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1.
Mol Psychiatry ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740879

RESUMEN

Non-invasive brain stimulation therapy for autism spectrum disorder (ASD) has shown beneficial effects. Recently, we and others demonstrated that visual sensory stimulation using rhythmic 40 Hz light flicker effectively improved cognitive deficits in mouse models of Alzheimer's disease and stroke. However, whether rhythmic visual 40 Hz light flicker stimulation can ameliorate behavioral deficits in ASD remains unknown. Here, we show that 16p11.2 deletion female mice exhibit a strong social novelty deficit, which was ameliorated by treatment with a long-term 40 Hz light stimulation. The elevated power of local-field potential (LFP) in the prefrontal cortex (PFC) of 16p11.2 deletion female mice was also effectively reduced by 40 Hz light treatment. Importantly, the 40 Hz light flicker reversed the excessive excitatory neurotransmission of PFC pyramidal neurons without altering the firing rate and the number of resident PFC neurons. Mechanistically, 40 Hz light flicker evoked adenosine release in the PFC to modulate excessive excitatory neurotransmission of 16p11.2 deletion female mice. Elevated adenosine functioned through its cognate A1 receptor (A1R) to suppress excessive excitatory neurotransmission and to alleviate social novelty deficits. Indeed, either blocking the A1R using a specific antagonist DPCPX or knocking down the A1R in the PFC using a shRNA completely ablated the beneficial effects of 40 Hz light flicker. Thus, this study identified adenosine as a novel neurochemical mediator for ameliorating social novelty deficit by reducing excitatory neurotransmission during 40 Hz light flicker treatment. The 40 Hz light stimulation warrants further development as a non-invasive ASD therapeutics.

2.
Sci Rep ; 14(1): 10205, 2024 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702383

RESUMEN

Mapping the localization of the functional brain regions in trigeminal neuralgia (TN) patients is still lacking. The study aimed to explore the functional brain alterations and influencing factors in TN patients using functional brain imaging techniques. All participants underwent functional brain imaging to collect resting-state brain activity. The significant differences in regional homogeneity (ReHo) and amplitude of low frequency (ALFF) between the TN and control groups were calculated. After familywise error (FWE) correction, the differential brain regions in ReHo values between the two groups were mainly located in bilateral middle frontal gyrus, bilateral inferior cerebellum, right superior orbital frontal gyrus, right postcentral gyrus, left inferior temporal gyrus, left middle temporal gyrus, and left gyrus rectus. The differential brain regions in ALFF values between the two groups were mainly located in the left triangular inferior frontal gyrus, left supplementary motor area, right supramarginal gyrus, and right middle frontal gyrus. With the functional impairment of the central pain area, the active areas controlling memory and emotion also change during the progression of TN. There may be different central mechanisms in TN patients of different sexes, affected sides, and degrees of nerve damage. The exact central mechanisms remain to be elucidated.


Asunto(s)
Imagen por Resonancia Magnética , Neuralgia del Trigémino , Humanos , Neuralgia del Trigémino/fisiopatología , Neuralgia del Trigémino/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Mapeo Encefálico/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Red en Modo Predeterminado/fisiopatología , Red en Modo Predeterminado/diagnóstico por imagen , Anciano , Adulto
3.
PLoS Comput Biol ; 20(4): e1011988, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38557416

