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

Objective:To develop a modified University of Wisconsin preservation solution (UW solution) containing α 2-adrenergic receptor agonists (dexmedetomidine) and noble gases (argon) and investigate its protective effect on the isolated amputated skeletal muscle of rats. Methods:Sixty male SD rats were selected to establish a hindlimb cold preservation/perfusion model and were divided into blank control group, hypothermic storage group, UW solution perfusion group, and modified UW solution perfusion group using a random number table, with 15 rats in each group. Simultaneously, a cold preservation model of rat skeletal muscle myoblasts (L6 cells) was established and the rats were also divided into four groups in the same way. Animal models were prepared in different ways: In the blank control group, the hindlimbs received no special treatment; In the hypothermic storage group, the amputated hindlimbs were stored in a dry centrifuge tube at 4℃ for 18 hours; In the UW solution perfusion group, the amputated hindlimbs were perfused with UW solution and then stored in a centrifuge tube containing UW solution at 4℃ for 18 hours; In the modified UW solution perfusion group, the amputated hindlimbs were perfused with modified UW solution (containing 0.1 nmol/L dexmedetomidine and 50% volume fraction of argon) and then stored in a centrifuge tube containing the modified UW solution at 4℃ for 18 hours. Cell models were treated as follows: In the blank control group, L6 cells were cultured under standard conditions; In the hypothermic storage group and UW solution group, L6 cells were treated with conventional culture medium or UW solution, stored in argon-filled sealed bags at 4℃ for 8 hours, and then rewarmed and cultured for 6 hours; In the modified UW solution group, L6 cells were treated with the modified solution, stored in argon-filled sealed bags at 4℃ for 8 hours, and then rewarmed and cultured for 6 hours. After sample collection, skeletal muscle morphology, tissue edema and ultrastructure features were assessed by HE staining, wet-to-dry weight ratio, and transmission electron microscopy, respectively. Additionally, L6 cell morphology was examined by light microscopy. L6 cell viability was determined by cell counting kit-8 (CCK-8) assay (expressed as absorbance A value). Expression levels of glutathione peroxidase 4 (GPX4) protein in both skeletal muscle tissue and L6 cells were evaluated by immunofluorescence staining and Western blot, respectively.Results:After 18 hours of in vitro preservation of rat isolated amputated limbs, the following results were obtained: (1) HE staining results showed that the muscle fiber morphology of the modified UW solution perfusion group was close to that of the blank control group. Moreover, the area ratio of skeletal muscle cells in the modified UW solution perfusion group was significantly higher than that in the hypothermic storage group and UW solution perfusion group ( P<0.05). (2) The wet-dry weight ratio results showed that there was no statistically significant difference among the modified UW solution perfusion group, the blank control group and UW solution group ( P>0.05), with significantly lower ratios in all three groups than that in the hypothermic storage group ( P<0.05). (3) Transmission electron microscopy results revealed that the modified UW solution perfusion group showed no statistically significant differences in ultrastructural metrics, including myofiber diameter, sarcomere length, mitochondrial short-axis/long-axis ratio, and mitochondrial cristae count, compared with those in the blank control group ( P>0.05), and performed significantly better than both the hypothermic storage group and UW solution perfusion group ( P<0.05). (4) Morphological observation of L6 cells showed that the cellular morphology was regular in the modified UW solution perfusion group, close to that in the blank control group, while it was severely damaged in the hypothermic storage group. Moreover, the cells were reduced in number and partially damaged in the UW solution group. The sequence of cell viability expressed as absorbance A value was blank control group >modified UW solution perfusion group > UW solution perfusion group > hypothermic storage group, with statistically significant differences among the four groups ( P<0.05). (5) Immunofluorescence staining showed that there was no statistically significant difference in fluorescence intensity of GPX4 protein expression between the modified UW solution perfusion group and blank control group ( P>0.05), while the fluorescence intensity was higher in the modified UW solution perfusion group than that in the hypothermic storage group and UW solution perfusion group ( P<0.05). Western blot analysis showed that the relative expression level of GPX4 in the modified UW solution group was significantly lower than that in the blank control group ( P<0.05), but higher than that in the hypothermic storage group and UW solution perfusion group ( P<0.05). Conclusion:The modified UW solution can stabilize the expression level of GPX4 protein, thereby inhibiting ferroptosis and alleviating cold preservation injury in both rat amputated isolated limb skeletal muscle tissue and L6 cells.

