Objective:To retrospectively analyze the clinical features and surgical efficacy of congenital cholesteatoma （CC） and acquired cholesteatoma （AC） in children. Methods:Clinical data of 169 children with middle ear cholesteatoma were reviewed in the Department of Otorhinolaryngology Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University from January 2010 to July 2020. The clinical characteristics, stages, surgical methods, and postoperative recurrence rates were analyzed and summarized. Results:The age distribution of enrolled children ranged from 2 to 14 years. The mean age of the CC group was （5.60±2.48） years compared with （6.45±2.48） years in the AC group, and the difference was statistically significant （P<0.05）. Preoperative hearing in the CC group was （40.06±13.52） dB HL, which was better than in the AC group at （48.40±13.84） dB HL （P<0.05）. The proportion of stage Ⅰ in the CC group was lower than that in the AC group according to EAONO/JOS staging （P<0.05）. The recurrence rate after primary surgery was 19.23% （10/52） in the CC group compared with 36.29% （45/124） in the AC group （P<0.05）. The mastoid retention rates after all operations were 28.85% （15/52） in the CC group and 5.65% （7/124） in the AC group （P<0.05）. Conclusion:Compared with congenital cholesteatoma, acquired cholesteatoma in children is more aggressive and has more complications, higher postoperative recurrence rate, and less possibility of mastoid retention. Early clinical detection and treatment are required, and canal wall-down tympanoplasty should be considered in surgery.
Humans ; Cholesteatoma, Middle Ear/congenital* ; Child ; Retrospective Studies ; Child, Preschool ; Adolescent ; Male ; Female ; Recurrence ; Cholesteatoma/congenital* ; Tympanoplasty ; Treatment Outcome

This study investigates the neuroprotective potential of extracellular vesicles (EVs) delivering quercetin-3-O-β-d-glucuronic acid (QG-EVs) in cerebral ischemia-reperfusion injury (CIRI). Targeted brain delivery of QG-EVs was confirmed, with neuron cells identified as pivotal in modulating CIRI through single-cell RNA sequencing (scRNA-seq). Activating transcription factor 4 (Atf4) was highlighted as a critical regulatory factor, and in vitro studies revealed that silencing Atf4 diminished the neuroprotective effects of QG-EVs, increasing oxidative stress levels and neuronal apoptosis. In a CIRI mouse model, the knockdown of Atf4 attenuated the protective outcomes provided by QG-EVs, further affirming the role of Atf4 in mediating neuroprotection. Behavioral assessments and protein analysis showed that QG-EVs significantly reduced neuronal damage and pro-apoptotic markers, while improving neurological function via Atf4 upregulation. The outcomes hint at the potential of QG-EVs as a beneficial therapeutic modality to mitigate neuronal damage in CIRI by enhancing Atf4 expression, highlighting its potential for improving ischemic stroke outcomes.

Objective To explore the differences in muscle synergies of healthy individuals,intact limbs and residual limbs of above-knee amputees under different gaits,provide references for electromyographic control of the prosthetics.Methods Surface electromyography(sEMG)signals of 7 muscles(4 thigh muscles,3 calf muscles)were collected from 7 healthy individuals and 3 lower-limb amputees during level walking,ascending/descending slopes,and ascending/descending stairs.Muscle synergy weights(W)and temporal activation coefficients(H)were extracted using concatenated non-negative matrix factorization(CNMF).The W matrices were compared using the coefficient of determination R2,and the activation coefficients were analyzed using statistical parametric mapping(SPM).Furthermore,peak activation and activation integral were used for hierarchical clustering analysis.Results The comparison of W matrices indicated a similar set of muscle synergies between the healthy group and the intact limb of amputees,whereas the residual limb showed greater variability in synergies.The analysis of H showed statistically significant differences in muscle activation throughout the gait cycle for all amputees.Clustering of time-domain features revealed that amputees exhibited higher activation integral and peak values in their intact limb during ascending slopes.Conclusions This study provides an in-depth investigation of the neuromuscular compensation strategies in lower-limb amputees under different gaits,offering theoretical insights for gait rehabilitation and assisting in the development of EMG-controlled prosthetics.

Objective The aim of this study is to discuss the causal relationship between periodontal disease(PD)and prostate cancer(PCa).Methods A two-sample bidirectional Mendelian randomization(MR)analysis based on publicly statistical data from genome-wide association studies(GWAS)was conducted.MR Egger,weighted medium,simple mode and weighted mode were supplemented,while inverse variance weighted analysis(IVW)was the main method of analysis.Heterogeneity testing,pleiotropy testing and leave-one-out testing were used to assess the sensitivity and stabili-ty.Results The results of MR analysis showed that PD had no significant impact on the occurrence of PCa:East Asian(IVW,PD:OR=1.07,P=0.48);European(IVW,PD:OR=1.00,P=0.37,periodontitis:OR=1.03,P=0.14,chronic gingivitis:OR=0.99,P=0.37,chronic periodontitis:OR=1.03,P=0.22).The reverse MR analysis also did not show a causal relationship between PCa and PD:East Asian(IVW,PD:OR=0.97,P=0.22);European(IVW,PD:OR=0.84,P=0.44,periodontitis:OR=1.01,P=0.75,chronic gingivitis:OR=0.93,P=0.23,chronic periodontitis:OR=0.99,P=0.80).The results of other analysis were consistent with those of IVW analysis.Conclusions The results of our two-sample bidirectional MR analysis do not support a causal relationship between PD and PCa.