RESUMEN

Accurate multiple sequence alignment (MSA) is imperative for the comprehensive analysis of biological sequences. However, a notable challenge arises as no single MSA tool consistently outperforms its counterparts across diverse datasets. Users often have to try multiple MSA tools to achieve optimal alignment results, which can be time-consuming and memory-intensive. While the overall accuracy of certain MSA results may be lower, there could be local regions with the highest alignment scores, prompting researchers to seek a tool capable of merging these locally optimal results from multiple initial alignments into a globally optimal alignment. In this study, we introduce Two Pointers Meta-Alignment (TPMA), a novel tool designed for the integration of nucleic acid sequence alignments. TPMA employs two pointers to partition the initial alignments into blocks containing identical sequence fragments. It selects blocks with the high sum of pairs (SP) scores to concatenate them into an alignment with an overall SP score superior to that of the initial alignments. Through tests on simulated and real datasets, the experimental results consistently demonstrate that TPMA outperforms M-Coffee in terms of aSP, Q, and total column (TC) scores across most datasets. Even in cases where TPMA's scores are comparable to M-Coffee, TPMA exhibits significantly lower running time and memory consumption. Furthermore, we comprehensively assessed all the MSA tools used in the experiments, considering accuracy, time, and memory consumption. We propose accurate and fast combination strategies for small and large datasets, which streamline the user tool selection process and facilitate large-scale dataset integration. The dataset and source code of TPMA are available on GitHub (https://github.com/malabz/TPMA).


Asunto(s)
Algoritmos , Ácidos Nucleicos , Alineación de Secuencia , Café , Programas Informáticos
4.
Immunobiology ; 229(3): 152802, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38569452

RESUMEN

BACKGROUND: Glioma, the most frequent and malignant central nervous system (CNS) cancer, has a bad outcome. Proteasome 26S subunit ATPase 2 (PSMC2) is an essential part of the 26S proteasome and promotes the development of several tumors. However, the pathway and function of PSMC2 in glioma have not been unelucidated. METHODS: This study analyzed PSMC2 expression in glioma tissues and its predictive significance for patients. We examined the link between PSMC2 and DNA methylation, immune cell infiltration, tumor immune cycle, immune cell homeostasis, and immune checkpoints. Subsequently, immunohistochemistry and in vitro trials were employed to validate the expression, prognostic potential, and function of PSMC2 in glioma. The mechanisms of PSMC2 in glioma were further explored. RESULTS: Our study revealed that PSMC2 expression increased in glioma tissues contrasted with healthy tissues, and patients with high PSMC2 glioma exhibited poor overall survival (OS) compared to the low-PSMC2 group. Immune profile analysis revealed that PSMC2 was positively related to immunosuppressive cell infiltration and immune checkpoints and adversely related to the cancer immune cycle and immune cell homeostasis. In cell-based investigations, the inhibition of PSMC2 was found to effectively suppress the aggressiveness and proliferation of glioma cell lines while also enhancing cell cycle arrest and promoting cell death. Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and in vitro experiments showed that PSMC2 promoted glioma development through the PI3K/AKT/mTOR pathway. CONCLUSIONS: PSMC2 was upregulated in glioma and promoted cancer progression by modulating the tumor immune microenvironment, cancer cell biological behavior, immune cell homeostasis, and the PI3K/AKT/mTOR pathway, providing a new option to treat glioma.


Asunto(s)
Glioma , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Microambiente Tumoral , Humanos , Glioma/inmunología , Glioma/patología , Glioma/genética , Glioma/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Microambiente Tumoral/inmunología , Fosfatidilinositol 3-Quinasas/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Pronóstico , Progresión de la Enfermedad , Masculino , Femenino , Proliferación Celular , Persona de Mediana Edad , Complejo de la Endopetidasa Proteasomal/metabolismo
5.
BMC Anesthesiol ; 24(1): 102, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38500035