Objective To investigate the effect of dexmedetomidine(DEX)on cognitive func-tion in rats with cerebral ischemic stroke(CIS)and analyze its potential underlying mechanisms.Methods A rat model of CIS was established using the middle cerebral artery occlusion(MCAO)method.The rats were randomly divided into sham-operation group,model group,low-dose DEX group(25 mg/kg DEX solution,administered by gavage),high-dose DEX group(50 mg/kg DEX solution,administered by gavage),and edaravone group(3.2 mg/kg edaravone solution,adminis-tered by gavage).After treatment,cognitive function was assessed using the neurological deficit score and the novel object recognition test.Brain infarction area and histopathological damage in brain tis-sue were detected using triphenyltetrazolium chloride(TTC)staining and hematoxylin and eosin(HE)staining,respectively.The expression of the microglial marker ionized calcium-binding adapter molecule 1(Iba-1)was analyzed using immunohistochemical staining.The levels of interleukin(IL)-6,IL-18,and IL-1β in brain tissue were measured using ELISA kits.The expression of proteins related to the toll-like receptor 4/nuclear factor KB/NOD-like receptor thermal protein do-main-containing protein 3(TLR4/NF-κB/NLRP3)signaling pathway was detected using western blot.Results Compared with the sham-operation group,the model group exhibited increased or enlarged neurological scores,brain infarction area,levels of IL-6,IL-1β,IL-18,Iba-1,TLR4,p-NF-κB,NLRP3,Cleaved Caspase-1,and GSDMD-N,as well as a decreased novel object discrimination in-dex.Compared with the model group,the low-dose DEX,high-dose DEX,and edaravone groups showed decreased or shrinked neurological scores,brain infarction area,levels of IL-6,IL-1β,IL-18,Iba-1,TLR4,p-NF-κB,NLRP3,Cleaved Caspase-1,and GSDMD-N,along with an increased novel object discrimination index.Compared with the low-dose DEX and edaravone groups,the high-dose DEX group demonstrated further decreases in neurological scores,brain in-farction area,levels of IL-6,IL-1β,IL-18,Iba-1,TLR4,p-NF-κB,NLRP3,Cleaved Caspase-1,and GSDMD-N-terminal domain(GSDMD-N),as well as an increased novel object discrimination index.The differences among the aforementioned groups were all statistically significant(P＜0.05).Conclusion DEX improves cognitive function in rats with CIS by inhibiting the activation of the TLR4/NF-κB/NLRP3 signaling pathway,thereby suppressing neuronal pyroptosis and micro-glial activation and alleviating the inflammatory response.

[This corrects the article DOI: 10.1016/j.jpha.2023.08.006.].

Objective To investigate the effect of microRNA(miR)-34a-5p on neurological function of rats with intracerebral hemorrhage(ICH)by adjusting PTEN-induced kinase 1(PINK1)/Parkin pathway.Methods SD rats were assigned into sham surgery group(Sham),ICH group,inhibitor NC group,miR-34a-5p inhibitor group,miR-34a-5p inhibitor+DMSO group,and miR-34a-5p inhibitor+Mdivi-1 group,with 8 rats in each group.Modified neurological severity score(mNSS)was used to assess changes in neurological function of rats;HE staining was used to observe the pathological changes in the brain tissue of rats;transmission electron microscopy was used to observe autophagy in brain tissue;TUNEL staining was used to observe cell apoptosis;qRT-PCR experiment was used to detect the mRNA levels of miR-34a-5p,PINK1 and Parkin in the brain tissues;Western blot experiments were used to measure PINK1,Parkin,Beclin1 and P62 proteins in the brain tissues of rats;dual luciferase reporter gene assay was used to determine the targeting relationship between miR-34a-5p and PINK1.Results Compared with the inhibitor NC group,the miR-34a-5p inhibitor group demonstrated lower levels of neuronal necrosis,red blood cell amount,inflammatory cell amount,autophagic vacuole amount,mNSS score,TUNEL positivity rate,miR-34a-5p expression and p62 protein,but higher levels of PINK1,Parkin mRNA and protein expression,and Beclin1 protein expression(P＜0.05).Compared with the miR-34a-5p inhibitor+DMSO group,the changes mentioned above in rat of the miR-34a-5p inhibitor+Mdivi-1 group are all reversed(P＜0.05).In the dual luciferase reporter gene experiment,the relative luciferase activity of cells in the miR-34a-5p mimic and PINK1-WT cotransfected group was greatly reduced(P＜0.05).Conclusion The downregulation of miR-34a-5p may alleviate neurological dysfunction in ICH rats by adjusting PINK1/Parkin pathway.

