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Objective:To analyze the mutation spectrum of 23-site chip newborn deafness genetic screening in Beijing, and to provide basis for genetic counseling and clinical diagnosis and treatment. Methods:The study included 21 006 babies born in Beijing from December 2022 to June 2023. All subjects underwent newborn deafness genetic screening in Beijing Tongren Hospital, covering 23 variants in 4 genes, the GJB2 geneï¼c.35delG, c.176_191del16, c.235delC, c.299_300delAT, c.109G>A, c.257C>G, c.512insAACG, c.427C>T, c.35insGï¼, SLC26A4 geneï¼c.919-2A>G, c.2168A>G, c.1174A>T, c.1226G>A, c.1229C>T, c.1975G>C, c.2027T>A, c.589G>A, c.1707+5G>A, c.917insG, c.281C>Tï¼, Mt12SrRNAï¼m.1555A>G, m.1494C>Tï¼ and GJB3 geneï¼c.538C>Tï¼. The mutation detection rate and allele frequency were analyzed. Results:The overall mutation detection rate was 11.516%ï¼2 419/21 006ï¼, with the GJB2 gene being the most frequently involved at 9.097%ï¼1 911/21 006ï¼, followed by the SLC26A4 gene at 2.123%ï¼446/21 006ï¼, the GJB3 gene at 0.362%ï¼76/21 006ï¼ and Mt12SrRNA at 0.176%ï¼37/21 006ï¼. Among the GJB2 genes, c.109G>A and c.235delC mutation detection rates were the highest, with 6.579%ï¼1 382/21 006ï¼ and 1.795%ï¼377/21 006ï¼, respectively. Of the SLC26A4 genes, c.919-2A>G and c.2168A>G had the highest mutation rates of 1.423%ï¼299/21 006ï¼ and 0.233%ï¼49/21 106ï¼, respectively. Regarding the allele frequency, GJB2 c.109G>A was the most common variant with an allele frequency of 3.359%ï¼1 411/42 012ï¼, followed by the GJB2 c.235delC at 0.897%ï¼377/42 012ï¼ and the SLC26A4 c.919-2A>G at 0.719%ï¼302/42 012ï¼. Conclusion:23-site chip newborn deafness genetic screening in Beijing showed that GJB2 c.109G>A mutation detection rate and allele frequency were the highest. This study has enriched the epidemiological data of 23-site chip genetic screening mutation profiles for neonatal deafness, which can provide evidence for clinical practice.
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Surdez , Perda Auditiva , Lactente , Recém-Nascido , Humanos , Conexinas/genética , Conexina 26/genética , Surdez/genética , Surdez/diagnóstico , Análise Mutacional de DNA , Transportadores de Sulfato/genética , Testes Genéticos , Mutação , Perda Auditiva/genética , Triagem Neonatal , ChinaRESUMO
Hearing loss is the third most prevalent physical condition affecting communication, well-being, and healthcare costs. Sensorineural hearing loss often occurs first in the high-frequency region (basal turn), then towards the low-frequency region (apical turn). However, the mechanism is still unclear. Supporting cells play a critical role in the maintenance of normal cochlear function. The function and supporting capacity of these cells may be different from different frequency regions. Hensen's cells are one of the unique supporting cell types characterized by lipid droplets (LDs) in the cytoplasm. Here, we investigated the morphological and gene expression differences of Hensen's cells along the cochlear axis. We observed a gradient change in the morphological characteristics of Hensen's cells along the cochlear tonotopic axis, with larger and more abundant LDs observed in apical Hensen's cells. Smart-seq2 RNA-seq revealed differentially expressed genes (DEGs) between apical and basal Hensen's cells that clustered in several pathways, including unsaturated fatty acid biosynthesis, cholesterol metabolism, and fatty acid catabolism, which are associated with different energy storage capacities and metabolic potential. These findings suggest potential differences in lipid metabolism and oxidative energy supply between apical and basal Hensen's cells, which is consistent with the morphological differences of Hensen's cells. We also found differential expression patterns of candidate genes associated with hereditary hearing loss (HHL), noise-induced hearing loss (NIHL), and age-related hearing loss (ARHL). These findings indicate functional heterogeneity of SCs along the cochlear axis, contribute to our understanding of cochlear physiology and provide molecular basis evidence for future studies of hearing loss.
