BACKGROUND:Adipose-derived stem cells have anti-aging effects,but whether adipose-derived stem cells from donors of different ages are different needs further study. OBJECTIVE:To compare the biological properties of adipose-derived stem cells in old and young mice. METHODS:Adipose-derived stem cells were extracted from adipose tissue of C57BL mice aged 8 and 14 weeks,respectively.The differences of cell cycle,apoptosis,and proliferation of adipose-derived stem cells in old and young mice were compared.The expression levels of aging-related P21 and P27 genes and proteins of adipose-derived stem cells in old and young mice were detected by quantitative PCR and western blot assay. RESULTS AND CONCLUSION:Compared with old mouse adipose-derived stem cells,young mouse adipose-derived stem cells were more active,more regular in morphology,less apoptosis,faster proliferation,and lower in expression of age-related P21 and P27 genes and proteins.It has been proven that adipose-derived stem cells from young mice have better anti-aging effects.

Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.

ObjectiveTo explore the possible mechanisms of Shujin Jiannao Formula （舒筋健脑方） for cerebral palsy. MethodsThirty 7-day-old SD rats were randomly divided into normal group， model group， and Shujin Jiannao Formula group， with 10 rats in each group. The model group and Shujin Jiannao Formula group established a cerebral palsy model by the classic Rice-Vannucci method. After successful modeling， rats in Shujin Jiannao Formula group were given Shujin Jiannao Formula 16 g/（kg·d） by gavage， while the normal group and model group were given normal saline 10 ml/（kg·d） by gavage once a day. After one week of intervention， the rats' body weight was measured， and Zea-Longa scores， the righting reflex test， and the hindlimb suspension test were conducted for assessment； hematoxylin-eosin （HE） staining and Nissl staining were used to observe pathological changes in brain tissue， and the number of Nissl-positive neurons was counted； enzyme-linked immunosorbent assay （ELISA） was employed to measure levels of inflammatory cytokines in the brain tissue， specifically interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）； immunofluorescence was used to detect the expression levels of neurofilament protein 200 （NF200） and myelin basic protein （MBP） in brain tissue； Western Blot analysis was conducted to determine the protein levels of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt/PKB/Rac）， and mammalian target of rapamycin （mTOR） in brain tissue. ResultsCompared with the normal group， rats in the model group showed significantly higher Zea-Longa scores and lower scores in the hindlimb suspension test （P＜0.01）； pathological findings revealed loose structure in the cerebral cortex， hippocampal atrophy， and neuronal damage in brain tissue. Levels of IL-1β and TNF-α elevated， and the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region reduced， and immunofluorescence intensity of NF200 and MBP， as well as protein expression levels of PI3K and mTOR， significantly decreased （P＜0.05 or P＜0.01）. Compared with the model group， rats in Shujin Jiannao Formula group showed decreased Zea-Longa scores and increased hindlimb suspension test scores （P＜0.05）； pathological damage in brain tissue alleviated， levels of IL-1β and TNF-α reduced， the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region increased， and the immunofluorescence intensity of NF200 and MBP， as well as the protein levels of PI3K and mTOR， significantly elevated （P＜0.05 or P＜0.01）. There were no statistically significant differences among the groups in body weight， body-turning time， or AKT protein levels in brain tissue （P＞0.05）. ConclusionShujin Jiannao Formula can improve the neurological function of rats with cerebral palsy， exert neurorestorative effects， and its mechanism of action may be related to the reduction of inflammatory response in brain tissue and the activation of the PI3K/AKT/mTOR signaling pathway.