Objective To study the effect of auditory and speech development after cochlear implant(CI)in children with bilateral cochlear nerve deficiency(CND)and its influencing factors.Methods A total of 20 children with bilateral CND were included in the study,of which 5 were implanted bilaterally and 15 unilaterally.CT of the temporal bone showed stenosis of the cochlear aperture in 14 cases and atresia of the cochlear aperture in 6 cases.There were 8 cases accompanied by other inner ear malformations,and 12 cases with no accompanying inner ear mal-formations.MRI of the internal auditory canal showed 1 nerve in 5 cases,2 nerves in 6 cases,3 nerves in 8 cases,and 4 nerves in 1 case.There were 6 cases in which the EABR was not elicited and 14 cases in which it was elicited.The postoperative auditory and speech abilities of the subjects were evaluated using categories of auditory perform-ance(CAP)and speech intelligibility rating(SIR).Results ① The CAP(P＜0.001)and SIR(P＜0.001)scores of the children with stenosis of the cochlea nerve canal were higher than those of the patients with atresia of the cochlea nerve canal.② The more nerve roots in the internal auditory canal,the higher the score of CAP(P=0.003)and SIR(P=0.008).③ CAP score of the children with EABR elicited was higher than that of the children without EABR elicited(P=0.030).The difference in SIR scores was not statistically significant(P=0.14).④The differences in CAP and SIR between those with bilateral CI and unilateral CI,as well as between those with and without other inner ear malformations,were not statistically significant(P＞0.05).Conclusion Children with bi-lateral CND had significant postoperative improvement in auditory function but poor speech development after CI.Postoperative auditory speech ability was related to the condition of the cochlear foramen,the number of nerve roots in the internal auditory canal,and whether or not the EABR was elicited intraoperatively.

Objective To investigate the effect of microRNA(miR)-34a-5p on neurological function of rats with intracerebral hemorrhage(ICH)by adjusting PTEN-induced kinase 1(PINK1)/Parkin pathway.Methods SD rats were assigned into sham surgery group(Sham),ICH group,inhibitor NC group,miR-34a-5p inhibitor group,miR-34a-5p inhibitor+DMSO group,and miR-34a-5p inhibitor+Mdivi-1 group,with 8 rats in each group.Modified neurological severity score(mNSS)was used to assess changes in neurological function of rats;HE staining was used to observe the pathological changes in the brain tissue of rats;transmission electron microscopy was used to observe autophagy in brain tissue;TUNEL staining was used to observe cell apoptosis;qRT-PCR experiment was used to detect the mRNA levels of miR-34a-5p,PINK1 and Parkin in the brain tissues;Western blot experiments were used to measure PINK1,Parkin,Beclin1 and P62 proteins in the brain tissues of rats;dual luciferase reporter gene assay was used to determine the targeting relationship between miR-34a-5p and PINK1.Results Compared with the inhibitor NC group,the miR-34a-5p inhibitor group demonstrated lower levels of neuronal necrosis,red blood cell amount,inflammatory cell amount,autophagic vacuole amount,mNSS score,TUNEL positivity rate,miR-34a-5p expression and p62 protein,but higher levels of PINK1,Parkin mRNA and protein expression,and Beclin1 protein expression(P＜0.05).Compared with the miR-34a-5p inhibitor+DMSO group,the changes mentioned above in rat of the miR-34a-5p inhibitor+Mdivi-1 group are all reversed(P＜0.05).In the dual luciferase reporter gene experiment,the relative luciferase activity of cells in the miR-34a-5p mimic and PINK1-WT cotransfected group was greatly reduced(P＜0.05).Conclusion The downregulation of miR-34a-5p may alleviate neurological dysfunction in ICH rats by adjusting PINK1/Parkin pathway.

