RESUMEN
The objective of this study was to develop a nomogram model based on the natural progression of tumor and other radiological features to discriminate between solitary nodular pulmonary mucinous adenocarcinoma and non-mucinous adenocarcinomas. A retrospective analysis was conducted on 15,655 cases of lung adenocarcinoma diagnosed at our institution between January 2010 and June 2023. Primary nodular invasive mucinous adenocarcinomas and non-mucinous adenocarcinomas with at least two preoperative CT scans were included. These patients were randomly assigned to training and validation sets. Univariate and multivariate analyses were employed to compare tumor growth rates and clinical radiological characteristics between the two groups in the training set. A nomogram model was constructed based on the results of multivariate analysis. The diagnostic value of the model was evaluated in both the training and validation sets using calibration curves and receiver operating characteristic curves (ROC). The study included 174 patients, with 58 cases of mucinous adenocarcinoma and 116 cases of non-mucinous adenocarcinoma. The nomogram model incorporated the maximum tumor diameter, the consolidation/tumor ratio (CTR), and the specific growth rate (SGR) to generate individual scores for each patient, which were then accumulated to obtain a total score indicative of the likelihood of developing mucinous or non-mucinous adenocarcinoma. The model demonstrated excellent discriminative ability with an area under the receiver operating characteristic curve of 0.784 for the training set and 0.833 for the testing set. The nomogram model developed in this study, integrating SGR with other radiological and clinical parameters, provides a valuable and accurate tool for differentiating between solitary nodular pulmonary mucinous adenocarcinoma and non-mucinous adenocarcinomas. This prognostic model offers a robust and objective basis for personalized management of patients with pulmonary adenocarcinomas.
Asunto(s)
Adenocarcinoma Mucinoso , Neoplasias Pulmonares , Nomogramas , Humanos , Femenino , Masculino , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/diagnóstico por imagen , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Nódulo Pulmonar Solitario/patología , Nódulo Pulmonar Solitario/diagnóstico , Nódulo Pulmonar Solitario/diagnóstico por imagen , Curva ROC , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/diagnóstico por imagen , Adulto , Anciano de 80 o más AñosRESUMEN
Optical nanoscopy of intact biological specimens has been transformed by recent advancements in hydrogel-based tissue clearing and expansion, enabling the imaging of cellular and subcellular structures with molecular contrast. However, existing high-resolution fluorescence microscopes have limited imaging depth, which prevents the study of whole-mount specimens without physical sectioning. To address this challenge, we developed "photochemical sectioning," a spatially precise, light-based sample sectioning process. By combining photochemical sectioning with volumetric lattice light-sheet imaging and petabyte-scale computation, we imaged and reconstructed axons and myelination sheaths across entire mouse olfactory bulbs at nanoscale resolution. An olfactory-bulb-wide analysis of myelinated and unmyelinated axons revealed distinctive patterns of axon degeneration and de-/dysmyelination in the neurodegenerative mouse, highlighting the potential for peta- to exabyte-scale super-resolution studies using this approach.
RESUMEN
It's currently a challenge to design a drug delivery system for chemotherapy with high drug contents and minimal side effects. Herein, we constructed a novel one-dimensional binary-drug delivery system for cancer treatment. In this drug delivery system, drugs (doxorubicin (DOX) and resveratrol (RES)) self-assemble on bacterial cellulose nano-whiskers (BCW) and are subsequently encapsulated by polydopamine (PDA) with high encapsulation efficiencies (DOX: 81.53â¯%, RES: 70.32â¯%) and high drug loading efficiencies (DOX: 51.54â¯%, RES: 36.93â¯%). The cumulative release efficiencies can reach 89.27â¯% for DOX and 80.05â¯% for RES in acidic medium within 96â¯h. The BCW/(DOXâ¯+â¯RES)/PDA can enter tumor cells easily through endocytosis and presents significant anti-cancer effects. Furthermore, the released-RES plays a protective role in normal cells through up-regulation of antioxidant enzymes activities and scavenging of reactive oxygen species. Taken together, the one-dimensional BCW/(DOXâ¯+â¯RES)/PDA binary-drug delivery system can be used for the anticancer treatment along with slight side effects.
