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1.
Ann Med ; 56(1): 2402949, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39268590

RESUMEN

INTRODUCTION: Tinnitus is a prevalent and disabling condition characterized by the perception of sound in the absence of external acoustic stimuli. The hyperactivity of the auditory pathway is a crucial factor in the development of tinnitus. This study aims to examine genetic expression variations in the dorsal cochlear nucleus (DCN) and inferior colliculus (IC) following the onset of tinnitus using transcriptomic analysis. The goal is to investigate the relationship between hyperactivity in the DCN and IC. METHODS: To confirm the presence of tinnitus behavior, we utilized the gap pre-pulse inhibition of the acoustic startle (GPIAS) response paradigm. In addition, we conducted auditory brainstem response (ABR) tests to determine the baseline hearing thresholds, and repeated the test one week after subjecting the rats to noise exposure (8-16 kHz, 126 dBHL, 2 h). Samples of tissue were collected from the DCN and IC in both the tinnitus and non-tinnitus groups of rats. We employed RNA sequencing and quantitative PCR techniques to analyze the changes in gene expression between these two groups. This allowed us to identify any specific genes or gene pathways that may be associated with the development or maintenance of tinnitus in the DCN and IC. RESULTS: Our results demonstrated tinnitus-like behavior in rats exposed to noise, as evidenced by GPIAS measurements. We identified 61 upregulated genes and 189 downregulated genes in the DCN, along with 396 upregulated genes and 195 downregulated genes in the IC. Enrichment analysis of the DCN revealed the involvement of ion transmembrane transport regulation, synaptic transmission, and negative regulation of neuron apoptotic processes in the development of tinnitus. In the IC, the enrichment analysis indicated that glutamatergic synapses and neuroactive ligand-receptor interaction pathways may significantly contribute to the process of tinnitus development. Additionally, protein-protein interaction (PPI) networks were constructed, and 9 hub genes were selected based on their betweenness centrality rank in the DCN and IC, respectively. CONCLUSIONS: Our findings reveal enrichment of differential expressed genes (DEGs) associated with pathways linked to alterations in neuronal excitability within the DCN and IC when comparing the tinnitus group to the non-tinnitus group. This indicates an increased trend in neuronal excitability within both the DCN and IC in the tinnitus model rats. Additionally, the enriched signaling pathways within the DCN related to changes in synaptic plasticity suggest that the excitability changes may propagate to IC. NEW AND NOTEWORTHY: Our findings reveal gene expression alterations in neuronal excitability within the DCN and IC when comparing the tinnitus group to the non-tinnitus group at the transcriptome level. Additionally, the enriched signaling pathways related to changes in synaptic plasticity in the differentially expressed genes within the DCN suggest that the excitability changes may propagate to IC.


Asunto(s)
Núcleo Coclear , Potenciales Evocados Auditivos del Tronco Encefálico , Colículos Inferiores , Ruido , Acúfeno , Animales , Colículos Inferiores/metabolismo , Colículos Inferiores/fisiopatología , Acúfeno/genética , Acúfeno/fisiopatología , Acúfeno/metabolismo , Núcleo Coclear/metabolismo , Núcleo Coclear/fisiopatología , Ratas , Masculino , Ruido/efectos adversos , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Transcriptoma , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Reflejo de Sobresalto , Perfilación de la Expresión Génica/métodos
2.
Org Lett ; 26(35): 7457-7462, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39186632

RESUMEN

An efficient rhodium-catalyzed asymmetric transfer hydrogenation of ß-cyano α-ketoesters via dynamic kinetic resolution has been developed. Despite the challenge posed by multiple functional groups, the reaction proceeded smoothly under mild conditions, generating versatile synthons with two adjacent stereocenters in high yields with excellent enantio- and diastereoselectivities. Furthermore, the power of this strategy is highlighted by the scale-up reaction and the follow-up synthesis of cytoxazone and paclitaxel intermediates.

