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1.
Chin Med J (Engl) ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38725346

RESUMO

BACKGROUND: Without timely and effective rehabilitation, hearing loss may profoundly affect human life quality. China has a large population of hearing-impaired individuals, which imposes a heavy health burden on society. Moreover, this population is projected to increase rapidly owing to China's aging society. METHODS: We used data from a population-representative epidemiological investigation of hearing loss and ear diseases in four Chinese provinces. We estimated the national prevalence using multiple linear regression of the age-group proportions and prevalence in 31 provinces with clustering analysis. We used years lived with disability (YLDs) to analyze the disease burden and forecasted the prevalence of hearing loss by 2060 in China. RESULTS: An estimated 115 million people had moderate-to-complete hearing loss in 2015 across the 31 provinces of China (8.4% of 1.37 billion people). Of these, 85.7% were older than age 50 years (99 million people) and 2.4% were younger than 20 years old (2.8 million people). Of all YLDs attributable to hearing loss, 68.9% were attributable to moderate-to-complete cases. By 2060, a projected 242 million people in China will have moderate-to-complete hearing loss, a 110.0% increase from 2015. CONCLUSIONS: The hearing loss prevalence in China is high. Population aging and socioeconomic factors substantially affect the prevalence and severity of hearing loss and the disease burden. The prevalence and severity of hearing loss are unevenly distributed across different provinces. Future public health policies should take these trends and regional variations into account.

2.
Eur J Med Chem ; 270: 116387, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38593589

RESUMO

Activating apoptosis has long been viewed as an anti-cancer process, but recently increasing evidence has accumulated that induction of ferroptosis has emerged as a promising strategy for cancer therapeutics. Glutathione peroxidase 4 (GPX4) is one of the pivotal factors regulating ferroptosis that targeted inhibition or degradation of GPX4 could effectively trigger ferroptosis. In this study, a series of ML162-quinone conjugates were constructed by using pharmacophore hybridization and bioisosterism strategies, with the aim of obtaining more active anticancer agents via the ferroptosis and apoptosis dual cell death processes. Of these compounds, GIC-20 was identified as the most active one that exhibited promising anticancer activity both in vitro and in vivo via ferroptosis and apoptosis dual-targeting processes, without obvious toxicity compared with ML162. On one hand, GIC-20 could trigger ferroptosis in cells by inducing intracellular lipid peroxide and ROS accumulation, and destroying mitochondrial structure. In addition to GPX4 inhibition, GIC-20 can also trigger ferroptosis via proteasomal-mediated degradation of GPX4, suggesting GIC-20 may function as a molecule glue degrader. On the other hand, GIC-20 can also induce apoptosis via upregulating the level of apoptotic protein Bax and downregulating the level of anti-apoptotic protein Bcl-2 in HT1080 cells. Furthermore, GIC-20 also enhanced the sensitivity of resistant MIA-PaCa-2-AMG510R cells to AMG510, suggesting the great potential of GIC-20 in overcoming the acquired resistance of KRASG12C inhibitors. Overall, GIC-20 represents a novel dual ferroptosis/apoptosis inducer warranting further development for cancer therapeutics and overcoming drug resistance.


Assuntos
Compostos de Anilina , Ferroptose , Naftoquinonas , Neoplasias , Tiofenos , Humanos , Naftoquinonas/farmacologia , Apoptose
3.
ACS Chem Neurosci ; 15(6): 1197-1205, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38451201

