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Nonexponential relaxations are universal characteristics for glassy materials. There is a well-known hypothesis that nonexponential relaxation peaks are composed of a series of exponential events, which have not been verified. In this Letter, we discover the exponential relaxation events during the recovery process using a high-precision nanocalorimetry, which are universal for metallic glasses and organic glasses. The relaxation peaks can be well fitted by the exponential Debye function with a single activation energy. The activation energy covers a broad range from α relaxation to ß relaxation and even the fast γ/ß' relaxation. We obtain the complete spectrum of the exponential relaxation peaks over a wide temperature range from 0.63Tg to 1.03Tg, which provides solid evidence that nonexponential relaxation peaks can be decomposed into exponential relaxation units. Furthermore, the contribution of different relaxation modes in the nonequilibrium enthalpy space is measured. These results open a door for developing the thermodynamics of nonequilibrium physics and for precisely modulating the properties of glasses by controlling the relaxation modes.
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Understanding the genetic mechanisms of phenotypic variation in hybrids between domestic animals and their wild relatives may aid germplasm innovation. Here, we report the high-quality genome assemblies of a male Pamir argali (O ammon polii, 2n = 56), a female Tibetan sheep (O aries, 2n = 54), and a male hybrid of Pamir argali and domestic sheep, and the high-throughput sequencing of 425 ovine animals, including the hybrids of argali and domestic sheep. We detected genomic synteny between Chromosome 2 of sheep and two acrocentric chromosomes of argali. We revealed consistent satellite repeats around the chromosome breakpoints, which could have resulted in chromosome fusion. We observed many more hybrids with karyotype 2n = 54 than with 2n = 55, which could be explained by the selfish centromeres, the possible decreased rate of normal/balanced sperm, and the increased incidence of early pregnancy loss in the aneuploid ewes or rams. We identified genes and variants associated with important morphological and production traits (e.g., body weight, cannon circumference, hip height, and tail length) that show significant variations. We revealed a strong selective signature at the mutation (c.334C > A, p.G112W) in TBXT and confirmed its association with tail length among sheep populations of wide geographic and genetic origins. We produced an intercross population of 110 F2 offspring with varied number of vertebrae and validated the causal mutation by whole-genome association analysis. We verified its function using CRISPR-Cas9 genome editing. Our results provide insights into chromosomal speciation and phenotypic evolution and a foundation of genetic variants for the breeding of sheep and other animals.
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Electromechanical instability (EMI) restricts the performance of dielectric elastomer actuators (DEAs), leading to premature electrical breakdown at a certain voltage. However, macro-level observations using traditional carbon grease electrodes have failed to capture the detailed features of EMI. In this study, we investigated EMI at the microscopic scale by fabricating transparent and conductive single-walled carbon nanotube (SWCNT) electrodes. Our findings reveal that EMI predominantly occurs in highly localized regions with dimensions on the order of tens of micrometers. This snap-through instability is likely induced by pre-existing defects within the elastomer, such as air voids or conductive particles, which reduce the critical voltage required for EMI in the flawed areas. From the perspective of phase transition principles, these defects act as heterogeneous nucleation sites for new phase embryos, thereby lowering the energy barrier for the electromechanical phase transition (i.e., EMI) compared to homogeneous nucleation in an ideally impurity-free elastomer. This study clarifies the longstanding discrepancy between theoretically predicted deformation bursts and the experimentally observed macroscopic continuous expansion of DEAs under low pre-stretch conditions. Additionally, it underscores the critical importance of material purity in mitigating electromechanical instability.