3.
J Am Chem Soc ; 146(28): 19019-19029, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38963153

RESUMEN

Photocatalysis has emerged as an effective tool for addressing the contemporary challenges in organic synthesis. However, the trial-and-error-based screening of feasible substrates and optimal reaction conditions remains time-consuming and potentially expensive in industrial practice. Here, we demonstrate an electrochemical-based data-acquisition approach that derives a simple set of redox-relevant electro-descriptors for effective mechanistic analysis and performance evaluation through machine learning (ML) in photocatalytic synthesis. These electro-descriptors correlate to the quantification of shifted charge transfer processes in response to the photoirradiation and enabled construction of reactivity diagram where high-yield reactive "hot zones" can reflect subtle changes of the reaction system. For the model reaction of photocatalytic deoxygenation reaction, the influence of varying carboxylic acids (substrate A, oxidation-intended) and alkenes (substrate B, reduction-intended) and varying reaction conditions on the reaction yield can be visualized, while mathematical analysis of the electro-descriptor patterns further revealed distinct mechanistic/kinetic impacts from different substrates and conditions. Additionally, in the application of ML algorithms, the experimentally derived electro-descriptors reflect an overall redox kinetic outcome contributed from vast reaction parameters, serving as a capable means to reduce the dimensionality in the case of complex multiparameter chemical space. As a result, utilization of electro-descriptors enabled efficient and robust quantitative evaluation of chemical reactivity, demonstrating promising potential of introducing operando-relevant experimental insights in the data-driven chemistry.

4.
Tomography ; 10(7): 1089-1098, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39058054

RESUMEN

Cross-species research has advanced human understanding of brain regions, with cross-species comparisons using magnetic resonance imaging technology becoming increasingly common. Currently, cross-species research on human language regions has primarily focused on traditional brain areas such as the Broca region. While some studies have indicated that human language function also involves other language regions, the corresponding relationships between these brain regions in humans and macaques remain unclear. This study calculated the strength of the connections between the high-level language processing regions in human and macaque brains, identified homologous target areas based on the structural connections of white-matter fiber bundles, and compared the connectivity profiles of both species. The results of the experiment demonstrated that macaques possess brain regions which exhibit connectivity patterns resembling those found in human high-level language processing regions. This discovery suggests that while the function of a human brain region is specialized, it still maintains a structural connectivity similar to that seen in macaques.


Asunto(s)
Encéfalo , Lenguaje , Macaca , Imagen por Resonancia Magnética , Animales , Humanos , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Masculino , Mapeo Encefálico/métodos , Femenino , Adulto , Sustancia Blanca/diagnóstico por imagen , Adulto Joven , Especificidad de la Especie
5.
Genes (Basel) ; 15(6)2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38927693

RESUMEN

The identification and expression of germ cells are important for studying sex-related mechanisms in fish. The vasa gene, encoding an ATP-dependent RNA helicase, is recognized as a molecular marker of germ cells and plays a crucial role in germ cell development. Silurus asotus, an important freshwater economic fish species in China, shows significant sex dimorphism with the female growing faster than the male. However, the molecular mechanisms underlying these sex differences especially involving in the vasa gene in this fish remain poorly understood. In this work, the vasa gene sequence of S. asotus (named as Savasa) was obtained through RT-PCR and rapid amplification of cDNA end (RACE), and its expression in embryos and tissues was analyzed using qRT-PCR and an in situ hybridization method. Letrozole (LT) treatment on the larvae fish was also conducted to investigate its influence on the gene. The results revealed that the open reading frame (ORF) of Savasa was 1989 bp, encoding 662 amino acids. The SaVasa protein contains 10 conserved domains unique to the DEAD-box protein family, showing the highest sequence identity of 95.92% with that of Silurus meridionalis. In embryos, Savasa is highly expressed from the two-cell stage to the blastula stage in early embryos, with a gradually decreasing trend from the gastrula stage to the heart-beating stage. Furthermore, Savasa was initially detected at the end of the cleavage furrow during the two-cell stage, later condensing into four symmetrical cell clusters with embryonic development. At the gastrula stage, Savasa-positive cells increased and began to migrate towards the dorsal side of the embryo. In tissues, Savasa is predominantly expressed in the ovaries, with almost no or lower expression in other detected tissues. Moreover, Savasa was expressed in phase I-V oocytes in the ovaries, as well as in spermatogonia and spermatocytes in the testis, implying a specific expression pattern of germ cells. In addition, LT significantly upregulated the expression of Savasa in a concentration-dependent manner during the key gonadal differentiation period of the fish. Notably, at 120 dph after LT treatment, Savasa expression was the lowest in the testis and ovary of the high concentration group. Collectively, findings from gene structure, protein sequence, phylogenetic analysis, RNA expression patterns, and response to LT suggest that Savasa is maternally inherited with conserved features, serving as a potential marker gene for germ cells in S.asotus, and might participate in LT-induced early embryonic development and gonadal development processes of the fish. This would provide a basis for further research on the application of germ cell markers and the molecular mechanisms of sex differences in S. asotus.