RESUMO

Vitamin C (Vc) plays a pivotal role in a series of pathological processes, such as tumors, immune diseases, and neurological disorders. However, its therapeutic potential for tinnitus management remains unclear. In this study, we find that Vc relieves tinnitus in noise-exposed rats. In the 7-day therapy groups, spontaneous firing rate (SFR) increases from 1.17 ± 0.10 Hz to 1.77 ± 0.15 Hz after noise exposure. Vc effectively reduces the elevated SFR to 0.99 ± 0.07 and 0.55 ± 0.05 Hz at different doses. The glutamate level in auditory cortex of noise-exposed rats (3.78 ± 0.42 µM) increases relative to that in the control group (1.34 ± 0.22 µM). High doses of Vc (500 mg/kg/day) effectively reduce the elevated glutamate levels (1.49 ± 0.28 µM). Mechanistic studies show that the expression of glutamate transporter 1 (GLT-1) is impaired following noise exposure and that Vc treatment effectively restores GLT-1 expression in the auditory cortex. Meanwhile, the GLT-1 inhibitor, dl-threo-beta-benzyloxyaspartic acid (dl-TBOA), invalidates the protection role of Vc. Our finding shows that Vc substantially enhances glutamate clearance by upregulating GLT-1 and consequently alleviates noise-induced tinnitus. This study provides valuable insight into a novel biological target for the development of therapeutic interventions that may prevent the onset of tinnitus.


Assuntos
Córtex Auditivo , Zumbido , Ratos , Animais , Córtex Auditivo/metabolismo , Ácido Ascórbico/farmacologia , Ácido Ascórbico/metabolismo , Neuroproteção , Zumbido/tratamento farmacológico , Zumbido/metabolismo , Ácido Glutâmico/metabolismo , Modelos Animais de Doenças , Sistema X-AG de Transporte de Aminoácidos/metabolismo , Transportador 2 de Aminoácido Excitatório/metabolismo
5.
RSC Med Chem ; 15(2): 506-518, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38389882

RESUMO

The emergence of multidrug resistance (MDR) in malignant tumors is one of the leading threats encountered currently by many chemotherapeutic agents. A proposed strategy to overcome MDR is to disable the efflux function of P-glycoprotein (P-gp/ABCB1), a critical member of the ABC transporter family that significantly increases the efflux of various anticancer drugs from tumor cells. In this study, structural modification of a third-generation P-gp inhibitor WK-X-34 based on bioisosteric and fragment-growing strategies led to the discovery of the adamantane derivative PID-9, which exhibited the best MDR reversal activity (IC50 = 0.1338 µM, RF = 78.6) in this series, exceeding those of the reported P-gp inhibitors verapamil and WK-X-34. In addition, compared with WK-X-34, PID-9 showed decreased toxicity to cells. Furthermore, the mechanism studies revealed that the reversal activity of adamantane derivatives PID-5, PID-7, and PID-9 stemmed from the inhibition of P-gp efflux. These results indicated that compound PID-9 is the most effective P-gp inhibitor among them with low toxicity and high MDR reversal activity, which provided a fundamental structural reference for further discovery of novel, effective, and non-toxic P-gp inhibitors.

6.
Biol Res ; 57(1): 3, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38217055

RESUMO

BACKGROUND: Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear. RESULTS: Exosomes derived from MSCs reduced hearing and hair cell loss caused by neomycin-induced damage in models in vivo and in vitro. In addition, MSC-derived exosomes modulated autophagy in hair cells to exert a protective effect. Mechanistically, exogenously administered exosomes were internalized by hair cells and subsequently upregulated endocytic gene expression and endosome formation, ultimately leading to autophagy activation. This increased autophagic activity promoted cell survival, decreased the mitochondrial oxidative stress level and the apoptosis rate in hair cells, and ameliorated neomycin-induced ototoxicity. CONCLUSIONS: In summary, our findings reveal the otoprotective capacity of exogenous exosome-mediated autophagy activation in hair cells in an endocytosis-dependent manner, suggesting possibilities for deafness treatment.