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Despite active clinical trials on the use of Oleandrin alone or in combination with other drugs for the treatment of solid tumors, the potential synergistic effect of Oleandrin with radiotherapy remains unknown. This study reveals a new mechanism by which Oleandrin targets ATM and ATR kinase-mediated radiosensitization in lung cancer. Various assays, including clonogenic, Comet, immunofluorescence staining, apoptosis and Cell cycle assays, were conducted to evaluate the impact of oleandrin on radiation-induced double-strand break repair and cell cycle distribution. Western blot analysis was utilized to investigate alterations in signal transduction pathways related to double-strand break repair. The efficacy and toxicity of the combined therapy were assessed in a preclinical xenotransplantation model. Functionally, Oleandrin weakens the DNA damage repair ability and enhances the radiation sensitivity of lung cells. Mechanistically, Oleandrin inhibits ATM and ATR kinase activities, blocking the transmission of ATM-CHK2 and ATR-CHK1 cell cycle checkpoint signaling axes. This accelerates the passage of tumor cells through the G2 phase after radiotherapy, substantially facilitating the rapid entry of large numbers of inadequately repaired cells into mitosis and ultimately triggering mitotic catastrophe. The combined treatment of Oleandrin and radiotherapy demonstrated superior inhibition of tumor proliferation compared to either treatment alone. Our findings highlight Oleandrin as a novel and effective inhibitor of ATM and ATR kinase, offering new possibilities for the development of clinical radiosensitizing adjuvants.
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Proteínas de la Ataxia Telangiectasia Mutada , Cardenólidos , Daño del ADN , Neoplasias Pulmonares , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Animales , Cardenólidos/farmacología , Daño del ADN/efectos de los fármacos , Línea Celular Tumoral , Ratones , Tolerancia a Radiación/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos , Fármacos Sensibilizantes a Radiaciones/farmacología , Ratones Desnudos , Ensayos Antitumor por Modelo de Xenoinjerto , Reparación del ADN/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células A549RESUMEN
The origin of ß-relaxation in metallic glasses is still not fully understood, and the guidance of slow atoms for caged dynamics and ß-relaxation is rarely mentioned. Using molecular dynamics simulations, we reveal the bridging role of slow atoms on unusual caged dynamics and ß-relaxation. In the stage of unusual caged dynamics, slow atoms are bounded by neighboring atoms. It is difficult for the slow atoms to break the cage, producing more high-frequency vibration, which causes more atoms to jump out of the cage randomly in the next stage. Precisely, the movement of the slow atoms changes from individual atoms vibrating inside the cage and gradually breaking out of the cage into a string-like pattern. The string-like collective atomic jumps cause decay of the cages, inducing ß-relaxation. This situation generally exists in binary systems with the large atomic mass difference. This work offers valuable insights for understanding the role of slow atoms in unusual caged dynamics and ß-relaxation, complementing studies on the origin of ß-relaxation in metallic glasses and their glass-forming liquids.
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Decalcified bone matrix (DBM) is a widely used alternative material for bone transplantation. In the DBM production process, an effective particle size and the highest utilization rate of raw materials can be achieved only through multiple high-speed circulating comminution. The rat posterolateral lumbar fusion model (PLF) is the most mature small animal model for the initial evaluation of the efficacy of graft materials for bone regeneration and spinal fusion. To evaluate the differences in the in vivo osteogenic effects of DBM pulverization through 1, 5, 9, and 14 high-speed cycles, sixty athymic rats were divided into six groups: single cycling crushing (CC1), 5 cycles of crushing (CC5), 9 cycles of crushing (CC9), 13 cycles of crushing (CC13), autogenous bone graft (ABG) and negative control (NC). Posterolateral lumbar fusion was performed. Six weeks after surgery, the bilateral lumbar fusion of athymic rats was evaluated through manual palpation, X-ray, micro-CT and histological sections. Rank data were tested by the rank-sum test, and nonparametric data were tested by the KruskalâWallis H test. The manual palpation and X-ray results showed that the fusion rate did not significantly differ between the CC1, CC5, CC9, CC13 and ABG groups. However, cavities appeared in CC9 and CC13 on the micro-CT image. The bone mass (BV/TV) of CC1, CC5, CC9 and CC13 was better than that of the ABG group, while almost no osteogenesis was observed in the NC group. Histologically, there was no obvious difference between the four groups except that the CC9 group and CC13 group had more fibrous tissues in the new bone. In conclusion, DMB with different cycling crushing times has no obvious difference in fusion rate of PLF, but it is slightly better than the ABG group.
