BACKGROUND:In recent years,with the rapid development of biomedicine,the study of brain aging and exosomes has attracted more and more attention,but there is no bibliometrics analysis in this field. OBJECTIVE:To objectively analyze domestic and foreign literature on brain aging and exosomes in the past 15 years,to summarize the research status,hot spots,and development trends in this field. METHODS:Using the core database of Web of Science as a search platform,we downloaded the literature on brain aging and exosomes published from the establishment of the database to December 28,2022,and analyzed the data from the aspects of country or region,institution,author,keywords,and co-cited literature using CiteSpace 6.1.R6 visualization software. RESULTS AND CONCLUSION:A total of 1 045 research articles were included,and the number of publications on brain aging and exosomes research both domestically and internationally was showing an increasing trend year by year.The United States ranked first with 429 papers,and China ranked second with 277 papers.Louisiana State University ranked first with 16 articles.Professor Lukiw Walter J from Louisiana State University in the United States was the author with the highest number of publications,and Professor Bartel DP from the Massachusetts Institute of Technology was the author with the most citations.The most prolific Journal was the International Journal of Molecular Sciences.Alzheimer's disease,microRNA,gene expression,extracellular vesicles,exosomes,oxidative stress,and biomarkers are the most relevant terms.According to the research on hot topics,biomarkers have become a new research hotspot.The above results indicate that the research on brain aging and exosomes has gradually increased in the past 15 years.The research direction has gradually shifted from the initial exploration of the expression of miRNAs in central nervous system diseases related to brain aging to the search for biomarkers that can identify and diagnose neurodegenerative diseases.The study of exocrine miRNAs to protect central nervous system from damage has emerged as promising therapeutic strategy.

Objective: To compare and analyze the antibacterial effects of platelets against five common clinical pathogenic bacteria including MRSA, SE, SA, E. coli, and CRKP, and to preliminarily explore the role of DCD sensitivity in the observed variations of antibacterial effects. Methods: The same number of platelets were used to establish co-culture systems of platelets and platelet lysates with the five pathogenic bacteria. The antibacterial effects of platelets and platelet lysates on the five pathogenic bacteria were evaluated by observing the turbidity of the bacterial solution, measuring the OD value of the bacterial solution and counting the colonies. The supernatant protein of platelets co-cultured with MRSA was collected for quantitative proteomics analysis to explore the important antibacterial proteins of platelets. The content of DCD in the supernatant after co-culture of platelets and platelet lysates with the five pathogenic bacteria was detected by ELISA to preliminarily analyze the reasons for the different antibacterial effects of platelets on the five pathogenic bacteria. Results: Compared with the control group of MRSA, SA, and SE, the turbidity of the bacterial solution decreased after co-culture of platelets and platelet lysates with MRSA, SA, and SE for 12 h, and the OD value and colony count were significantly reduced (P<0.05). The turbidity of the bacterial solution did not change significantly after co-culture of platelets and platelet lysates with E. coli for 24 h, but the OD value decreased (P<0.05), and the colony count decreased to 10 CFU/mL but the difference was not statistically significant (P>0.05). Compared with the control group of CRKP, the turbidity, OD value, and colony count of the bacterial solution did not change significantly after co-culture of platelets and platelet lysates with CRKP (P>0.05). Proteomics results showed that after co-culture with MRSA, important proteins related to platelet activation, including collagen, fibrinogen, von Willebrand factor, integrin αIIbβ3, platelet glycoprotein V and IV were significantly up-regulated. ELISA results showed that after co-culture with the five pathogenic bacteria, platelets could secrete a large amount of DCD, with the content around 3 μg/mL. Conclusion: The antibacterial effect of platelets on Gram-positive bacteria MRSA, SA, and SE is better than that on Gram-negative bacteria E. coli and CRKP, and platelets have the best antibacterial effect on MRSA. The differences in antibacterial effects of platelets on the five pathogenic bacteria may be related to the sensitivity of DCD antibacterial peptides to the five pathogenic bacteria.