Assuntos
Exossomos , Neomicina , Neomicina/toxicidade , Neomicina/metabolismo , Exossomos/metabolismo , Células Ciliadas Auditivas , Autofagia/fisiologia
7.
Biol. Res ; 57: 3-3, 2024. ilus, graf, tab
Artigo em Inglês | LILACS | ID: biblio-1550058

RESUMO

BACKGROUND: Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear. RESULTS: Exosomes derived from MSCs reduced hearing and hair cell loss caused by neomycin-induced damage in models in vivo and in vitro. In addition, MSC-derived exosomes modulated autophagy in hair cells to exert a protective effect. Mechanistically, exogenously administered exosomes were internalized by hair cells and subsequently upregulated endocytic gene expression and endosome formation, ultimately leading to autophagy activation. This increased autophagic activity promoted cell survival, decreased the mitochondrial oxidative stress level and the apoptosis rate in hair cells, and ameliorated neomycin-induced ototoxicity. CONCLUSIONS: In summary, our findings reveal the otoprotective capacity of exogenous exosome-mediated autophagy activation in hair cells in an endocytosis-dependent manner, suggesting possibilities for deafness treatment.


Assuntos
Neomicina/metabolismo , Neomicina/toxicidade , Exossomos/metabolismo , Autofagia/fisiologia , Células Ciliadas Auditivas
8.
Bioorg Med Chem ; 90: 117352, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-37257255

RESUMO

Ferroptosis is a new type of regulated, non-apoptotic cell death driven by iron-dependent phospholipid peroxidation. Inducing cell ferroptosis by inactivating glutathione peroxidase 4 (GPX4) has been considered as an effective cancer treatment strategy, but only few GPX4 inhibitors have been reported to date. Targeted protein degradation is receiving increasing attention in the discovery and development of therapeutic modality, particularly proteolysis targeting chimeras (PROTACs). Herein, we reported the design, synthesis, and evaluation of different types of GPX4-targeting PROTACs using ML162 derivatives and ligands for CRBN/VHL E3 ligases. Among them, CRBN-based PROTAC GDC-11 showed a relatively balanced biological profile in GPX4 degradation (degradation rate of 33% at 10 µM), cytotoxicity (IC50 = 11.69 µM), and lipid peroxides accumulation (2-foldincreaserelatedtoDMSO), suggesting a typical characteristic of ferroptosis. In silico docking and quantum chemistry theoretical calculations provided a plausible explanation for the moderate degrading effect of these synthesized PROTACs. Overall, this work lays the foundation for subsequent studies of GPX4-targeting PROTACs, and further design and synthesis of GPX4-targeting degrader are currently in progress in our group, which will be reported in due course.


Assuntos
Ferro , Peróxidos Lipídicos , Proteólise , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Peróxidos , Quimera de Direcionamento de Proteólise
9.
Artigo em Inglês | MEDLINE | ID: mdl-37006743

RESUMO

Objective: The aim of this study is to evaluate the Chinese Version of the Tinnitus Primary Function Questionnaire (TPFQ). Methods: One hundred and sixteen patients who had been suffering from tinnitus for over 3 months were included in this study. Those tinnitus patients were administered the TPFQ, the Tinnitus Handicap Inventory (THI), the Beck Anxiety Inventory (BAI), the Beck Depression Inventory (BDI), and the Pittsburgh Sleep Quality Index (PSQI). Additionally, the magnitude estimate of tinnitus loudness, pure tone audiogram, and tinnitus matching was obtained. The factor structure was measured using the Kaiser-Meyer-Olkin test. The internal consistency was examined using Cronbach's α coefficient. The relationships between the TPFQ scores and other measurements were compared using Spearman's rank correlation coefficient. Results: The Cronbach's α of the 20-item version of TPFQ was 0.94, and that of the 12-item version of TPFQ was 0.92. Both the 20- and 12-item versions of TPFQ were significantly correlated with magnitude estimation of tinnitus loudness, THI, PSQI, BDI, and BAI. The average pure tone hearing threshold was significantly correlated with the hearing subscale. Conclusion: The 20- and 12-item Chinese versions of TPFQ are reliable and valid measures of tinnitus. The TPFQ can be applied to the assessment and management of tinnitus among the Chinese-speaking population.

