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.

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

AIM: To determine the patient-related risk factors for pain during phacoemulsification.METHODS: Retrospective case-control study. A total of 62 patients(62 eyes)diagnosed as cataract in the First Affiliated Hospital of Zhengzhou University from December 2023 to January 2024 were included. The numeric rating scale was used to assess the pain level within 5 min postoperatively. The highest pain value was used as the primary outcome during the procedure. Based on pain values, patients were divided into pain group(n=25)and pain-free group(n=37). Subsequently, patients in the pain group were further divided into mild(n=16), moderate(n=7), and severe groups(n=2). Spearman correlation and Logistic regression analysis were conducted to determine risk factors for pain during the phacoemulsification.RESULTS: Binary Logistic regression showed preoperative sleep durations and times of operations were important risk factors for intraoperative pain(all P<0.05). Spearman analysis showed that intraoperative pain was negatively correlated with sleep duration(rs=-0.386, P=0.002), and positively correlated with times of operations(rs=0.421, P<0.001). The results of the ordinal Logistic regression analysis showed that for every additional hour of sleep, the likelihood of experiencing one higher level of intraoperative pain decreased by 37.60%(OR=0.376, P=0.014). In contrast, the times of operations did not show a statistically significant difference(P=0.083). Receiver operating characteristic curve showed a joint prediction model of sleep duration and operative times with an area under the curve of 0.809, 84% sensitivity, and 73% specificity.CONCLUSION: The intraoperative pain during phacoemulsification is negatively correlated with sleep duration and positively correlated with times of operations.

OBJECTIVE To study the effect of fluoropezil on embryo-fetal developmental toxicity and toxicokinetics in rabbits,and provide reference for clinical medication.METHODS According to the sequence of pregnancy,pregnant rabbits were divided into five groups:vehicle control group(1%hydroxy-propyl methylcellulose+1.5%polyethylene glycol 400 aqueous solution),positive control group(cyclo-phosphamide 18 mg·kg-1),and fluoropezil(3.6,9.0 and 22.5 mg·kg-1)groups.The vehicle control group and the fluoropezil groups were ig administrated on the 6th to 18th day of gestation(GD6-18)while the positive control group was ig given cyclophosphamide on GD6-20.The pregnant rabbits were sacri-ficed on GD28,and the embryo-fetal development was detected.Sex hormone levels of pregnant rabbits on GD5,GD18 and GD28 were detected by ELISA method.Blood samples with toxokinetics were collected for concomitant toxic generation at the first and last administration,and drug concentrations in fetal,placenta and amniotic fluid were detected with liquid chromatography tandem mass spectrometry(LC-MS/MS).RESULTS Fluoropezil 3.6,9.0 and 22.5 mg·kg-1 had no significant effect on body mass,mass gain,food consumption,pregnancy outcomes,fetal appearance,viscera,skeletal and physical growth and development of pregnant rabbits.Only on GD18 or GD28,the levels of follicle stimulating hormone,estra-diol and progesterone in each dose group fluctuated to some extent.The combined toxokinetics results indicated that fluoropezil could cross the placental barrier of the rabbits,but did not accumulate in preg-nant rabbits or fetuses.Fetal mass,crown-rump length and uterus mass in the cyclophosphamide group were lower than those in the vehicle control group.The appearance and bone of the cyclophos-phamide group were positive.CONCLUSION The no observed adverse effect level(NOAEL)of fluoro-pezil toxicity on rabbit embryo-fetal development is 22.5 mg·kg-1,which is 125 times of the effective dose.At the dosage level of 22.5 mg·kg-1,Cmax is 1093 μg·L-1,and AUC(0-24 h)6650 μg·h·L-1 on GD18.

