical University from November 2023 to May 2024 were selected as the case group (MCI group). Cognitively normal (CN) volunteers, matched for age and education level and recruited from the physical examination center during the same period, served as the control group (CN group). The general demographic data of the study participants were collected. The Beijing versions of the Montreal Cognitive Assessment (MoCA), clinical dementia rating (CDR), and activities of daily living scale (ADL) were used to assess neuropsychological functions. Clinical periodontal examinations were conducted, the periodontal inflamed surface area (PISA) was calculated, and the periodontitis stage was determined in accordance with the 2018 classification. Fasting elbow venous blood samples were collected in the morning, and blood biochemical indicators were measured. Plasma p-tau217 levels were detected using enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using t-test, Mann-Whitney U test, chi-square test, partial correlation analysis, multivariate Logistic regression analysis, multiple linear regression analysis, restricted cubic spline (RCS) regression analysis, and mediation effect analysis. RESULTS: Among the 192 participants, 96 belong to the MCI group and 96 to the CN group. The prevalence of periodontitis was 63.5% in the MCI group and 43.8% in the CN group, with a statistically significant difference (χ²=7.561, P=0.006). The plasma p-tau217 levels in the MCI group were significantly higher than those in the CN group [7.00 (4.27-9.65) ng/mL versus 2.02 (0.80-3.81) ng/mL, Z=-8.108, P<0.001]. Partial correlation analysis revealed that plasma p-tau217 levels were positively correlated with all the clinical periodontal indices (all P<0.001). After adjustments for baseline covariates, multivariate Logistic regression indicated that periodontitis was an independent risk factor for MCI. Patients with periodontitis had a 1.977-fold higher MCI risk than those without periodontitis (OR=1.977, 95%CI: 1.088-3.594, P=0.025). Moreover, the MCI risk for stage Ⅰ/Ⅱ periodontitis and stage Ⅲ/Ⅳ periodontitis was 1.878 times (OR=1.878, 95%CI: 1.029-3.425, P=0.040) and 2.625 times (OR=2.625, 95%CI: 1.073-6.246, P=0.035) higher than that for patients without periodontitis, respectively. Trend test showed that the MCI risk increased with periodontitis severity (P_trend=0.016). After adjustments for baseline covariates, multiple linear regression analysis showed that periodontitis was an independent risk factor for increased plasma p-tau217 levels (β=3.309, 95%CI: 2.363-4.254, P<0.001). Compared with patients without periodontitis, those with stage Ⅰ/Ⅱ periodontitis (β=1.838, 95%CI: 0.869-2.806, P<0.001) and stage Ⅲ/Ⅳ periodontitis (β=5.539, 95%CI: 4.442-6.636, P<0.001) had significantly higher plasma p-tau217 levels. In addition, trend test indicated that plasma p-tau217 levels increased with periodontitis severity (P_trend<0.001). After adjustments for baseline covariates, RCS regression analysis further revealed that PISA had a positive linear dose-response relationship with MCI risk (P_overall=0.002, P_nonlinear=0.344) and plasma p-tau217 levels (P_overall<0.001, P_nonlinear=0.140). After adjustments for baseline covariates, mediation analysis showed that plasma p-tau217 mediated the association between periodontitis and MCI, with a mediation proportion of 13.99% (95% Bootstrap CI: 0.38%-49.39%, P=0.038). CONCLUSIONS Periodontitis was independently positively associated with MCI risk, and plasma p-tau217 plays a mediating role in this association.
