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OBJECTIVE: To investigate the expression of the precursor of brain-derived neurotrophic factor (proBDNF) and its high-affinity receptor p75NTR in neurons of emotion-related brain areas (prefrontal cortex, hippocampus, and amygdala) in rats with post-stroke depression (PSD), and to explore the expression levels of proBDNF and p75NTR in neurons of emotion-related brain areas by injecting tissue plasminogen activator (t-PA) into the lateral ventricle of PSD rats, this significantly improved the stress-induced depression-like behavior,thus further validating the above results. METHODS: Rats were randomly divided into four groups: a normal control group (n = 8), a depression group (n = 8), a stroke group (n = 8), and a PSD group (n = 8). The rat model of stroke was established by thread embolism, and the PSD animal model was induced by chronic unpredictable mild stress (CUMS) and solitary feeding. Behavioral tests were conducted, including weight measurement, open field tests, and sucrose preference tests. Immunofluorescence double labeling was used to detect the expression of proBDNF and p75NTR in neurons of emotion-related brain regions in the PSD rat model. Four weeks after CUMS treatment, the PSD group was selected. Rats were infused with t-PA (3 µg dissolved in 6 µL saline, Boehringer Ingelheim), proBDNF (3 µg dissolved in 6 µL saline, Abcam), or equal-volume NS once per day for 7 consecutive days using the syringe pump connecting to injection needles. After 7 days of continuous administration, animal behavior was assessed through scoring, and the expression of proBDNF and p75NTR in the emotion-related brain regions of the PSD rat model was detected using immunofluorescence double labeling. RESULTS: Compared with the normal control group and the stroke group, the body weight, sucrose water consumption, and vertical movement distance in the PSD group were significantly lower (P < 0.05). In contrast, when compared with the proBDNF injection group and saline injection group, the weight, sucrose water consumption, field horizontal movement, and vertical movement distance of the t-PA injection group significantly increased after PSD lateral ventricle intubation.Double immunofluorescence revealed a higher neuronal expression of proBDNF as well as p75NTR in the prefrontal cortex and hippocampus of PSD rats compared to control animals (P < 0.05). In the amygdala, the expression levels of proBDNF and P75NTR were significantly reduced in the PSD group compared to the control group (P < 0.05). The results of the expression levels of proBDNF and P75NTR in the emotion-related brain regions of PSD rats injected with t-PA showed that proBDNF and P75NTR was significantly reduced in the prefrontal cortex, hippocampus, and amygdala of PSD rats compared to those of the NS and proBDNF groups (P < 0.05). CONCLUSIONS: The increased expression of the brain-derived neurotrophic factor precursor proBDNF and its receptor p75NTR in neurons of emotion-related brain regions may play an important role in the pathogenesis of PSD.t-PA reduced the expression of proBDNF and its receptor p75NTR in neurons emotion-related brain regions and significantly improved the stress-induced depression-like behavior. Therefore, it is reasonable to assume that exogenous injection of t-PA may alleviate the depressive symptoms of PSD patients.Reducing the expression of proBDNF by injecting t-PA may provide a novel therapeutic approach for the treatment of stress-related mood disorders.