Objective This study aimed to identify PAX9 variants in non-syndromic tooth agenesis families of Chi-na,as well as to analyze the genotype-phenotype of non-syndromic tooth agenesis caused by PAX9 variants,which can provide a basis for the genetic diagnosis of tooth agenesis.Methods We collected the data of 44 patients with non-syn-dromic oligodontia who underwent treatment at Stomatological Hospital of Hebei Medical University between 2018 and 2023.Whole-exome sequencing was performed on the peripheral blood of the proband and its core family members,and the variants were verified by Sanger sequencing.Pathogenicity analysis and function prediction of the variants were per-formed using bioinformatics tools.The correlation between the genotype of PAX9 variant and its corresponding pheno-type was examined by reviewing 55 publications retrieved from PubMed.The studies involved 232 tooth agenesis pa-tients with PAX9 variants.Results A novel PAX9 c.447delG(p.Pro150Argfs*62)and a reported PAX9 c.406C>T(p.Gln136*)were identified in two Chinese families.Through bioinformatics analysis and three-dimensional structural mod-eling,we postulated that the frameshift variant was pathogenic.The outcome was the premature cessation of PAX9 pro-tein,which caused severe structural and functional deficiencies.Summarizing the PAX9 genotype-phenotype relationship revealed that patients carrying the PAX9 variant commonly led to loss of the second molars.Conclusion We identified the novel PAX9 c.447delG(p.Pro150Argfs*62)in a Chinese family of non-syndromic oligodontia,expanding the known variant spectrum of PAX9.The most susceptible tooth position for PAX9 variants of tooth agenesis was the second mo-lars and the deciduous molars during the deciduous dentition.

ObjectiveTo observe the clinical effectiveness and safety of Sanjie Waifu Formula （散结外敷方） application therapy for benign thyroid nodules of qi constraint and phlegm obstruction syndrome. MethodsEighty patients with benign thyroid nodules of qi constraint and phlegm obstruction syndrome were randomly divided into 40 cases each in a treatment group and a control group. The control group was given health education and follow-up observation， while the treatment group applied Sanjie Waifu Formula externally on the basis of the control group，6~8 h each time ， once a day. Both groups took 30 days as a course， and were observed for 3 consecutive courses. The main effectiveness indexes of both groups were compared before and after treatment， including the volume of thyroid nodules， the maximum diameter of the largest nodule， the scores of traditional Chinese medicine （TCM） syndrome， and the secondary effectiveness indexes of serum thyroid function including free triiodothyronine （FT₃）， free thyroxine （FT₄）， thyrotropin （TSH） levels were also observed. The effectiveness of the TCM syndrome of both groups was compared after treatment. Meanwhile， the safety indexes were observed before and after treatment， such as the blood routine， liver and kidney function indexes， and the occurrence of adverse reactions during the study was recorded. ResultsCompared with in group before treatment， the volume of thyroid nodules， the maximum diameter of the largest nodule， and the TCM symptom scores were lowered in both groups after treatment （P＜0.05 or P＜0.01）. Comparing between groups after treatment， the difference in thyroid nodule volume was not statistically significant （P＞0.05）， but the maximum diameter of the largest nodule and the TCM symptom scores of the treatment group were lower than those of the control group （P＜0.01）. The total effective rate of TCM syndrome in the treatment group was 77.50% （31/40）， which was significantly higher than that of the control group with 52.5% （21/40， P＜0.01）. Thyroid function， blood routine and liver and kidney function indexes of both groups before and after treatment were compared between and within groups， and the differences were not statistically significant （P＞0.05）， and they were all within the normal range. During the treatment period， no allergic reactions such as skin itching， red rash and blisters occurred in the treatment group. ConclusionThe external application of Sanjie Waifu Formula can improve the clinical symptoms of patients with benign thyroid nodules， reduce volume and the maximum diameter of nodules， and has no significant effects on thyroid function and show good safety.

Objective:To construct and purify four respiratory syncytial virus (RSV) PreF proteins through gene sequence design and optimization and evaluate their immunogenicity.Methods:Coronin-1A and T4 trimer protein gene sequences were optimized with Human and CHO codons, and then added to RSV F protein sequence. The above plasmids were transfected into Expi293F cells for protein expression. After purification by nickel column, four trimer proteins were prepared. SDS-PAGE and Western blot were performed for protein identification. BALB/c mice were immunized at week 0 and week 3, and blood samples were collected to measure the activities of binding and neutralizing antibodies in serum.Results:SDS-PAGE and Western blot showed that the four proteins had stable trimer structure. Antigen-antibody affinity test showed that the four trimer proteins had strong affinity with RSV-specific monoclonal antibodies 8897, D25, Motavizumab, AM14 and Palivizumab. The titers of antibodies induced by the two T4 trimers were higher after the initial immunization, while there was a substantial increase in the titers of antibodies induced by Human codon-optimized trimer protein after the second immunization.Conclusions:PreF trimer protein can be prepared by adding any of the two different heterotrimer motifs, and induce effective binding and neutralizing antibodies in mice.