RESUMEN

BACKGROUND: Early extubation (EEx) is defined as the removal of the endotracheal tube within 8 h postoperatively. The present study involved determining the availability and threshold of the vasoactive-inotropic score (VIS) for predicting EEx in adults after elective rheumatic heart valve surgery. METHODS: The present study was designed as a single-center retrospective cohort study which was conducted with adults who underwent elective rheumatic heart valve surgery with CPB. The highest VIS in the immediate postoperative period was used in the present study. The primary outcome, the availability of VIS for EEx prediction and the optimal threshold value were determined using ROC curve analysis. The gray zone analysis of the VIS was performed by setting the false negative or positive rate R = 0.05, and the perioperative risk factors for prolonged EEx were identified by multivariate logistic analysis. The postoperative complications and outcomes were compared between different VIS groups. RESULTS: Among the 409 patients initially screened, 379 patients were ultimately included in the study. The incidence of EEx was determined to be 112/379 (29.6%). The VIS had a good predictive value for EEx (AUC = 0.864, 95% CI: [0.828, 0.900], P < 0.001). The optimal VIS threshold for EEx prediction was 16.5, with a sensitivity of 71.54% (65.85-76.61%) and a specificity of 88.39% (81.15-93.09%). The upper and lower limits of the gray zone for the VIS were determined as (12, 17.2). The multivariate logistic analysis identified age (OR, 1.060; 95% CI: 1.017-1.106; P = 0.006), EF% (OR, 0.798; 95% CI: 0.742-0.859; P < 0.001), GFR (OR, 0.933; 95% CI: 0.906-0.961; P < 0.001), multiple valves surgery (OR, 4.587; 95% CI: 1.398-15.056; P = 0.012), and VIS > 16.5 (OR, 12.331; 95% CI: 5.015-30.318; P < 0.001) as the independent risk factors for the prolongation of EEx. The VIS ≤ 16.5 group presented a greater success rate for EEx, a shorter invasive ventilation support duration, and a lower incidence of complications than did the VIS > 16.5 group, while the incidence of reintubation was similar between the two groups. CONCLUSION: In adults, after elective rheumatic heart valve surgery, the highest VIS in the immediate postoperative period was a good predictive value for EEx, with a threshold of 16.5.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Cardiopatías Congénitas , Adulto , Humanos , Cardiopatías Congénitas/cirugía , Estudios Retrospectivos , Extubación Traqueal , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Válvulas Cardíacas/cirugía
6.
Cell Rep ; 43(2): 113766, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38349792

RESUMEN

Deep brain stimulation (DBS) in the basal lateral amygdala (BLA) has been established to correct symptoms of refractory post-traumatic stress disorder (PTSD). However, how BLA DBS operates in correcting PTSD symptoms and how the BLA elicits pathological fear and anxiety in PTSD remain unclear. Here, we discover that excitatory synaptic transmission from the BLA projection neurons (PNs) to the adBNST, and lateral central amygdala (CeL) is greatly suppressed in a mouse PTSD model induced by foot shock (FS). BLA DBS revises the weakened inputs from the BLA to these two areas to improve fear and anxiety. Optogenetic manipulation of the BLA-adBNST and BLA-CeL circuits shows that both circuits are responsible for anxiety but the BLA-CeL for fear in FS mice. Our results reveal that synaptic transmission dysregulation of the BLA-adBNST or BLA-CeL circuits is reversed by BLA DBS, which improves anxiety and fear in the FS mouse model.


Asunto(s)
Ansiedad , Trastornos por Estrés Postraumático , Animales , Ratones , Ansiedad/terapia , Pie , Miedo , Modelos Animales de Enfermedad , Transmisión Sináptica
7.
Biomed Pharmacother ; 170: 116052, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38141280

RESUMEN

Chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated impressive success in the treatment of patients with hematologic tumors yet achieved very limited efficacy for solid tumors due to hurdles unique to solid tumors. It is also noted that the tumor microenvironment composition varies between tumor type, which again imposes unique set of hurdles in each solid tumor. Therefore, elucidation of individual hurdles is key to achieving successful CAR-T therapy for solid tumors. In the present study, we employed an orthotopic human PDAC xenograft model, in which quantitative, spatial and functional dynamics of CAR-T cells in tumor tissues were analyzed to obtain insights into ways of overcoming PDAC related hurdles. Contrary to previous studies that demonstrated a limited persistency and infiltration of CAR-T cells in many solid tumors, they persist and accumulated in PDAC tumor tissues. Ex vivo analysis revealed that CAR-T cells that had been recovered at different time points from mice bearing an orthotopic PDAC tumor exhibited a gradual loss of tumor reactivity. This loss of tumor reactivity of CAR-T cells was associated with the increased expression of AMP-activated protein kinase and Mitofusin 1/ Dynamin-related protein 1 ratio.