10.
Quant Imaging Med Surg ; 13(3): 1577-1591, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36915310

RESUMO

Background: Automatic segmentation of temporal bone computed tomography (CT) images is fundamental to image-guided otologic surgery and the intelligent analysis of CT images in the field of otology. This study was conducted to test a convolutional neural network (CNN) model that can automatically segment almost all temporal bone anatomy structures in adult and pediatric CT images. Methods: A dataset comprising 80 annotated CT volumes was collected, of which 40 samples were obtained from adults and 40 from children. A further 60 annotated CT volumes (30 from adults and 30 from children) were used to train the model. The remaining 20 annotated CT volumes were employed to determine the model's generalizability for automatic segmentation. Finally, the Dice coefficient (DC) and average symmetric surface distance (ASSD) were utilized as metrics to evaluate the performance of the CNN model. Two independent-sample t-tests were used to compare the test set results of adults and children. Results: In the adult test set, the mean DC values of all the structures ranged from 0.714 to 0.912, and the ASSD values were less than 0.24 mm for 11 structures. In the pediatric test set, the mean DC values of all the structures ranged from 0.658 to 0.915, and the ASSD values were less than 0.18 mm for 11 structures. There was no statistically significant difference between the adult and child test sets in most temporal bone structures. Conclusions: Our CNN model shows excellent automatic segmentation performance and good generalizability for both adult and pediatric temporal bone CT images, which can help to advance otologist education, intelligent imaging diagnosis, surgery simulation, application of augmented reality, and preoperative planning for image-guided otology surgery.

11.
IEEE Trans Cybern ; 53(4): 2412-2425, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34673501

RESUMO

A realistic 2-D motion can be treated as a deforming process of an individual appearance texture driven by a sequence of human poses. In this article, we thereby propose to transform the 2-D motion synthesis into a pose conditioned realistic motion image generation task considering the promising performance of pose estimation technology and generative adversarial nets (GANs). However, the problem is that GAN is only suitable to do the region-aligned image translation task while motion synthesis involves a large number of spatial deformations. To avoid this drawback, we design a two-step and multistream network architecture. First, we train a special GAN to generate the body segment images with given poses in step-I. Then in step-II, we input the body segment images as well as the poses into the multistream network so that it only needs to generate the textures in each aligned body region. Besides, we provide a real face as another input of the network to improve the face details of the generated motion image. The synthesized results with realism and sharp details on four training sets demonstrate the effectiveness of the proposed model.

12.
Artigo em Chinês | MEDLINE | ID: mdl-36543402

RESUMO

Objective:To analyze the expression of type Ⅱ inflammatory-related cytokines in nasal secretions of patients with eosinophilic chronic rhinosinusitis with nasal polyps(ECRSwNP), and to preliminarily explore the role of type Ⅱ inflammatory cytokines in nasal secretions in predicting ECRSwNP. Methods:A prospective analysis was made of 91 patients with CRSwNP who underwent endoscopic sinus surgery in Peking University Third Hospital from November 2020 to June 2021. All the selected patients had their SNOT-22 score, Lund-Mackay score and blood eosinophilia collected before surgery. Percentage and absolute value; the nasal secretions of patients were collected before operation, and enzyme-linked immunosorbent assay was used to detect the typeⅡinflammatory cytokines(IL-4, IL-5, IL-13, IL-25, IL-33, Eotaxin-3, periostin), intraoperative nasal polyp tissue was collected for eosinophil count. According to the proportion of eosinophils in the tissue≥10%, they were divided into ECRSwNP group and nECRSwNP group. The clinical baseline data and type Ⅱ inflammatory cytokines were compared between the two groups, and the related factors of ECRSwNP were evaluated by univariate logistic regression analysis. The receiver operating characteristic(ROC) curve was used to evaluate the predictive potential of each clinical index. Results:The SNOT-22 score, Lund-Mackay score, blood eosinophil percentage and absolute value in the ECRSwNP group were higher than those in the nECRSwNP group(P<0.05). In the nECRSwNP group(P<0.01). Logistic regression analysis found that IL-5, Eotaxin-3 and blood eosinophil percentage were risk factors for ECRSwNP(P<0.05). ROC analysis found that IL-5, Eotaxin-3 and blood eosinophil percentage had predictive diagnostic value(P<0.01), among which blood eosinophil percentage had the greatest predictive value(AUC=0.756). The prediction model composed of Eotaxin-3, SNOT-22 score, sinus CT Lund-Mackay score, blood eosinophil percentage and blood eosinophil absolute value had better prediction effect on ECRSwNP(AUC=0.873). Conclusion:Type Ⅱ inflammatory cytokines IL-5 and Eotaxin-3 in nasal secretions may be involved as biomarkers for early diagnosis of ECRSwNP.