RESUMEN
BACKGROUND: Branched-chain amino acids (BCAAs) have been affected epilepsy, yet conclusions remain inconclusive, lacking causal evidence regarding whether BCAAs affect epilepsy. Systematic exploration of the causal relationship between BCAAs and epilepsy could hand out new ideas for the treatment of epilepsy. METHODS: Utilizing bidirectional Mendelian randomization (MR) study, we investigated the causal relationship between BCAA levels and epilepsy. BCAA levels from genome-wide association studies (GWAS), including total BCAAs, leucine levels, isoleucine levels, and valine levels, were employed. Causal relationships were explored applying the method of inverse variance-weighted (IVW) and MR-Egger, followed by sensitivity analyses of the results to evaluate heterogeneity and pleiotropy. RESULTS: Through strict genetic variant selection, we find some related SNPs, total BCAA levels (9), leucine levels (11), isoleucine levels (7), and valine levels (6) as instrumental variables for our MR analysis. Following IVW and sensitivity analysis, total BCAAs levels (OR = 1.14, 95 % CI = 1.019 â¼ 1.285, P = 0.022) and leucine levels (OR = 1.15, 95 % CI = 1.018 â¼ 1.304, P = 0.025) had significant correlation with epilepsy. CONCLUSIONS: There exists a causal relationship between the levels of total BCAAs and leucine with epilepsy, offering the new ideas into epilepsy potential mechanisms, holding significant implications for its prevention and treatment.
Asunto(s)
Aminoácidos de Cadena Ramificada , Epilepsia , Estudio de Asociación del Genoma Completo , Humanos , Aminoácidos de Cadena Ramificada/sangre , Epilepsia/genética , Isoleucina/genética , Leucina/genética , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Valina/genéticaRESUMEN
A metasurface array for electromagnetic (EM) energy harvesting for Wi-Fi bands is presented in this paper; the metasurface array consists of a metasurface unit, a rectifier, and a load resistor. Each row of unit cells in the array is interconnected to form an energy transfer channel, which enables the transfer and concentration of incident power. Furthermore, at the terminal of the channel, a single series diode rectifier circuit and a load resistor are integrated in a coplanar manner. It is used to rectify the energy in Wi-Fi bands and enables DC energy harvesting across the load. Finally, a 5 × 7 prototype of the metasurface array is fabricated and measured for the verification of the rationality of the design. Testing in an anechoic chamber shows that the prototype achieves a 72% RF-DC efficiency at 5.9 GHz when the available incident power is about 7 dBm.
RESUMEN
Background: The preoperative conversion therapy for advanced hepatocellular carcinoma (HCC) is still being explored. This study reported the potential of combination of transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), programmed cell death protein-1 (PD-1) inhibitors and lenvatinib as preoperative conversion therapy for nonmetastatic advanced HCC. Methods: This retrospective study gathered data on patients with nonmetastatic advanced HCC who received this combination therapy. We used drug-eluting bead (DEB) instead of conventional iodized oil in TACE. The clinical data, conversion rate, adverse events (AEs) and short-term survival were summarized. A stratified analysis based on whether or not the patient received surgery was conducted. Results: A total of 28 patients were included in the analysis. No grade 4 AEs were observed. The overall objective response rate (ORR) was 64.3%. Ten (35.7%) patients eventually received R0 resection after 2 cycles of combination therapy. Patients succeeding to resection (surgery group) had significantly higher ORR (90.0% vs. 50.0%, P=0.048). The proportion of patients with alpha-fetoprotein (AFP) >1,000 µg/L was significantly lower in surgery group (10.0% vs. 66.7%, P=0.006). After combination therapy, more patients in surgery group experienced significant reduction of >90% in AFP levels (75.0% vs. 23.1%, P=0.03), as well as standardized uptake value (SUV) of 18F-fluorodeoxyglucose (18F-FDG) both in primary tumors and portal vein tumor thrombosis (PVTT) (60.0% vs. 5.6%, P=0.003; 57.1% vs. 8.3%, P=0.04). Of note, 85.7% of PVTT exhibited major pathological response (MPR) in pathological examination although only 28.6% achieved downstage in preoperative imaging examination. MPR was more commonly observed in PVTT than in main tumors (85.7% vs. 20.0%). In non-surgery group, the median overall survival (OS) was 7 months with a 1-year survival rate of 27.8%, while in surgery group, the median OS was not reached and 1-year survival rate was 60.0%. Conclusions: The combination of TACE-HAIC, PD-1 inhibitors and lenvatinib showed its benefit as a preoperative conversion therapy for nonmetastatic advanced HCC. In addition to imaging evaluation, significant reduction of 18F-FDG uptake and AFP can be used as predictors of successful conversion, especially for PVTT.