Asunto(s)
Neoplasias , Receptores Quiméricos de Antígenos , Humanos , Animales , Ratones , Receptores de Antígenos de Linfocitos T , Linfocitos T , Xenoinjertos , Inmunoterapia Adoptiva , Neoplasias/metabolismo , Microambiente Tumoral
8.
Cancer Biomark ; 38(4): 505-522, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37980651

RESUMEN

BACKGROUND: STEAP3 is a metal reductase located on the plasma membrane close to the nucleus and vesicles. Despite numerous studies indicating the involvement of STEAP3 in tumor advancement, the prognostic value of STEAP3 in glioma and the related mechanisms have not been fully investigated. METHODS: Initially, we examined the correlation between STEAP3 expression and the survival rate in various glioma datasets. To assess the prognostic capability of STEAP3 for one-year, three-year, and five-year survival, we created receiver operating characteristic (ROC) curves and nomograms. Additionally, an investigation was carried out to examine the mechanisms that contribute to the involvement of STEAP3 in gliomas, including immune and enrichment analysis. To confirm the expression of STEAP3 in LGG and GBM, tumor tissue samples were gathered, and cell experiments were conducted to explore the impacts of STEAP3. The function of STEAP3 in the tumor immune microenvironment was assessed using the M2 macrophage infiltration assay. RESULTS: We found that STEAP3 expressed differently in group with different age, tumor grade IDH and 1p19q status. The analysis of survival illustrated that glioma patients with high level of STEAP3 experienced shorter survival durations, especially for IDH-mutant astrocytoma. Cox analysis demonstrated that STEAP3 had potential to act as an independent prognostic factor for glioma. The predictive value of STEAP3 for glioma prognosis was demonstrated by ROC curves and nomogram. Immune analysis showed that STEAP3 may lead to a suppressive immune microenvironment through the control of immunosuppressive cell infiltration and Cancer-Immunity Cycle. Combining enrichment analysis and cell experiments, we discovered that STEAP3 can promote glioma progression through regulation of PI3K-AKT pathway and M2 macrophage infiltration. CONCLUSION: STEAP3 plays significant roles in the advancement of glioma by regulating immune microenvironment and PI3K-AKT pathway. It has the potential to serve as a therapy target for glioma.


Asunto(s)
Glioma , Fosfatidilinositol 3-Quinasas , Humanos , Proteínas Proto-Oncogénicas c-akt , Pronóstico , Glioma/genética , Biomarcadores , Microambiente Tumoral/genética
9.
iScience ; 26(9): 107658, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37664633

RESUMEN

Humans can distinguish flying birds from drones based solely on motion features when no image information is available. However, it remains unclear which motion features of animate motion induce our animacy perception. To address this, we first analyzed the differences in centroid motion between birds and drones, and discovered that birds exhibit greater acceleration, angular speed, and trajectory fluctuations. We further determined the order of their importance in evoking animacy perception was trajectory fluctuations, acceleration, and speed. More interestingly, people judge whether a moving object is alive using a feature-matching strategy, implying that animacy perception is induced in a key feature-triggered way rather than relying on the accumulation of evidence. Our findings not only shed light on the critical motion features that induce animacy perception and their relative contributions but also have important implications for developing target classification algorithms based on motion features.