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Osteoarthritis (OA) is a chronic degenerative joint disease that affects worldwide. Oxidative stress plays a critical role in the chronic inflammation and OA progression. Scavenging overproduced reactive oxygen species (ROS) could be rational strategy for OA treatment. Bilirubin (BR) is a potent endogenous antioxidant that can scavenge various ROS and also exhibit anti-inflammatory effects. However, whether BR could exert protection on chondrocytes for OA treatment has not yet been elucidated. Here, chondrocytes were exposed to hydrogen peroxide with or without BR treatment. The cell viability was assessed, and the intracellular ROS, inflammation cytokines were monitored to indicate the state of chondrocytes. In addition, BR was also tested on LPS-treated Raw264.7 cells to test the anti-inflammation property. An in vitro bimimic OA microenvironment was constructed by LPS-treated Raw264.7 and chondrocytes, and BR also exert certain protection for chondrocytes by activating Nrf2/HO-1 pathway and suppressing NF-κB signalling. An ACLT-induced OA model was constructed to test the in vivo therapeutic efficacy of BR. Compared to the clinical used HA, BR significantly reduced cartilage degeneration and delayed OA progression. Overall, our data shows that BR has a protective effect on chondrocytes and can delay OA progression caused by oxidative stress.
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NF-kappa B , Osteoartrite , Humanos , NF-kappa B/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Bilirrubina/farmacologia , Lipopolissacarídeos/farmacologia , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Inflamação/tratamento farmacológico , Condrócitos/metabolismo , Interleucina-1beta/farmacologiaRESUMO
Bacterial infections pose a significant risk to human health. Magnolol, derived from Magnolia officinalis, exhibits potent antibacterial properties. Synthetic biology offers a promising approach to manufacture such natural compounds. However, the plant-based biosynthesis of magnolol remains obscure, and the lack of identification of critical genes hampers its synthetic production. In this study, we have proposed a one-step conversion of magnolol from chavicol using laccase. After leveraging 20 transcriptomes from diverse parts of M. officinalis, transcripts were assembled, enriching genome annotation. Upon integrating this dataset with current genomic information, we could identify 30 laccase enzymes. From two potential gene clusters associated with magnolol production, highly expressed genes were subjected to functional analysis. In vitro experiments confirmed MoLAC14 as a pivotal enzyme in magnolol synthesis. Improvements in the thermal stability of MoLAC14 were achieved through selective mutations, where E345P, G377P, H347F, E346C, and E346F notably enhanced stability. By conducting alanine scanning, the essential residues in MoLAC14 were identified, and the L532A mutation further boosted magnolol production to an unprecedented level of 148.83 mg/L. Our findings not only elucidated the key enzymes for chavicol to magnolol conversion, but also laid the groundwork for synthetic biology-driven magnolol production, thereby providing valuable insights into M. officinalis biology and comparative plant science.
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Compostos Alílicos , Lignanas , Magnolia , Fenóis , Humanos , Magnolia/genética , Magnolia/química , Lacase , Lignanas/química , Compostos de Bifenilo/químicaRESUMO
Introduction: Olivetolic acid (OLA) is a key intermediate in cannabidiol (CBD) synthesis, and cannabinoids are important neuroactive drugs. However, the catalytic activity of olivetolic acid synthase (OLS), the key enzyme involved in OLA biosynthesis, remains low and its catalytic mechanism is unclear. Materials and Methods: In this study, we conducted a scrupulous screening of the pivotal rate-limiting enzyme and analyzed its amino acid sites that are critical to enzyme activity as validated by experiments. Results: Through stringent enzyme screening, we pinpointed a highly active OLS sequence, OLS4. Then, we narrowed down three critical amino acid sites (I258, D198, E196) that significantly influence the OLS activity. Conclusions: Our findings laid the groundwork for the efficient biosynthesis of OLA, and thereby facilitate the biosynthesis of CBD.
