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 To investigate the effect of deoxyelephantopin(Deo)on regulation of cell apoptosis pathway by reactive oxygen species(ROS)in human non-small cell lung cancer A549 cells.Methods A549 cells were treated with different concentrations of Deo.Cell counting kit 8(CCK-8)assay was used to detect the cell viability,2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)staining was used to measure cellular ROS content,and Hoechst 33342 staining was used to detect apoptotic bodies.Cell apoptosis and mitochondrial membrane potential were examined by flow cytometry.Quantitative polymerase chain reaction and Western blotting were used to detect the expression of apoptosis-related proteins.A549 xenograft tumor model in nude mice was used to evaluate the anti-tumor effect of Deo in vivo.Hematoxylin-eosin staining and TUNEL assay were used to observe the necrosis and cell apoptosis in tumor tissues.Results With the increase of Deo concentration(1,2,4,8,16,32 μmol/L),the viability of A549 cells showed a decreasing trend.Deo at 10 μmol/L could increase the ROS content in A549 cells,reduce mitochondrial membrane potential and promote cell apoptosis.Deo at 10 and 20 μmol/L promoted the mRNA and protein expression of Bax and caspase-3 and inhibited the mRNA and protein expression of Bcl-2,accompanied by significantly increased protein expression of cytochrome C in the cytoplasm.The volume and weight of transplanted tumor in nude mice were significantly inhibited after 17 d of administration of Deo of 10 and 20 mg·kg-1·d-1,and the necrotic area and the number of apoptotic cells in the tumor tissue were increased.Conclusion Deo can induce intracellular ROS production,and then activate the mitochondrial apoptosis pathway and consequently promote the apoptosis of A549 cells.

Objective To compare the effects of two exercise intensities on metabolic syndrome(MS).Methods Forty-nine MS patients hospitalized in Taiyuan Central Hospital from December,2022 to January 2024 were selected and randomly divided into two groups:a standard group(n=24)and individual group(n=25).All patients underwent cardiopulmonary exercise test(CPET)before and after treatment,collecting major indexes including body parameter,body component,and metabolic indicator for prescribing exercise programs.The standard group was trained with exercise intensity prescribed on heart rate reserve,while the individual group received the exercise with intensity prescribed on ventilatory threshold.Both groups received equal energy consumption exercise intervention with the same exercise frequency for 12 weeks.Results The two groups demonstrated significant improvements in waist circumference(WC),body mass index(BMI),body fat related indexes,and systolic blood pressure after intervention(P<0.05).The individual group showed significant improvements inWC,BMI and body fat related indexes as compared to the standard group(P<0.05).Both groups showed significant improvements in peak oxygen uptake,(PeakVO2),peak load power(Peak WR),peak metabolic equivalent(PeakMets),and peak respiratory exchange ratio(Peak RER)after intervention(P<0.05).The individual group presented significant improvements in peak heart rate(HRpeak),peak oxygen pulse(Peak VO2/HR),and maximum voluntary ventilation(MVV)(P<0.05)after intervention.Before intervention,the standard group demonstrated significantly higher levels in PeakVO2 and Peak MET compared to the individual group(P<0.05),but after intervention the two groups showed no significant differences in the two indexes.After the intervention,the individual group demonstrated insignificant improvements in all indexes compared to the standard group(P>0.05).Conclusions Both exercise prescriptions based on CPET can effectively improve the health-related indicators of MS patients on condition of moderate exercise intensity.However,the program prescribed based on individualized ventilatory threshold shows superiority to the program prescribed based on maximum physiological value in improving these indicators.

Objective To analyze the expression of microRNA-451 (miR-451) in children with microcytic anemia and chronic infectious anemia, and to explore the correlation between miR-451 and erythrocyte-related parameters and its diagnostic value for anemia in children. Methods The expression levels of miR-451 in serum were detected in children with microcytic anemia (n=80), chronic infectious anemia (n=80), and healthy controls (n=80) using real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). The correlation between serum miR-451 and erythrocyte-related parameters[red blood cell distribution width (RDW), red blood cells (RBC), mean corpuscular hemoglobin concentration (MCHC), hemoglobin (Hb), mean corpuscular hemoglobin content (MCH), mean corpuscular volume (MCV)]was analyzed using Pearson correlation analysis. The receiver operating characteristic (ROC) curve was plotted to analyze the diagnostic value of miR-451 for microcytic anemia, chronic infectious anemia, and the severity of anemia. Multivariate Logistic regression analysis was used to investigate the influencing factors for the occurrence of microcytic anemia and chronic infectious anemia in children. Results The expression levels of serum miR-451 in the microcytic anemia group and chronic infectious anemia group were lower than those in the healthy control group(P < 0.05). The miR-451 was negatively correlated with RDW (r=-0.388, P < 0.05), and positively correlated with Hb, RBC, MCHC, MCH, and MCV (r=0.402, 0.393, 0.391, 0.360, 0.323, P < 0.05). ROC curve analysis showed that the areas under the curve of serum miR-451 for diagnosing microcytic anemia and chronic infectious anemia was 0.718 and 0.735, respectively, which was higher than that of erythrocyte-related parameters such as RDW, Hb, RBC, MCHC, MCH, and MCV (P < 0.05). Multivariate Logistic regression analysis showed that body mass index, RDW, Hb, RBC, MCHC, MCH, MCV, and miR-451 were influencing factors for the occurrence of microcytic anemia and chronic infectious anemia in children (P < 0.05). With the aggravation of anemia in children, the expression level of serum miR-451 gradually decreased (P < 0.05). ROC curve analysis showed that the level of serum miR-451 had a high diagnostic value for the severity of anemia in children. Conclusion The expression of miR-451 is reduced in serum of children with microcytic anemia and chronic infectious anemia, and its expression level is correlated with erythrocyte-related parameter levels. Serum miR-451 has a high diagnostic value for microcytic anemia, chronic infectious anemia, and the severity of anemia.

Objective To explore the effect of Lee-Silverman voice treatment (LSVT) on language re-habilitation of dysarthria in Parkinson's disease (PD).Methods A total of 84 patients with PD dysarthria ad-mitted to our hospital from February 2019 to February 2022 were selected as the research objects.According to the random number table method,they were divided into observation group and control group,with 42 cases in each group.The control group received routine speech rehabilitation training,and the observation group re-ceived LSVT for four weeks.The scores of Western Aphasia Battery (WAB) and Aphasia Quotient (AQ) be-fore and after intervention were compared between the two groups,and the differences of electroglottographic parameters such as jitter,F0,shimmer,normalized noise energy (NNE) and harmonic noise ratio (HNR) were compared between the two groups.Results Before intervention,there was no significant difference in WAB scores (listening comprehension,repetition,spontaneous speech,naming) and AQ scores between the two groups (P>0.05).After intervention,the above scores of the two groups were significantly improved,and the observation group was higher than the control group,the difference was statistically significant (P<0.05). Before intervention,the jitter,F0,shimmer,NNE,HNR of vowels "a""i""u" in the two groups were not sta-tistically significant (P>0.05).After intervention,the above-mentioned electroglottic parameters of the two groups were significantly improved.The jitter and NNE of vowels "a""i""u" in the observation group were lower than those in the control group,and the HNR was higher than that in the control group,the differences were statistically significant (P<0.05).Conclusion LSVT can improve the electroglottographic parameters and speech function of patients with PD dysarthria,and the language rehabilitation effect of PD dysarthria is obvious.

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.

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.

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.