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1.
Med Res Rev ; 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38711187

RESUMEN

Previously, lysosomes were primarily referred to as the digestive organelles and recycling centers within cells. Recent discoveries have expanded the lysosomal functional scope and revealed their critical roles in nutrient sensing, epigenetic regulation, plasma membrane repair, lipid transport, ion homeostasis, and cellular stress response. Lysosomal dysfunction is also found to be associated with aging and several diseases. Therefore, function of macroautophagy, a lysosome-dependent intracellular degradation system, has been identified as one of the updated twelve hallmarks of aging. In this review, we begin by introducing the concept of lysosomal quality control (LQC), which is a cellular machinery that maintains the number, morphology, and function of lysosomes through different processes such as lysosomal biogenesis, reformation, fission, fusion, turnover, lysophagy, exocytosis, and membrane permeabilization and repair. Next, we summarize the results from studies reporting the association between LQC dysregulation and aging/various disorders. Subsequently, we explore the emerging therapeutic strategies that target distinct aspects of LQC for treating diseases and combatting aging. Lastly, we underscore the existing knowledge gap and propose potential avenues for future research.

2.
J Transl Med ; 20(1): 291, 2022 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-35761337

RESUMEN

Central nervous system (CNS) diseases, such as multiple sclerosis, Alzheimer's disease (AD), and Parkinson's disease (PD), affect millions of people around the world. Great efforts were put in disease related research, but few breakthroughs have been made in the diagnostic and therapeutic approaches. Exosomes are cell-derived extracellular vesicles containing diverse biologically active molecules secreted by their cell of origin. These contents, including nucleic acids, proteins, lipids, amino acids, and metabolites, can be transferred between different cells, tissues, or organs, regulating various intercellular cross-organ communications and normal and pathogenic processes. Considering that cellular environment and cell state strongly impact the content and uptake efficiency of exosomes, their detection in biological fluids and content composition analysis potentially offer a multicomponent diagnostic readout of several human diseases. Recently, studies have found that aberrant secretion and content of exosomes are closely related to the pathogenesis of CNS diseases. Besides, loading natural cargoes, exosomes can deliver drugs cross the blood brain barrier, making them emerging candidates of biomarkers and therapeutics for CNS diseases. In this review, we summarize and discuss the advanced research progress of exosomes in the pathological processes of several CNS diseases in regarding with neuroinflammation, CNS repair, and pathological protein aggregation. Moreover, we propose the therapeutic strategies of applying exosomes to the diagnosis, early detection, and treatment of CNS diseases.


Asunto(s)
Enfermedad de Alzheimer , Enfermedades del Sistema Nervioso Central , Exosomas , Vesículas Extracelulares , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/terapia , Comunicación Celular , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Enfermedades del Sistema Nervioso Central/terapia , Exosomas/metabolismo , Humanos
3.
Cell Mol Biol Lett ; 27(1): 97, 2022 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-36348288

RESUMEN

BACKGROUND: Endothelial cells (ECs) play an important role in angiogenesis and vascular reconstruction in the pathophysiology of ischemic stroke. Previous investigations have provided a profound cerebral vascular atlas under physiological conditions, but have failed to identify new disease-related cell subtypes. We aimed to identify new EC subtypes and determine the key modulator genes. METHODS: Two datasets GSE174574 and GSE137482 were included in the study. Seurat was utilized as the standard quality-control pipeline. UCell was used to calculate single-cell scores to validate cellular identity. Monocle3 and CytoTRACE were utilized in aid of pseudo-time differentiation analysis. CellChat was utilized to infer the intercellular communication pathways. The angiogenesis ability of ECs was validated by MTS, Transwell, tube formation, flow cytometry, and immunofluorescence assays in vitro and in vivo. A synchrotron radiation-based propagation contrast imaging was introduced to comprehensively portray cerebral vasculature. RESULTS: We successfully identified a novel subtype of EC named "healing EC" that highly expressed pan-EC marker and pro-angiogenic genes but lowly expressed all the arteriovenous markers identified in the vascular single-cell atlas. Further analyses showed its high stemness to differentiate into other EC subtypes and potential to modulate inflammation and angiogenesis via excretion of signal molecules. We therefore identified X-box binding protein 1 (Xbp1) as a key modulator in the healing EC phenotype. In vitro and in vivo experiments confirmed its pro-angiogenic roles under both physiological and pathological conditions. Synchrotron radiation-based propagation contrast imaging further proved that Xbp1 could promote angiogenesis and recover normal vasculature conformation, especially in the corpus striatum and prefrontal cortex under middle cerebral artery occlusion (MCAO) condition. CONCLUSIONS: Our study identified a novel disease-related EC subtype that showed high stemness to differentiate into other EC subtypes. The predicted molecule Xbp1 was thus confirmed as a key modulator that can promote angiogenesis and recover normal vasculature conformation.