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OBJECTIVES: This study aimed to explore the effects of different duration and daily frequency of vestibular rehabilitation (VR) in patients with residual symptoms after benign paroxysmal positional vertigo (BPPV) successful repositioning. METHOD: Patients with successful BPPV repositioning (n = 118) were divided into 3 groups according to VR duration and frequency: group A (n = 30; 15 minutes, 3 times/day), group B (n = 30; 30 minutes, 3 times/day), group C (n = 28; 15 minutes, 6 times/day), and control group D (n = 30; no VR). All patients completed the dizziness handicap inventory (DHI) and vestibular rehabilitation benefit questionnaire (VRBQ) at baseline and after 2 and 4 weeks. RESULTS: The emotional scores and the proportion of severe dizziness disability in the DHI scores were significant differences between VR groups A to C and control group D after 2 and 4 weeks (all P < .05). There were significant differences in total DHI and VRBQ scores among the VR groups A to C after 2 and 4 weeks (all P < .05). Interestingly, emotion scores were not significantly different in group A (P = .385), group B (P = .569), and group C (P = .340) between 2 and 4 weeks. Meanwhile at 2 weeks, the difference in motion-provoked dizziness score between group A and B was statistically significant (P = .02). CONCLUSIONS: A total VR duration over 4 weeks can reduce dizziness and improve VR benefits in routine therapy in patients with residual dizziness after successful BPPV repositioning. Emotional improvement can be observed after 2 weeks. VR may help to relieve motion-provoked dizziness earlier if patients are willing to consider increasing the duration to more than 15 minutes.
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Vertigem Posicional Paroxística Benigna , Tontura , Humanos , Vertigem Posicional Paroxística Benigna/diagnóstico , Vertigem Posicional Paroxística Benigna/terapia , Tontura/etiologia , Tontura/terapia , Posicionamento do Paciente , Inquéritos e QuestionáriosRESUMO
Universal newborn hearing screening (UNHS) and audiological diagnosis are crucial for children with congenital hearing loss (HL). The objective of this study was to analyze hearing screening techniques, audiological outcomes and risk factors among children referred from a UNHS program in Beijing. A retrospective analysis was performed in children who were referred to our hospital after failing UNHS during a 9-year period. A series of audiological diagnostic tests were administered to each case, to confirm and determine the type and degree of HL. Risk factors for HL were collected. Of 1839 cases, 53.0% were referred after only transient evoked otoacoustic emission (TEOAE) testing, 46.1% were screened by a combination of TEOAE and automatic auditory brainstem response (AABR) testing, and 1.0% were referred after only AABR testing. HL was confirmed in 55.7% of cases. Ears with screening results that led to referral experienced a more severe degree of HL than those with results that passed. Risk factors for HL were identified in 113 (6.1%) cases. The main risk factors included craniofacial anomalies (2.7%), length of stay in the neonatal intensive care unit longer than 5 days (2.4%) and birth weight less than 1500 g (0.8%). The statistical data showed that age (P < 0.001) and risk factors, including craniofacial anomalies (P < 0.001) and low birth weight (P = 0.048), were associated with the presence of HL. This study suggested that hearing screening plays an important role in the early detection of HL and that children with risk factors should be closely monitored.