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Matriz Ósea , Fusión Vertebral , Ratas , Animales , Matriz Ósea/trasplante , Ratas Desnudas , Vértebras Lumbares/cirugía , Huesos , Fusión Vertebral/métodos , Trasplante Óseo/métodosRESUMEN
OBJECTIVE: To observe the diurnal difference of acute gout attacks in men, and provide reference for accurate clinical prevention and treatment. METHODS: Using a single-center, cross-sectional study design, the patients diagnosed with gout in the outpatient department of Rheumatology and Immuno-logy of PLA Joint Logistic Support Force No.980 Hospital from October 2021 to April 2022 were selected. The information about the patient's current/last acute gout attacks (less than 2 weeks from visit), date and time of attacks, joint symptoms and signs, medication use, and relevant biochemical tests on the day of visit was recorded. The diurnal time difference of acute gout attacks in male patients was analyzed, and univariate comparison and multivariate Logistic regression analyses were conducted to compare the diurnal difference of acute gout attacks with clinical characteristics and biochemical indicators. RESULTS: A total of 100 male gout patients were included, and 100 acute attacks were recorded. Diurnal distribution of acute gout attacks: morning (6:00~11:59, 18, 18%), afternoon (12:00~17:59, 11, 11%), the first half of the night (18:00~23:59, 22, 22%), the second half of the night (0:00~05:59, 49, 49%); During the day (included morning and afternoon, 29, 29%) and at night (included the first half of the night and the second half of the night, 71, 71%). The rate of acute gout attack was significantly higher at night than in the day (about 2.5 â¶1). No matter the first or recurrent gout, no matter the duration of the disease, the number of acute gout attacks had the difference of less in the day and more in the night. Serum urate (SU) level was higher in the patients with nocturnal attack than in those with daytime attack (P=0.044). Comorbidities were significantly different in the day-night ratio of the number of acute gout attack (P=0.028). Multiple Logistic regression analysis showed that SU level (OR=1.005, 95%CI: 1.001-1.009) and comorbidities (OR=3.812, 95%CI: 1.443-10.144) were the correlative factors of nocturnal acute gout attacks. CONCLUSION: No matter the first or recurrent gout, no matter the duration of the disease, it has a diurnal variation characterized by multiple attacks at night, increased SU level and comorbidities are correlative factors for nocturnal acute attack of gout.
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Artritis Gotosa , Gota , Humanos , Masculino , Estudios Transversales , Gota/tratamiento farmacológico , Supresores de la Gota/uso terapéutico , ComorbilidadRESUMEN
The fictive temperature (Tf ) is widely applied to understand the relaxation thermodynamics of a glass; however, its atomic structural origin is still unclear. Here, we report two novel AZnP3 O9 glasses obtained by melting the composition identical single crystals. These glasses exhibit structural inheritance within 5â Å from the single crystal counterparts that is quantified by δ=nglass /ncry (0≤δ≤1, n is the number of pair correlation functions). Among the available glass-formers, glass KZnP3 O9 exhibits the highest structural inheritance (δ=1, nglass =8). More insightfully, a reverse correlation between δ and the relaxation thermodynamic parameters is observed in glass AZnP3 O9 , revealing for the first time the atomic structural origin of fictive temperature.