Asunto(s)
Células Endoteliales , Infarto de la Arteria Cerebral Media , Humanos , Células Endoteliales/metabolismo , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patología , Proteína 1 de Unión a la X-Box/genética , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Fenotipo , Neovascularización Fisiológica/genética
4.
Neurol Sci ; 43(4): 2461-2467, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34750685

RESUMEN

PURPOSE: Hospital-acquired pneumonia (HAP) is becoming a serious problem in China, especially caused by multi-drug resistant (MDR), which is a risk factor for poor prognosis of intracranial cerebral hemorrhage (ICH). We investigate the risk factors for HAP among patients with ICH and study the antibiotic use and medical costs of MDR infection. METHODS: We performed a retrospective, case-control, parallel study in Xiangya Hospital. Patients included in this study and diagnosed with basal ganglia hemorrhage were admitted between January 2017 and December 2019. RESULTS: Univariate analysis discovered some personal risk factors including gender (p = .002), age (p = .023), and underlying conditions such as diabetes (p = .036), coronary heart disease (p = .009), and renal insufficiency (p = .001). Invasive medical operations including endotracheal intubation, tracheotomy, ventilator use, lumbar puncture, urinary catheter insertion, and peripherally inserted central catheter (PICC) (p < .001 all) were also risk factors for HAP. Binary logistics regression indicated hospital duration, antibiotic exposure, and urinary catheter insertion explained 91.4% of the variance on HAP (p < 0.01). As for the antibiotic treatment, there were no difference in the duration of use days and total dose per patient between MDR and non-MDR group, except for Tigecycline. Antibiotic costs for the MDR group were significantly higher than those for the non-MDR group and no infection group (p < 0.001). CONCLUSION: To better prevent HAP particularly caused by MDR bacteria, we emphasize the aseptic technique especially in the management of equipment in patient care.


Asunto(s)
Infección Hospitalaria , Neumonía , Antibacterianos/uso terapéutico , Bacterias , Hemorragia Cerebral/complicaciones , Costo de Enfermedad , Infección Hospitalaria/complicaciones , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/epidemiología , Hospitales , Humanos , Neumonía/epidemiología , Estudios Retrospectivos , Factores de Riesgo
5.
Neurol Sci ; 42(4): 1631-1635, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33433757

RESUMEN

Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline mutations in DNA mismatch repair (MMR) genes, including MLH1, MSH2, MSH6, and PMS2, which predisposes patients to various malignant neoplasms. Previous studies showed that MLH1, MSH2, MSH6, and PMS2 mutation in LS were associated with an elevated risk of colorectal, gastric, endometria, ovarian, and other cancers among family members. Patients of these kinds of cancers had high incidence of synchronous and metasynchronus. We describe the case of a 34-year-old female patient with 50 days of sudden dizziness and left limb weakness, whose head CT scan showed large infarction in the right frontal temporal parietal lobe and basal ganglia area. Imaging examinations and pathological biopsy indicated high-grade serous carcinoma (HGSC) IIIA1 of the right ovary. In addition, a novel frame-shift mutation in the MLH1 gene (c.1621dupG, p.A541Gfs*16) was found in the genetic panel sequence. It may render declining of MLH1 protein and also associate with the patient's progressive clinical manifestations of multiple systems. Therefore, the timely use of prenatal diagnosis to prevent unnecessary new cases of this severe genetic disease is available.


Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis , Homólogo 1 de la Proteína MutL , Accidente Cerebrovascular , Adulto , Neoplasias Colorrectales Hereditarias sin Poliposis/complicaciones , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico por imagen , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Reparación de la Incompatibilidad de ADN , Femenino , Predisposición Genética a la Enfermedad , Humanos , Homólogo 1 de la Proteína MutL/genética , Mutación
6.
J Public Health (Oxf) ; 43(3): 466-471, 2021 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-33480432

RESUMEN

BACKGROUND: To investigate the knowledge, attitudes and anxiety toward COVID-19 among Chinese college students studying in China and abroad. METHOD: A structured questionnaire, comprised of demographic characteristics, knowledge and attitudes toward COVID-19 and the State-Trait Anxiety Inventory (STAI), was used to collect data for 566 domestic students and 126 students studying abroad. RESULTS: Domestic students were better than students abroad in knowledge of epidemiology and manifestations. Domestic students showed a significant higher enthusiasm for voluntary services than students abroad, including medical science popularization, community services, traffic dispersion, logistics transportation and being volunteers for vaccine trials. The scores (Mean ± SD) of S-AI and T-AI among students abroad were 59.48 ± 8.63 and 54.10 ± 7.20, respectively, which were significantly higher than those of domestic students (39.46 ± 8.16 and 39.25 ± 7.72). CONCLUSIONS: Our study showed a better understanding of knowledge, more positive attitudes and less anxiety toward COVID-19 among domestic students, compared with students studying abroad. In light of this information, more attention and appropriate psychological and social intervention should be paid to college students with anxiety, especially those studying abroad.


Asunto(s)
COVID-19 , Ansiedad/epidemiología , China/epidemiología , Estudios Transversales , Conocimientos, Actitudes y Práctica en Salud , Humanos , SARS-CoV-2 , Estudiantes , Encuestas y Cuestionarios
7.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(5): 536-544, 2021 May 28.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-34148891

RESUMEN

RNA methylation is of great significance in the regulation of gene expression, among which the more important methylation modifiers are N6-methyladenosine (m6A) and 5-methylcytosine (m5C). The methylation process is mainly regulated by 3 kinds of proteins: methyltransferase, demethylase, and reader. m6A, m5C, and their related proteins have high abundance in the brain, and they have important roles in the development of the nervous system and the repair and remodeling of the vascular system. The neurovascular unit (NVU) is a unit of brain structure and function composed of neurons, capillaries, astrocytes, supporting cells, and extracellular matrix. The local microenvironment for NVU has an important role in nerve cell function repair, and the remodeling of NVU is of great significance in the prognosis of various neurological diseases.


Asunto(s)
Adenosina , Metiltransferasas , 5-Metilcitosina , Adenosina/metabolismo , Metilación , Metiltransferasas/metabolismo , ARN
9.
Vaccines (Basel) ; 12(3)2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38543885

RESUMEN

Vascular cognitive impairment (VCI) encompasses a wide range of cognitive disorders stemming from cerebrovascular issues, such as strokes or small vessel disease. These conditions often pose challenges to traditional diagnostic approaches due to their multifactorial nature and varied clinical presentations. Recently, next-generation sequencing (NGS) technologies have provided detailed analyses of long non-coding RNAs (lncRNAs) in the molecular pathobiology of VCI. These new findings help with molecular-based diagnostics and treatments of VCI. Within this realm, the concept of immune modulation, especially through specific vaccinations, emerges as a promising therapeutic strategy in VCI mitigation. In this review, we comprehensively elucidate the function of lncRNAs in VCI, emphasizing the advanced understanding of VCI's molecular underpinnings made possible through NGS technologies. Significant focus is placed on the immune system's role in VCI, particularly the neuroinflammatory processes which are consequential to cerebrovascular abnormalities. We believe that lncRNAs participate in regulating these immunological pathways, potentially guiding the development of vaccines targeting VCI. In this context, we propose a novel perspective: using knowledge about lncRNA profiles and functions to guide vaccine development, we can potentially exploit the body's immune response to mitigate or prevent VCI. This approach has the potential to revolutionize VCI management by introducing targeted immunization strategies informed by molecular signatures, a concept that remains largely unexplored in current research endeavors. In addition, we summarize current progress and propose future directions, advocating for robust, interdisciplinary studies to validate the potential intersections between lncRNA landscapes, VCI pathology, and immunology. This review aims to spur innovative research and promote the development of lncRNA-informed vaccine strategies as proactive interventions against the cognitive consequences of VCI.