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Potenciais Evocados Auditivos do Tronco Encefálico , Triagem Neonatal , Recém-Nascido , Criança , Humanos , Pequim/epidemiologia , Estudos Retrospectivos , Triagem Neonatal/métodos , Testes Auditivos/métodos , Emissões Otoacústicas Espontâneas/fisiologia , Recém-Nascido de muito Baixo PesoRESUMO
Colon cancer in patients with situs inversus totalis is rarely associated with dextrocardia, and chemotherapy is commonly used for treatment. Central venous access devices are used to administer intravenous fluids and chemotherapy in patients with colon cancer. Compared with peripherally inserted central catheters and Hickman-type tunneled catheters, totally implantable vascular access devices (TIVADs) are safer and more effective. However, positioning the catheter tip may be challenging in patients with dextrocardia and situs inversus. We herein describe a novel case involving a patient with dextrocardia and colon cancer who was treated by TIVAD insertion with intracavitary electrocardiography-aided tip localization.
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Cateteres Venosos Centrais , Neoplasias do Colo , Dextrocardia , Situs Inversus , Humanos , Cateteres de Demora/efeitos adversos , Dextrocardia/complicações , Dextrocardia/diagnóstico por imagem , Situs Inversus/complicações , Neoplasias do Colo/complicações , Neoplasias do Colo/tratamento farmacológicoRESUMO
Age-related variations in many regions and/or networks of the human brain have been uncovered using resting-state functional magnetic resonance imaging. However, these findings did not account for the dynamical effect the brain's global activity (global signal [GS]) causes on local characteristics, which is measured by GS topography. To address this gap, we tested GS topography including its correlation with age using a large-scale cross-sectional adult lifespan dataset (n = 492). Both GS topography and its variation with age showed frequency-specific patterns, reflecting the spatiotemporal characteristics of the dynamic change of GS topography with age. A general trend toward dedifferentiation of GS topography with age was observed in both spatial (i.e., less differences of GS between different regions) and temporal (i.e., less differences of GS between different frequencies) dimensions. Further, methodological control analyses suggested that although most age-related dedifferentiation effects remained across different preprocessing strategies, some were triggered by neuro-vascular coupling and physiological noises. Together, these results provide the first evidence for age-related effects on global brain activity and its topographic-dynamic representation in terms of spatiotemporal dedifferentiation.
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Mapeamento Encefálico , Longevidade , Humanos , Adulto , Mapeamento Encefálico/métodos , Estudos Transversais , Imageamento por Ressonância Magnética/métodos , Encéfalo/fisiologiaRESUMO
Hearing loss is one of the most common sensory disorders in humans. The purpose of this review is to summarize the history and current status of newborn hearing screening in China and to investigate future developmental trends in newborn hearing screening with the intention of sharing experiences and providing a reference for other populations. In the 1980s, the research on hearing monitoring for high-risk infants led to the gradual development of newborn hearing screening in China. With the continuous improvement of screening technology, the newborn hearing screening program was gradually extended to the whole country and became a government-led multidisciplinary public health program. Genetic screening for deafness has been incorporated into newborn hearing screening in many regions of China to help screen for potential and late-onset deafness in newborns. In the future, it is necessary to further establish and improve whole life-cycle hearing screening and healthcare, conduct screening for congenital cytomegalovirus infection, and create a full-coverage, whole life course hearing screening and intervention system. Screening for deafness in China has been marked by 40 years of achievements, which have been a source of pride for entrepreneurs and comfort for patients and their families. Managing hearing screening data information more efficiently and establishing a quality control index system throughout the whole screening process are of paramount importance. The genetic screening for concurrent newborn hearing and deafness has a great clinical importance for the management of congenital deafness and prevention of ototoxicity. A hearing screening and intervention system across the whole life course should be developed.