RESUMEN
AIM: To investigate botulinum toxin A (BTXA) efficacy on small-angle (≤25Δ) acute acquired concomitant esotropia (AACE) in early-stage patients. METHODS: The electronic medical record data of AACE patients during March 2019 and June 2023 were collected in this retrospective and hospital-based cohort study. A total of 72 small-angle AACE patients received BTXA extraocular muscle injection. Patients were grouped by onset-to-treatment time (Group A: ≤6mo, Group B: >6mo). Deviation of esotropia, eye alignment and stereopsis were analyzed at the period of pre/post-injection (1wk, 1, 3, and 6mo). Orthophoria rate at 6mo (horizontal deviation <10Δ and binocular single vision) were considered as outcome index. RESULTS: There were no significant baseline differences (P>0.05) between two groups except onset-to-treatment time (2mo vs 11mo, P<0.001). Higher orthophoria rates were in Group A at last follow-up (94.74% vs 73.53%, P=0.013). Post-BTXA deviations of two groups at 1mo showed no difference (P>0.05); while in 3 and 6mo Group A was significantly smaller than group B (all P<0.001). No statistically significant differences were observed among all post-BTXA deviations of near and distance in Group A. In Group B, deviation at 3mo (near: 2Δ vs 0, P<0.001; distance: 4Δ vs 0, P<0.001) and 6mo (near: 6Δ vs 0, P<0.001; distance: 6Δ vs 0, P<0.001) was significant increased compared to deviation at 1wk after treatment. Group A showed better stereopsis recovery in last follow-up compared to Group B (80â³ vs 200â³, P=0.002). Both groups obtained improved stereopsis after treatment (Group A: 80â³ vs 300â³, P<0.001; Group B: 200â³ vs 300â³, P=0.037). CONCLUSION: BTXA is effective for AACE with small deviation (≤25Δ) in early stage. Delayed treatment (>6mo) may reduce BTXA efficacy. Early BTXA intervention benefits long-term eye alignment and stereopsis recovery.
RESUMEN
At present, an in-depth knowledge of polycyclic aromatic hydrocarbons (PAHs) in the multimedia system of the urban environment remains limited. Taking the Naples metropolitan area (NMA) for instance, we simulated the cross-media transfer of PAHs using a multimedia urban model, involving air, water, soil, sediment, vegetation, and impervious film. The results indicated that the predicted PAH values in 2015 match well with their corresponding in-situ monitoring data. The PAH emission inventory and the simulated mass in various media all showed a downward trend from 2015 to 2020 due to national energy conservation policies and Corona Virus Disease 2019. The simulated mass of PAHs in the soil and sediment phases was 896.8 and 232.7 kg in 2020, respectively, contributing together to 96.7% of PAHs in the NMA. And they were identified as the greatest sinks for PAHs, and exhibited the longest retention duration, with values of PAH persistence reaching approximately 548.8 - 2,0642.3 hours. The results of transfer fluxes indicated that local emissions and atmospheric advection were the primary routes affecting the distribution of PAHs. The sensitivity analysis indicated that atmospheric advection rate was the most critical parameter for air, soil, vegetation, and film, whereas water concentration and sediment degradation rate were vital for water and sediment, respectively. This study offered valuable insights into how human activity contributes to the status and fate of PAHs in the urban environment.