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Inhibition of Shaker K+ channel activity by external Na+ was previously reported in the melon (Cucumis melo L.) inwardly rectifying K+ channel MIRK and was hypothesized to contribute to salt tolerance. In this study, two inward Shaker K+ channels, CsKAT2 from cucumber (Cucumis sativus) and ClKAT2 from watermelon (Citrullus lanatus), were identified and characterized in Xenopus oocytes. Both channels were inwardly rectifying K+ channels with higher permeability to potassium than other monovalent cations and more active when external pH was acidic. Similarly to MIRK, their activity displayed an inhibition by external Na+, thus suggesting a common feature in Cucurbitaceae (Cucumis spp., Citrullus spp.). CsKAT2 and ClKAT2 are highly expressed in guard cells. After 24 h of plant treatment with 100 mM NaCl, the three KAT2-like genes were significantly downregulated in leaves and guard cells. Reciprocal chimeras were obtained between MIRK and Na+-insensitive AtKAT2 cDNAs. The chimera where the MIRK S5-P-S6 segment was replaced by that from AtKAT2 no longer showed Na+ sensitivity, while the inverse chimera gained Na+ sensitivity. These results provide evidence that the molecular basis of the channel blockage by Na+ is located in the S5-P-S6 region. Comparison of the electrostatic property in the S5-P-S6 region in AtKAT2 and MIRK revealed four key amino acid residues potentially governing Na+ sensitivity.
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Tolerancia a la Sal , Sodio , Transporte Biológico , Oocitos/metabolismo , Hojas de la Planta , Potasio/metabolismo , Sodio/metabolismoRESUMEN
We investigated the stretched dynamics of the structural relaxation in molecular glass formers by using dielectric and thermal (or enthalpic) relaxations. The dielectric stretching exponents ßdie are determined by the Havriliak-Negami function, while the enthalpic ßTNMH is quantified by using the Tool-Narayanaswamy-Moynihan-Hodge formalism. We found ßTNMH is anticorrelated with the degree of freedom, a molecule addressed by the concept of beads. Referring to the reported relation of ßdie to the dipole moment µ, we proposed a combined parameter of µ2*beads, which can rationalize the difference in stretching exponents obtained by dielectric and enthalpic relaxations. For the majority of glass-forming molecules, the difference is trivial, but for those molecules with both unusually high dipole moments and flexibility, a large difference is obvious. The interplay of the degree of freedom and dielectric dipole-dipole interaction in molecular dynamics is addressed.
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In this work, we conducted a proof-of-concept experiment based on biofunctionalized magneto-plasmonic nanoparticles (MPNs) and magneto-optical Faraday effect for in vitro Alzheimer's disease (AD) assay. The biofunctionalized γ-Fe2O3@Au MPNs of which the surfaces are modified with the antibody of Tau protein (anti-τ). As anti-τ reacts with Tau protein, biofunctionalized MPNs aggregate to form magnetic clusters which will hence induce the change of the reagent's Faraday rotation angle. The result showed that the γ-Fe2O3@Au core-shell MPNs can enhance the Faraday rotation with respect to the raw γ-Fe2O3 nanoparticles. Because of their magneto-optical enhancement effect, biofunctionalized γ-Fe2O3@Au MPNs effectively improve the detection sensitivity. The detection limit of Tau protein as low as 9 pg/mL (9 ppt) was achieved. Furthermore, the measurements of the clinical samples from AD patients agreed with the CDR evaluated by the neurologist. The results suggest that our method has the potential for disease assay applications.
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Enfermedad de Alzheimer , Nanopartículas , Humanos , Enfermedad de Alzheimer/diagnóstico , Compuestos Férricos , Oro , Inmunoensayo , Proteínas tau , Nanopartículas del MetalRESUMEN
BACKGROUND: Cognitive decline is one of the greatest concerns for patients with Parkinson's disease (PD) and their care partners. Repetitive transcranial magnetic stimulation (rTMS) is a nonpharmacological treatment option used to improve cognitive function in PD, but its efficacy is unclear. We performed a meta-analysis to determine whether rTMS improves cognition in PD patients. METHODS: Eligibility criteria (PICOS) were as follows: (1) 'P': The patients participating were diagnosed with idiopathic PD; (2) 'I': Intervention using rTMS; (3) 'C': Sham stimulation as control; (4) 'O': The outcome of the study included cognitive evaluations; (5) 'S': The study adopted randomized controlled design. The standardized mean difference (SMD) of change of score was applied to measure efficacy, and we used Version 2 of the Cochrane tool to assess risk of bias. RESULTS: Twelve studies met the inclusion criteria. Compared with sham-controlled group, the pooled result showed a non-significant short-term effect of rTMS on global cognition (SMD: -0.15, 95% CI: -0.59 to 0.29, I2 = 36.7%), executive function (SMD: 0.03, 95% CI: -0.21 to 0.26, I2 = 0.0%), and attention and working memory (SMD: 0.05, 95% CI: -0.25 to 0.35, I2 = 0.0%). Long-term outcomes were either shown to be statistically nonsignificant. CONCLUSIONS: Based on a limited number of studies, rTMS fails to improve cognition in PD. We call for additional high-quality randomized controlled trials with adequate sample sizes to determine the efficacy of rTMS.