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OBJECTIVE: To evaluate the feasibility of using an intrarectal Foley catheter during ultrasound-guided high-intensity focused ultrasound (US-HIFU) in patients with benign uterine diseases of the posterior wall beyond the HIFU therapeutic range. METHODS: Patients were treated with US-HIFU and lesion changes were monitored using contrast-enhanced MRI from June 2020 to September 2021. A Foley catheter was inserted into the rectum to facilitate a successful US-HIFU ablation. Complications and lesion responses were recorded during the treatment and follow-up. RESULTS: Thirteen patients with 14 lesions beyond the device's treatable area were enrolled. The average placement time and insertion depth of the intrarectal Foley catheter was 7.6 ± 2.7 min and 23.2 ± 7.6 cm, respectively. A median of 50 mL degassed water was injected into the Foley catheter balloon. All 14 lesions were successfully pushed into a treatable area and subjected to HIFU. The average treatment time, irradiation time, and total therapeutic energy of HIFU were 44.2 ± 17.3 min, 394.4 ± 295.7 s, and 73.3 ± 46.6 kJ, respectively. The mean non-perfusion volume (NPV) in all treated lesions was 23.2 ± 19.2 cm3, and the mean NPV ratio was 57.8 ± 16.9%. Major complications were not observed. CONCLUSION: Intrarectal Foley catheter-assisted US-HIFU is effective and safe. Its clinical application could benefit patients with benign uterine diseases outside the HIFU therapeutic range.
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Ablação por Ultrassom Focalizado de Alta Intensidade , Leiomioma , Doenças Uterinas , Neoplasias Uterinas , Feminino , Humanos , Neoplasias Uterinas/cirurgia , Leiomioma/cirurgia , Resultado do Tratamento , Doenças Uterinas/diagnóstico por imagem , Doenças Uterinas/cirurgia , CateteresRESUMO
Overgeneralisation is one of the aetiologies of anxiety disorders and is closely associated with elevated intolerance of uncertainty (IU) levels. However, the underlying mechanisms are unclear. Considering the inconsistency of previous results and the high sensitivity of IU to uncertainty, the present study investigated the effect of IU on threat generalisation in predictable and unpredictable conditions. We compared self-reported unconditioned stimuli (US) expectancy and event-related potentials (ERPs) during generalisation in high IU (n = 34) and low IU (n = 35) participants. The results indicated that high IU was associated with higher US expectancy for generalisation stimuli (GS) than with low IU. At the electrophysiological level, compared to low IU, high IU showed increased P1 to ambiguous GS as well as decreased early late positive potential (LPP) to GS in unpredictable conditions, and no differential response to GS in late LPP in predictable conditions. These findings suggest that IU enhances threat generalisation and may be related to increased early automatic attention to ambiguous stimulus and inadequate late elaborate processing in a high uncertainty context. These findings might contribute to the treatment of mood disorders characterized by high IU.
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Transtornos de Ansiedade , Potenciais Evocados , Humanos , Incerteza , Potenciais Evocados/fisiologia , Sinais (Psicologia) , Cognição , AnsiedadeRESUMO
Oxaliplatin (OXA) resistance remains the major obstacle to the successful chemotherapy of colorectal cancer (CRC). As a self-protection mechanism, autophagy may contribute to tumor drug resistance, therefore autophagy suppression could be regarded as a possible treatment option in chemotherapy. Cancer cells, especially drug-resistant tumor cells, increase their demand for specific amino acids by expanding exogenous supply and up-regulating de novo synthesis, to meet the needs for excessive proliferation. Therefore, it is possible to inhibit cancer cell proliferation through pharmacologically blocking the entry of amino acid into cancer cells. SLC6A14 (ATB0,+) is an essential amino acid transporter, that is often abnormally up-regulated in most cancer cells. Herein, in this study, we designed oxaliplatin/berbamine-coloaded, ATB0,+-targeted nanoparticles ((O + B)@Trp-NPs) to therapeutically target SLC6A14 (ATB0,+) and inhibit cancer proliferation. The (O + B)@Trp-NPs utilize the surface-modified tryptophan to achieve SLC6A14-targeted delivery of Berbamine (BBM), a compound that is found in a number of plants used in traditional Chinese medicine, which could suppress autolysosome formation though impairing autophagosome-lysosome fusion. We verified the feasibility of this strategy to overcome the OXA resistance during colorectal cancer treatment. The (O + B)@Trp-NPs significantly inhibited the proliferation and decreased the drug resistance of resistant colorectal cancer cells. In vivo, (O + B)@Trp-NPs greatly suppressed the tumor growth in tumor-bearing mice, which is consistent with the in vitro data. This research offers a unique and promising chemotherapeutic treatment for colorectal cancer.
