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Coronavirus disease-2019 (COVID-19) first emerged in late 2019 and has since spread worldwide. More than 600 million people have been diagnosed with COVID-19, and over 6 million have died. Vaccination against COVID-19 is one of the best ways to protect humans. Epilepsy is a common disease, and there are approximately 10 million patients with epilepsy (PWE) in China. However, China has listed "uncontrolled epilepsy" as a contraindication for COVID-19 vaccination, which makes many PWE reluctant to get COVID-19 vaccination, greatly affecting the health of these patients in the COVID-19 epidemic. However, recent clinical practice has shown that although a small percentage of PWE may experience an increased frequency of seizures after COVID-19 vaccination, the benefits of COVID-19 vaccination for PWE far outweigh the risks, suggesting that COVID-19 vaccination is safe and recommended for PWE. Nonetheless, vaccination strategies vary for different PWE, and this consensus provides specific recommendations for PWE to be vaccinated against COVID-19.
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COVID-19 , Epilepsia , Humanos , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Consenso , Pueblos del Este de Asia , Epilepsia/complicaciones , Epilepsia/epidemiología , VacunaciónRESUMEN
Hypoxia-ischemia (HI) is one of the most common causes of death and disability in neonates. Apoptosis contributes to HI development. Interleukin-11(IL-11) has been shown to protect mice from cerebral ischemia/reperfusion injury. However, whether IL-11 exerts the anti-apoptotic effect on HI injury is unclear. In this study, we demonstrated that recombinant human IL-11 (rhIL-11) prevented apoptosis of rat neonates with HI through activating IL-11Rα/STAT3 signaling. Sprague-Dawley rat pups on the 7th day after birth were used to establish an HI injury model. The expression levels of IL-11Rα and GP130 were increased first and then decreased after HI. In contrast, IL-11 expression was first decreased and then increased. Immunofluorescence staining showed that IL-11Rα was localized in neurons and oligodendrocytes. RhIL-11 treatment alleviated hippocampal and cortical damages, significantly reduced cerebral infarction volumes, cerebral edema, and loss of the Nissl body and nerve cells, and also ameliorated the outcomes of HI injury and long-term neurological deficits. In addition, rhIL-11 treatment upregulated the expressions levels of Bcl-2 and p-STAT3/STAT3, and downregulated the protein concentrations of the lytic protease, and cleaved-caspase-3. Furthermore, GP130 inhibitor and JAK1 inhibitor reversed the protective effects of rhIL-11. Overall, rhIL-11 showed an anti-apoptosis effect on the brain after HI injury. Our results indicated that rhIL-11 reduced neuronal apoptosis by activating the brain IL-11Rα/STAT3 pathway.
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Hipoxia-Isquemia Encefálica , Interleucina-11 , Animales , Humanos , Ratas , Animales Recién Nacidos , Receptor gp130 de Citocinas , Hipoxia , Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Interleucina-11/farmacología , Interleucina-11/metabolismo , Isquemia , Ratas Sprague-Dawley , Transducción de Señal , Factor de Transcripción STAT3/metabolismo , Subunidad alfa del Receptor de Interleucina-11RESUMEN
Nowadays, hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) dual-functional electrocatalyst in the field of water electrolysis has great advantages in reducing costs and simplifying electrolytic cell installations. Herein, Co-Mo particles were electrodeposited on the carbon nanotubes (CNTs)/reduced graphene oxide (rGO)-modified copper foam to form the Co-Mo-CNTs/rGO-copper foam (CF), then it was subjected to a certain potential for alkaline etching, thus needle-like E-Co-Mo-CNTs/rGO-CF was synthesized. Results showed that the material surface mainly formed by the interlacing of Co oxide was more conducive to capturing the intermediates in the HER/OER reaction, while the CNTs/rGO-CF structure was closely connected to the metal layer, making excellent performance of total hydrolysis in KOH. The electrocatalyst exhibited remarkable electrocatalytic activity for HER and OER in 1 M KOH, requiring only 71 and 268 mV overpotential to drive 10 mA·cm-2, respectively. Especially, only a battery voltage of 1.52 V was needed to drive 10 mA·cm-2in two-electrode system for overall water splitting. This work provides a method for the construction of dual-functional electrocatalyst that combined carbon materials and metals.