10.
Appl Radiat Isot ; 201: 110996, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37657224

RESUMEN

The terbium (Tb) family has attracted much attention in recent years thanks to the diagnostic and therapeutic applications of the quadruplet 149Tb, 152Tb, 155Tb and 161Tb. However, the scarce availability of Tb radioisotopes is one of the main reasons hindering its clinical applications. To increase its availability, this work proposes to use enriched gadolinium (Gd) targets to produce some Tb radioisotopes (149Tb, 152Tb, and 155Tb) via deuteron-induced reactions in cyclotrons. The production of the Auger and gamma emitter 155Tb was chosen as a case study because the 155Gd enrichment (92.8%) is the highest available from all Gd stable isotopes. The involved reaction is 155Gd(d,2n)155Tb. Using enriched thin Gd-containing targets, cross-sections of the reactions 155Gd(d,x)153,154,155,156Tb have been measured at the GIP ARRONAX cyclotron facility with a beam energy ranging from 8 MeV to 30 MeV. This measurement allows for estimating the production yield and the purity of 155Tb, and for determining the irradiation parameters for large production batches. A thick enriched 155Gd2O3 target has been then irradiated with an incident energy of 15.1 MeV and a beam current of 368 nA for 1 h. The production yield of 155Tb is 10.2 MBq/µA/h at End Of Bombardment (EOB) and the purity is 89% after 14 days of decay. These experimental values are consistent with estimation based on measured cross-sections. A comparison of the deuteron-induced and proton-induced production routes is also presented in this paper.

11.
Int J Mol Sci ; 24(13)2023 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-37446055

RESUMEN

The benefits of CAR-T therapy could be expanded to the treatment of solid tumors through the use of derived autologous αß T cell, but clinical trials of CAR-T therapy for patients with solid tumors have so far been disappointing. CAR-T therapy also faces hurdles due to the time and cost intensive preparation of CAR-T cell products derived from patients as such CAR-T cells are often poor in quality and low in quantity. These inadequacies may be mitigated through the use of third-party donor derived CAR-T cell products which have a potent anti-tumor function but a constrained GVHD property. Vγ9Vδ2 TCR have been shown to exhibit potent antitumor activity but not alloreactivity. Therefore, in this study, CAR-T cells were prepared from Vγ9Vδ2 T (CAR-γδ T) cells which were expanded by using a novel prodrug PTA. CAR-γδ T cells suppressed tumor growth in an antigen specific manner but only during a limited time window. Provision of GITR co-stimulation enhanced anti-tumor function of CAR-γδ T cells. Our present results indicate that, while further optimization of CAR-γδ T cells is necessary, the present results demonstrate that Vγ9Vδ2 T cells are potential source of 'off-the-shelf' CAR-T cell products for successful allogeneic adoptive immunotherapy.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Neoplasias , Profármacos , Receptores Quiméricos de Antígenos , Humanos , Inmunoterapia Adoptiva/métodos , Difosfonatos , Receptores de Antígenos de Linfocitos T gamma-delta , Profármacos/farmacología , Profármacos/uso terapéutico , Linfocitos T , Inmunoterapia
12.
BMC Neurol ; 23(1): 242, 2023 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-37353754

RESUMEN

Treating prolonged disorders of consciousness (pDoC) is challenging. Thus, accurate assessment of residual consciousness in patients with pDoC is important for the management and recovery of patients. Functional near-infrared spectroscopy (fNIRS) can be used to detect brain activity through changes of oxygenated hemoglobin/deoxygenated hemoglobin (HbO/HbR) concentrations changes and has recently gained increasing attention for its potential applications in assessing residual consciousness. However, the number of fNIRS studies assessing residual awareness in patients with pDoC is still limited. In this study, fNIRS was used to evaluate the brain function in 18 patients with pDoC, including 14 vegetative states (VS) and 4 minimally conscious states (MCS), and 15 healthy controls (HC). All participants accepted two types of external stimuli, i.e., active stimulation (motor imagery, MI) and passive stimulation (subject's own name, SON). The results showed that the mean concentrations of HbO/HbR in the prefrontal cortex of the HC during the passive stimulation were significantly lower than those of the active stimulation, and the fitting slope was high. However, the hemodynamic responses of the patients with pDoC were opposite to those of the HC. Additionally, the mean concentrations of HbO/HbR increased as the level of consciousness decreased during passive stimulation. Our findings suggest that the residual level of consciousness in pDoC patients can be assessed by measuring brain responses to different stimulations using fNIRS. The present study further demonstrates the feasibility and reliability of fNIRS in assessing residual consciousness in patients with pDoC, providing a basis for its expanded clinical application.