10.
BMJ Open ; 14(3): e077242, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38553073

RESUMEN

INTRODUCTION: Anterior cruciate ligament (ACL) rupture can be treated surgically or non-surgically, with several surgical interventions available at present. However, the comparatively effective surgical intervention with relatively fewer side effects remains unknown. This study aims to fill in this gap by conducting a Bayesian network meta-analysis (NMA) and provide a theoretical basis for the clinical application. METHOD AND ANALYSIS: We will perform a Bayesian NMA and will include randomised controlled trials (RCTs) published in English or Chinese that compare surgical intervention (ie, standard ACL reconstruction, ACL remnant-preserving reconstruction and ACL repair with suture augmentation to conservative therapy or studies that compare one surgical intervention to another for the symptom relief and function recovery of patients with ACL rupture. Primary outcome will be the proportion of patients with symptomatic and functional improvement measured by the Knee Injury and Osteoarthritis Outcome Score before and 6 months after treatment, with scores ranging from 0 (worst) to 100 (best). Secondary outcomes will be knee-specific quality of life (ACL QoL), return to activity and level of sport participation (Tegner or modified Tegner score), health-related QoL (EuroQol Group 5-Dimension 5-Level, EQ-5D-5L), resource use, intervention-related complications and patient satisfaction. We have developed search strategies for PubMed, Embase, the Cochrane Library and Web of Science, retrieving RCTs that meet the inclusion criteria from database inception to 1 December 2023. The methodological quality of the included RCTs will be assessed based on the Cochrane risk of bias table. The relative ranking probability of the best intervention will be estimated using the surface under the cumulative ranking curve. The Bayesian NMA will be conducted by using WinBUGS V.1.4.3. The Grading of Recommendations Assessment, Development and Evaluation approach will be applied to determine our confidence in an overall treatment ranking from the NMA. ETHICS AND DISSEMINATION: Ethical approval for this study is not required because no private or confidential patient data will be used in this study. Findings of this study would be disseminated through the publication in a peer-reviewed medical journal. PROSPERO REGISTRATION NUMBER: CRD42023437115.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Humanos , Metaanálisis en Red , Articulación de la Rodilla , Tratamiento Conservador , Reconstrucción del Ligamento Cruzado Anterior/efectos adversos , Metaanálisis como Asunto
11.
EPMA J ; 14(4): 645-661, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38094579

RESUMEN

At present, stroke remains the second highest cause of death globally and a leading cause of disability. From 1990 to 2019, the absolute number of strokes worldwide increased by 70.0%, and the prevalence of stroke increased by 85.0%, causing millions of deaths and disability. Ischemic stroke accounts for the majority of strokes, which is caused by arterial occlusion. Effective primary prevention strategies, early diagnosis, and timely interventions such as rapid reperfusion are in urgent implementation to control ischemic stroke. Otherwise, the stroke burden will probably continue to grow across the world as a result of population aging and an ongoing high prevalence of risk factors. To help with the diagnosis and management of ischemic stroke, newer techniques such as artificial intelligence (AI) are highly anticipated and may bring a new revolution. AI is a recent fast-growing research area which aims to mimic cognitive processes through a number of techniques such as machine learning (ML) methods of random forest learning (RFL) and convolutional neural networks (CNNs). With the help of AI, several momentous milestones have already been attained across diverse dimensions of ischemic stroke. In the context of predictive, preventive, and personalized medicine (PPPM/3PM), we aim to transform stroke care from a reactive to a proactive and individualized paradigm. In this way, AI demonstrates strong clinical utility across all three levels of prevention in ischemic stroke. In this paper, we synoptically illustrated the history and current situation of AI and ML. Then, we summarized their clinical applications and efficacy in the management of stroke. We finally provided an outlook on how AI approaches might contribute to enhancing favorable outcomes after stroke and proposed our suggestions on developing AI-based PPPM strategies. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00343-3.