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Disfunción Cognitiva , Enfermedad de Parkinson , Cognición , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Estimulación Magnética Transcraneal , Resultado del TratamientoRESUMEN
Long noncoding RNAs (lncRNAs) have been identified as functional modulators in human tumors. The purpose of our study was to determine the expressing trend, clinical significance and functions of lncRNA LINC02381(LINC02381) in osteosarcoma. We observed that the expression of LINC02381 and cell division cycle-associated protein 4 (CDCA4) were distinctly increased in osteosarcoma specimens and cells, while miR-503-5p expression was decreased. Additionally, ETS transcription factor ELK1 (ELK1) could bind directly to the LINC02381 promoter region and activate its transcription. Clinical assays revealed that high LINC02381 was associated with advanced clinical progress and poor clinical outcome. Functionally, knockdown of LINC02381 suppressed the proliferation, migration and invasion of osteosarcoma cells. What's more, LINC02381 could down-regulate CDCA4 via sponging miR-503-5p, and there existed a negative correlation between LINC02381 expression and miR-503-5p expression in 92 osteosarcoma samples. Rescue experiments proved the carcinogenic role of LINC02381/miR-503-5p/CDCA4 axis in osteosarcoma progression. Overall, our data illustrated how LINC02381 played an oncogenic role in osteosarcoma and might offer a novel diagnostic and prognostic biomarker and potential therapeutic target for osteosarcoma.
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Carcinogénesis/genética , Proteínas de Ciclo Celular/metabolismo , Regulación Neoplásica de la Expresión Génica , MicroARNs/metabolismo , Osteosarcoma/genética , Osteosarcoma/patología , Regulación hacia Arriba/genética , Proteína Elk-1 con Dominio ets/metabolismo , Secuencia de Bases , Carcinogénesis/patología , Línea Celular Tumoral , Proliferación Celular/genética , Silenciador del Gen , Humanos , MicroARNs/genética , Metástasis de la Neoplasia , Resultado del Tratamiento , Proteína Elk-1 con Dominio ets/genéticaRESUMEN
Structural α-relaxation dispersion in binary molecular glass forming mixtures with distinct mixing enthalpy ΔHmix was investigated using enthalpic and dielectric relaxation measurements across the entire composition range. This study focused on the dependence of the relaxation dispersion on the mixing thermodynamics by determining the non-exponential exponent ß, and its composition dependence. The ß values determined by the enthalpic and dielectric relaxations agree well. Remarkably, it is found that the systems with positive enthalpy of mixing (exothermic, ΔHmix >0) have positive deviations in the composition dependence of ß from the linear averaging of the two ß values of the pure components, while negative deviations are observed for the systems with negative enthalpy of mixing (endothermic, ΔHmix <0). Furthermore, the relation between the non-exponential behaviors and entropy of mixing is discussed, revealing that the positive or negative deviation of ß in its composition dependence on mixing is accompanied by the same sign of the excess entropy of mixing relative to the ideal one.