Objective To compare the dosimetric differences in the heart and its substructures between two hybrid plans for hypofractionated whole-breast radiotherapy after breast-conserving surgery in patients with early-stage left-sided breast cancer. Methods A total of 46 patients with early-stage left-sided breast cancer who underwent hypofractionated whole-breast radiotherapy were randomly selected. Two hybrid radiotherapy plans were used, including hybrid intensity-modulated radiotherapy (H_IMRT) and hybrid volumetric-modulated arc therapy (H_VMAT). The heart and its substructures were contoured, including left anterior descending (LAD), left ventricle (LV), right coronary artery (RCA), and right ventricle (RV). The heart and substructure doses, as well as monitor units, were compared between H_IMRT and H_VMAT. Results Both hybrid plans met the clinical requirements. H_IMRT significantly outperformed H_VMAT for the heart (V₁₀, V₃₀, and D_mean), LAD (V₃₀, V₄₀, D_max and D_mean), LV (V₁₀, V₂₀ and D_mean), RCA (D_max, D_mean), and RV (V₅, V₁₀, D_mean) (P < 0.001). Additionally, H_IMRT was significantly superior to H_VMAT for heart V₅, LAD V₂₀, and RV V₂₀ (P = 0.005, 0.035 and 0.037). For LAD (V₁₅, V₄₀) and LV (V₅, V₂₅), H_IMRT was slightly better than H_VMAT, and the difference was not statistically significant. Conclusion Both H_IMRT and H_VMAT hybrid radiotherapy plans are suitable for hypofractionated whole-breast radiotherapy after breast-conserving surgery in patients with early-stage left-sided breast cancer. H_IMRT is slightly better than H_VMAT in dose sparing for the heart and its substructures.

The gut microbiota regulates intestinal nutrient absorption, participates in modulating host glucolipid metabolism, and contributes to ameliorating glucolipid metabolism disorder. Dysbiosis of the gut microbiota can compromise the integrity of the intestinal mucosal barrier, induce inflammatory responses, and exacerbate insulin resistance and abnormal lipid metabolism in the host. Dangua Humai Oral Liquid, a hospital-developed formulation for regulating glucolipid metabolism, has been granted a national invention patent and demonstrates significant clinical efficacy. This study aimed to investigate the effects of Dangua Humai Oral Liquid on gut microbiota and the intestinal mucosal barrier in a mouse model with glucolipid metabolism disorder. A glucolipid metabolism disorder model was established by feeding mice a high-glucose and high-fat diet. The mice were divided into a normal group, a model group, and a treatment group, with eight mice in each group. The treatment group received a daily gavage of Dangua Humai Oral Liquid(20 g·kg~(-1)), while the normal group and model group were given an equivalent volume of sterile water. After 15 weeks of intervention, glucolipid metabolism, intestinal mucosal barrier function, and inflammatory responses were evaluated. Metagenomics and untargeted metabolomics were employed to analyze changes in gut microbiota and associated metabolic pathways. Significant differences were observed between the indicators of the normal group and the model group. Compared with the model group, the treatment group exhibited marked improvements in glucolipid metabolism disorder, alleviated pathological damage in the liver and small intestine tissue, elevated expression of recombinant claudin 1(CLDN1), occluding(OCLN), and zonula occludens 1(ZO-1) in the small intestine tissue, and reduced serum levels of inflammatory factors lipopolysaccharides(LPS), lipopolysaccharide-binding protein(LBP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). At the phylum level, the relative abundance of Bacteroidota decreased, while that of Firmicutes increased. Lipid-related metabolic pathways were significantly altered. In conclusion, based on the successful establishment of the mouse model of glucolipid metabolism disorder, this study confirmed that Dangua Humai Oral Liquid effectively modulates gut microbiota and mucosal barrier function, reduces serum inflammatory factor levels, and regulates lipid-related metabolic pathways, thereby ameliorating glucolipid metabolism disorder.
Animals ; Gastrointestinal Microbiome/drug effects* ; Mice ; Intestinal Mucosa/microbiology* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL ; Humans ; Glycolipids/metabolism* ; Lipid Metabolism/drug effects* ; Administration, Oral ; Disease Models, Animal