Objective:To understand the potential categories of e-health literacy of elderly diabetic patients in community, and analyze the relationship between each category and physical activity level, in order to provide theoretical basis for formulating intervention measures to improve e-health literacy of elderly diabetic patients.Methods:This study was across-sectional survey. Elderly diabetic patients from 3 community health service centers in Fenyang City, Shanxi Province were selected by convenient sampling method from January to June 2023. General data questionnaire, e-Health Literacy Scale and International Physical Activity Questionnaire were used to investigate the elderly diabetic patients. Mplus8.0 was used for potential profile analysis, and SPSS 26.0 software was used to compare the differences in physical activity levels among different categories of e-health literacy.Results:Totally 248 elderly diabetes patients in the community aged 60-88 (63.8 ± 6.4) years, 135 males (54.4%) and 113 females (45.6%). The e-health literacy scores of 248 elderly diabetic patients in community were (17.70 ± 5.30), which could be divided into three potential categories: general low literacy group (56.0%, 139/248), high evaluation ability-medium literacy group (18.2%, 45/248) and high access ability-high literacy group (25.8%, 64/248). Three potential categories of physical activity levels were (1 464.74 ± 190.37), (2 094.40 ± 139.70), (2 368.44 ± 157.27) metabolic equivalent-min per week, and the difference was statistically significant ( F=118.83, P<0.001). Conclusions:The e-health literacy of elderly diabetic patients in community can be divided into three potential categories, and the physical activity level of patients with different e-health literacy categories is different. It is suggested that targeted intervention should be conducted based on the homogenous group of elderly diabetic patients with e-health literacy to improve their physical activity level.

Objective:To investigate the symptoms and symptom clusters of elderly stroke patients in the acute phase, analyze the factors influencing the symptom clusters and to provide a basis for the implementation of targeted symptom management in elderly stroke patients.Methods:Convenience sampling method was used to select 257 acute-phase elderly stroke patients who attended Fenyang Hospital in Shanxi Province from October 2022 to January 2023, and a cross-sectional survey was conducted by the General Information Questionnaire, Memory Symptom Evaluation Inventory, Modified Barthel Index Scale (MBI), and the National Institutes of Health Stroke Scale (NIHSS), and the symptom clusters were extracted by means of exploratory factor analysis, and the factors influencing symptom clusters were explored by means of binary logistic regression analysis.Results:Of the 257 patients, 138 were male and 119 were female, aged 60 to 90 (70.34 ± 6.94) years old. Factor analysis yielded four symptom clusters, which were named oral-intestinal symptom cluster, negative emotional symptom cluster, fatigue symptom cluster, and perceptual symptom cluster according to the symptom characteristics; regression analysis showed that: stroke site and NIHSS scores were the influencing factors of the oral-intestinal symptom cluster (all P<0.05); per capita monthly family income, number of episodes and MBI scores were the influencing factors of the negative emotional symptom cluster (all P<0.05); number of chronic diseases, type of stroke, and gender were the influencing factors of the fatigue emotional symptom cluster (all P<0.05); and literacy and stroke site were influencing factors of the perception symptom cluster (all P<0.05). Conclusions:Elderly stroke patients in the acute phase of the existence of more symptoms, symptoms interact with each other to form symptom clusters, health care personnel should be symptom clusters as a unit, the implementation of interventions for their influencing factors, effective symptom management, in order to improve the quality of life of patients.

Objective To investigate the genetic causes of auditory neuropathy with optic atrophy in a family.Methods The proband's medical history and family history were inquired in detail,and relevant clinical examina-tions were performed to confirm the diagnosis of auditory neuropathy with optic atrophy,and the genetic pedigree of the family was drawn.Peripheral blood of proband(Ⅲ-7)was collected for whole exome sequencing,and the patho-genicity of the detected mutations were interpreted.Blood samples of proband's wife(Ⅲ-8),eldest daughter(Ⅳ-7),second daughter(Ⅳ-9)and son(Ⅳ-10)were tested for mutation sites by Sanger sequencing.Combined with clinical manifestations and examination results,the family was studied.Results The genetic pattern of this family was autosomal dominant.The proband showed decreased visual acuity at the age of 19,bilateral sensorineural deaf-ness at the age of 30,and decreased speech recognition rate.Among 20 members of the family of 5 generations,10(2 deceased)showed similar symptoms of hearing and visual impairment.Proband(Ⅲ-7),eldest daughter(Ⅳ-7)and son(Ⅳ-10)underwent relevant examination.Pure tone audiometry showed bilateral sensorineural deafness.ABR showed no response bilaterally.The 40 Hz AERP showed no response in both ears.OAE showed responses in some or all of the frequencies.No stapedial reflex was detected.The eye movement of Ⅲ-7 and Ⅳ-10 were reasona-ble in all directions,and color vision was normal.Ocular papilla atrophy was observed in different degrees in fundus examination.OCT showed thinning of optic disc nerve fibers in both eyes,and visual evoked potential showed pro-longed P100 wave peak.They were diagnosed as hereditary auditory neuropathy with optic atrophy.A mutation of the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)at a pathogenic locus on chromosome 3 was detected by whole exon detection in Ⅲ-7.The results of generation sequencing analysis showed that the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)mutation of chromosome 3 was also found in Ⅳ-7 and Ⅳ-10.Meanwhile,the gen-otypes of Ⅲ-8 and Ⅳ-9 were wild homozygous,that is,no mutation occurred.Conclusion The OPA1 c.1334G＞A(p.Arg445His,NM_015560.2)mutation site might be the pathogenic mutation in this family.