Assuntos
Pólipos Nasais , Rinite , Sinusite , Humanos , Quimiocina CCL26 , Doença Crônica , Citocinas , Eosinófilos/metabolismo , Interleucina-5 , Pólipos Nasais/metabolismo , Rinite/metabolismo , Sinusite/metabolismo
13.
J Int Adv Otol ; 18(6): 471-477, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36349667

RESUMO

BACKGROUND: The measurement of low-frequency cubic distortion product otoacoustic emission, for example, 0.5-kHz cubic distortion product otoacoustic emission, is often severely affected by background noise, and currently 0.5-kHz cubic distortion product otoacoustic emission is not commonly applicable in clinical setting. METHODS: The fundamental part of current study was the optimization of recording technology to reduce noise interference with the measurement of 0.5-kHz cubic distortion product otoacoustic emission and to establish the response patterns of cubic distortion product otoacoustic emission across speech frequencies from 0.5 to 8kHz in the presence of normal hearing and noise-induced hearing loss. RESULTS: After a series of optimization, a clinically applicable technology of measuring 0.5-kHz cubic distortion product otoacoustic emission was successfully completed via animal model. Cubic distortion product otoacoustic emission was recorded in 6 guinea pigs across speech frequencies from 0.5 to 8kHz before and after exposure to white bandnoise between 0.5 and 2 kHz. After noise exposure, significant reduction in the signal-to-noise ratio of cubic distortion product otoacoustic emission was found at 0.5 and 2 kHz, indicating our recording technology was sensitive and accurate. Other interesting finding was the reduction in cubic distortion product otoacoustic emiss ion-s ignal -to-n oise ratio at 4 and 6 kHz although the reduction was not statistically significant probably because of short exposure time. The result implied that the damaging effect induced by low-frequency noise exposure might spread upward to high-frequency region. CONCLUSIONS: Our recording technology was stable and reliable and had the great potentiality to be used in clinical setting.


Assuntos
Perda Auditiva Provocada por Ruído , Emissões Otoacústicas Espontâneas , Cobaias , Animais , Emissões Otoacústicas Espontâneas/fisiologia , Perda Auditiva Provocada por Ruído/diagnóstico , Perda Auditiva Provocada por Ruído/etiologia , Ruído/efeitos adversos , Testes Auditivos
14.
Am J Otolaryngol ; 43(5): 103561, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35952528