Asunto(s)
Trastornos de la Conciencia , Espectroscopía Infrarroja Corta , Humanos , Trastornos de la Conciencia/diagnóstico , Reproducibilidad de los Resultados , Estado Vegetativo Persistente/diagnóstico , Hemodinámica , Estado de Conciencia , Hemoglobinas
13.
Cancers (Basel) ; 15(3)2023 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-36765558

RESUMEN

Chimeric antigen receptor engineered T cell (CAR-T) therapy has high therapeutic efficacy against blood cancers, but it has not shown satisfactory results in solid tumors. Therefore, we examined the therapeutic effect of CAR-T therapy targeting carcinoembryonic antigen (CEA) in pancreatic adenocarcinoma (PDAC). CEA expression levels on the cell membranes of various PDAC cell lines were evaluated using flow cytometry and the cells were divided into high, medium, and low expression groups. The relationship between CEA expression level and the antitumor effect of anti-CEA-CAR-T was evaluated using a functional assay for various PDAC cell lines; a significant correlation was observed between CEA expression level and the antitumor effect. We created orthotopic PDAC xenograft mouse models and injected with anti-CEA-CAR-T; only the cell line with high CEA expression exhibited a significant therapeutic effect. Thus, the therapeutic effect of CAR-T therapy was related to the target antigen expression level, and the further retrospective analysis of pathological findings from PDAC patients showed a correlation between the intensity of CEA immunostaining and tumor heterogeneity. Therefore, CEA expression levels in biopsies or surgical specimens can be clinically used as biomarkers to select PDAC patients for anti-CAR-T therapy.

14.
Nat Commun ; 13(1): 6890, 2022 11 12.
Artículo en Inglés | MEDLINE | ID: mdl-36371436

RESUMEN

Therapeutic hypothermia at 32-34 °C during or after cerebral ischaemia is neuroprotective. However, peripheral cold sensor-triggered hypothermia is ineffective and evokes vigorous counteractive shivering thermogenesis and complications that are difficult to tolerate in awake patients. Here, we show in mice that deep brain stimulation (DBS) of warm-sensitive neurones (WSNs) in the medial preoptic nucleus (MPN) produces tolerable hypothermia. In contrast to surface cooling-evoked hypothermia, DBS mice exhibit a torpor-like state without counteractive shivering. Like hypothermia evoked by chemogenetic activation of WSNs, DBS in free-moving mice elicits a rapid lowering of the core body temperature to 32-34 °C, which confers significant brain protection and motor function reservation. Mechanistically, activation of WSNs contributes to DBS-evoked hypothermia. Inhibition of WSNs prevents DBS-evoked hypothermia. Maintaining the core body temperature at normothermia during DBS abolishes DBS-mediated brain protection. Thus, the MPN is a DBS target to evoke tolerable therapeutic hypothermia for stroke treatment.


Asunto(s)
Hipotermia , Animales , Ratones , Área Preóptica/fisiología , Tiritona/fisiología , Encéfalo , Modelos Animales de Enfermedad , Isquemia
15.
Basic Clin Pharmacol Toxicol ; 131(5): 364-371, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35968751