AIM: To investigate the effects of hypobaric hypoxia in plateau on tear indexes and related anatomical structures in rabbits.METHODS: A total of 18 healthy New Zealand rabbits were selected and randomly divided into plateau group and control group, with 9 rabbits(18 eyes)in each group. The plateau group was housed in the Simulated Climate Cabin for Special Environment of Northwest of China, simulating hypobaric hypoxia at an altitude of 6 000 m. The control group was housed in a clean animal room with atmospheric pressure and oxygen. Changes in the tear meniscus height and non-invasive tear break-up time were detected by using RHCT-1 corneal topographer dry eye comprehensive analysis system, changes in tear secretion was measured by Schirmer Ⅰ test, before intervention and on the 3, 7 d, 2 and 4 wk. Meanwhile, the changes in tear composition before and after intervention in the plateau environment were analyzed using Raman Spectroscopy. The histopathological changes of the lower lid conjunctiva, cornea, lacrimal gland, and Hardarian gland were observed by hematoxylin-eosin(HE)staining after 4 wk of intervention, and the expression of mucin 5AC(MUC5AC)in conjunctiva was detected by immunohistochemistry.RESULTS: Compared with the control group, Schirmer Ⅰ test, tear meniscus height, first and average non-invasive tear break-up time in the plateau group decreased significantly since 3 d, and the difference was significant with the extension of observation time(P<0.05). The above indexes increased from 2 wk. After 4 wk of intervention, the protein and lipid content of the tear composition of rabbits in the plateau group increased, and the nucleic acid content decreased compared with the pre-intervention period. Compared with the control group, rabbits in the plateau group showed thickening of corneal stromal edema, an increase in the number of conjunctival cup cells, increase in the level of expression of MUC5AC, an increase in the level of expression of MUC5AC, an atrophy and flattening of cytoplasm in lacrimal epithelial cells, an enlargement of glandular lumen, and no obvious destructive changes in the Hardarian glands.CONCLUSION: Acute plateau environment can destroy the homeostasis of rabbit ocular surface, so that the tear secretion and the tear film stability decreases, but within a certain period of time, rabbits undergo compensation with the habituation to the hypobaric hypoxia environment, which can increase the tear secretion to a certain extent and restore the tear film stability.

Objective To investigate the value of tranexamic acid combined with aspirin,low molecular weight heparin calcium in regulating inflammatory mediators and TEG in blood management of Total knee arthroplast(TKA).Methods 120 elderly patients with TKA in our hospital from January 2020 to October 2022 were randomly divided into group A(n=60)and group B(n=60).They were given tranexamic acid+aspirin and tranexamic acid+low molecular weight heparin calcium,respectively,for 2 weeks.Perioperative indexes,complications[lower limb deep vein thrombosis(DVT),intermuscular vein thrombosis(MCVT),incision infection],blood transfusion rate,adverse reactions(gastrointestinal discomfort,subcutaneous ecchymosis),TEG parameters[coagulation reaction time(R),blood coagulation time(K),maximum amplitude(MA),coagulation angle(α)],inflammatory mediators[soluble CD40 ligand(sCD40L),Toll-like receptor 4(TLR4),tumor necrosis factor(TNF-α)],vascular endothelial injury factors[soluble thromboregulatory protein(sTM),vascular endothelial cell growth factor(VEGF),E-selectin]were compared between the two groups.Results There was no significant difference in the 24 h postoperative drainage volume,latent blood loss,total blood loss,intraoperative blood loss,Hb and HCT levels 72 h after surgery between the two groups(P＞0.05).There was no statistically significant difference in TEG parameters between the two groups,at different time points,and between groups at different time points(P＞0.05);The serum levels of TLR4,sCD40L and TNF-α in group A were lower than those in group B 2 weeks after surgery(P＜0.05).The levels of plasma sTM and serum VEGF and E-selectin in group A were lower than those in group B 2 weeks after surgery(P＜0.05).There was no significant difference in the incidence of deep vein thrombosis(DVT),intermuscular vein thrombosis(MCVT),incision infection and blood transfusion rate between group A and group B(P＞0.05).There was no significant difference in the total incidence of adverse reactions between group A and group B(P＞0.05).Conclusion Compared with the combination of low molecular weight heparin calcium,the combination of tranexamic acid and aspirin can protect vascular endothelium and inhibit inflammatory response.However,both can maintain the patient's coagulation function and avoid massive blood loss or thrombosis.There is no significant difference in safety and effectiveness.