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Factor Neurotrófico Derivado del Encéfalo , Depresión , Receptor de Factor de Crecimiento Nervioso , Accidente Cerebrovascular , Animales , Ratas , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Depresión/genética , Depresión/metabolismo , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Neuronas/metabolismo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/metabolismo , Sacarosa/metabolismo , Activador de Tejido Plasminógeno/uso terapéutico , Receptor de Factor de Crecimiento Nervioso/genética , Receptor de Factor de Crecimiento Nervioso/metabolismoRESUMEN
BACKGROUND: Echinacoside (ECH), a natural active compound, was found to exert neuroprotection in Parkinson's disease (PD). However, the underlying molecular mechanisms remain controversial. PURPOSE: This study aimed to explore the roles of ECH in PD and its engaged mechanisms. CONCLUSION: In vivo, MPTP was adapted to construct subacute PD mouse model to explore the regulation of ECH on NLRP3 inflammasome. In vitro, α-synuclein (α-syn)/MPP+ was used to mediate the activation of NLRP3 inflammasome in BV2 cells, and the mechanism of ECH regulation of it was explored with molecular docking, immunofluorescence, Western blotting, and small molecule inhibitors. CONCLUSION: The activation of microglial NLRP3 inflammasome could be evoked by MPTP in vitro, but its toxic metabolite MPP+ alone cannot trigger the activation of NLRP3 inflammasome in vitro, which requires α-synuclein (α-syn) priming. Exogenous α-syn could evoke microglial TLR2/NF-κB/NLRP3 axis, playing the priming role in MPP+ -mediated NLRP3 inflammasome activation. ECH can suppress the upregulation of α-syn in MPTP-treated mice and BV2 microglia. It can also suppress the activation of the TLR2/NF-κB/NLRP3 axis induced by α-syn. CONCLUSION: ECH exerts neuroprotective effects by downregulating the TLR2/NF-κB/NLRP3 axis via reducing the expression of α-syn in the PD models.
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Glicósidos , Proteína con Dominio Pirina 3 de la Familia NLR , Enfermedad de Parkinson , Ratones , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamasomas , FN-kappa B/metabolismo , Microglía , alfa-Sinucleína/metabolismo , Receptor Toll-Like 2/metabolismo , Neuroprotección , Simulación del Acoplamiento Molecular , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Ratones Endogámicos C57BLRESUMEN
Background: Neurocysticercosis (NCC), a predominant parasitic disease that affects the central nervous system and presents with diverse clinical manifestations, is a major contributor to acquired epilepsy worldwide, particularly in low-, middle-, and upper middle-income nations, such as China. In China, the Yunnan Province bears a significant burden of this disease. Objective: To describe the demographic, clinical, and radiological features as well as serum and cerebrospinal fluid antibodies to cysticercus in patients with NCC from Dali, Yunnan Province, China. Materials and Methods: This retrospective study included patients who were diagnosed with NCC at The First Affiliated Hospital of Dali University between January 2018 and May 2023 and were residing in Dali, Yunnan Province, China. Results: A total of 552 patients with NCC were included, of which 33.3% belonged to Bai ethnicity. The clinical presentation of NCC exhibited variability that was influenced by factors such as the number, location, and stage of the parasites. Epilepsy/seizure (49.9%) was the most prevalent symptom, with higher occurrence in the degenerative stage of cysts (P < 0.001). Compared with other locations, cysticerci located in the brain parenchyma are more likely to lead to seizures/epilepsy (OR = 17.45, 95% CI: 7.96-38.25) and headaches (OR = 3.02, 95% CI: 1.23-7.41). Seizures/epilepsy are more likely in patients with cysts in the vesicular (OR = 2.71, 95% CI: 1.12-6.61) and degenerative (OR = 102.38, 95% CI: 28.36-369.60) stages than those in the calcified stage. Seizures was not dependent on the number of lesions. All NCC patients underwent anthelminthic therapy, with the majority receiving albendazole (79.7%). Conclusion: This study provides valuable clinical insights into NCC patients in Dali and underscores the significance of NCC as a leading preventable cause of epilepsy.