Objective:To explore the trend of hearing changes in infants with GJB2 gene p.V37I mutation at different months. Methods:The subjects were 54 children（108 ears） with p.V37I homozygous or compound heterozygous mutation in GJB2 gene. All the subjects underwent auditory brainstem response, auditory steady-state response, acoustic immittance and other audiological tests. Children were divided into three groups according to their age, 26 cases in group A were ≤3 months old, 17 cases in group B were>3~≤6 months old, and 11 cases in group C were>6 months old. Statistical analysis was performed on the three groups of ABR response threshold, hearing degree, the ASSR average response threshold of four frequencies and the ASSR response thresholds for each frequency of 500, 1 000, 2 000 and 4 000 Hz. Results:Among the 54 cases, 35 were male and 19 were female, with an age rang of 2-27 months and a median age of 4 months. The ABR response threshold of the three groups were ranked from low to high as group A, group B and group C, and the difference was statistically significant（P<0.05）. The ABR response thresholds of the three groups were ranked from low to high as group A, group B, and group C. The comparison between groups showed that the ABR response thresholds of group C was higher than that of group A（P=0.006）. The proportion of confirmed hearing loss in the three groups was 34.61%, 50.00% and 63.64%, respectively, and the difference of hearing level among the three groups was statistically significant（P<0.05）. The comparison between groups showed that the difference between group A and group C was statistically significant（P=0.012）, normal hearing accounted for the highest proportion in group A（65.39%）, while mild hearing loss accounted for the highest proportion in group C（45.46%）. The ASSR average response thresholds of the four frequencies in the three groups were ranked from low to high as group A, group B and group C, and the difference is statistically significant（P<0.05）. The comparison between groups showed that response ASSR thresholds of group C was higher than that of group A（P=0.002）. Response thresholds of ASSR in each frequency in the three groups were all ranked from low to high as in group A, group B and group C, and the differences were statistically significant（P<0.05）. Compared with each other between groups, response ASSR thresholds of group C was higher than those of group A（P=0.003） and group B（P=0.015） at 500 Hz, while response ASSR thresholds of group C was higher than group A at 1 000 Hz（P=0.010） and 2 000 Hz（P<0.001）, and there was no statistical difference at 4 000 Hz. Conclusion:The incidence of hearing loss in GJB2 gene p.V37I mutation increased with age, and the degree of hearing loss increased, the hearing progression was mainly 500, 1 000 and 2 000 Hz suggesting regular follow-up and alert to hearing changes.
Humans ; Connexin 26 ; Male ; Female ; Infant ; Child, Preschool ; Mutation ; Evoked Potentials, Auditory, Brain Stem ; Connexins/genetics* ; Auditory Threshold ; Hearing/genetics* ; Hearing Loss/genetics*

Objective:To explore the hearing changes of children with different genotypes of SLC26A4 with enlarged vestibular aqueduct（EVA） using the linear mixed effect model（LMM）, providing evidence for the risk prediction of progressive hearing loss. Methods:A total of 48 children with EVA diagnosed in our hospital from January 2017 to January 2024. All subjects underwent two or more auditory tests. According to the results of deafness gene screening and sequencing, the genotypes are divided into: type A: homozygous mutation of c. 919-2A>G, type B: compound heterozygous or heterozygous mutation containing c. 919-2A>G, and type C: no mutation site of c. 919-2A>G of SLC26A4 gene. LMM was used to analyze the hearing thresholds change of 500 Hz, 1 000 Hz, 2 000 Hz, 4 000 Hz and the average in children with different genotypes with age. Results:A total of 92 ears, 314 audiograms of 48 children were included, the median number of audiograms was 3, the median age of initial diagnosis was 4 months, and the median follow-up time was 13 months. According to LMM, the standard deviation of random effects between patients and ears was large. There was no significant difference in hearing thresholds of different frequencies and the average in genotype A, genotype B, and genotype C, indicating that genotype had no effect on hearing threshold. There is an interaction between age and genotype. Taking genotype C as the reference, children with genotype B had the lowest increase in 500 Hz, 1000 Hz, and the average hearing threshold, followed by type A. Conclusion:EVA children exhibit substantial inter-individual/ear hearing threshold variability. Low-frequency thresholds progress slower than high frequencies. Genotype modulates progression rates, with wild-type（Type C） demonstrating fastest deterioration, supporting personalized auditory monitoring strategies.
Humans ; Vestibular Aqueduct/abnormalities* ; Genotype ; Sulfate Transporters ; Mutation ; Auditory Threshold ; Hearing Loss, Sensorineural/genetics* ; Male ; Female ; Child ; Child, Preschool ; Hearing Loss/genetics* ; Hearing Tests ; Linear Models ; Infant

This study aims to analyze the international research trends and frontier hotspots related to the application of growth mindset in medical education from 2016 to 2024. The objective is to provide insights and references for the development of relevant research in China.