Humans ; Cognitive Dysfunction/complications* ; tau Proteins/blood* ; Periodontitis/complications* ; Case-Control Studies ; Male ; Female ; Phosphorylation ; Aged ; Middle Aged ; Activities of Daily Living

Objective:To analyze the effect of long noncoding RNA (lncRNA) small nucleolar RNA host gene 16 (SNHG16) on the radiosensitivity of cervical cancer cells and explore its regulatory role in the miR-455-3p/ nuclear factor-κB (NF-κB) signaling pathway.Methods:The expression levels of lncRNA SNHG16 and miR-455-3p in human normal cervical epithelial cells H8, human cervical cancer cells SiHa, and radioresistant cervical cancer cells SiHa-R were detected by real-time reverse transcription polymerase chain reaction. SiHa-R cells were transfected separately, and then given a single dose of 4 Gy X-ray irradiation and continued to be cultured for subsequent experiments. The cells in each group were named siRNA-NC, siRNA-SNHG16 (interfering lncRNA SNHG16), NC mimic, miR-455-3p mimic (overexpressing miR-455-3p), siRNA-SNHG16+inhibitor NC, and siRNA-SNHG16+miR-455-3p inhibitor groups, respectively. The survival fraction of SiHa-R cells was detected by clone formation assay. The apoptosis rate of SiHa-R cells was analyzed by flow cytometry. The expression levels of apoptotic proteins [cysteine-containing aspartate-specific protease (Caspase)-3, Caspase-9, Bax] and NF-κB signaling pathway related proteins [NF-κB p65, phosphorylated (p)-NF-κB p65, p-IκB (inhibitory protein of NF-κB)] were measured by Western blot. The targeting relationship between lncRNA SNHG16 and miR-455-3p was determined by dual luciferase reporter gene assay. Comparison among different groups was conducted by one-way ANOVA, and paired comparison was carried out by LSD t-test. Comparison between two groups was performed by t-test. Results:Compared with H8 cells, the expression levels of lncRNA SNHG16 were increased in SiHa and SiHa-R cells, and SiHa-R cells had a higher level than SiHa cells. The expression levels of miR-455-3p were decreased in SiHa and SiHa-R cells, and SiHa-R cells had a lower level than SiHa cells (all P<0.001). Compared with the siRNA-NC group, the survival fraction of SiHa-R cells in the siRNA-SNHG16 group was decreased, the radiosensitization ratio (SER) was 1.571 (>1), the apoptosis rate and levels of Caspase-3, Caspase-9, and Bax proteins were increased, while the levels of p-NF-κB p65 and p-IκB proteins were decreased (all P<0.001). lncRNA SNHG16 could target miR-455-3p. Compared with the NC mimic group, miR-455-3p level in the miR-455-3p mimic group was increased, cell survival fraction was decreased, the SER was 1.826 (>1), the apoptosis rate and the levels of Caspase-3, Caspase-9, Bax proteins were increased, and the levels of p-NF-κB p65 and p-IκB proteins were decreased (all P<0.001). Inhibition of miR-455-3p expression could weaken the effect of interfering with lncRNA SNHG16 expression on SiHa-R cell apoptosis, radiotherapy sensitivity, and NF-κB signaling pathway (all P<0.001). Conclusions:Interference with lncRNA SNHG16 expression could induce the apoptosis of cervical cancer cells and enhance their radiation sensitivity by regulating the miR-455-3p/NF-κB signaling pathway.