Asunto(s)
Bagres , ARN Helicasas DEAD-box , Proteínas de Peces , Letrozol , Animales , Letrozol/farmacología , Femenino , Masculino , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , Bagres/genética , Bagres/crecimiento & desarrollo , Bagres/metabolismo , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Células Germinativas/metabolismo , Células Germinativas/efectos de los fármacos , Células Germinativas/crecimiento & desarrollo , Filogenia
6.
Front Plant Sci ; 15: 1353352, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38689842

RESUMEN

Among tropical fruit trees, coconut holds significant edible and economic importance. The natural growth of coconuts faces a challenge in the form of low temperatures, which is a crucial factor among adverse environmental stresses impacting their geographical distribution. Hence, it is essential to enhance our comprehension of the molecular mechanisms through which cold stress influences various coconut varieties. We employed analyses of leaf growth morphology and physiological traits to examine how coconuts respond to low temperatures over 2-hour, 8-hour, 2-day, and 7-day intervals. Additionally, we performed transcriptome and metabolome analyses to identify the molecular and physiological shifts in two coconut varieties displaying distinct sensitivities to the cold stress. As the length of cold stress extended, there was a prominent escalation within the soluble protein (SP), proline (Pro) concentrations, the activity of peroxidase (POD) and superoxide dismutase (SOD) in the leaves. Contrariwise, the activity of glutathione peroxidase (GSH) underwent a substantial reduction during this period. The widespread analysis of metabolome and transcriptome disclosed a nexus of genes and metabolites intricately cold stress were chiefly involved in pathways centered around amino acid, flavonoid, carbohydrate and lipid metabolism. We perceived several stress-responsive metabolites, such as flavonoids, carbohydrates, lipids, and amino acids, which unveiled considerably, lower in the genotype subtle to cold stress. Furthermore, we uncovered pivotal genes in the amino acid biosynthesis, antioxidant system and flavonoid biosynthesis pathway that presented down-regulation in coconut varieties sensitive to cold stress. This study broadly enriches our contemporary perception of the molecular machinery that contributes to altering levels of cold stress tolerance amid coconut genotypes. It also unlocks several unique prospects for exploration in the areas of breeding or engineering, aiming to identifying tolerant and/or sensitive coconut varieties encompassing multi-omics layers in response to cold stress conditions.

7.
J Alzheimers Dis ; 99(4): 1273-1283, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38728186

RESUMEN

Background: Cardiovascular Risk Factors, Ageing and Dementia (CAIDE) risk score serves as a credible predictor of an individual's risk of dementia. However, studies on the link of the CAIDE score to Alzheimer's disease (AD) pathology are scarce. Objective: To explore the links of CAIDE score to cerebrospinal fluid (CSF) biomarkers of AD as well as to cognitive performance. Methods: In the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study, we recruited 600 cognitively normal participants. Correlations between the CAIDE score and CSF biomarkers of AD as well as cognitive performance were probed through multiple linear regression models. Whether the correlation between CAIDE score and cognitive performance was mediated by AD pathology was researched by means of mediation analyses. Results: Linear regression analyses illustrated that CAIDE score was positively associated with tau-related biomarkers, including pTau (p < 0.001), tTau (p < 0.001), as well as tTau/Aß42 (p = 0.008), while it was in negative association with cognitive scores, consisting of MMSE score (p < 0.001) as well as MoCA score (p < 0.001). The correlation from CAIDE score to cognitive scores was in part mediated by tau pathology, with a mediation rate varying from 3.2% to 13.2%. Conclusions: A higher CAIDE score, as demonstrated in our study, was linked to more severe tau pathology and poorer cognitive performance, and tau pathology mediated the link of CAIDE score to cognitive performance. Increased dementia risk will lead to cognitive decline through aggravating neurodegeneration.