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Objective: To compare the diagnostic value of cytobrush, ERCP-guided biopsy, SpyGlass direct visual impression and SpyGlass-guided biospy (SpyBite) in the differential diagnosis of benign and malignant bile duct strictures. Methods: The data of 1,008 patients who were clinically diagnosed with indeterminate biliary strictures and underwent ERCP-guided biopsy, cytobrush, SpyGlass direct visual impression or SpyBite at the First Affiliated Hospital of Nanchang University between January 2010 and December 2019 were collected and analyzed retrospectively. The final diagnose was determined by surgical pathological specimen or follow-up (Malignant stricture can be identified if the stricture showed malignant progression during one year of follow-up). The differential diagnostic value of the above endoscopic diagnostic methods was evaluated by means of sensitivity, specificity, accuracy, positive predictive value, negative predictive value, etc. and safety was evaluated by the incidence rate of adverse events. Results: In terms of sensitivity, standard biopsy group (48.6%) and SpyBite group (61.5%) were significantly higher than cytobrush group (32.0%), and visual impression group (100%) was significantly higher than any other group. As far as specificity was concerned, cytobrush group (99.0%), standard biopsy group (99.3%) and the SpyBite group (100%) were significantly higher than visual impression (55.6%), but there was no statistical difference among the three groups above. As far as accuracy was concerned, standard biopsy group (65.3%), and SpyBite group (80.0%) were significantly higher than cytobrush group (44.4%), and SpyBite group (80.0%) was significantly higher than visual impression group (54.8%). In terms of safety, visual impression group and SpyBite group were significantly higher than cytobrush group and standard biopsy group in post-ERCP cholangitis. Conclusion: SpyBite combined with SpyGlass-guided visual impression was better for differential diagnosis of benign and malignant bile duct strictures in terms of sensitivity and accuracy compared with conventional endoscopic diagnostic methods such as cytobrush and standard biopsy. Furthmore, the incidence rates of adverse events after SpyGlass examination was similar to those after conventional endoscopic diagnostic methods except for higher cholangitis, which could be controlled by antibiotics and might be avoided by adequate biliary drainage.
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Objective: Alzheimer's disease (AD), a prevalent neurodegenerative affliction that predominantly affects the elderly population, imposes a substantial burden on not only patients but also their families and society at large. Mitochondrial dysfunction plays an important role in its pathogenesis. In this study, we conducted a bibliometric analysis of research on mitochondrial dysfunction and AD over the past 10 years, with the aim of summarizing current research hotspots and trends in this field. Methods: On February 12, 2023, we searched for publications about mitochondrial dysfunction and AD in the Web of Science Core Collection database from 2013 to 2022. VOSview software, CiteSpace, SCImago, and RStudio were used to analyze and visualize countries, institutions, journals, keywords, and references. Results: The number of publications on mitochondrial dysfunction and AD were on the rise until 2021 and decreased slightly in 2022. The United States ranks first in the number of publications, H-index, and intensity of international cooperation in this research. In terms of institutions, Texas Tech University in the United States has the most publications. The Journal of Alzheimer's Disease has the most publications in this field of research, while Oxidative Medicine and Cellular Longevity have the highest number of citations. Mitochondrial dysfunction is still an important direction of current research. Autophagy, mitochondrial autophagy, and neuroinflammation are new hotspots. The article from Lin MT is the most cited by analyzing references. Conclusion: Research on mitochondrial dysfunction in AD is gaining significant momentum as it provides a crucial research avenue for the treatment of this debilitating condition. This study sheds light on the present research trajectory concerning the molecular mechanisms underlying mitochondrial dysfunction in AD.
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BACKGROUND: Temporal lobe epilepsy is a group of neurological diseases caused by the repeated abnormal discharge of brain neurons. Patients with this disease are often accompanied with cognitive impairment. However, the pathogenesis of the cognitive impairment remains unclear. Resting state functional magnetic resonance imaging is a kind of magnetic resonance imaging method based on blood oxygen level dependence. This can reflect the spontaneous brain functional activity of a human brain in the resting state. In recent years, a number of researchers have used resting state functional magnetic resonance imaging to study the changes in resting spontaneous brain function in patients with temporal lobe epilepsy with cognitive impairment (TLE-CI). However, due to the differences in sample and methodology, the results of these studies were inconsistent. Therefore, the present study aimed to investigate the characteristics of the resting spontaneous brain function in patients with TLE-CI through a meta-analysis. METHODS: A search was conducted on electronic databases, including PubMed, Cochrane Library, EMBASE, Web of Science, China National Knowledge Infrastructure, WANGFANG DATA and Chinese Biomedical Literature Database, and Baidu scholar Database, from the establishment of the database to April 20, 2021. Randomized controlled trials that employed amplitude of low-frequency fluctuations/regional homogeneity to investigate the changes in resting spontaneous brain function in patients with TLE-CI were selected. Anisotropic effect size version of signed differential mapping was applied to perform the data analysis. RESULTS: The study summarized the changes in spontaneous brain function in patients with TLE-CI. CONCLUSION: The conclusion for the functional cerebral alterations based on the latest studies will be provided.