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OBJECTIVE: To explore the effect of COVID-19 outbreak on the treatment time of patients with ST-segment elevation myocardial infarction (STEMI) in Hangzhou, China. METHODS: We retrospectively reviewed the data of STEMI patients admitted to the Hangzhou Chest Pain Center (CPC) during a COVID-19 epidemic period in 2020 (24 cases) and the same period in 2019 (29 cases). General characteristics of the patients were recorded, analyzed, and compared. Moreover, we compared the groups for the time from symptom onset to the first medical contact (SO-to-FMC), time from first medical contact to balloon expansion (FMC-to-B), time from hospital door entry to first balloon expansion (D-to-B), and catheter room activation time. The groups were also compared for postoperative cardiac color Doppler ultrasonographic left ventricular ejection fraction (LVEF),the incidence of major adverse cardiovascular and cerebrovascular events (MACCE),Kaplan-Meier survival curves during the 28 days after the operation. RESULTS: The times of SO-to-FMC, D-to-B, and catheter room activation in the 2020 group were significantly longer than those in the 2019 group (P < 0.05). The cumulative mortality after the surgery in the 2020 group was significantly higher than the 2019 group (P < 0.05). CONCLUSION: The pre-hospital and in-hospital treatment times of STEMI patients during the COVID-19 epidemic were longer than those before the epidemic. Cumulative mortality was showed in Kaplan-Meier survival curves after the surgery in the 2020 group was significantly different higher than the 2019 group during the 28 days.The diagnosis and treatment process of STEMI patients during an epidemic should be optimized to improve their prognosis.
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COVID-19/complicaciones , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST/terapia , Tiempo de Tratamiento/estadística & datos numéricos , Enfermedad Aguda , China , Ecocardiografía Doppler en Color , Humanos , Pronóstico , Estudios Retrospectivos , Infarto del Miocardio con Elevación del ST/mortalidad , Volumen Sistólico , Análisis de Supervivencia , Factores de Tiempo , Función Ventricular IzquierdaRESUMEN
To investigate the association between COVID-19 and Parkinson's disease (PD) via a single-center study and a Mendelian randomization (MR) study. A questionnaire-based survey was conducted among PD patients at a single center from December 7, 2022, to March 10, 2023. Logistic regression analysis was performed to identify the infection-related risk factors. Subsequently, bidirectional two-sample Mendelian randomization was employed to explore the association between COVID-19 and PD. In the cross-sectional analysis, it was found that the prevalence of COVID-19 infection in PD patients was 65.7%. Forty-eight (35.3%) PD patients experienced exacerbation of motor symptoms following COVID-19 infection. Long PD disease duration (≥ 10 years) (OR: 3.327, P = 0.045) and long time since last vaccination (> 12 m) (OR: 4.916, P = 0.035) were identified as significant risk factors related to infection. The MR analysis results supported that PD increases the COVID-19 susceptibility (ß = 0.081, OR = 1.084, P = 0.006). However, the MR analysis showed that PD did not increases the COVID-19 severity and hospitalization, and no significant association of COVID-19 on PD was observed. The findings from this cross-sectional study suggest that individuals with PD may experience worsened motor symptoms following COVID-19 infection. Long disease duration (≥10 years) and long time since last vaccination (> 12 m) are identified as important risk factors for infection in these patients. Furthermore, our MR study provides evidence supporting an association between PD and COVID-19 susceptibility.
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COVID-19 , Análisis de la Aleatorización Mendeliana , Enfermedad de Parkinson , SARS-CoV-2 , Humanos , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/complicaciones , COVID-19/epidemiología , COVID-19/complicaciones , COVID-19/virología , Masculino , Femenino , Anciano , Persona de Mediana Edad , Estudios Transversales , Factores de Riesgo , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/genética , PrevalenciaRESUMEN
Several COVID-19 vaccines have been approved for emergency use according to China's immunization programs. These vaccines has created hope for patients with epilepsy, because the vaccines can help to reduce their risk of becoming infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to investigate the COVID-19 vaccine safety in patients with epilepsy. Here, we assessed the time of symptom control and the features of adverse events of seizure patients following their COVID-19 vaccinations. The results showed that adverse events of COVID-19 vaccinations for epilepsy patients included local pain at the injection site, dizziness and headache, epileptic attack, somnolence, limb weakness, limb pain, allergy, and fever. In addition, the average recovery time of the adverse events was approximately 42 h. More importantly, our study showed that it was relatively safe to vaccinate epilepsy patients who did not experience seizures for approximately 12 months prior to the immunization date.