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Neoplasias Colorretais , Nanopartículas , Animais , Camundongos , Oxaliplatina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Autofagia , Neoplasias Colorretais/tratamento farmacológico , Linhagem Celular TumoralRESUMO
Acute liver failure (ALF) is a severe liver disease caused by many reasons. One of them is the overdosed acetaminophen (APAP), which is metabolized into N-acetyl-p-benzoquinone imine (NAPQI), an excessive toxic metabolite, by CYP2E1, resulting in excessive reactive oxygen species (ROS), exhausted glutathione (GSH), and thereafter hepatocyte necrosis. N-acetylcysteine is the Food and Drug Administration-approved drug for detoxification of APAP, but it has limited clinical application due to the short therapeutic time window and concentration-related adverse effects. In this study, a carrier-free and bilirubin dotted nanoparticle (B/BG@N) is developed, which is formed using bilirubin and 18ß-Glycyrrhetinic acid, and bovine serum albumin (BSA) is then adsorbed to mimic the in vivo behavior of the conjugated bilirubin for hitchhiking. The results demonstrate that B/BG@N can effectively reduce the production of NAPQI as well as exhibit antioxidant effects against intracellular oxidative stress via regulating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signal axis and reducing the production of inflammatory factors. In vivo study shows that B/BG@N can effectively improve the clinical symptom of the mice model. This study suggests that B/BG@N own increases circulation half-life, improves accumulation in the liver, and dual detoxification, providing a promising strategy for clinical ALF treatment.
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Acetaminofen , Falência Hepática Aguda , Animais , Camundongos , Acetaminofen/efeitos adversos , Acetaminofen/metabolismo , Citocromo P-450 CYP2E1/metabolismo , Citocromo P-450 CYP2E1/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Biomimética , Fígado/metabolismo , Falência Hepática Aguda/tratamento farmacológico , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/metabolismo , Glutationa/metabolismo , Bilirrubina/metabolismo , Bilirrubina/farmacologiaRESUMO
Threat generalisation is an adaptive process that is essential for individual survival. In contrast, over-generalisation is a pathological process that underlies the development of anxiety disorders. Intolerance of uncertainty (IU) is an individual characteristic known to influence threat generalisation by altering the responses to threat in uncertain situations. However, how it affects contextual threat generalisation remains unclear. Here, we used a novel paradigm to investigate whether contextual threat generalisation varied between individuals depending on their IU level (high or low) and the predictability of a situation (predictable or unpredictable). We analysed shock expectancy in 82 participants (age: 18-27 years) during threat acquisition and generalisation. Results showed that compared with the low IU group, the high IU group exhibited increased contextual threat generalisation to threat-related cues in unpredictable situation. These findings suggest that IU could be a marker for anxiety disorder susceptibility, as well as a target for anxiety treatment.