Asunto(s)
Enfermedad de Alzheimer , Biomarcadores , Cognición , Proteínas tau , Humanos , Masculino , Femenino , Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/psicología , Anciano , Cognición/fisiología , Biomarcadores/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeo , Persona de Mediana Edad , Péptidos beta-Amiloides/líquido cefalorraquídeo , Envejecimiento/psicología , Factores de Riesgo , Pruebas Neuropsicológicas/estadística & datos numéricos , Enfermedades Cardiovasculares , Anciano de 80 o más Años , Fragmentos de Péptidos/líquido cefalorraquídeo
8.
Food Funct ; 15(10): 5287-5299, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38639730

RESUMEN

Catechol-O-methyltransferase (COMT) plays a central role in the metabolic inactivation of endogenous neurotransmitters and xenobiotic drugs and hormones having catecholic structures. Its inhibitors are used in clinical practice to treat Parkinson's disease. In this study, a fluorescence-based visualization inhibitor screening method was developed to assess the inhibition activity on COMT both in vitro and in living cells. Following the screening of 94 natural products, Pu-erh tea extract exhibited the most potent inhibitory effect on COMT with an IC50 value of 0.34 µg mL-1. In vivo experiments revealed that Pu-erh tea extract substantially hindered COMT-mediated levodopa metabolism in rats, resulting in a significant increase in levodopa levels and a notable decrease in 3-O-methyldopa in plasma. Subsequently, the chemical components of Pu-erh tea were analyzed using UHPLC-Q-Exactive Orbitrap HRMS, identifying 24 major components. Among them, epigallocatechin gallate, gallocatechin gallate, epicatechin gallate, and catechin gallate exhibited potent inhibition of COMT activity with IC50 values from 93.7 nM to 125.8 nM and were the main bioactive constituents in Pu-erh tea responsible for its COMT inhibition effect. Inhibition kinetics analyses and docking simulations revealed that these compounds competitively inhibit COMT-mediated O-methylation at the catechol site. Overall, this study not only explained how Pu-erh tea catechins inhibit COMT, suggesting Pu-erh tea as a potential dietary intervention for Parkinson's disease, but also introduced a new strategy for discovering COMT inhibitors more effectively.


Asunto(s)
Catequina , Inhibidores de Catecol O-Metiltransferasa , Catecol O-Metiltransferasa , Levodopa , Extractos Vegetales , Ratas Sprague-Dawley , , Animales , Ratas , Inhibidores de Catecol O-Metiltransferasa/farmacología , Catecol O-Metiltransferasa/metabolismo , Catequina/análogos & derivados , Catequina/farmacología , Catequina/química , Levodopa/metabolismo , Té/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Masculino , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Camellia sinensis/química , Simulación del Acoplamiento Molecular
9.
J Vis Exp ; (206)2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38682934

RESUMEN

The eustachian tube (ET) is one of the most complex organs in the human body, and its dysfunction may lead to a variety of diseases. In recent years, an increasing number of scholars have opted to conduct ET-related studies using large experimental animals such as miniature pigs or sheep, yielding promising results. Typically, conventional endoscopic procedures are performed through the nasal approach for large experimental animals. However, due to the elongated and narrow nasal cavity in these animals, transnasal surgeries are challenging. To address this issue, we explored an ET surgery approach via the soft palate. The animal was placed in a supine position. After endotracheal intubation under general anesthesia, a mouth opener was used to fully expose the upper palate. Local infiltration with diluted adrenal fluid was performed for anesthesia of the area. A sickle knife was then used to make a longitudinal soft palate incision at the junction of the soft and hard palates. After hemostasis, an endoscope was inserted into the nasopharynx cavity, allowing the visualization of the pharyngeal opening of the ET on the posterior lateral wall of the nasal cavity. Subsequently, a specialized pusher was used to insert a balloon into ET. The balloon was inflated, maintained at 10 bar for 2 min, and then removed. The incision in the soft palate was then sutured to ensure proper alignment. The soft palate healed well after the operation. This surgical approach is suitable for ET-related procedures in large experimental animals (e.g., miniature pigs, sheep, and dogs). The surgical procedure is simple, with a short surgical time, and wound healing is rapid. Under endoscopy, the pharyngeal opening of the ET is visible, and it is thus a good choice for procedures such as balloon dilation of the ET.