Objective:To investigate effect of esketamine combined with ultrasound-guided stellate ganglion block(SGB)on stress response and postoperative immune function in elderly patients undergoing colorectal resection.Methods:A retrospective analy-sis was conducted in clinical data from 70 cases of elderly patients undergoing elective colorectal resection in Xuzhou Hospital of Tradi-tional Chinese Medicine,Nanjing University of Chinese Medicine from September 2020 to April 2022,who were randomly divided into observation group(n=35)and control group(n=35),control group was treated with ultrasound-guided SGB,observation group was treated with esketamine combined ultrasound-guided SGB.Heart rate(HR),mean arterial pressure(MAP),product of heart rate and systolic blood pressure(RPP)and stress response levels[cortisol(CORT),SOD,MDA,IL-6,TNF-α,IL-1β]were compared between two groups at 5 min before SGB(t0),immediately after tracheal intubation(t1),1 h after operation(t2)and end of operation(t3).CD3+T,CD4+T,CD8+T and CD4+T/CD8+T at t0,t3,24 h after operation(t4)and 72 h after operation(t5)were compared,respec-tively.Recovery time,first exhaust time,bowel sound recovery time and first oral feeding time and incidence of adverse reactions during anesthesia were compared between two groups.Results:HR,MAP,RPP,CORT,SOD,MDA,IL-6,TNF-α,IL-1β,CD3+T,CD4+T,CD8+T and CD4+T/CD8+T at different time points in two groups were compared by repeated measures analysis of variance,and there were significant differences between groups and at different time points(P<0.05).Compared with control group,observation group had shorter recovery time,first exhaust time,bowel sound recovery time,first oral feeding time,postoperative time out of bed(P<0.05),and less intraoperative pain medication consumption,incidence of adverse reactions during anesthesia was reduced[48.57%(17/35)vs 25.71%(9/35),P<0.05].Conclusion:Esketamine combined with ultrasound-guided SGB in elderly patients undergoing enterectomy can promote recovery of postoperative gastrointestinal function,reduce perioperative stress response,has little impact on immune function of patients,reduce perioperative adverse reactions.

Objective:To investigate ferroptosis-related genes in pterygium tissue by using bioinformatic analysis.Methods:The pterygium gene expression profile dataset GSE2513 was downloaded from the Gene Expression Omnibus Database to identify differentially expressed genes (DEGs) related to ferroptosis.Functional annotation and enrichment analysis of the DEGs were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG).Hub genes were identified from the DEGs using LASSO logistic regression analysis and a support vector machine recursive feature elimination (SVM-REF).Single-gene GSEA analysis was performed on hub genes and a competitive endogenous RNA interaction network was constructed to determine the RNA regulatory relationships of the hub genes.Pterygium tissue samples from 9 patients (9 eyes) undergoing pterygium surgery and conjunctival tissue samples from 9 patients (9 eyes) undergoing strabismus surgery who visited the First Affiliated Hospital of Zhengzhou University were collected from 2022 to 2023 during surgery, and the expression of hub genes and ferroptosis-related marker genes was detected by fluorescence quantitative PCR.This study followed the Declaration of Helsinki, and the study protocol was reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (No.2022-KY-0006-001).Results:In the dataset, there were 37 ferroptosis-related genes with significant expression differences, including 16 upregulated genes and 21 downregulated genes.GO analysis revealed significant enrichment in responses to external stimuli, responses to nutritional levels, responses to extracellular stimuli, responses to oxidative stress and starvation, transcription regulatory complexes, and RNA polymerase Ⅱ transcription regulatory complexes, RNA polymerase Ⅱ-specific transcription, and DNA-binding transcription.KEGG analysis showed that the DEGs were primarily enriched in ferroptosis and NOD-like receptor signaling pathways.LASSO regression analysis identified DUOX2, ATF3, NDRG1, EGR1, and ALDH3A2 as hub genes, and SVM-REF analysis identified NDRG1, NF2, IDH2, DUOX2, CHP1, ATF3, and SREBF1 as hub genes. DUOX2, ATF3, and NDRG1 were identified as the intersection hub genes.Single-gene GSEA analysis revealed that DUOX2 was enriched in the cell adhesion molecule CAMs pathway, the heparan sulfate glycosaminoglycan biosynthesis pathway, and the glycosaminoglycan biosynthesis ganglioside series pathway. ATF3 and NDRG1 were enriched in the PPAR signaling pathway and other pathways.Compared with normal conjunctival tissue, the relative expression levels of the ferroptosis markers PTGS2 and TFRC mRNA were increased in pterygium tissue, while the relative expression levels of FTH1, GPX4, SLC40A1, HSPB1, and NFE2L2 mRNA were decreased, with statistically significant differences ( t=12.220, 16.580, 5.664, 6.455, 8.691, 9.883, 17.590; all P<0.01). Conclusions:Ferroptosis may play an important role in the pathogenesis of pterygium. DUOX2, ATF3, and NDRG1 may be the hub genes affecting this complicated process.