RESUMO

The etiologies of chronic rhinosinusitis with nasal polyps (CRSwNP)-associated olfactory dysfunction have several potentially overlapping hypotheses. Understanding the association of tissue eosinophils and mucous inflammatory cytokines with olfactory function and identifying predictors of olfactory outcomes in patients with nasal polyposis after surgery is fundamental for future clinical care and research. METHODS: Eighty-five patients who underwent endoscopic surgery for nasal polyposis were enrolled in this study. Olfactory measurements were performed before surgery and 3-6 months after surgery using a T&T olfactometer. Baseline characteristics of CRSwNP patients were collected, and Spearman's rho correlation was performed to assess the association of olfactory function with tissue eosinophils and mucous inflammatory cytokines. A multivariate logistic regression model was used to assess the independent predictors of olfactory outcomes after surgery. RESULTS: Here, 85 CRSwNP patients, including 25 patients without olfactory disorder and 60 patients with hypo-anosmia, were evaluated. Of the 60 patients with preoperative hypo-anosmia, 22 did not have improved olfactory function, and 38 demonstrated normal olfactory function after surgery based on the T&T olfactometer results. The levels of tissue eosinophil, interleukin-5 (IL-5), IL-13, eotaxin-3, and periostin in the preoperative hypo-anosmia group were higher than those in the preoperative normosmia group. Tissue eosinophil count, IL-5, and periostin levels in patients without olfactory improvement were higher than those in patients with olfactory improvement. The tissue eosinophil count, blood eosinophil count, and nasal mucus levels of IL-5, eotaxin-3, and periostin were significantly correlated with olfactory function in all patients with CRSwNP. The IL-5 level remained a strong predictor of poor olfactory outcomes after surgery. CONCLUSIONS: Both tissue eosinophils and mucous inflammatory cytokines, including IL-5, IL-13, eotaxin-3, and periostin, may contribute to the pathogenesis of CRSwNP-associated olfactory dysfunction. Higher IL-5 levels are associated with a lower chance of olfactory function recovery after each surgical revision.


Assuntos
Mucosite , Pólipos Nasais , Rinite , Sinusite , Anosmia , Quimiocina CCL26 , Doença Crônica , Citocinas , Eosinófilos , Humanos , Interleucina-13 , Interleucina-5 , Pólipos Nasais/complicações , Pólipos Nasais/cirurgia , Rinite/complicações , Rinite/cirurgia , Sinusite/complicações , Sinusite/cirurgia
15.
Laryngoscope Investig Otolaryngol ; 7(2): 564-570, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35434351

RESUMO

Background: With little attention given to low-frequency traffic noise and our understanding that cochlear function may be highly susceptible to low-frequency noise, there is an urgent need to determine traffic noise-induced hearing loss (NIHL), not only the hearing loss at low frequency but also the possible high-frequency hearing loss. Methods: The current study aims to investigate the potential for extensive hearing loss induced by exposure to 0.063 kHz octave band noise (OBN), which is an important component of low-frequency traffic noise. The threshold of auditory brainstem response (ABR) was used to evaluate hearing function before and after noise exposure. Chinchillas were randomly assigned into seven different groups. Group 63-3 h/6 h, Group 2 k-3 h/6 h, and group 4 k-3 h/6 h were exposed for either 3 or 6 h to 0.063, 2, and 4 kHz OBN at 90 dB SPL, respectively. The control group was not exposed to noise. Results: Significant ABR threshold-shifts (TS) were observed at 0.88, 2, 4, and 5.7 kHz in Group 63-6 h, and at 2.8 and 4 kHz in Group 2 k-6 h, and at 5.7 kHz in Group 4 k-6 h. ABR-TS were consistent with outer hair cell (OHC) losses, exposure to 0.063 kHz OBN at 90 dB SPL for 6 h induced large-scale losses of OHC both in low- and high-frequency region. Conclusions: Exposure to 0.063 kHz low-frequency OBN at 90 dB SPL for 6 h leads to significant hearing loss over an extensive range from low to high frequencies.