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OBJECTIVE: To assess the efficacy and safety of intrathecal morphine (ITM) for postoperative analgesia in primary total joint arthroplasty (TJA) under spinal anesthesia and to explore the dose-response relationship for analgesic efficacy or risk of side effects. METHODS: We searched MEDLINE, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov for any studies meeting the inclusion criteria. All the data were summarized using the random effects model. Subgroup analyses were performed based on the surgical procedure and dose of ITM. Meta-regression was used to explore the dose-response relationship. RESULTS: Eighteen randomized controlled trials were included. Compared with the placebo or blank control, ITM reduced the postoperative 24-h morphine consumption by 10.07 mg and prolonged the duration of analgesia. However, ITM significantly increased the risk of pruritus by 2.79 fold, with a tendency to increase the risk of postoperative nausea and/or vomiting (P = 0.08). No difference was observed regarding the length of stay (LOS) and incidence of respiratory depression or urinary retention. Furthermore, meta-regression showed a linear dose-response relationship for the postoperative 24-h morphine consumption but no linear dose-response relationship for the risk of side effects. CONCLUSIONS: Adding morphine to intrathecal anesthetics provides a prolonged and robust analgesic effect without significantly increasing the risk of side effects other than pruritus. Although we found a linear dose-response relationship for the postoperative 24-h morphine consumption, the optimal dose of ITM remains to be further explored in high-quality RCTs with a large sample size.
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Analgesia , Anestesia Raquidea , Artroplastia de Reemplazo de Rodilla , Analgésicos Opioides/uso terapéutico , Humanos , Inyecciones Espinales , Morfina/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológicoRESUMEN
Here, we provide calorimetric and dielectric studies in asymmetric binary mixtures constituted by 2-picoline and triphenylethylene. Extreme broadening of the calorimetric glass transition is observed in the mixtures, which is accompanied by a large mismatch of the glass transition temperatures defined by the two techniques. As large broadening in the relaxation dispersion is identified in the mixtures of intermediate concentrations, strong temperature dependence of the relaxation dispersion is detected. The relation between the stretching exponent and non-linear factor derived from the Tool-Narayanaswamy-Moynihan-Hodge model shows a remarkable shift from the one established by pure molecular glass formers and symmetric mixtures. The unusual behaviors suggest an extreme dynamical decoupling mode imposed by the occurrence of strong concentration fluctuation.
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Cellulose, as a natural polymer with an abundant source, has been widely used in many fields including the electric field responsive medium that we are interested in. In this work, cellulose micron particles were applied as an electrorheological (ER) material. Because of the low ER effect of the raw cellulose, a composite particle of cellulose and Laponite was prepared via a dissolution-regeneration process. Scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) were used to observe the morphologies and structures of the composite particles, which were different from pristine cellulose and Laponite, respectively. The ER performances of raw cellulose and the prepared composite were measured by an Anton Paar rotational rheometer. It was found that the ER properties of the composite were more superior to those of raw cellulose due to the flake-like shapes of the composite particles with rough surface. Moreover, the sedimentation stability of composite improves drastically, which means better suspension stability.
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Celulosa/química , Electricidad , Silicatos/química , Microscopía Electrónica de Rastreo/métodos , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Suspensiones/química , Difracción de Rayos X/métodosRESUMEN
OBJECTIVE: To study the clinical effect of transurethral columnar balloon dilation of the prostate (TUCBDP) in the treatment of BPH and introduce the experience with the surgical procedure. METHODS: We retrospectively analyzed the clinical data on 265 cases of BPH treated by TUCBDP from August 2016 to August 2019. RESULTS: Operations were successfully completed in all the cases, with the mean operation time of (24.67 ± 7.6) min and the average intraoperative blood loss of (26.5 ± 21.4) ml, and all the patients had urinary patency after removal of the catheter. Follow-up examinations every 3 months after surgery showed significant improvement over the baseline in IPSS, quality of life score (QOL), maximum urinary flow rate (Qmax), postvoid residual urine (PVR) and other indicators (P < 0.05). Forty-five of the patients with sexual life exhibited no significant difference from the baseline in IIEF-5 and erectile hardness scale (EHS) scores (P > 0.05). Postoperative complications were observed in 53 cases (20%), including 28 cases of transient urinary incontinence (10.56%), 3 cases of hemorrhage (1.13%), 11 cases of urinary tract infection (4.15%), 1 case of urethral stricture (0.37%), and 8 cases of acute urinary retention (3.01%), which were all improved after regular treatment, with no occurrence of true urinary incontinence. Retrograde ejaculation occurred in 2 (4.45%) of the 45 patients with sexual life. CONCLUSIONS: Transurethral columnar balloon dilation of the prostate, with the advantages of short operation time and less intraoperative bleeding, has a significant short-term clinical effect in the treatment of BPH, particularly suitable for the elderly and those who want to retain the sexual function. Intraoperative localization of the protrusion may significantly influence the outcome of surgery, which deserves strengthened studies. Special attention should be paid to the incidence of postoperative transient urinary incontinence.