RESUMEN
Purpose: This study aimed to analyze myopia distribution in Hubei and the impact of regional Sunshine Duration on myopia in children and adolescents. Patients and Methods: The Cross-sectional study included students (kindergarten to grade 12) through multistage cluster stratified sampling in 17 cities (103 areas) of Hubei, China, who underwent ophthalmic examinations from September 2021 to November 2021. The association of sunshine duration with the prevalence and distribution of myopia was analyzed. Using Moran's index to quantify the distribution relationship, a spatial analysis was constructed. Results: A total of 435,996 students (53.33% male; mean age, 12.16±3.74 years) were included in the study. A negative association was identified between myopia prevalence and sunshine duration in the region, especially in population of primary students (r=-0.316, p<0.001). Each 1-unit increment in the sunshine duration was associated with a decreased risk of myopia prevalence (OR=0.996; 95% CI, 0.995-0.998; P <0.001). Regression showed a linear relationship between sunshine duration and myopia rates of primary school students [Prevalence%= (-0.1331*sunshine duration+47.73)%, p = 0.02]. Sunshine duration influenced the distribution of myopia rates among primary (Moran's I=-0.206, p<0.001) and junior high school (Moran's I=-0.183, p=0.002). Local spatial analysis showed that areas with low sunshine duration had high myopia prevalence concentration. Conclusion: This study revealed sunshine duration associations with myopia prevalence at the regional and population levels. The results may emphasize the significance of promptly implementing myopia control in regions with poor sunshine. The effect of sunshine on myopia is pronounced in the early years of education, especially in primary students.
RESUMEN
This study presents a case of weakly consolidated strata developed in Dananhu No.7 coal mine. Using a combination of numerical simulation, field measurement comparison, and the critical hydraulic gradient criterion, we investigate the overburden failure and the risk possibility of water-sand mixture inrush during excavation. The following are the principal findings: (1) Weakly consolidated rocks have poor physical characteristics, particularly when they are mudded and disintegrated after encountering water, which may become a favorable source of water-sand inrush; (2) The water-conducting zone develops to a height of 160.5 m with a crack-mining ratio of 15.29 times, extending upward to Toutunhe Formation aquifer. The predictions are consistent with measurements in adjacent mines with similar geological conditions; (3) Cracks without larger subsidence are developed at the front edge of the mining direction, and some parallel stepped cracks behind the goaf could be easily observed. Ground subsidence along the goaf center finally displays a symmetrically wide-gentle U shape; (4) The critical hydraulic gradient of Toutunhe Formation aquifer, aquifer above 3# coal seam, and aquifer of 3#-7# coal seam in Xishanyao Formation is 1.314, 1.351, and 1.380, the actual value is 0.692, 2.089, and 7.418 accordingly. It is inferred water-sand mixture outburst will not occur in Toutunhe Formation aquifer, while the potential risk exists in the aquifers of Xishanyao Formation. Through drainage and depressurization projects, a water-sand mixture outburst accident does not occur during excavation. This study reveals the overburden failure characteristics and the initiation mechanism of water-sand inrush in weakly cemented strata, as well as the internal relationship between them, which provides new research ideas for safe operation in other mining areas with similar geological conditions. The research work has certain practical guiding significance.
RESUMEN
NPC intracellular cholesterol transporter 1 (NPC1) is a multipass, transmembrane glycoprotein mostly recognized for its key role in facilitating cholesterol efflux. Mutations in the NPC1 gene result in Niemann-Pick disease, type C (NPC), a fatal, lysosomal storage disease. Due to the progressively expanding implications of NPC1-related disorders, we investigated endogenous NPC1 protein-protein interactions in the mouse cortex and human-derived iPSCs neuronal models of the disease through coimmunoprecipitation-coupled with LC-MS based proteomics. The current study investigated protein-protein interactions specific to the wild-type and the most prevalent NPC1 mutation (NPC1I1061T) while filtering out any protein interactor identified in the Npc1-/- mouse model. Additionally, the results were matched across the two species to map the parallel interactome of wild-type and mutant NPC1I1061T. Most of the identified wild-type NPC1 interactors were related to cytoskeleton organization, synaptic vesicle activity, and translation. We found many putative NPC1 interactors not previously reported, including two SCAR/WAVE complex proteins that regulate ARP 2/3 complex actin nucleation and multiple membrane proteins important for neuronal activity at synapse. Moreover, we identified proteins important in trafficking specific to wild-type and mutant NPC1I1061T. Together, the findings are essential for a comprehensive understanding of NPC1 biological functions in addition to its classical role in sterol efflux.