Objective To explore the differences in muscle synergies of healthy individuals,intact limbs and residual limbs of above-knee amputees under different gaits,provide references for electromyographic control of the prosthetics.Methods Surface electromyography(sEMG)signals of 7 muscles(4 thigh muscles,3 calf muscles)were collected from 7 healthy individuals and 3 lower-limb amputees during level walking,ascending/descending slopes,and ascending/descending stairs.Muscle synergy weights(W)and temporal activation coefficients(H)were extracted using concatenated non-negative matrix factorization(CNMF).The W matrices were compared using the coefficient of determination R2,and the activation coefficients were analyzed using statistical parametric mapping(SPM).Furthermore,peak activation and activation integral were used for hierarchical clustering analysis.Results The comparison of W matrices indicated a similar set of muscle synergies between the healthy group and the intact limb of amputees,whereas the residual limb showed greater variability in synergies.The analysis of H showed statistically significant differences in muscle activation throughout the gait cycle for all amputees.Clustering of time-domain features revealed that amputees exhibited higher activation integral and peak values in their intact limb during ascending slopes.Conclusions This study provides an in-depth investigation of the neuromuscular compensation strategies in lower-limb amputees under different gaits,offering theoretical insights for gait rehabilitation and assisting in the development of EMG-controlled prosthetics.

Objective To investigate the effect and potential mechanism of rat mesenchymal stem cells(MSC)on D-galactose-induced brain-tissue aging.Methods A rat brain-aging model was established by injecting D-galactose,and rats in the treatment group received MSC injections via the tail vein.Superoxide dismutase(SOD)activity and malondialdehyde(MDA)levels were assessed in rat brain tissue at the end of the experiment,and pathological changes in brain tissue were observed by hematoxylin-eosin(HE)staining.Expression levels of the inflammatory factors interleukin(IL)-1 and IL-6,the pathway proteins brain-derived neurotrophic factor(BDNF)-tropomyosin receptor kinase B(TrkB),the negative growth regulators p53 and p16,as well as vascular endothelial growth factor(VEGF)and basic fibroblast growth factor(bFGF)were observed by polymerase chain reaction(PCR)and Western Blot.Results Brain levels of SOD activity were significantly increased and MDA levels were significantly decreased in rats in the modle group compared with the treatment group(P＜0.05).The pathological state of the cerebral cortex and hippocampus were improved and the number of neurons and nucleus pulposus ratio in the brain were increased in the treatment group,as shown by HE staining.Expression levels of IL-1,IL-6,p53,and p16 were significantly decreased,while BDNF,TrkB,VEGF,and bFGF were significantly increased in the treatment group compared with the model group,as shown by PCR and Western Blot(P＜0.05).Conclusions These result suggest that MSCs potentially mitigate D-galactose-induced cerebral senescence by concurrently modulating the BDNF-TrkB axis to attenuate oxidative/inflammatory damage,while enhancing the secretion of vasculotrophic(VEGF)and neurotrophic(bFGF)factors for neuronal maintenance.

Objective To screen the mutations of ABCC8 gene in probands of maturity-onset diabetes of the young pedigrees,and investigate it sgenetic and clinical characteristics.Methods Whole exome sequencing were performed to screen ABCC8 mutations in 56 MODY probands who were admitted to Department of Endocrinology and Metabolism,Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2021 to December 2023.The mutations were verified by Sanger sequencing,and all participants were genotyped.Clinical phenotypes of the mutation carriers were compared with non-DM controls within the families.The identified mutations were evaluated by bioinformatic softwires.Then the pharmacogenomic characteristics of the mutation carriers were analyzed.Results Two heterozygous mutations D655V and R825Q were identified in two MODY probands and their families respectively,and the D655V was a novel mutation.Bioinformatics studies showed that both mutations were deleterious and pathogenic.In comparison with non-DM controls in the two families,mutation carriers with diabetes exhibited significantly lower fasting insulin/fasting plasma glucose,two-hour postprandial insulin/two-hour postprandial insulin plasma glucose,homeostatic model assessment-β(P<0.05).Treatment with oral hypoglycemic agents such as metformin or insulin in these mutation carriers resulted in a moderate reduction in plasma glucose levels.However,switching to targeted Sulfonylurea's(SUs)proved to be more effective.Conclusions In this study,the prevalence of MODY12 is 3.6%in these MODY pedigrees.The remarkable hypoglycemic efficacy of SUs suggests that both D655V and R825Q were activating mutations of ABCC8,and maybe the cause of MODY12 characterized by impaired insulin secretion.