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Hiperplasia Prostática , Anciano , Dilatación , Humanos , Masculino , Próstata/cirugía , Hiperplasia Prostática/cirugía , Calidad de Vida , Estudios RetrospectivosRESUMEN
BACKGROUND: Consolation is a type of empathy-like behavior that has recently been observed in some socially living rodents. Despite the growing body of literature suggesting that stress affects empathy, the relationship between stress and consolation remains understudied at the preclinical level. Here, we examined the effects of chronic emotional stress or physical stress exposure on consolation and emotional behaviors by using the socially monogamous mandarin vole (Microtus mandarinus) in both males and females. METHOD/RESULTS: Physical stress voles were exposed to 14-day social defeat stress, whereas emotional stress voles vicariously experienced the defeat of their partners. We found that physical stress, but not emotional stress, voles showed reduced grooming toward their defeated partners and increased anxiety- and despair-like behaviors. Meanwhile, physical stress voles exhibited decreased neural activity in the anterior cingulate cortex, which is centrally involved in empathy. The densities of oxytocin receptors, dopamine D2 receptors, and serotonin 1A-receptors within the anterior cingulate cortex were significantly decreased in the physical stress group compared with controls. All the behavioral and physiological changes were similar between the sexes. Finally, we found that the reduced consolation behavior and some anxiety-like syndromes in physical stress voles could be alleviated by pretreatment with an oxytocin receptor, D2 receptors, or serotonin 1A-receptor agonist within the anterior cingulate cortex, whereas injections of corresponding receptor antagonists to the control voles decreased the consolation behavior and increased some anxiety-like behaviors. CONCLUSIONS: Our results indicated that chronic physical stress exposure impaired consolation and induced anxiety-like behaviors in mandarin voles and oxytocin receptors, 5-HT1A receptors, and D2 receptors within the anterior cingulate cortex may play important roles in these processes.
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Conducta Animal , Empatía , Giro del Cíngulo/metabolismo , Oxitocina/metabolismo , Receptor de Serotonina 5-HT1A/metabolismo , Receptores de Dopamina D2/metabolismo , Derrota Social , Estrés Psicológico/metabolismo , Estrés Psicológico/psicología , Agresión , Animales , Arvicolinae , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Giro del Cíngulo/efectos de los fármacos , Giro del Cíngulo/fisiopatología , Vivienda para Animales , Masculino , Neurotransmisores/farmacología , Transducción de Señal , Estrés Psicológico/fisiopatología , Factores de TiempoRESUMEN
As opposed to the common monotonic relaxation process of glasses, the Kovacs memory effect describes an isothermal annealing experiment, in which the enthalpy and volume of a preannealed glass first increases before finally decreasing toward equilibrium. This interesting behavior has been observed for many materials and is generally explained in terms of heterogeneous dynamics. In this Letter, the memory effect in a model Au-based metallic glass is studied using a high-precision high-rate calorimeter. The activation entropy (S^{*}) during isothermal annealing is determined according to the absolute reaction rate theory. We observe that the memory effect appears only when the second-annealing process has a large S^{*}. These results indicate that a large value of S^{*} is a key requirement for observation of the memory effect and this may provide a useful perspective for understanding the memory effect in both thermal and athermal systems.