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Encéfalo/fisiopatología , Disfunción Cognitiva/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Disfunción Cognitiva/complicaciones , Epilepsia del Lóbulo Temporal/complicaciones , Humanos , Imagen por Resonancia Magnética/métodos , Metaanálisis como Asunto , Revisiones Sistemáticas como AsuntoRESUMEN
ABSTRACT: There is increasing evidence that angiotensin (1-7) [Ang (1-7)] is an endogenous biologically active component of the renin-angiotensin system. However, the role of the Ang (1-7)-MasR axis in postresuscitation myocardial dysfunction (PRMD) and its associated mechanism are still unclear. In this study, we investigated the effect of the Ang (1-7)-MasR axis on myocardial injury after cardiac arrest-cardiopulmonary resuscitation-restoration of spontaneous circulation. We established a model of oxygen/glucose deprivation-reperfusion in myocardial cells in vitro and a rat model of cardiac arrest-cardiopulmonary resuscitation-restoration of spontaneous circulation in vivo. The cell apoptosis rate and the expression of the superoxide anion 3-nitrotyrosine were decreased in the Ang (1-7) group in vitro and in vivo. The mean arterial pressure was decreased, whereas +LVdp/dtmax and -LVdp/dtmax were increased in rats in the Ang (1-7) group. The mRNA and protein levels of Ang II type 1 receptor, MasR, phosphoinositide 3-kinase, protein kinase B, and endothelial nitric oxide synthase were increased in the Ang (1-7) group in vivo. These results indicate that the Ang (1-7)-MasR axis can alleviate PRMD by reducing myocardial tissue damage and oxidative stress through activation of the phosphoinositide 3-kinase-protein kinase B-endothelial nitric oxide synthase signaling pathway and provide a new direction for the clinical treatment of PRMD.
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Angiotensina I/farmacología , Reanimación Cardiopulmonar/efectos adversos , Paro Cardíaco/terapia , Cardiopatías/prevención & control , Miocitos Cardíacos/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo III/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Apoptosis/efectos de los fármacos , Células Cultivadas , Modelos Animales de Enfermedad , Paro Cardíaco/fisiopatología , Cardiopatías/enzimología , Cardiopatías/etiología , Cardiopatías/fisiopatología , Masculino , Miocitos Cardíacos/enzimología , Miocitos Cardíacos/patología , Proto-Oncogenes Mas/agonistas , Proto-Oncogenes Mas/genética , Proto-Oncogenes Mas/metabolismo , Ratas Sprague-Dawley , Receptor de Angiotensina Tipo 1/genética , Receptor de Angiotensina Tipo 1/metabolismo , Receptor de Angiotensina Tipo 2/genética , Receptor de Angiotensina Tipo 2/metabolismo , Retorno de la Circulación Espontánea , Transducción de Señal , Función Ventricular Izquierda/efectos de los fármacos , Presión Ventricular/efectos de los fármacosRESUMEN
BACKGROUND: Post-anesthetic shivering incurs discomfort to patients or even exacerbates their condition. However, no ideal drug has been well established for preventing post-anesthetic shivering. Currently, subarachnoid and epidural dexmedetomidine have demonstrated to have an anti-shivering effect. METHODS: An electronic search was conducted to identify randomized placebo-controlled trials reporting shivering and then compared subarachnoid and epidural dexmedetomidine with placebo in adults undergoing selective surgery. Data assessment and pooling were analyzed by Review Manager 5.3, STATA 15.0 and GRADE-pro 3.6 software. RESULTS: Twenty-two studies (1389 patients) were subjected to this meta-analysis. The incidence of post-anesthetic shivering decreased from 20.10% in the placebo group to 10.30% in the dexmedetomidine group (RR, 0.48; 95% CI, 0.39-0.59; Z=6.86, P<0.00001, I 2=32%). Non-Indian, epidural-space route and cesarean subgroups indicated a better anti-shivering effect. In the subarachnoid-space route subgroup, a dosage of >5 µg showed significantly superior anti-shivering effects than that of ≤5 µg. Subarachnoid and epidural dexmedetomidine increased the incidence of bradycardia, had no impact on nausea and vomiting, shortened the onset of block and lengthened the duration of block and analgesia. However, its effect on hypotension and sedation remained uncertain. The overall risk of bias was relatively low. The level of evidence was high, and the recommendation of voting results was strong. CONCLUSION: Dexmedetomidine as a subarachnoid and epidural adjunct drug could decrease the incidence of post-anesthetic shivering in a dose-dependent manner. However, caution should be taken in patients with original bradycardia.