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BACKGROUND: Multiple sclerosis (MS) is a chronic immune-mediated, inflammatory, demyelinating, neurodegenerative disorder of the central nervous system, and it causes major socioeconomic burden for the individual patient and for society. An inflammatory pathology occurs during the early relapsing stage of MS and a neurodegenerative pathology dominates the later progressive stage of the disease. Not all MS patients respond adequately to currently available disease-modifying drugs (DMDs). Alternative MS treatments with new modes of action are required to expand the current options for disease-modifying therapies (DMTs) and to aim for freedom from relapses, inflammatory lesions, disability progression and neurodegeneration. Laquinimod has dual properties of immunomodulation and neuroprotection and is a potentially promising new oral DMD in the treatment of relapsing MS. OBJECTIVES: To assess the effectiveness and safety profile of laquinimod as monotherapy or combination therapy versus placebo or approved DMDs (interferon-ß, glatiramer acetate, natalizumab, mitoxantrone, fingolimod, teriflunomide, dimethyl fumarate) for modifying the disease course in patients with MS. SEARCH METHODS: The Review Group Trials Search Co-ordinator searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Specialised Register which, among other sources, contains trials from CENTRAL (The Cochrane Library 2013, Issue 2), MEDLINE, EMBASE, CINAHL, LILACS, PEDro and Clinical trials registries (29 April 2013). We checked references in identified trials and manually searched the reports (2004 to March 2013) from neurological associations and MS societies. We also communicated with researchers participating in trials on laquinimod and contacted Teva Pharmaceutical Industries. SELECTION CRITERIA: All randomised, double-blind, controlled, parallel group clinical trials (RCTs) with a length of follow-up of at least one year evaluating laquinimod, as monotherapy or combination therapy, versus placebo or approved DMDs for patients with MS. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. Disagreements were discussed and resolved by consensus among review authors. Principal investigators of included studies were contacted for additional data or confirmation of information. MAIN RESULTS: Only one study met our inclusion criteria, involving 1106 adult patients with relapsing-remitting MS (RRMS) and an entry Expanded Disability Status Scale (EDSS) score of ≤ 5.5 and an entry disease duration of ≥ 6 months. Five hundred and fifty patients treated with laquinimod at a dose of 0.6 mg orally administered once daily in a capsule were compared with 556 patients treated with a matching placebo capsule. The study had a high risk for attrition bias (21.9%). Laquinimod had potential benefits in reducing relapse rates and was safe for most patients with RRMS in the short term. The most common adverse events included headache, back pain, arthralgia, diarrhoea, cough, urinary tract infection, elevated alanine aminotransferase, insomnia, nausea, abdominal pain and sinusitis. One ongoing trial was identified. AUTHORS' CONCLUSIONS: We found low-level evidence for the use of laquinimod as a disease-modifying therapy for MS because only one study with limited quality (high risk of attrition bias) was included. The published study suggests that laquinimod at a dose of 0.6 mg orally administered once daily may be safe and have potential benefits for most patients with RRMS in the short term. We are waiting for the publication of ongoing trials.
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Inmunosupresores/administración & dosificación , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Quinolonas/administración & dosificación , Administración Oral , Adulto , Humanos , Esclerosis Múltiple Recurrente-Remitente/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Prevención SecundariaRESUMEN
Signaling pathways play significant roles in the occurrence, development, and treatment of pancreatic cancer (PC). The main treatment options are surgery, chemotherapy, radiotherapy, arterial infusion chemotherapy in interventional therapy, and immunotherapy. Many studies have shown that signaling pathways perform a function in the occurrence and development of PC, for instance, phosphoinositide 3-kinase (PI3K)/AKT, nuclear factor-κB, Ras, interleukin (IL)-17B/IL-17RB, Wnt, and hepatocyte growth factor/c-MET, which play roles in the proliferation, metastasis, invasion, inhibition of apoptosis, promotion of angiogenesis, and drug resistance of PC. Interaction of signaling pathways has an impact on the biological behavior of PC; for example, activation of the neurotensin/NTSR1 pathway, which can activate mitogen-activated protein kinase, nuclear factor-κB, and other pathways related to PC stem cells, play an important role in PC, and an increase in their number is associated with the Wnt/ß-catenin and PI3K pathways. Chemotherapy is the main method for the treatment of PC, but drug resistance limits its use. In addition, abnormal activation of IL-17B/IL-17RB signaling pathway is associated with drug resistance. This article discusses the signaling pathways that play different roles in the occurrence and development of PC, as well as current research on signaling pathways in PC treatment.