16.
Neural Plast ; 2022: 6894794, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35422857

RESUMO

Auditory deprivation affects normal age-related changes in the central auditory maturation. Cochlear implants (CIs) have already become the best treatment strategy for severe to profound hearing impairment. However, it is still hard to evaluate the speech-language outcomes of the pediatric CI recipients because of hearing-impaired children with limited speech-language abilities. The cortical auditory evoked potential (CAEP) provides a window into the development of the auditory cortical pathways. This preliminary study is aimed at assessing electrophysical characteristics of P1-N1 of electrically CAEP in children with CIs and at exploring whether these changes could be accounted for in auditory and speech outcomes of these patients. CAEP responses were recorded in 48 children with CIs in response to electrical stimulus to determine the presence of the P1-N1 response. Speech perception and speech intelligibility of the implanted children were further evaluated with the categories of auditory performance (CAP) test and speech intelligibility rating (SIR) test, respectively, to explore the relationship between the latency of P1-N1 and auditory and speech performance. This study found that P1 and N1 of the intracochlear CAEP were reliably evoked in children fitted with CIs and that the latency of the P1 as opposed to that of N1 was negative in relation to the wearing time of the cochlear implant. Moreover, the latency of the P1 produced significantly negative scores in both CAP and SIR tests, which indicates that P1 latency may be reflective of the auditory performance and speech intelligibility of pediatric CI recipients. These results suggest that the latency of P1 could be used for the objective assessment of auditory and speech function evaluation in cochlear-implanted children, which would be helpful in clinical decision-making regarding intervention for young hearing-impaired children.


Assuntos
Implante Coclear , Implantes Cocleares , Percepção da Fala , Criança , Implante Coclear/métodos , Potenciais Evocados Auditivos/fisiologia , Humanos , Fala , Percepção da Fala/fisiologia
17.
Microbiol Spectr ; 10(1): e0132221, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35019676

RESUMO

Clostridioides difficile, which causes life-threatening diarrheal disease, presents an urgent threat to health care systems. In this study, we present a retrospective genomic and epidemiological analysis of C. difficile in a large teaching hospital. First, we collected 894 nonduplicate fecal samples from patients during a whole year to elucidate the C. difficile molecular epidemiology. We then presented a detailed description of the population structure of C. difficile based on 270 isolates separated between 2015 and 2020 and clarified the genetic and phenotypic features by MIC and whole-genome sequencing. We observed a high carriage rate (19.4%, 173/894) of C. difficile among patients in this hospital. The population structure of C. difficile was diverse with a total of 36 distinct STs assigned. In total, 64.8% (175/270) of the isolates were toxigenic, including four CDT-positive (C. difficile transferase) isolates, and 50.4% (135/268) of the isolates were multidrug-resistant. Statistically, the rates of resistance to erythromycin, moxifloxacin, and rifaximin were higher for nontoxigenic isolates. Although no vancomycin-resistant isolates were detected, the MIC for vancomycin was higher for toxigenic isolates (P < 0.01). The in-hospital transmission was observed, with 43.8% (110/251) of isolates being genetically linked to a prior case. However, no strong correlation was detected between the genetic linkage and epidemiological linkage. Asymptomatic colonized patients play the same role in nosocomial transmission as infected patients, raising the issue of routine screening of C. difficile on admission. This work provides an in-depth description of C. difficile in a hospital setting and paves the way for better surveillance and effective prevention of related diseases in China. IMPORTANCE Clostridioides difficile infections (CDI) are the leading cause of healthcare-associated diarrhea and are known to be resistant to multiple antibiotics. In the past decade, C. difficile has emerged rapidly and has spread globally, causing great concern among American and European countries. However, research on CDI remains limited in China. Here, we characterized the comprehensive spectrum of C. difficile by whole-genome sequencing (WGS) in a Chinese hospital, showing a high detection rate among patients, diverse genome characteristics, a high level of antibiotic resistance, and an unknown nosocomial transmission risk of C. difficile. During the study period, two C. difficile transferase (CDT)-positive isolates belonging to a new multilocus sequence type (ST820) were detected, which have caused serious clinical symptoms. This work describes C. difficile integrally and provides new insight into C. difficile surveillance based on WGS in China.