Objective:To discuss the inhibitory effect of microRNA-487a(miR-487a)on the M2 polarization of tumor-associated macrophages(TAMs)in gastric cancer,and to clarify its effect on the proliferation,invasion,and migration of the gastric cancer AGS cells.Methods:The TAMs from gastric cancer tissue and adjacent normal tissue macrophages(NTMs)from adjacent tissue of the primary gastric cancer patients were isolated and cultured.The human monocyte THP-1 cells were induced in vitro to differentiate into TAMs,and the differentiated M0,M1,and M2 macrophages were cultured for 24 h by conditioned medium(CM)to obtain the TAMs,M1-TAMs,and M2-TAMs respectively.The TAMs were transfected and then divided into blank group,inhibitor-NC group,miR-487a inhibitor group,miR-487a inhibitor+si-NC group,and miR-487a inhibitor+si-TIA1 group.The transfection efficiencies of the cells in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods.The M2-TAMs were co-cultured with the AGS cells,and divided into AGS group,AGS+inhibitor-NC group,AGS+miR-487a inhibitor group,AGS+miR-487a inhibitor+si-NC group,and AGS+miR-487a inhibitor+si-TIA1 group.RT-qPCR method was used to detect the expression levels of miR-487a and lymphocyte intracytoplasmic antigen-1(TIA1)mRNA in TAMs from gastric cancer tissue and NTMs from adjacent normal tissue in various groups;Western blotting method was used to detect the expression level of TIA1 protein in TAMs from gastric cancer tissue and NTMs from adjacent normal tissue and TAMs in various groups;flow cytometry was used to detect the levels of CD206 and CD163 in TAMs in various groups;enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of interleukin-10(IL-10),transforming growth factor-beta(TGF-β),vascular endothelial growth factor A(VEGF-A),and arginase-1(Arg-1)in culture supernatant of the TAMs cells;CCK-8 assay was used to detect the proliferative activity of the AGS cells in various groups;wound healing assay was used to detect the migration rates of the AGS cells in various groups;Transwell assay was used to detect the number of invasion AGS cells in various groups.Results:The RT-qPCR results shoued that compared with NTMs from adjacent tissue,the expression level of miR-487a in the TAMs from gastric cancer tissue was significantly increased(P<0.01)and the expression level of TIA1 mRNA was significantly decreased(P<0.01).Compared with TAMs,the expression level of miR-487a in M1-TAMs was significantly decreased(P<0.01),and the expression level of TIA1 mRNA was increased(P<0.01);the expression level of miR-487a in M2-TAMs was significantly increased(P<0.01),and the expression level of TIA1 mRNA was decreased(P<0.01).After transfection,compared with blank group and inhibitor-NC group,the expression level of miR-487a in the cells in miR-487a inhibitor group was significantly decreased(P<0.01),indicating successful transfection.The Western blotting results showed that compared with NTMs from adjacent normal tissue,the expression level of TIA1 protein in TAMs from gastric cancer tissue was decreased(P<0.01);compared with TAMs,the expression level of T1A1 protein in M1-TAMs was significantly increased(P<0.01),and the expression of TIA1 protein in M2-TAMs was significantly decreased(P<0.01);after co-transfection,compared with inhibitor-NC group,the expression level of TIA1 protein in the cells in miR-487a inhibitor group was significantly increased(P<0.01);compared with miR-487a inhibitor+si-NC group,the expression level of TIA1 protein in the cells in miR-487a inhibitor+si-TIA1 group was significantly decreased(P<0.01).The flow cytometry results showed that compared with blank group and inhibitor-NC group,the levels of CD206 and CD163 in the cells in miR-487a inhibitor group were significantly decreased(P<0.01);after co-transfection,compared with inhibitor-NC group,the levels of CD206 and CD163 in the cells in miR-487a inhibitor group were significantly decreased(P<0.01);compared with miR-487a inhibitor+si-NC group,the levels of CD206 and CD163 in the cells in miR-487a inhibitor+si-TIA1 group were significantly increased(P<0.01).The ELISA results showed that compared with blank group and inhibitor-NC group,the levels of IL-10,TGF-β,VEGF-A,and Arg-1 in culture supernatant of the TAMs in miR-487a inhibitor group were significantly decreased(P<0.01);after co-transfection,compared with inhibitor-NC group,the levels of IL-10,TGF-β,VEGF-A,and Arg-1 in culture supernatant of the TAMs in miR-487a inhibitor group were significantly decreased(P<0.01);compared with miR-487a inhibitor+si-NC group,the levels of IL-10,TGF-β,VEGF-A,and Arg-1 in culture supernatant of the TAMs in miR-487a inhibitor+si-TIA1 group were significantly increased(P<0.01).The CCK-8 assay results showed that compared with AGS group,the proliferation activity of the cells in AGS+inhibitor-NC group was significantly increased(P<0.01);compared with AGS+inhibitor-NC group,the proliferation activity of the cells in AGS+miR-487a inhibitor group was significantly decreased(P<0.01);compared with AGS+miR-487a inhibitor+si-NC group,the proliferation activity of the cells in AGS+miR-487a inhibitor+si-TIA1 group was significantly increased(P<0.01).The wound healing assay results showed that compared with AGS group,the migration rate of the cells in AGS+inhibitor-NC group was significantly(P<0.05);compared with AGS+inhibitor-NC group,the migration rate of the cells in AGS+miR-487a inhibitor group was significantly decreased(P<0.01);compared with AGS+miR-487a inhibitor+si-NC group,the migration rate of the cells in AGS+miR-487a inhibitor+si-TIA1 group was significantly increased(P<0.05).The Transwell assay results showed that compared with AGS group,the number of invasion AGS cells in AGS+inhibitor-NC group was significantly increased(P<0.01);compared with AGS+inhibitor-NC group,the number of invasion AGS cells in AGS+miR-487a inhibitor group was significantly decreased(P<0.01);compared with AGS+miR-487a inhibitor+si-NC group,the number of invasion AGS cells in AGS+miR-487a inhibitor+si-TIA1 group was significantly increased(P<0.01).Conclusion:Silencing the miR-487a expression can inhibit the M2 polarization of the gastric cancer-associated macrophages by targeted upregulation of TIA1,and suppress the proliferation,migration,and invasion of the gastric cancer cells.