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Ansiedade , Individualidade , Humanos , Adolescente , Adulto Jovem , Adulto , Incerteza , Transtornos de Ansiedade , Sinais (Psicologia)RESUMO
Concurrent screening has been proven to provide a comprehensive approach for management of congenital deafness and prevention of ototoxicity. The SLC26A4 gene is associated with late-onset hearing loss and is of great clinical concern. For much earlier detection of newborns with deafness-causing mutations in the SLC26A4 gene, the Beijing Municipal Government launched a chip for optimized genetic screening of 15 variants of 4 genes causing deafness based on a chip to screen for 9 variants of 4 genes, and 6 variants of the SLC26A4 gene have now been added. To ascertain the advantage of a screening chip including 15 variants of 4 genes, the trends in concurrent hearing and genetic screening were analyzed in 2019 and 2020. Subjects were 76,460 newborns who underwent concurrent hearing and genetic screening at 24 maternal and child care centers in Beijing from January 2019 to December 2020. Hearing screening was conducted using transiently evoked otoacoustic emissions (TEOAEs), distortion product otoacoustic emissions (DPOAE), or the automated auditory brainstem response (AABR). Dried blood spots were collected for genetic testing and 15 variants of 4 genes, namely GJB2, SLC26A4, mtDNA 12S rRNA, and GJB3, were screened for using a DNA microarray platform. The initial referral rate for hearing screening decreased from 3.60% (1,502/41,690) in 2019 to 3.23% (1,124/34,770) in 2020, and the total referral rate for hearing screening dropped form 0.57% (236/41,690) in 2019 to 0.54% (187/34,770) in 2020, indicating the reduced false positive rate of newborn hearing screening and policies to prevent hearing loss conducted by the Beijing Municipal Government have had a significant effect. Positivity according to genetic screening was similar in 2019 (4.970%, 2,072/41,690) and 2020 (4.863%,1,691/34,770), and the most frequent mutant alleles were c.235 del C in the GJB2 gene, followed by c.919-2 A > G in the SLC26A4 gene, and c.299 del AT in the GJB2 gene. In this cohort study, 71.43% (5/7) of newborns with 2 variants of the SLC26A4 gene were screened for newly added mutations, and 28.57% (2/7) of newborns with 2 variants of the SLC26A4 gene passed hearing screening, suggesting that a screening chip including 15 variants of 4 genes was superior at early detection of hearing loss, and especially in early identification of newborns with deafness-causing mutations in the SLC26A4 gene. These findings have clinical significance.
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Surdez , Perda Auditiva , Humanos , Recém-Nascido , Pequim , Estudos Transversais , Estudos de Coortes , Conexinas/genética , Conexina 26/genética , Testes Genéticos , Surdez/genética , Perda Auditiva/diagnóstico , Perda Auditiva/genética , Mutação/genética , China , Audição , Análise Mutacional de DNARESUMO
Objective:To investigate the clinical audiological characteristics of children referred from maternal and child institutions and analyze the high risk factors of hearing loss, so as to provide scientific basis for further improvement of children's ear and hearing care. Methods:The subjects of this study were 868 children who were referred by maternal and child institutions in Beijing to the otology outpatient of Beijing Tongren Hospital, Capital Medical University for hearing diagnosis. All subjects underwent acoustic immittance, auditory brainstem response, distortion products otoacoustic emission and other audiological tests. Children were divided into groups according to the age of diagnosis: 0-<3 months groupï¼242 casesï¼, 3-<6 months groupï¼328 casesï¼, 6-<12 months groupï¼180 casesï¼, ≥12 months groupï¼118 casesï¼, the results of hearing diagnosis, hearing loss degree and types, the relationship between high risk factors and hearing loss in each group were compared and analyzed. Results:The age of diagnosis of 868 children wasï¼7.13±8.29ï¼ months. 