Asunto(s)
Trompa Auditiva , Paladar Blando , Porcinos Enanos , Animales , Trompa Auditiva/cirugía , Porcinos , Paladar Blando/cirugía , Endoscopía/métodos , Dilatación/métodos
10.
Am J Audiol ; 33(2): 433-441, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38661487

RESUMEN

PURPOSE: So far, there have been no in-depth analyses of the connection between tinnitus sensation-level loudness and sleep quality. Accordingly, the present study was formulated as a mediation analysis focused on exploring this relationship. METHOD: Overall, 1,255 adults with consecutive subjective tinnitus who had sought outpatient treatment were enrolled in the present study. RESULTS: Direct effects of tinnitus sensation-level loudness on sleep quality were not statistically significant (95% confidence intervals [CI] include zero), as measured by the point estimate, -0.016. However, the 95% CI for indirect effects did not include zero when assessing the Self-Rating Anxiety Scale (SAS) scores, the Self-Rating Depression Scale (SDS) scores, the visual analogue scale (VAS) scores, and self-reported tinnitus annoyance. CONCLUSIONS: These results suggest that tinnitus sensation-level loudness does not directly have an effect on sleep quality. However, it indirectly impacts sleep quality, mediated by SAS scores, SDS scores, the impact of tinnitus on life measured using the VAS, and self-reported tinnitus annoyance. As such, alleviating anxiety and depression in patients with tinnitus may result in reductions in their insomnia even if there is no reduction in tinnitus loudness. Importantly, otolaryngologists and other clinicians treating tinnitus should refer patients with tinnitus suffering from insomnia with comorbid depression or anxiety for appropriate psychological and/or psychiatric treatment.


Asunto(s)
Ansiedad , Depresión , Percepción Sonora , Análisis de Mediación , Calidad del Sueño , Acúfeno , Humanos , Acúfeno/psicología , Acúfeno/fisiopatología , Acúfeno/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Autoinforme , Trastornos del Inicio y del Mantenimiento del Sueño
11.
Exp Biol Med (Maywood) ; 249: 10057, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38562529

RESUMEN

Tinnitus is a disturbing condition defined as the occurrence of acoustic hallucinations with no actual sound. Although the mechanisms underlying tinnitus have been explored extensively, the pathophysiology of the disease is not completely understood. Moreover, genes and potential treatment targets related to auditory hallucinations remain unknown. In this study, we examined transcriptional-profile changes in the medial geniculate body after noise-induced tinnitus in rats by performing RNA sequencing and validated differentially expressed genes via quantitative polymerase chain reaction analysis. The rat model of tinnitus was established by analyzing startle behavior based on gap-pre-pulse inhibition of acoustic startles. We identified 87 differently expressed genes, of which 40 were upregulated and 47 were downregulated. Pathway-enrichment analysis revealed that the differentially enriched genes in the tinnitus group were associated with pathway terms, such as coronavirus disease COVID-19, neuroactive ligand-receptor interaction. Protein-protein-interaction networks were established, and two hub genes (Rpl7a and AC136661.1) were identified among the selected genes. Further studies focusing on targeting and modulating these genes are required for developing potential treatments for noise-induced tinnitus in patients.