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Neoplasias Pancreáticas , Fosfatidilinositol 3-Quinasas , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , FN-kappa B/metabolismo , Transducción de Señal , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias PancreáticasRESUMEN
Seizure is associated with pathological changes of hippocampus, but the mechanism by which hippocampal neuronal apoptosis promotes epilepsy is unclear. Our previous study showed that the expression of NHE-1 was increased in epileptic model rats. Therefore, this study further explores the effect of NHE-1 on hippocampal cells apoptosis and seizure in lithium chloride-pilocarpine epileptic model rats. First, we established a lithium chloride-pilocarpine induced epileptic rat model and detected the expression of NHE-1, calpain1 and apoptosis in the hippocampus. Then, we further down-regulated NHE-1 to observe the expression of calpain1 and apoptosis in the hippocampus, as well as its effect on seizures in rats. We found that the expression of NHE-1 and calpain1 and apoptosis in the hippocampus was significant increased in the model group. After down-regulating NHE-1, the expression of calpain1 was decreased, and hippocampal cell apoptosis was alleviated. In addition, down-regulation of NHE-1 reduced the frequency and duration of seizures in epileptic rats. Therefore, hippocampal NHE-1 overexpression is closely related to the development of neuronal apoptosis in a rat model of epilepsy, and downregulating NHE-1 expression can reduce cell apoptosis. Moreover, the NHE-1/calpain1 signaling pathway may be an important mechanism leading to hippocampal cell apoptosis.
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OBJECTIVE: Na(+)/H(+) exchanger isoform 1 (NHE1), a membrane protein that regulates intracellular pH, is abundantly expressed in brain tissues. It is associated with pathophysiologies in several brain diseases. The present study aimed to investigate the effects of NHE1 on the apoptosis of primary neurons of an epilepsy model. METHODS: Primary hippocampal neurons were cultured in an Mg2+-free medium to establish an epilepsy cell model. Designed shNHE1 lentivirus was used to silence NHE1 level in primary neurons. Nonselective pharmacological inhibitor MDL-28170 (20 µmol/L) was used to inhibit calpain-1 protein in neurons treated with Mg2+-free medium. The expression levels of NHE1 and calpain-1, intracellular Ca2+ (Ca2+i) and H+ (H+i) levels, and the expression levels of apoptosis-related proteins Bcl-2 and Bax were detected in neurons. TUNEL staining was performed to determine apoptosis in different groups. RESULTS: NHE1 expression was increased in primary neurons treated with an Mg2+-free medium, and it was correlated with increased expression of calpain-1 and cell apoptosis. Neurons from the in vitro epilepsy model showed significantly decreased Bcl-2 protein expression and significantly increased Bax protein expression. In the presence of LV-shNHE1 and the calpain-1 inhibitor MDL-28170, the changes in the expression of apoptosis-related proteins Bcl-2 and Bax were blocked in the epileptic model, and the percentage of apoptotic neurons among neurons from the in vitro epilepsy model was significantly decreased. The increase in calpain-1 expression was suppressed by LV-shNHE1; however, the inhibition of calpain-1 did not affect NHE1 expression. CONCLUSION: These results demonstrate that NHE1 participates in the promotion of neuronal apoptosis of epilepsy model in vitro through the calpain-1 pathway. Downregulation of NHE1 expression could exert a neuroprotective effect on epilepsy.
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Parkinson's disease (PD) is a neurodegenerative disease. Ferroptosis shares several features with PD pathophysiology, and anti-ferroptosis molecules are neuroprotective in PD animal models. As an antioxidant and iron chelating agent, alpha lipoic acid (ALA) has a neuroprotective effect on PD; however, the influence of ALA on ferroptosis in PD remains unclear. This study aimed to determine the mechanism of ALA in regulating ferroptosis in PD models. Results showed that ALA could ameliorate motor deficits in PD models and regulate iron metabolism by upregulating ferroportin (FPN) and ferritin heavy chain 1 (FTH1) and downregulating iron importer divalent metal transporter 1 (DMT1). Moreover, ALA decreased the accumulation of reactive oxygen species (ROS) and lipid peroxidation, rescued mitochondrial damage, and prevented ferroptosis effectively by inhibiting the downregulation of glutathione peroxidase 4 (GPX4) and cysteine/glutamate transporter (xCT) in PD. Mechanistic study indicated that the activation of SIRT1/NRF2 pathway was involved in the upregulation effect of GPX4 and FTH1. Thus, ALA ameliorates motor deficits in PD models by regulating iron metabolism and mitigating ferroptosis through the SIRT1/NRF2 signaling pathway.