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Analgesia Epidural/efectos adversos , Dexmedetomidina/farmacología , Dexmedetomidina/uso terapéutico , Tiritona/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Estructura Molecular , Relación Estructura-ActividadRESUMEN
OBJECTIVE: To investigate the effect of obstructive sleep apnea syndrome (OSAS) on blood lipid and blood glucose in elderly hypertensive patients. METHOD: a One hundred and seven elderly hypertensive patients received examinations by polysomnography and according to the apnea-hypopnea index (AHI), the patients were divided into four groups, namely uncomplicated hypertension group (n=23) and 3 hypertension groups with mild (n=31), moderate (n=29) and severe (n=24) OSAS. The fasting and 2-hour postprandial plasma glucose, glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), Apo-A, and Apo-B of these patients were measured. RESULTS: aCompared with the non-OSAS patients, all the OSAS patients showed increased fasting and 2-hour postprandial plasma glucose, HbA1c, TC, TG, LDL and TC/HDL, and the increments were statistically significant in severe OSAS patients (P<0.05). The level of HDL was lowered in the OSAS groups, showing significant difference between severe OSAS group and the non-OSAS group (P<0.05). Apo-A level was lowered and Apo-B increased in the OSAS groups, but the differences were not statistically significant (P>0.05). CONCLUSIONS: OSAS may produce harmful affect on the blood glucose and blood lipids in elderly hypertensive patients.
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Glucemia/metabolismo , Hipertensión/complicaciones , Lípidos/sangre , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/complicaciones , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hipertensión/sangre , Masculino , Persona de Mediana Edad , PolisomnografíaRESUMEN
OBJECTIVE: To compare the therapeutic effects of pricking blood therapy combined with acupuncture and routine western medicine on herpes zoster. METHODS: Two hundred and forty cases were randomly divided into 2 groups, 120 cases in each group. The treatment group were treated with acupuncture combined with pricking blood therapy on the point with the most pain, and cupping and surround needling; the control group with external application and oral administration of Aciclovir plaster and Aciclovir tablets, respectively. Their therapeutic effects were compared. RESULTS: The total effective rate was 92.5% in the treatment group and 55.8% in the control group with a very significant difference between the two groups (P < 0.01). The time of producing killing pain, stopping vesication and scabbing in the treatment group was shorter than that in the control group. CONCLUSION: The pricking blood therapy combined with acupuncture is an effective therapy for herpes zoster.
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Terapia por Acupuntura/métodos , Herpes Zóster/terapia , Flebotomía/métodos , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Medicina Tradicional China , Persona de Mediana EdadRESUMEN
Free electron laser (FEL) have been developed as tunable lasers over a wide range of wavelenths. Equipment in the region of 6-16 microns (1,660-630 cm-1) is available in the Beijing free electron laser erected by Institute of High Energy Physics, CAS. In this study we report first measurements of infrared-induced molecular change under irradiation by FEL of 9.414 microns and 6.228 microns, respectively. Taking o-amino-benzoic acid as an example, FTIR characterization indicates that the peak positions of both N-H and C=O stretching vibrations shift before and after the irradiation of FEL. It demonstrates that FEL induces the re-arrangement of H-bonds between COOH and NH2 by stimulating the vibration of carboxyl groups. It suggests that the presence of stable/metastable phases in the title compound.