Objective To develop a data-driven model for estimating tangential ground reaction force(GRFt)from lower limb kinematic data and select the most suitable input based on a balance between input quantity and estimation accuracy,with the aim of measuring GRFt in outdoor gait experiments.Methods Gait data from ten subjects walking at five different inclines(-10°,-5°,0°,5°,10°)were used to train two data-driven models,namely a backpropagation neural network(BPNN)-based model and a polynomial sparse identification(PSI)-based model.The performance of these models was evaluated using eight kinematic data combinations and the normal ground reaction force(GRFn)as inputs to determine the optimal model and input combination.Results Under the same input dimensionality,the combination of hip-knee joint angles proved more accurate in estimating GRF,than the knee-ankle joint angle combination.Specifically,the BPNN and PSI models based on the former combination predicted GRF,with errors of 1.61％BW(body weight)and 1.84％BW,respectively,while the latter combination resulted in errors of 2.82％BW and 3.15％BW.When GRFn and all joint angles were used as inputs,the model's prediction error was only 1.46％BW.Conclusions The combination of GRFn and hip-knee joint angles achieves an optimal balance between computational complexity and estimation accuracy.This study supports the accurate estimation of GRF,in outdoor gait testing.

Objective To investigate the effect and potential mechanism of rat mesenchymal stem cells(MSC)on D-galactose-induced brain-tissue aging.Methods A rat brain-aging model was established by injecting D-galactose,and rats in the treatment group received MSC injections via the tail vein.Superoxide dismutase(SOD)activity and malondialdehyde(MDA)levels were assessed in rat brain tissue at the end of the experiment,and pathological changes in brain tissue were observed by hematoxylin-eosin(HE)staining.Expression levels of the inflammatory factors interleukin(IL)-1 and IL-6,the pathway proteins brain-derived neurotrophic factor(BDNF)-tropomyosin receptor kinase B(TrkB),the negative growth regulators p53 and p16,as well as vascular endothelial growth factor(VEGF)and basic fibroblast growth factor(bFGF)were observed by polymerase chain reaction(PCR)and Western Blot.Results Brain levels of SOD activity were significantly increased and MDA levels were significantly decreased in rats in the modle group compared with the treatment group(P＜0.05).The pathological state of the cerebral cortex and hippocampus were improved and the number of neurons and nucleus pulposus ratio in the brain were increased in the treatment group,as shown by HE staining.Expression levels of IL-1,IL-6,p53,and p16 were significantly decreased,while BDNF,TrkB,VEGF,and bFGF were significantly increased in the treatment group compared with the model group,as shown by PCR and Western Blot(P＜0.05).Conclusions These result suggest that MSCs potentially mitigate D-galactose-induced cerebral senescence by concurrently modulating the BDNF-TrkB axis to attenuate oxidative/inflammatory damage,while enhancing the secretion of vasculotrophic(VEGF)and neurotrophic(bFGF)factors for neuronal maintenance.

Objective To screen the mutations of ABCC8 gene in probands of maturity-onset diabetes of the young pedigrees,and investigate it sgenetic and clinical characteristics.Methods Whole exome sequencing were performed to screen ABCC8 mutations in 56 MODY probands who were admitted to Department of Endocrinology and Metabolism,Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2021 to December 2023.The mutations were verified by Sanger sequencing,and all participants were genotyped.Clinical phenotypes of the mutation carriers were compared with non-DM controls within the families.The identified mutations were evaluated by bioinformatic softwires.Then the pharmacogenomic characteristics of the mutation carriers were analyzed.Results Two heterozygous mutations D655V and R825Q were identified in two MODY probands and their families respectively,and the D655V was a novel mutation.Bioinformatics studies showed that both mutations were deleterious and pathogenic.In comparison with non-DM controls in the two families,mutation carriers with diabetes exhibited significantly lower fasting insulin/fasting plasma glucose,two-hour postprandial insulin/two-hour postprandial insulin plasma glucose,homeostatic model assessment-β(P<0.05).Treatment with oral hypoglycemic agents such as metformin or insulin in these mutation carriers resulted in a moderate reduction in plasma glucose levels.However,switching to targeted Sulfonylurea's(SUs)proved to be more effective.Conclusions In this study,the prevalence of MODY12 is 3.6%in these MODY pedigrees.The remarkable hypoglycemic efficacy of SUs suggests that both D655V and R825Q were activating mutations of ABCC8,and maybe the cause of MODY12 characterized by impaired insulin secretion.