Asunto(s)
Corteza Cerebral , Proteína Niemann-Pick C1 , Mapas de Interacción de Proteínas , Animales , Corteza Cerebral/metabolismo , Ratones , Humanos , Proteómica/métodos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Enfermedad de Niemann-Pick Tipo C/metabolismo , Enfermedad de Niemann-Pick Tipo C/genética , Mutación , Ratones Noqueados , Colesterol/metabolismo , Neuronas/metabolismoRESUMEN
Ovarian cancer (OC) is deadly, and likely arises from the fallopian tube epithelium (FTE). Despite the association of OC with ovulation, OC typically presents in post-menopausal women who are no longer ovulating. The goal of this study was to understand how ovulation and aging interact to impact OC progression from the FTE. Follicular fluid released during ovulation induces DNA damage in the FTE, however, the role of aging on FTE exposure to follicular fluid is unexplored. Follicular fluid samples were collected from 14 women and its effects on FTE cells was assessed. Follicular fluid caused DNA damage and lipid oxidation in an age-dependent manner, but instead induced cell proliferation in a dose-dependent manner, independent of age in FTE cells. Follicular fluid regardless of age disrupted FTE spheroid formation and stimulated attachment and growth on ultra-low attachment plates. Proteomics analysis of the adhesion proteins in the follicular fluid samples identified vitronectin, a glycoprotein responsible for FTE cell attachment and spreading.
RESUMEN
Background: Gallbladder cancer (GBC) is different from other biliary tract cancers in terms of molecular phenotype and microenvironment. Specific treatments for GBC need to be urgently explored. This study preliminarily investigated the clinical value of hepatic artery infusion chemotherapy (HAIC) combined with bevacizumab plus a programmed death receptor-1 (PD-1) inhibitor for treatment of GBC with hepatic oligometastasis. Methods: We retrospectively collected data on GBC patients with hepatic oligometastasis, who received this combination therapy. The clinical data, conversion rate, treatment response, adverse events (AEs), and short-term survival were summarized. The responses of primary gallbladder lesions and hepatic metastasis, and their effect on prognosis, were investigated. Results: A total of 27 patients were included in the analysis. No grade 4 AEs were observed. The overall objective response rate (ORR) was 55.6% and the disease control rate (DCR) was 85.2%. Median overall survival (OS) time was 15.0 months and the 1-year survival rate was 64.0%. Median progression-free survival (PFS) time was 7.0 months and the 1-year PFS rate was 16.2%. Six patients (22.2%) were successfully converted to resection. Compared with primary gallbladder lesions, it appeared more difficult for patients with hepatic metastasis to achieve remission (ORR: 40.7% vs. 77.8%; P=0.012), but its response appeared to be closely related to the prognosis [median OS: 16.0 months in the complete response (CR) or partial response (PR) group vs. 11.0 months in the stable disease (SD) or progressive disease (PD) group, P=0.070; median PFS: 12.0 months in the CR or PR group vs. 6.5 months in the SD or PD group, P<0.001]. Preoperative CA19-9 of >1,900 U/mL and >5 cm metastatic lesions were associated with an unsatisfactory response, whereas a significant decrease of 18F-fluorodeoxyglucose (18F-FDG) uptake may be a marker of tumor remission. Conclusions: The combination of HAIC, a PD-1 inhibitor, and bevacizumab shows potential for advanced GBC with hepatic oligometastasis. The therapeutic response of hepatic metastasis had a greater influence on prognosis than that of primary gallbladder lesions.