RESUMEN

BACKGROUND: Dexmedetomidine is commonly used in hysteroscopy surgery due to its analgesia and sedation without respiratory depression. Many studies have shown that dexmedetomidine can reduce the consumption of sevoflurane. However, the optimal end-tidal concentration of sevoflurane when it is co-administered with dexmedetomidine has not been established. The primary purpose of this study was to investigate the minimal alveolar concentration (MAC) of sevoflurane for cervical dilatation combined with different doses of dexmedetomidine in patients with hysteroscopy surgery. METHODS: One-hundred patients undergoing hysteroscopy surgery were enrolled in this clinical trial. All the patients were randomly assigned into four groups (C, D1 , D2 , D3 ) and received a loading dose of dexmedetomidine (0, 0.6, 0.8 and 1.0 µg/kg) over 10 min before anaesthesia induction, respectively. Anaesthesia was induced in each patient with 5% sevoflurane in 100% oxygen via a facemask. A laryngeal mask (LMA) was inserted when the patient had lost consciousness and the BIS value decreased below 40. The response to cervical dilatation stimulus (movement vs non-movement) by the insert of hysteroscope was recorded. The MAC of sevoflurane was measured by up and down sequential method of Dixon and Mood and centred isotonic regression analysis. RESULTS: The calculated MAC of sevoflurane using up-and-down method of Dixon and Mood in patients with hysteroscopy surgery was (1.90 ± 0.13)%, (1.23 ± 0.16)%, (1.03 ± 0.10)% and (0.93 ± 0.08)% in groups C, D1 , D2 and D3 , respectively. CONCLUSIONS: The administration of dexmedetomidine can significantly decrease the MAC of sevoflurane for hysteroscopy surgery. However, a ceiling effect of the reduction was observed when the dose of dexmedetomidine was higher than 0.8 µg/kg.


Asunto(s)
Anestésicos por Inhalación , Dexmedetomidina , Éteres Metílicos , Dexmedetomidina/farmacología , Femenino , Humanos , Histeroscopía , Éteres Metílicos/análisis , Oxígeno , Embarazo , Sevoflurano
16.
Sci Adv ; 8(35): eabn5899, 2022 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-36044580

RESUMEN

Restoring limb movements after central nervous system injury remains a substantial challenge. Recent studies proved that crossing nerve transfer surgery could rebuild physiological connectivity between the contralesional cortex and the paralyzed arm to compensate for the lost function after brain injury. However, the neural mechanism by which this surgery mediates motor recovery remains still unclear. Here, using a clinical mouse model, we showed that this surgery can restore skilled forelimb function in adult mice with unilateral cortical lesion by inducing cortical remapping and promoting corticospinal tract sprouting. After reestablishing the ipsilateral descending pathway, resecting of the artificially rebuilt peripheral nerve did not affect motor improvements. Furthermore, retaining the sensory afferent, but not the motor efferent, of the transferred nerve was sufficient for inducing brain remapping and facilitating motor restoration. Thus, our results demonstrate that surgically rebuilt sensory input triggers neural plasticity for accelerating motor recovery, which provides an approach for treating central nervous system injuries.


Asunto(s)
Lesiones Encefálicas , Transferencia de Nervios , Animales , Lesiones Encefálicas/patología , Miembro Anterior , Ratones , Plasticidad Neuronal/fisiología , Tractos Piramidales/patología
17.
BMC Anesthesiol ; 22(1): 203, 2022 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-35780106