12.
Pharmaceutics ; 15(11)2023 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-38004615

RESUMEN

Currently, adipose-derived mesenchymal stromal/stem cells (ADMSCs) are recognized as a highly promising material for stem cell therapy due to their accessibility and safety. Given the frequently irreversible damage to neural cells associated with CNS disorders, ADMSC-related therapy, which primarily encompasses ADMSC transplantation and injection with exosomes derived from ADMSCs or secretome, has the capability to inhibit inflammatory response and neuronal apoptosis, promote neural regeneration, as well as modulate immune responses, holding potential as a comprehensive approach to treat CNS disorders and improve prognosis. Empirical evidence from both experiments and clinical trials convincingly demonstrates the satisfactory safety and efficacy of ADMSC-related therapies. This review provides a systematic summary of the role of ADMSCs in the treatment of central nervous system (CNS) disorders and explores their therapeutic potential for clinical application. ADMSC-related therapy offers a promising avenue to mitigate damage and enhance neurological function in central nervous system (CNS) disorders. However, further research is necessary to establish the safety and efficacy of clinical ADMSC-based therapy, optimize targeting accuracy, and refine delivery approaches for practical applications.

13.
Front Mol Neurosci ; 16: 1102147, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36896007

RESUMEN

N6-methyladenosine (m6A) is the most abundant internal RNA modification in eukaryotic cells, which participates in the functional regulation of various biological processes. It regulates the expression of targeted genes by affecting RNA translocation, alternative splicing, maturation, stability, and degradation. As recent evidence shows, of all organs, brain has the highest abundance of m6A methylation of RNAs, which indicates its regulating role in central nervous system (CNS) development and the remodeling of the cerebrovascular system. Recent studies have shown that altered m6A levels are crucial in the aging process and the onset and progression of age-related diseases. Considering that the incidence of cerebrovascular and degenerative neurologic diseases increase with aging, the importance of m6A in neurological manifestations cannot be ignored. In this manuscript, we focus on the role of m6A methylation in aging and neurological manifestations, hoping to provide a new direction for the molecular mechanism and novel therapeutic targets.

14.
Aging Dis ; 14(2): 290-298, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37008058

RESUMEN

Coronavirus disease-19 (COVID-19) has been spreading all over the world for more than two years. Though several kinds of vaccines are currently available, emergence of new variants, spike mutations and immune escape have raised new challenges. Pregnant women are vulnerable to respiratory infections due to their altered immune defence and surveillance functions. Besides, whether pregnant persons should receive a COVID-19 vaccine is still under debate because limited data are available on the efficacy and safety of receiving a vaccine during pregnancy. Physiological features and lack of effective protection making pregnant women at high risk of getting infected. Another concern is that pregnancy may trigger the onset of underlying existing neurological disease, which is highly similar to those neurological symptoms of pregnant women caused by COVID-19. These similarities interfere with diagnosis and delay timely and effective management. Therefore, providing efficient emergency support for pregnant women suffering from neurological symptoms caused by COVID-19 remains a challenge among neurologists and obstetricians. To improve the diagnosis and treatment efficiency of pregnant women with neurological symptoms, we propose an emergency management framework based on the clinicians' experience and available resources. This emergency care system aimed at addressing the conundrums faced by the emergency guarantee system under COVID-19 pandemic and could serve as a potential multisystem project for clinical practice and medical education.