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Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Ácido Tióctico , Animales , Ácido Tióctico/farmacología , Ácido Tióctico/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Sirtuina 1 , Factor 2 Relacionado con NF-E2 , Hierro , Quelantes del HierroRESUMEN
Background: Since the end of 2019, the coronavirus disease (COVID-19) outbreak rapidly became a pandemic. The psychological state of people during the COVID-19 pandemic has gained interest. Our aim was to study the prevalence of anxiety, depression, and stress in college students during the COVID-19 pandemic. Methods: A systematic search of Medline, Embase, Web of Science, and the Cochrane Library was conducted up to September 20, 2020. Reviewers independently assessed full-text articles according to predefined criteria. Stata14/SE was used to calculate the prevalence and 95% confidence intervals (CIs) of anxiety, depression, and stress among college students from different countries. A random effects model was adopted. The Egger test was used to determine publication bias. Results: A total of 280 references were retrieved, and 28 papers met our inclusion criteria, for a total of 436,799 college students. Thirteen studies involved non-Chinese college students, and 15 studies involved Chinese college students. The prevalence of anxiety, depression, and stress was 29% (95% CI, 19-25%), 37% (95% CI, 32-42%), and 23% (95% CI, 8-39%), respectively. Conclusion: The COVID-19 pandemic has had a negative psychological effect on college students, and the prevalence of anxiety, depression, and stress among Chinese college students is lower than among non-Chinese college students.
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Acute ischemic stroke (AIS) is a syndrome characterized by high morbidity, prevalence, mortality, recurrence and disability. The longer the delay before proper treatment of a stroke, the greater the likelihood of brain damage and disability. Computed tomography and nuclear magnetic resonance are the primary choices for fast diagnosis of AIS in the early stage, which can provide certain information about infarction location and degree, and even the vascular distribution of lesions responsible for strokes. However, this is quite difficult to achieve in small clinics or at-home diagnoses. Hematology tests could quickly obtain a large number of pathology-related indicators, and offer an effective method for rapid AIS diagnosis when combined with the machine learning technique. To explore a reliable, predictable method for early clinical etiologic diagnosis of AIS, a retrospective study was deployed on 456 AIS patients at the early stage and 28 reference subjects without the symptoms of AIS, by means of the selected significant traits amongst 64 clinical and blood traits in conjunction with powerful machine learning strategies. Five representative biomarkers were closely related to cardioembolic (CE), 22 to large artery atherosclerosis (LAA), and 15 to small vessel occlusion (SVO) strokes, respectively. With these biomarkers, different etiologic subtypes of stroke patients were determined with high accuracy of >0.73, sensitivity of >0.73, and specificity of >0.70, which was comparable to the accuracy obtained in the emergency department by clinical diagnosis. The proposed method may offer an alternative strategy for the etiologic diagnosis of AIS at the early stage when integrating significant blood traits into machine learning.
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Background: Many studies have shown that the pollution of fine particles in the air is related to the incidence of chronic diseases. However, research on air pollution and metabolism-associated fatty liver disease (MAFLD) is limited. Objective: The purpose of this study was to explore the relationship between short-term ambient air pollution and daily outpatient visits for metabolic-related fatty liver. Methods: We used a quasi-Poisson regression generalized additive model to stratify analyses by season, age, and gender. Results: From January 1, 2017, to August 31, 2019, 10,562 confirmed MAFLD outpatient visits were recorded. A 10 µg/m3 increase of fine particular matter (PM10and PM2.5) and NO2 concentrations corresponding with percent change were 0.82 (95% confidence interval [CI], 0.49-1.15), 0.57 (95% CI, 0.18-0.98), and 0.86 (95% CI, 0.59-1.13) elevation in MAFLD outpatient visits. In terms of season, the impact estimates of NO2 and PM2.5% change were 3.55 (95% CI, 1.23-5.87) and 1.12 (95% CI, 0.78-1.46) in the hot season and transition season, respectively. Compared with the warm season, the impact estimates of PM10were more significant in the cool season: 2.88 (95% CI, 0.66-5.10). NO2 has the greatest effect in the transition season, whereas PM10 has the greatest highest effect in the cool and hot seasons. Compared with other pollutants, PM2.5 has the greatest impact in the age stratification, which percent change are 2.69 (95% CI, 0.77-5.61) and 2.88 (95% CI, 0.37-6.40) respectively. The impact values of PM2.5 in male and female percent change were 3.60 (95% CI, 0.63-6.57) and 1.65 (95% CI, 1.05-2.25), respectively. Conclusion: This study shows that the air pollutants are related to the number of outpatient visits for MAFLD. The effects of different air pollutants on MAFLD outpatient visits were different by season, ages, and gender.