Asunto(s)
Acúfeno , Humanos , Ratas , Animales , Acúfeno/genética , Acúfeno/metabolismo , Cuerpos Geniculados/metabolismo , Ruido/efectos adversos
12.
Clin Exp Med ; 24(1): 70, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38578316

RESUMEN

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is an autoimmune disease that involves inflammation of blood vessels. There is increasing evidence that platelets play a crucial role not only in hemostasis but also in inflammation and innate immunity. In this study, we explored the relationship between platelet count, clinical characteristics, and the prognosis of patients with AAV. We divided 187 patients into two groups based on their platelet count. Clinicopathological data and prognostic information were retrospectively gathered from medical records. Univariate and multivariate regression analyses were used to identify risk factors for prognosis, including end-stage renal disease (ESRD) and mortality. The cutoff point for platelet count was set at 264.5 × 109/L, as determined by the receiver operating characteristic (ROC) curve for predicting progression to ESRD in patients with AAV. We observed patients with low platelet count (platelets < 264.5 × 109/L) had lower leukocytes, hemoglobin, complement, acute reactants, and worse renal function (P for eGFR < 0.001). They were also more likely to progress to ESRD or death compared to the high platelet count group (platelets > 264.5 × 109/L) (P < 0.0001, P = 0.0338, respectively). Low platelet count was potentially an independent predictor of poor renal prognosis in the multivariate regression analysis [HR 1.670 (95% CI 1.019-2.515), P = 0.014]. Lower platelet count at diagnosis is associated with more severe clinical characteristics and impaired renal function. Therefore, platelet count may be an accessible prognostic indicator for renal outcomes in patients with AAV.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Fallo Renal Crónico , Humanos , Estudios Retrospectivos , Recuento de Plaquetas , Pronóstico , Riñón/patología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/etiología , Inflamación/complicaciones , Índice de Severidad de la Enfermedad
13.
Artículo en Chino | MEDLINE | ID: mdl-38297861

RESUMEN

Objective:To investigate the technique of personalized flap making under otoscopy and its clinical application. Methods:The clinical data of patients who underwent 301 Military Hospital myringoplasty in the Department of otoendoscopic surgery, Department of Otorhinolaryngology, head and neck surgery, Department of Otorhinolaryngology, from October 2022 to 2023 August were analyzed retrospectively, all enrolled patients were performed independently by the same skilled otoendoscopic surgeon. The patients' general condition, medical history, tympanic membrane perforation scope, perforation size, need for tympanic cavity exploration, thickness of skin flap, tympanic cavity lesion scope, skin flap making method and postoperative rehabilitation were collected. Results:Many factors such as the location of tympanic membrane perforation, the thickness of the skin flap, the degree of curvature or stricture of the ear canal and the extent of the lesion in the tympanic cavity should be considered in the manufacture of the individualized tympanic membrane skin flap, the way of skin flap making does not affect the long-term postoperative rehabilitation, but it can effectively avoid unnecessary ear canal skin flap injury and improve the operation efficiency. Conclusion:Scientific flap fabrication is important for improving surgical efficiency and enhancing surgical confidence.


Asunto(s)
Perforación de la Membrana Timpánica , Membrana Timpánica , Humanos , Membrana Timpánica/lesiones , Perforación de la Membrana Timpánica/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Miringoplastia/métodos , Endoscopía/métodos , Timpanoplastia/métodos
14.
Artículo en Chino | MEDLINE | ID: mdl-38297858

RESUMEN

The application of microscope is a milestone in the history of otosurgery, which makes otologists deal with middle ear lesions more clearly and finely, and helps otologists expand the scope of treatment to the lateral skull base area, which greatly promotes the development of otosurgery. In the past 20 years, with the continuous improvement of endoscopic equipment research and development and the gradual improvement of endoscopic technology, the application of endoscopic technology in China has shown an explosive development, and Chinese otolaryngologists have experienced from the initial attempts of endoscopic technology, to the widespread popularization of innovative and applicable technology, and then to the feasibility of exploring the future innovative concepts. Endoscopic technology is another revolutionary push for the development of otosurgery after the microscope.