488 cases with hearing loss accounted for 56.22% and 380 cases with normal hearing accounted for 43.78%. Proportion of different degree of hearing loss of 792 ears from high to low was as follows: mild, 366 earsï¼46.21%ï¼; moderate, 214 earsï¼27.02%ï¼; severe, 151 earsï¼19.07%ï¼; profound, 61 earsï¼7.70%ï¼. There were statistically significant differences in the proportion of different hearing loss degree among 0-<3 months group, 3-<6 months group, 6-<12 months group and ≥12 months groupï¼P<0.001ï¼. Pairwise comparison between groups showed that the proportion of mild hearing loss of 0-<3 months group was higher than that in the other three groupsï¼P<0.05ï¼, there was no significant difference of moderate hearing loss among all groupsï¼P>0.05ï¼, the proportion of severe hearing loss of ≥12 months group was higher than that of 0-<3 months groupï¼P<0.05ï¼. The proportion of profound hearing loss with 0-<3 months group was lower than the other three groupsï¼P<0.05ï¼. In 792 ears with hearing loss, sensorineural hearing loss accounted for 67.42%, conductive hearing loss accounted for 20.71% and mixed hearing loss accounted for 11.87%. Among 98 cases with high risk factors for hearing loss, 58 casesï¼59.18%ï¼ were diagnosed with hearing loss. The incidence of hearing loss with high risk factors ranked from high to low was: craniofacial malformationï¼93.75%ï¼, family history/congenital genetic syndromeï¼61.11%ï¼, neonatal intensive care unitï¼NICUï¼ hospitalizationï¼46.43%ï¼ and othersï¼20.00%ï¼. Conclusion:Referrals from maternal and child institutions play an important role in the early detection of children with mild to moderate sensorineural hearing loss. Children with craniofacial malformation, family history/congenital genetic syndrome, hospitalization history of NICU and other high risk factors have a high incidence of hearing loss and should be attached with great importance.
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Surdez , Perda Auditiva Neurossensorial , Perda Auditiva , Recém-Nascido , Criança , Humanos , Lactente , Perda Auditiva Neurossensorial/diagnóstico , Audição , Perda Auditiva/epidemiologia , Testes Auditivos/métodos , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologiaRESUMO
Electrochemical oxidase biosensors have been widely applied in healthcare, environmental measurements and the biomedical field. However, the low and fluctuant oxygen levels in solution and the high anodic detection potentially restrict the assay accuracy. To address these problems, in this work, we constructed a three-phase interface enzyme electrode by sequentially immobilizing H2O2 electrocatalysts and an oxidase layer on a superhydrophobic laser-induced graphene (LIG) array substrate. The LIG-based enzyme electrode possesses a solid-liquid-air three-phase interface where constant and sufficient oxygen can be supplied from the air phase to the enzymatic reaction zone, which enhances and stabilizes the oxidase kinetics. We discovered that the enzymatic reaction rate is 21.2-fold improved over that of a solid-liquid diphase system where oxygen is supplied from the liquid phase, leading to a 60-times wider linear detection range. Moreover, the three-phase enzyme electrode can employ a cathodic measuring principle for oxidase catalytic product H2O2 detection, which could minimize interferences arising from oxidizable molecules in biofluids and increase the detection selectivity. This work provides a simple and promising approach to the design and construction of high-performance bioassay systems.
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At present, the high re-combination rate of photogenerated carriers and the low redox capability of the photocatalyst are two factors that severely limit the improvement of photocatalytic performance. Herein, a dual Z-scheme photocatalyst bismuthzirconate/graphitic carbon nitride/silver phosphate (Bi2Zr2O7/g-C3N4/Ag3PO4 (BCA)) was synthesized using a co-precipitation method, and a dual Z-scheme heterojunction photocatalytic system was established to decrease the high re-combination rate of photogenerated carriers and consequently improve the photocatalytic performance. The re-combination of electron-hole pairs (e- and h+) in the valence band (VB) of g-C3N4 increases the redox potential of e- and h+, leading to significant improvements in the redox capability of the photocatalyst and the efficiency of e--h+ separation. As a photosensitizer, Ag3PO4 can enhance the visible light absorption capacity of the photocatalyst. The prepared photocatalyst showed strong stability, which was attributed to the efficient suppression of photo-corrosion of Ag3PO4 by transferring the e- to the VB of g-C3N4. Tetracycline was degraded efficiently by BCA-10% (the BCA with 10 wt.% of AgPO4) under visible light, and the degradation efficiency was up to 86.2%. This study experimentally suggested that the BCA photocatalyst has broad application prospects in removing antibiotic pollution.