RESUMEN
BACKGROUND: To investigate the trend of refractive error among elementary school students in grades 1 to 3 in Hubei Province, analyze the relevant factors affecting myopia progression, and develop a model to predict myopia progression and the risk of developing high myopia in children. METHODS: Longitudinal study. Using a cluster-stratified sampling method, elementary school students in grades 1 to 3 (15,512 in total) from 17 cities in Hubei Province were included as study subjects. Visual acuity, cycloplegic autorefraction, and height and weight measurements were performed for three consecutive years from 2019 to 2021. Basic information about the students, parental myopia and education level, and the students' behavioral habits of using the eyes were collected through questionnaires. RESULTS: The baseline refractive errors of children in grades 1 ~ 3 in Hubei Province in 2019 were 0.20 (0.11, 0.27)D, -0.14 (-0.21, 0.06)D, and - 0.29 (-0.37, -0.22)D, respectively, and the annual myopia progression was - 0.65 (-0.74, -0.63)D, -0.61 (-0.73, -0.59)D and - 0.59 (-0.64, -0.51)D, with the prevalence of myopia increasing from 17.56%, 20.9%, and 34.08% in 2019 to 24.16%, 32.24%, and 40.37% in 2021 (Χ2 = 63.29, P < 0.001). With growth, children's refractive error moved toward myopia, and the quantity of myopic progression gradually diminished. (F = 291.04, P = 0.027). The myopia progression in boys was less than that in girls in the same grade (P < 0.001). The change in spherical equivalent refraction in myopic children was smaller than that in hyperopic and emmetropic children (F = 59.28, P < 0.001), in which the refractive change in mild myopia, moderate myopia, and high myopia children gradually increased (F = 73.12, P < 0.001). Large baseline refractive error, large body mass index, and high frequency of eating sweets were risk factors for myopia progression, while parental intervention and strong eye-care awareness were protective factors for delaying myopia progression. The nomogram graph predicted the probability of developing high myopia in children and found that baseline refraction had the greatest predictive value. CONCLUSION: Myopia progression varies by age, sex, and myopia severity. Baseline refraction is the most important factor in predicting high myopia in childhood. we should focus on children with large baseline refraction or young age of onset of myopia in clinical myopia prevention and control.
Asunto(s)
Miopía , Errores de Refracción , Masculino , Niño , Femenino , Humanos , Estudios Longitudinales , Miopía/epidemiología , Factores de Riesgo , Aprendizaje AutomáticoRESUMEN
Purpose: Perceived discrimination among higher vocational college students is a prevalent issue in China and is linked to various mental and behavioral problems, including mobile phone addiction. Yet, the mechanisms underlying the relationship between perceived discrimination and mobile phone addiction remain ambiguous. Methods: To address this issue, we recruited 1253 higher vocational college students to elucidate the relationship between perceived discrimination and mobile phone addiction. Participants completed a series of self-report questionnaires assessing perceived discrimination, mobile phone addiction, negative emotions, and learning burnout. Results: Our findings suggest that perceived discrimination positively influences mobile phone addiction. The negative emotions and learning burnout play mediating effects between perceived discrimination and mobile phone addiction, respectively. Notably, we observe a chain mediating role of negative emotions and learning burnout play between perceived discrimination and mobile phone addiction. Conclusion: The results of our study demonstrate that higher vocational college students who perceived stronger discrimination are inclined to exhibit heightened emotional, cognitive, and learning challenges, such as increased negative emotions and learning burnout, which contribute to more serious excessive mobile phone use. These findings elucidate the mechanisms underlying the relationship between perceived discrimination and mobile phone addiction, enriching our understanding of the underlying emotional, cognitive, and learning dynamics in higher vocational college students.