Asunto(s)
Invenciones , Procedimientos Quirúrgicos Otológicos , Humanos , Endoscopía , Oído Medio/cirugía , Base del Cráneo/cirugía
15.
Artículo en Chino | MEDLINE | ID: mdl-38297862

RESUMEN

Objective:To compare the application of endoscope and microscope in all kinds of stapes surgeries. Methods:Fifty-nine stapes surgeries have been collected from April 2020 to May 2023 in Senior Department of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Chinese PLA Medical School. Hearing level, hospital stay post-operation, times of hospital visit post-operation, etc. have been compared between the endoscopic group and microscopic group. Patients who were failed to place the stapes prosthesis because of the poor exposure of the oval window have been analyzed. Results:Otosclerosis was the most common diagnosis in both groups. There was 1(1/23) middle ear malformation in the endoscopic group and 5(5/36) middle ear malformations in the microscopic group. There were 2 Van Der Hover syndromes and 4 Treacher Collins syndromes in the microscopic group. In the endoscopic group ABG of 10 ears(43.5%) ≤ 10 dB, and ABG of 21 ears(91.3%) ≤20 dB.In the microscopic group ABG of 13 ears(41.9%) ≤ 10 dB, and ABG of 28 ears(90.3%) ≤ 20 dB. There was no statistic difference between 2 groups. Times of hospital visit post-operation in the endoscopic group was less than in the microscopic group(P<0.01). There was no facial palsy, tympanic perforation or profound sensorineural hearing loss in both groups. Conclusion:Endoscope is more suitable for patients who are evaluated with no severe stapes malformation, or less manipulation of drilling the bone. It could also reduce the hospital visit post-operation. Patients with narrow ear canal or severe middle ear malformation are recommended to perform the surgery with microscope, because it provides the chance of manipulation with 2-hands of surgeons.


Asunto(s)
Otosclerosis , Cirugía del Estribo , Humanos , Estribo , Oído Medio/cirugía , Oído Medio/anomalías , Otosclerosis/diagnóstico , Endoscopios , Poliésteres , Estudios Retrospectivos , Resultado del Tratamiento
16.
J Ethnopharmacol ; 325: 117893, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38336184

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Erzhu Jiedu Recipe (EZJDR) is a formula of traditional Chinese medicine (TCM) for treating hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). However, its effective components and the mechanism of action remain unclear. AIM OF THE STUDY: To explain how the active compounds of EZJDR suppress the growth of hepatoma cells. METHODS: UHPLC-Q-Exactive Orbitrap HRMS was used to identify the chemical constituents of EZJDR and their distribution in the serum and liver of mice. Together with experimental investigations, network pharmacology unraveled the molecular mechanism of components of EZJDR underlying the inhibited Hep3B cells. RESULTS: A total of 138 compounds which can be divided into 18 kinds of components (such as sesquiterpenoids, diterpenoids, anthraquinones, flavonoids and so on) were found in the aqueous extract of EZJDR. Of these components, the tricyclic-diterpenoids exhibited a highest exposure in the serum (74.5%) and liver (94.7%) of mice. The network pharmacology revealed that multiple components of EZJDR interacted with key node genes involved in apoptosis, proliferation, migration and metabolism through various signaling pathways, including ligand binding and protein phosphorylation. In vitro experiments demonstrated that 6 tricyclic-diterpenoids, 2 anthraquinones and 1 flavonoid inhibited the viability of Hep3B cells, with IC50 values ranging from 3.81 µM to 37.72 µM. Dihydrotanshinone I had the most potent bioactivity, arresting the S phase of cell cycle and inducing apoptosis. This compound changed the expression of proteins, including Bad, Bax, Bcl-2, Bal-x, caspase3 and catalase, which were associated with mitochondria-mediated apoptotic pathways. Moreover, dihydrotanshinone I increased the levels of p21 proteins, but decreased the phosphorylated p53, suggesting accumulation of p53 protein prevented cell cycle progression of Hep3B cells with damaged DNA. CONCLUSIONS: These results suggested that multiple components of EZJDR-diterpenoid, anthraquinone and flavonoid-could be the effective material for the treatment of HBV-HCC. This research provided valuable insights into the molecular mechanism of action underlying the therapeutic effects of EZJDR.