Objective:To develop an Enteral Nutrition Knowledge, Attitude and Practice Questionnaire for ICU Nurses in Prone Position Ventilation Patients, and test its reliability and validity.Methods:Based on the theory of knowledge, attitude and practice, the item pool was initially constructed through literature review, group discussions, and semi-structured interviews. The initial questionnaire was formed through two rounds of Delphi expert consultation, and the initial questionnaire items were adjusted based on semi-structured interviews. From November to December 2023, convenience sampling was used to select 254 ICU nurses from six Class Ⅲ Grade A hospitals in Henan Province to test the reliability and validity of the questionnaire. Project analysis method was used for item screening, exploratory factor analysis and expert consultation method were used to evaluate the validity of the questionnaire, and internal consistency coefficient, split half reliability, and test-retest reliability were used to evaluate the reliability of the questionnaire.Results:The Enteral Nutrition Knowledge, Attitude and Practice Questionnaire for ICU Nurses in Prone Position Ventilation Patients was divided into three levels, with a total of 7 dimensions and 30 items. The knowledge level included three dimensions and 12 items, the attitude level consisted of three dimensions and 8 items, and the practice level includes one dimension and 10 items. Exploratory factor analysis proposed 7 common factors with a cumulative variance contribution rate of 65.516%. The content validity index at the questionnaire level was 0.92, and the content validity index at the item level was 0.80 to 1.00. The overall Cronbach's α coefficient of the questionnaire was 0.874, the split half reliability coefficient was 0.813, and the test-retest reliability coefficient was 0.989.Conclusions:The Enteral Nutrition Knowledge, Attitude and Practice Questionnaire for ICU Nurses in Prone Position Ventilation Patients has good reliability and validity, and can be used as an evaluation tool for ICU nurses to assess the knowledge, attitude, and practice of enteral nutrition for prone position ventilation patients.

The clinical data of one child with metanephric stromal tumor (MST) and BRAF V600E gene mutation admitted to the First Affiliated Hospital of Zhengzhou University in June 2022 was analyzed retrospectively.Literature was reviewed.The patient, a 2-year-old girl, was diagnosed with a tumor in the left abdomen.The maximum diameter of the tumor was 10.5 cm.A radical nephrectomy was performed on the left kidney, and postoperative pathology revealed MST.Microscopically, the tumor had no envelope and exhibited expansive growth.The tumor cells were fusiform or stellate, and nuclear division was visible in the cell-rich region.Dysplastic blood vessels were seen inside the tumor.The tumor cells around the blood vessels and invaginated renal tubules were arranged like onion skin.CD34 was detected positive by immunohistochemical staining, and BRAF V600E mutation was also detected positive by fluorescent polymerase chain reaction.A total of 21 relevant case reports were retrieved, including 16 in English and 5 in Chinese.Fifty-eight MST patients, including the one in this report were analyzed.These patients were aged 2 days to 15 years, with a median age of 2 years.Except for 2 patients with unknown sex, the ratio of male to female was about 1.4∶1.0.Most MST patients were asymptomatic, with an average tumor size of 5.3 cm.The tumor cell CD34 showed positive expression in different degrees.Eight patients received the BRAF V600E mutation detection, and the results were all positive.Fifty-eight patients underwent nephrectomy and were followed up for 0-156 months, of which 7 patients were assisted with radiotherapy and chemotherapy.During the follow-up, 1 patient died, and 1 patient had a relapse.MST is a rare benign renal stromal tumor. BRAF V600E mutations are detected in a variety of malignancies.This paper is the first to report MST with BRAF V600E mutation in China and points out the importance of molecular detection of BRAF mutation for accurate diagnosis of MST.

Objective:To explore the clinical features and genetic etiology of a child with Central core disease (CCD).Methods:A child with CCD who was treated at the Children′s Hematology Department of the First Affiliated Hospital of Zhengzhou University in February 2022 was selected as the study subject. Muscle biopsy was performed. Peripheral blood samples were collected from the child and his parents for the extraction of genomic DNA. The child was subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing.Results:The child, a 12-year-old boy, had manifested motor retardation, facial weakness, ptosis, pectus carinatum, scoliosis, etc. Muscle biopsy showed that the central nucleus muscle fibers and atrophic muscle fibers were mainly type I. WES revealed that the child has harbored c. 10561G>A (p.G3521S) and c. 3448T>C (p.C1150R) compound heterozygous variants of the RYR1 gene. Sanger sequencing confirmed that they were inherited from his mother and father, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were considered as likely pathogenic (PS4+ PM1+ PM2_Supporting+ PP3; PM1+ PM2_Supporting+ PM3+ PP3). Conclusion:By combining his clinical manifestation and results of muscle pathology and genetic testing, the child was diagnosed with CCD, which may be attributed to the c. 10561G>A (p.G3521S) and c.3448T>C (p.C1150R) compound heterozygous variants of the RYR1 gene.

Tuberculosis is caused by Mycobacterium tuberculosis,and the problem of its drug resistance has become increasingly prominent in recent years,attracting widespread attention globally.Currently,the situation of drug-resistant tuberculosis is grim,and effective strategies are urgently needed to deal with it.Understanding the drug resistance mechanism and treatment status of drug-resistant tuberculosis can provide an important basis for clinical prevention and treatment of drug-resistant tuberculosis.This paper reviews the progress of drug resistance mechanism and treatment of drug-resistant tuberculosis,in order to provide a reference for clinical intervention.