15.
Bioengineering (Basel) ; 9(3)2022 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-35324788

RESUMEN

Osteoarthritis (OA) is a prevalent and debilitating age-related joint disease characterized by articular cartilage degeneration, synovial membrane inflammation, osteophyte formation, as well as subchondral bone sclerosis. OA drugs at present are mainly palliative and do not halt or reverse disease progression. Currently, no disease-modifying OA drugs (DMOADs) are available and total joint arthroplasty remains a last resort. Therefore, there is an urgent need for the development of efficacious treatments for OA management. Among all novel pharmaco-therapeutical options, exosome-based therapeutic strategies are highly promising. Exosome cargoes, which include proteins, lipids, cytokines, and various RNA subtypes, are potentially capable of regulating intercellular communications and gene expression in target cells and tissues involved in OA development. With extensive research in recent years, exosomes in OA studies are no longer limited to classic, mesenchymal stem cell (MSC)-derived vesicles. New origins, structures, and functions of exosomes are constantly being discovered and investigated. This review systematically summarizes the non-classic origins, biosynthesis, and extraction of exosomes, describes modification and delivery techniques, explores their role in OA pathogenesis and progression, and discusses their therapeutic potential and hurdles to overcome in OA treatment.

16.
Int J Biol Sci ; 18(2): 552-571, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35002509

RESUMEN

As an important method to accurately and timely diagnose stroke and study physiological characteristics and pathological mechanism in it, imaging technology has gone through more than a century of iteration. The interaction of cells densely packed in the brain is three-dimensional (3D), but the flat images brought by traditional visualization methods show only a few cells and ignore connections outside the slices. The increased resolution allows for a more microscopic and underlying view. Today's intuitive 3D imagings of micron or even nanometer scale are showing its essentiality in stroke. In recent years, 3D imaging technology has gained rapid development. With the overhaul of imaging mediums and the innovation of imaging mode, the resolution has been significantly improved, endowing researchers with the capability of holistic observation of a large volume, real-time monitoring of tiny voxels, and quantitative measurement of spatial parameters. In this review, we will summarize the current methods of high-resolution 3D imaging applied in stroke.


Asunto(s)
Encéfalo/irrigación sanguínea , Imagenología Tridimensional/métodos , Accidente Cerebrovascular/diagnóstico por imagen , Animales , Medios de Contraste/química , Humanos
17.
Front Med (Lausanne) ; 9: 1071414, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36698791

RESUMEN

Purpose: To construct a diversified and comprehensive network teaching model to provide highly qualified medical teaching in neurology under COVID-19 pandemic. Materials and methods: Published studies on medical education were systematically reviewed and summarized. Based on previous studies and our experience, we constructed a novel online neurology teaching model and applied it to real scene. Students taking traditional in class lessons and online lessons were asked to finish the test, respectively, to compare the efficiency of learning. Questionnaires were designed and assigned to get the feedback from students. Results: The average test score of students who take online class (84.27 ± 4.64) was significantly higher than those who take in class lessons (82.08 ± 6.17) (P < 0.01). According to the feedbacks from students, online classes were more attractive to students than the conventional one. Conclusion: Traditional single-mode teaching can no longer meet the needs of current medical education, especially under the rampant epidemic. This novel teaching mode, which orchestrates high-tech tools, diverse teaching methods and traditional teaching concepts, provides the solution to the challenge faced by traditional medical education. We believe that this novel online teaching mode will boost neurology education and inspire educators in other fields during this tough period.

18.
Cancer Med ; 10(20): 7418-7439, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34482648

RESUMEN

BACKGROUND: Glioma is the most common central nervous system tumor in adults, and a considerable part of them are high-degree ones with high malignancy and poor prognosis. At present, the classification and treatment of glioma are mainly based on its histological characteristics, so studies at the molecular level are needed. METHODS: RNA-seq data from The Cancer Genome Atlas (TCGA) datasets (n = 703) and Chinese Glioma Genome Atlas (CGGA) were utilized to find out the differentially expressed RNA-binding proteins (RBPs) between normal cerebral tissue and glioma. A prediction system for the prognosis of glioma patients based on 11 RBPs was established and validated using uni- and multi-variate Cox regression analyses. STITCH and CMap databases were exploited to identify putative drugs and their targets. Single sample gene set enrichment analysis (ssGSEA) was used to calculate scores of specific immune-related gene sets. IC50 of over 20,000 compounds in 60 cancer cell lines was collected from the CellMiner database to test the drug sensitivity prediction value of the RBP-based signature. RESULTS: We established a reliable prediction system for the prognosis of glioma patients based on 11 RBPs including THOC3, LSM11, SARNP, PABPC1L2B, SMN1, BRCA1, ZC3H8, DZIP1L, HEXIM2, LARP4B, and ZC3H12B. These RBPs were primarily associated with ribosome and post-transcriptional regulation. RBP-based risk scores were closely related to immune cells and immune function. We also confirmed the potential of the signature to predict the drug sensitivity of currently approved or evaluated drugs. CONCLUSIONS: Differentially expressed RBPs in glioma can be used as a basis for prognosis prediction, new drugs screening and drug sensitivity prediction. As RBP-based glioma risk scores were associated with immunity, immunotherapy may become an important treatment for glioma in the future.


Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Regulación Neoplásica de la Expresión Génica/genética , Glioma/tratamiento farmacológico , Terapia de Inmunosupresión/métodos , Proteínas de Unión al ARN/metabolismo , Neoplasias Encefálicas/patología , Glioma/patología , Humanos , Pronóstico
19.
Front Neurol ; 11: 555202, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33192989

RESUMEN

Importance: Corona virus disease 2019 (COVID-19) has long latent period, strong infectivity, and non-specific symptoms and signs in the upper respiratory tract. Some initial neurological symptoms appear, including dizziness, headache, seizures, slurred speech, disturbance of consciousness, and limb paralysis among a few COVID-19 patients, which share similar manifestations with central nervous system (CNS) infection. Improving the diagnostic efficiency of suspected CNS infection patients on the basis of preventing and controlling COVID-19 plays a key role in preventing nosocomial and cross infections. This study intends to formulate a hospital emergency management system of fastlane treatment of CNS infection for epidemic prevention and control, aiming at providing references and guidelines for the government and medical institutions to improve the efficiency of treating CNS infection patients in the clinical practice during COVID-19. Observations: This study formulated a framework of a fastlane treatment of CNS infection based on the cooperation of resources and experience, aiming at the key and difficult problems faced by the hospital emergency management system during the COVID-19 outbreak in Changsha, China. The main problem of formulating the hospital emergency management system is efficiently identifying whether CNS infection was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The framework improves the efficiency of diagnosing and treating CNS infections by standardizing the diagnosis and treatment process of patients in emergency observation and strengthening the management of inpatient wards, aiming at assisting medical staff during clinical practice. Conclusions and Relevance: The hospital emergency management system of a fastlane treatment of CNS infection for epidemic prevention and control of the COVID-19 outbreak is a professional and multisystem project, which needs the cooperation of various resources and the experience of clinical leadership.

20.
Front Neurol ; 11: 604907, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33329365

RESUMEN

Background: Coronavirus disease 2019 (COVID-19) has a long incubation period and a high degree of infectivity. Patients may not show specific signs or symptoms of upper respiratory tract infection, and the age of onset is similar to that of stroke. Furthermore, an increase in neurological conditions, specifically acute cerebrovascular disease, has been detected. Providing emergency treatment for acute stroke in accordance with the strict epidemic control measures is currently one of the main challenges, as acute stroke is rapid onset and a major cause of death and disability globally. We aimed to evaluate the emergency treatment system for acute stroke during the epidemic control period to provide a reference and basis for informing government and medical institutions on improving patient treatment rates during this period. Methods: Difficulties faced in providing emergency treatment for stroke during an epidemic were investigated and combined with medical educational resources and clinical management experiences to construct an emergency treatment framework for acute stroke during the epidemic. Findings: Currently, emergency treatment measures for acute stroke during the epidemic control period are limited because the main focus is on identifying COVID-19 comorbidities during the critical period. Establishing standards for patients in the neurological outpatient consultation rooms and emergency observation and resuscitation zones; implementing a fast-lane system for the emergency treatment of patients with acute stroke, and strengthening ward management and medicine popularization, can improve the treatment efficiency for stroke patients during the epidemic and provide a reference for peers in clinical practice. Interpretation: Emergency treatment for acute stroke during COVID-19 epidemic control period requires a joint promotion of clinical, popularization, and teaching resources.

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