Asunto(s)
Carcinoma Hepatocelular , Diterpenos , Medicamentos Herbarios Chinos , Furanos , Neoplasias Hepáticas , Fenantrenos , Quinonas , Humanos , Ratones , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Proteína p53 Supresora de Tumor , Cromatografía Líquida de Alta Presión , Farmacología en Red , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Flavonoides/farmacología , Flavonoides/uso terapéutico , Antraquinonas/uso terapéutico , Diterpenos/uso terapéutico
17.
Anal Chim Acta ; 1295: 342273, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38355234

RESUMEN

Several microRNAs (miRNAs) are expressed at lower levels in specific tumors, e.g., miR-let-7a in non-small cell lung cancer (NSCLC). This makes it challenging to analyze their lower abundance versus specifically elevated miRNAs. Here, we describe a novel fluorescent biosensor for the highly selective and sensitive detection of miR-let-7a constructed by combining miRNA screening assisted by a duplex-specific nuclease (DSN) with CRISPR-Cas12a system signal amplification. We meticulously designed a mismatch in the first three to four bases at the 5'-end of the capture DNA to improve the signal-to-noise ratio of the CRISPR-Cas12a system. Within this "DSN-mismatched CRISPR" fluorescence strategy, miR-let-7a was accurately screened by DSN-assisted cleavage, and the mismatched capture DNA unbound to target miRNA could trigger the CRISPR-Cas12a system to produce a mass of trans-cleave fluorescence signals. This "turn-off" approach was suitable for detecting decreased levels of miRNAs. This approach can not only discriminate the single-base mismatched let-7 family but also reach a limit of detection at 64.17 fM as well as be quantified from 100 fM to 500 pM. The miR-let-7a levels were then measured in clinical serum samples from healthy volunteers and patients with NSCLC. This study holds promise for the development of a universal under-expressed miRNA assay for early diagnosis and treatment of cancers.


Asunto(s)
Técnicas Biosensibles , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , MicroARNs/genética , ADN , Colorantes
19.
J Laryngol Otol ; 138(4): 381-387, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38148683

RESUMEN

OBJECTIVE: This study was designed to determine whether extended high-frequency audiometry was capable of better differentiating between participants with normal hearing who did or did not have subjective tinnitus. METHODS: A total of 96 study participants were enrolled: 36 patients with unilateral tinnitus, 28 patients with bilateral tinnitus and 32 volunteers as controls. All 96 participants exhibited normal audiometry findings and hearing thresholds. Extended high-frequency audiometry was used to evaluate these patients. RESULTS: There were differences between the extended high-frequency hearing thresholds of affected and unaffected ears in those with unilateral tinnitus, and in the 20-29-year-old bilateral tinnitus group, at 11.2, 12.5 and 14 kHz. Unilateral tinnitus subgroups had higher extended high-frequency hearing thresholds than those in control subjects, at all extended high frequencies. CONCLUSION: Extended high-frequency audiometry can offer additional information regarding the hearing status of patients with tinnitus who exhibit normal pure tone thresholds when analysed via conventional hearing thresholds.


Asunto(s)
Acúfeno , Humanos , Adulto Joven , Adulto , Acúfeno/diagnóstico , Audiometría de Tonos Puros , Umbral Auditivo , Audición , Audiometría , Oído
20.
Life (Basel) ; 13(11)2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-38004347

RESUMEN

Corydalis yanhusuo is a medicinal herb in China that has been widely used to treat various kinds of pain. The tuber is the main organ of C. yanhusuo used for medicinal purposes, but changes in related genes during the development of the tuber have rarely been reported. To identify the differentially expressed genes during tuber development, C. yanhusuo full-length transcriptomic sequencing was performed using single-molecule real-time technology, and tubers at three development stages were selected for comparative transcriptome analysis. A total of 90,496 full-length non-chimeric transcripts were obtained, and 19,341 transcripts were annotated in at least one public database. A total of 9221 differentially expressed genes were identified during the swelling process of C. yanhusuo tuber. A Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis revealed that differentially expressed genes associated with a "starch and sucrose metabolism pathway", "phenylpropanoid biosynthesis pathway", "isoquinoline alkaloid biosynthesis pathway", "zeatin biosynthesis pathway", and "brassinosteroid biosynthesis pathway" were predominantly enriched. In addition, the genes involved in cell wall metabolism were potentially associated with tuber swelling. These processes regulated and were involved in C. yanhusuo tuber development. The results provide a foundation for further research on tuber formation in medicinal plants.

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