RESUMEN

BACKGROUND: Spray-as-you-go (SAYGo) airway topical anesthesia and nerve block are common techniques used during awake tracheal intubation. However, their effects have not been described during double-lumen tube intubation. We report on a prospective randomized study that aimed to compare the intubation effects of SAYGo and nerve block patients undergoing thoracic surgery. METHODS: Sixty-six American Society of Anesthesiologists (ASA) physical status I and II patients were scheduled to undergo double-lumen tube (DLT) tracheal intubation for thoracic surgery. The patients were randomly assigned into control (Group C), ultrasound (Group U), and flexible intubation scope (Group F) groups with 22 cases in each group. Patients in Group C were induced with a standard anesthetic regimen. Patients in Groups U and F were treated with superior laryngeal nerve (SLN) block combined with transtracheal injection (TTI) and given a SAYGo airway topical anesthesia before intubation. Hemodynamic variables during intubation process were recorded as the primary outcome. Additional patient data were recorded including the occurrence of adverse events, the level of hoarseness, the occurrence of sore throats, memory function and the level of patient satisfaction with anesthesia. RESULTS: The blood pressure (BP) and heart rate (HR) of patients in group C was significantly increased 1 min after tracheal intubation (P < 0.05) compared to before anesthesia. The BP and HR of patients in Groups U and F remained stable. 10 cases of hypertension were observed in Group C, 6 cases in Group U and 1 case in Group F. In Group C, tachycardia was observed in 9 patients along with 9 cases in Group U and 4 cases in Group F. In Group U, 4 patients experienced puncture and bleeding were and 8 patients had a poor memory of TTI. No significant differences were found in the incidence of hoarseness, sore throats, and satisfaction with anesthesia in postoperative follow-up. CONCLUSIONS: SAYGo airway topical anesthesia and SLN block combined with the TTI technique can inhibit the cardiovascular response during DLT tracheal intubation. The SAYGo technique has fewer complications and more advantages compared to other approaches.


Asunto(s)
Ronquera , Faringitis , Anestesia Local/métodos , Ronquera/etiología , Humanos , Intubación Intratraqueal/efectos adversos , Intubación Intratraqueal/métodos , Faringitis/etiología , Estudios Prospectivos
18.
Front Oncol ; 12: 845036, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35494053

RESUMEN

Calcium/calmodulin-dependent protein ID (CAMK1D) is widely expressed in many tissues and involved in tumor cell growth. However, its role in gliomas has not yet been elucidated. This study aimed to investigate the roles of CAMK1D in the proliferation, migration, and invasion of glioma. Through online datasets, Western blot, and immunohistochemical analysis, glioma tissue has significantly lower CAMK1D expression levels than normal brain (NB) tissues, and CAMK1D expression was positively correlated with the WHO classification. Kaplan-Meier survival analysis shows that CAMK1D can be used as a potential prognostic indicator to predict the overall survival of glioma patients. In addition, colony formation assay, cell counting Kit-8, and xenograft experiment identified that knockdown of CAMK1D promotes the proliferation of glioma cells. Transwell and wound healing assays identified that knockdown of CAMK1D promoted the invasion and migration of glioma cells. In the above experiments, the results of overexpression of CAMK1D were all contrary to those of knockdown. In terms of mechanism, this study found that CAMK1D regulates the function of glioma cells by the PI3K/AKT/mTOR pathway. In conclusion, these findings suggest that CAMK1D serves as a prognostic predictor and a new target for developing therapeutics to treat glioma.

20.
Postgrad Med ; 134(5): 480-486, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35503235

RESUMEN

Trigeminal neuralgia (TN) is a severe facial pain disorder that often requires surgical treatment. Neurovascular compression (NVC) has been widely accepted as the primary cause of classical TN (cTN). Vascular compression involving the near half of the cisternal segment of trigeminal nerve was the most likely cause of patient's symptoms. And severe NVC was a strong imaging predictor of an optimal surgical outcome. Operative treatments for cTN include microvascular decompression (MVD) and various ablative procedures. However, a significant proportion of cTN patients with significant NVC fail to achieve long-term pain relief after technically successful surgery. Neuroimaging using magnetic resonance imaging (MRI) provides a noninvasive method to generate objective biomarkers of eventual response to TN surgery. This paper reviewed the progress of research on the prediction of surgical outcomes in TN with MRI.


Asunto(s)
Cirugía para Descompresión Microvascular , Neuralgia del Trigémino , Humanos , Imagen por Resonancia Magnética/efectos adversos , Imagen por Resonancia Magnética/métodos , Cirugía para Descompresión Microvascular/efectos adversos , Resultado del Tratamiento , Nervio Trigémino/diagnóstico por imagen , Nervio Trigémino/patología , Nervio Trigémino/cirugía , Neuralgia del Trigémino/diagnóstico por imagen , Neuralgia del Trigémino/cirugía
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