RESUMEN
Alzheimer's disease (AD) is the most common form of dementia and results in neurodegeneration and cognitive impairment. White matter (WM) is affected in AD and has implications for neural circuitry and cognitive function. The trajectory of these changes across age, however, is still not well understood, especially at earlier stages in life. To address this, we used the AppNL-G-F/NL-G-F knock-in (APPKI) mouse model that harbors a single copy knock-in of the human amyloid precursor protein (APP) gene with three familial AD mutations. We performed in vivo diffusion tensor imaging (DTI) to study how the structural properties of the brain change across age in the context of AD. In late age APPKI mice, we observed reduced fractional anisotropy (FA), a proxy of WM integrity, in multiple brain regions, including the hippocampus, anterior commissure (AC), neocortex, and hypothalamus. At the cellular level, we observed greater numbers of oligodendrocytes in middle age (prior to observations in DTI) in both the AC, a major interhemispheric WM tract, and the hippocampus, which is involved in memory and heavily affected in AD, prior to observations in DTI. Proteomics analysis of the hippocampus also revealed altered expression of oligodendrocyte-related proteins with age and in APPKI mice. Together, these results help to improve our understanding of the development of AD pathology with age, and imply that middle age may be an important temporal window for potential therapeutic intervention.
Asunto(s)
Enfermedad de Alzheimer , Sustancia Blanca , Animales , Humanos , Ratones , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Encéfalo/metabolismo , Imagen de Difusión Tensora/métodos , Modelos Animales de Enfermedad , Sustancia Blanca/metabolismoRESUMEN
To estimate the safety and effectiveness of endoscopic nasal dacryocystorhinostomy in the remedy of chronic dacryocystitis. The clinical data of 105 subjects with chronic dacryocystitis enrolled into our hospital were analyzed retrospectively. The subjects were distinguished into nasal endoscopic group (endoscopic dacryocystorhinostomy; i.e., 51 cases) according to their surgical methods and external-route group (external-route dacryocystorhinostomy; i.e., 54 cases). The therapeutic effect, lacrimal gland secretion function, tear film stability, degree of epiphora, lacrimal passage patency, complications, and recurrence rate were contrasted between the 2 groups. The nasal endoscopic group exhibited a higher effective remedy rate (98.04%) compared with the external-route group (83.33%). Three months postoperation, both groups showed improvements in lacrimal gland secretion function and tear film stability, with the nasal endoscopic group demonstrating more significant enhancement in lacrimal gland secretion function than the external-route group. Six months postoperation, a reduction in the degree of epiphora was observed in both groups, with the nasal endoscopic group displaying a more pronounced decrease in epiphora severity and a higher lacrimal passage patency rate than the external-route group. Furthermore, the nasal endoscopic group experienced lower incidences of postoperative complications and recurrence rates. Endoscopic dacryocystorhinostomy is safe and effective in the remedy of chronic dacryocystitis.
Asunto(s)
Dacriocistitis , Dacriocistorrinostomía , Enfermedades del Aparato Lagrimal , Conducto Nasolagrimal , Humanos , Dacriocistorrinostomía/efectos adversos , Dacriocistorrinostomía/métodos , Estudios Retrospectivos , Dacriocistitis/cirugía , Nariz , Enfermedades del Aparato Lagrimal/cirugía , Endoscopía/métodos , Conducto Nasolagrimal/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: We evaluated the hypothesis that central orexin application could counteract motion sickness responses through regulating neural activity in target brain areas. EXPERIMENTAL APPROACH: Thec effects of intracerebroventricular (i.c.v.) injection of orexin-A and SB-334867 (OX1 antagonist) on motion sickness-induced anorexia, nausea-like behaviour (conditioned gaping), hypoactivity and hypothermia were investigated in rats subjected to Ferris wheel-like rotation. Orexin-A responsive brain areas were identified using Fos immunolabelling and were verified via motion sickness responses after intranucleus injection of orexin-A, SB-334867 and TCS-OX2-29 (OX2 antagonist). The efficacy of intranasal application of orexin-A versus scopolamine on motion sickness symptoms in cats was also investigated. KEY RESULTS: Orexin-A (i.c.v.) dose-dependently attenuated motion sickness-related behavioural responses and hypothermia. Fos expression was inhibited in the ventral part of the dorsomedial hypothalamus (DMV) and the paraventricular nucleus (PVN), but was enhanced in the ventral part of the premammillary nucleus ventral part (PMV) by orexin-A (20 µg) in rotated animals. Motion sickness responses were differentially inhibited by orexin-A injection into the DMV (anorexia and hypoactivity), the PVN (conditioned gaping) and the PMV (hypothermia). SB-334867 and TCS-OX2-29 (i.c.v. and intranucleus injection) inhibited behavioural and thermal effects of orexin-A. Orexin-A (60 µg·kg-1) and scopolamine inhibited rotation-induced emesis and non-retching/vomiting symptoms, while orexin-A also attenuated anorexia with mild salivation in motion sickness cats. CONCLUSION AND IMPLICATIONS: Orexin-A might relieve motion sickness through acting on OX1 and OX2 receptors in various hypothalamus nuclei. Intranasal orexin-A could be a potential strategy against motion sickness.