OBJECTIVE To analyze the difference of genotypes and hearing phenotypes in infants with biallelic allele variant in GJB2,and to provide reference for clinical practice. METHODS One hundred and forty-two subjects with biallelic allele variant in GJB2 were recruited in Beijing Tongren Hospital from August 2012 to March 2024. All subjects received universal newborn hearing screening(UNHS),neonatal deafness genetic screening and audiological tests. The subjects were divided into three groups according to the genotypes:T/T groups(truncated/truncated mutations,59 cases),T/NT group(truncated/non-truncated mutations,50 cases) and NT/NT group(non-truncated/non-truncated mutations,33 cases). Three groups of genotypes,newborn hearing screening results,age at first diagnosis and hearing diagnosis results were analyzed. RESULTS The homozygous mutation of c.235delC/c.235delC was the dominant in T/T group(57.63％),the compound heterozygous mutation of c.235delC/c.109G>A was the dominant in T/NT group(74.00％),and the homozygous mutation of c.109G>A/c.109G>A was the dominant in NT/NT group(96.97％). The overall refer rate of UNHS was 80.28％,and the refer rate of T/T group was 89.83％,which was significantly higher than that of T/NT group 70.00％(P=0.009). The age of first diagnosis of 142 cases was (3.70±1.56) months,there was no significant difference between the three groups(P>0.05). In 142 cases,104 cases with hearing loss accounted for 73.24％,38 cases with normal hearing accounted for 26.76％. The proportion of confirmed hearing loss in T/T group was 100.00％,which was significantly higher than that in T/NT group 52.00％(P<0.001) and NT/NT group 57.58％(P<0.001). In side of hearing loss,of the 104 patients with hearing loss,86 cases(82.69％) had bilateral hearing loss and 18 cases(17.31％) had unilateral hearing loss. The proportion of bilateral hearing loss in T/T group was 100.00％,which was significantly higher than that in T/NT group 57.69％(P<0.001) and NT/NT group 63.16％(P<0.001). Among 190 ears of 104 patients with hearing loss,the degree of hearing loss was predominantly mild to moderate(63.16％),followed by profound(24.74％) and severe(12.10％). Among them,the T/T group was mainly marked by severe to profound hearing loss(58.47％),while both the T/NT group and the NT/NT group were mainly characterized by mild hearing loss(58.54％ and 74.19％),and the differences among the three groups were statistically significant(P<0.001). CONCLUSION In the T/T group,all patients were diagnosed as bilateral hearing loss at first diagnosis,and was mainly severe and profound hearing loss. The bilateral and unilateral hearing loss were 52.00％ and 57.58％ in the T/NT group and NT/NT group at first diagnosis respectively,and was mainly mild hearing loss.