Assuntos
Antibacterianos/farmacologia , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/genética , Infecções por Clostridium/microbiologia , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana , Adolescente , Adulto , Idoso , Proteínas de Bactérias/genética , Criança , Pré-Escolar , China/epidemiologia , Clostridioides difficile/classificação , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/transmissão , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/transmissão , Eritromicina/farmacologia , Feminino , Genoma Bacteriano , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Moxifloxacina/farmacologia , Filogenia , Estudos Retrospectivos , Rifaximina/farmacologia , Vancomicina/farmacologia , Sequenciamento Completo do Genoma , Adulto Jovem
18.
BMC Med Imaging ; 21(1): 166, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34753454

RESUMO

BACKGROUND: Segmentation of important structures in temporal bone CT is the basis of image-guided otologic surgery. Manual segmentation of temporal bone CT is time- consuming and laborious. We assessed the feasibility and generalization ability of a proposed deep learning model for automated segmentation of critical structures in temporal bone CT scans. METHODS: Thirty-nine temporal bone CT volumes including 58 ears were divided into normal (n = 20) and abnormal groups (n = 38). Ossicular chain disruption (n = 10), facial nerve covering vestibular window (n = 10), and Mondini dysplasia (n = 18) were included in abnormal group. All facial nerves, auditory ossicles, and labyrinths of the normal group were manually segmented. For the abnormal group, aberrant structures were manually segmented. Temporal bone CT data were imported into the network in unmarked form. The Dice coefficient (DC) and average symmetric surface distance (ASSD) were used to evaluate the accuracy of automatic segmentation. RESULTS: In the normal group, the mean values of DC and ASSD were respectively 0.703, and 0.250 mm for the facial nerve; 0.910, and 0.081 mm for the labyrinth; and 0.855, and 0.107 mm for the ossicles. In the abnormal group, the mean values of DC and ASSD were respectively 0.506, and 1.049 mm for the malformed facial nerve; 0.775, and 0.298 mm for the deformed labyrinth; and 0.698, and 1.385 mm for the aberrant ossicles. CONCLUSIONS: The proposed model has good generalization ability, which highlights the promise of this approach for otologist education, disease diagnosis, and preoperative planning for image-guided otology surgery.


Assuntos
Redes Neurais de Computação , Cirurgia Assistida por Computador , Osso Temporal/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Conjuntos de Dados como Assunto , Humanos , Processamento de Imagem Assistida por Computador , Osso Temporal/patologia , Osso Temporal/cirurgia
19.
Emerg Infect Dis ; 27(9): 2502-2504, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34424179

RESUMO

In response to the spread of colistin resistance gene mcr-1, China banned the use of colistin in livestock fodders. We used a time-series analysis of inpatient colonization data from 2011-2019 to accurately reveal the associated fluctuations of mcr-1 that occurred in inpatients in response to the ban.


Assuntos
Farmacorresistência Bacteriana , Proteínas de Escherichia coli , Antibacterianos/farmacologia , China/epidemiologia , Escherichia coli , Humanos , Pacientes Internados , Prevalência
20.
Artigo em Chinês | MEDLINE | ID: mdl-34304477

RESUMO

In recent years, medical imaging technology and computer technology have made great progress. On the one hand, with the development and popularization of electronic laryngoscope, the image of electronic laryngoscope plays a very important role in the diagnosis of vocal cord lesions. On the other hand, deep learning algorithm,especially convolutional neural networkhas gradually become the first choice of medical image recognition since the foundation of deep learning algorithm. So far, deep learning algorithm has made great contributions in many disciplines. In this paper, the basic concept of deep learning, the current status of image recognition of vocal cord lesions, and the prospect of research based on deep learning in vocal cord image lesions recognition are reviewed.


Assuntos
Aprendizado Profundo , Doenças da Laringe , Laringoscópios , Eletrônica , Humanos , Processamento de Imagem Assistida por Computador , Leucoplasia
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