Asunto(s)
Benzoxazoles , Hipotermia , Mareo por Movimiento , Naftiridinas , Urea/análogos & derivados , Ratas , Gatos , Animales , Orexinas/farmacología , Receptores de Orexina/metabolismo , Anorexia/metabolismo , Hipotálamo/metabolismo , Mareo por Movimiento/tratamiento farmacológico , Mareo por Movimiento/metabolismo , Escopolamina/metabolismo , Escopolamina/farmacología , Antagonistas de los Receptores de Orexina/metabolismo , Antagonistas de los Receptores de Orexina/farmacologíaRESUMEN
The mechanisms underlying adult hippocampal neurogenesis (AHN) are not fully understood. AHN plays instrumental roles in learning and memory. Understanding the signals that regulate AHN has implications for brain function and therapy. Here we show that Caveolin-1 (Cav-1), a protein that is highly enriched in endothelial cells and the principal component of caveolae, autonomously regulates AHN. Conditional deletion of Cav-1 in adult neural progenitor cells (nestin +) led to increased neurogenesis and enhanced performance of mice in contextual discrimination. Proteomic analysis revealed that Cav-1 plays a role in mitochondrial pathways in neural progenitor cells. Importantly, Cav-1 was localized to the mitochondria in neural progenitor cells and modulated mitochondrial fission-fusion, a critical process in neurogenesis. These results suggest that Cav-1 is a novel regulator of AHN and underscore the impact of AHN on cognition.
RESUMEN
INTRODUCTION/AIMS: Individuals with dysferlinopathies, a group of genetic muscle diseases, experience delay in the onset of muscle weakness. The cause of this delay and subsequent muscle wasting are unknown, and there are currently no clinical interventions to limit or prevent muscle weakness. To better understand molecular drivers of dysferlinopathies, age-dependent changes in the proteomic profile of skeletal muscle (SM) in wild-type (WT) and dysferlin-deficient mice were identified. METHODS: Quadriceps were isolated from 6-, 18-, 42-, and 77-wk-old C57BL/6 (WT, Dysf+/+ ) and BLAJ (Dysf-/- ) mice (n = 3, 2 male/1 female or 1 male/2 female, 24 total). Whole-muscle proteomes were characterized using liquid chromatography-mass spectrometry with relative quantification using TMT10plex isobaric labeling. Principle component analysis was utilized to detect age-dependent proteomic differences over the lifespan of, and between, WT and dysferlin-deficient SM. The biological relevance of proteins with significant variation was established using Ingenuity Pathway Analysis. RESULTS: Over 3200 proteins were identified between 6-, 18-, 42-, and 77-wk-old mice. In total, 46 proteins varied in aging WT SM (p < .01), while 365 varied in dysferlin-deficient SM. However, 569 proteins varied between aged-matched WT and dysferlin-deficient SM. Proteins with significant variation in expression across all comparisons followed distinct temporal trends. DISCUSSION: Proteins involved in sarcolemma repair and regeneration underwent significant changes in SM over the lifespan of WT mice, while those associated with immune infiltration and inflammation were overly represented over the lifespan of dysferlin-deficient mice. The proteins identified herein are likely to contribute to our overall understanding of SM aging and dysferlinopathy disease progression.