Objective To observe the value of 2D SECara-Net and 3D U2-Net models constructed based on 2D maximal intensity projection(MIP)and 3D time-of-flight MR angiography(3D TOF-MRA)images,respectively,also of their combination for MRA detecting unruptured saccular intracranial aneurysms(USIA).Methods Totally 973 patients with single USIA and 300 subjects who underwent healthy physical examination were retrospectively collected and divided into training set(n=923,containing 723 cases of USIA and 200 healthy subjects)and test set(n=350,containing 250 cases of USIA and 100 healthy subjects)at the ratio of 7:3.Pre-processed 3D TOF-MRA and the obtained 2D-MIP images in training set were imported into 3D U2-Net and 2D SECara-Net models for training and adjusting parameters,respectively.The efficiency of 2 models and their combination for detecting USIA were evaluated.Results The sensitivity,specificity and accuracy of 2D SECara-Net model for detecting USIA in test set was 78.80％(197/250),95.00％(95/100)and 83.43％(292/350),of 3D U2-Net model was 82.80％(207/250),86.00％(86/100)and 83.71％(293/350),respectively.The specificity of 2D SECara-Net model was higher than that of 3D U2-Net model(P=0.030),while no significant difference of sensitivity nor accuracy was found between 2 models(both P＞0.05).The specificity of the combination of the 2 models was 99.00％(99/100),higher than that of 3D U2-Net model(P＜0.05),and the sensitivity and accuracy of the combination was 91.20％(228/250)and 93.43％(327/350),respectivelty,both higher than those of 2 single models(all P＜0.05).Conclusion 2D SECara-Net and 3D U2-Net models had similar,sensitivity and accuracy for MRA detecting USIA.Combination of them could improve the detecting efficacy.

Objective To observe the value of 2D SECara-Net and 3D U2-Net models constructed based on 2D maximal intensity projection(MIP)and 3D time-of-flight MR angiography(3D TOF-MRA)images,respectively,also of their combination for MRA detecting unruptured saccular intracranial aneurysms(USIA).Methods Totally 973 patients with single USIA and 300 subjects who underwent healthy physical examination were retrospectively collected and divided into training set(n=923,containing 723 cases of USIA and 200 healthy subjects)and test set(n=350,containing 250 cases of USIA and 100 healthy subjects)at the ratio of 7:3.Pre-processed 3D TOF-MRA and the obtained 2D-MIP images in training set were imported into 3D U2-Net and 2D SECara-Net models for training and adjusting parameters,respectively.The efficiency of 2 models and their combination for detecting USIA were evaluated.Results The sensitivity,specificity and accuracy of 2D SECara-Net model for detecting USIA in test set was 78.80％(197/250),95.00％(95/100)and 83.43％(292/350),of 3D U2-Net model was 82.80％(207/250),86.00％(86/100)and 83.71％(293/350),respectively.The specificity of 2D SECara-Net model was higher than that of 3D U2-Net model(P=0.030),while no significant difference of sensitivity nor accuracy was found between 2 models(both P＞0.05).The specificity of the combination of the 2 models was 99.00％(99/100),higher than that of 3D U2-Net model(P＜0.05),and the sensitivity and accuracy of the combination was 91.20％(228/250)and 93.43％(327/350),respectivelty,both higher than those of 2 single models(all P＜0.05).Conclusion 2D SECara-Net and 3D U2-Net models had similar,sensitivity and accuracy for MRA detecting USIA.Combination of them could improve the detecting efficacy.

Objective To study the effect of auditory and speech development after cochlear implant(CI)in children with bilateral cochlear nerve deficiency(CND)and its influencing factors.Methods A total of 20 children with bilateral CND were included in the study,of which 5 were implanted bilaterally and 15 unilaterally.CT of the temporal bone showed stenosis of the cochlear aperture in 14 cases and atresia of the cochlear aperture in 6 cases.There were 8 cases accompanied by other inner ear malformations,and 12 cases with no accompanying inner ear mal-formations.MRI of the internal auditory canal showed 1 nerve in 5 cases,2 nerves in 6 cases,3 nerves in 8 cases,and 4 nerves in 1 case.There were 6 cases in which the EABR was not elicited and 14 cases in which it was elicited.The postoperative auditory and speech abilities of the subjects were evaluated using categories of auditory perform-ance(CAP)and speech intelligibility rating(SIR).Results ① The CAP(P＜0.001)and SIR(P＜0.001)scores of the children with stenosis of the cochlea nerve canal were higher than those of the patients with atresia of the cochlea nerve canal.② The more nerve roots in the internal auditory canal,the higher the score of CAP(P=0.003)and SIR(P=0.008).③ CAP score of the children with EABR elicited was higher than that of the children without EABR elicited(P=0.030).The difference in SIR scores was not statistically significant(P=0.14).④The differences in CAP and SIR between those with bilateral CI and unilateral CI,as well as between those with and without other inner ear malformations,were not statistically significant(P＞0.05).Conclusion Children with bi-lateral CND had significant postoperative improvement in auditory function but poor speech development after CI.Postoperative auditory speech ability was related to the condition of the cochlear foramen,the number of nerve roots in the internal auditory canal,and whether or not the EABR was elicited intraoperatively.