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1.
J Adv Res ; 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39019110

RESUMEN

INTRODUCTION: Lipid metabolism disorders have been confirmed to be closely related to kidney injury caused by adriamycin (ADR) and obesity, respectively. However, it has not been explored whether lipid metabolism disorders are related to kidney injury caused by ADR aggravated by obesity, and the specific molecular mechanism needs to be further clarified. OBJECTIVES: This study was designed to examine the role of p53-fibroblast growth factor 21 (FGF21) axis in ADR-induced renal injury aggravated by high fat diet (HFD). METHODS: We engineered Fgf21 KO mice and used long-term (4 months) and short-term (0.5 months) HFD feeding, and ADR-injected mice, as well as STZ-induced type 1 diabetic mice and type 2 (db/db) diabetic mice to produce a in vivo model of nephrotoxicity. The specific effects of p53/FGF21 on regulation of lipid metabolism disorders and its downstream mediators in kidney were subsequently elucidated using a combination of functional and pathological analysis, RNA-sequencing, molecular biology and in vitro approaches. RESULTS: Long-term HFD feeding mice exhibited compromised effects of FGF21 on alleviation of renal dysfunction and lipid accumulation following ADR administration. However, these impairments were reversed by p53 inhibitor (pifithrin-α, PFT-α). PFT-α sensitized FGF21 actions in kidney tissues, while knockout of Fgf21 impaired the protective effects of PFT-α on lipid metabolism. Mechanistically, p53 impaired the renal expression of FGF recepter-1 (FGFR1) and thereby developed gradually into FGF21 resistance via inhibiting hepatocyte nuclear factor alpha (HNF4α)-mediated transcriptional activation of Fgfr1. More importantly, exogenous supplementation of FGF21 or PFT-α could not only alleviate ADR-induced lipid metabolism disorder aggravated by HFD, but also reduce lipid accumulation caused by diabetic nephropathy. CONCLUSION: Given the difficulties in developing the long-acting recombinant FGF21 analogs for therapeutic applications, sensitizing obesity-impaired FGF21 actions by suppression of p53 might be a therapeutic strategy for maintaining renal metabolic homeostasis during chemotherapy.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39044405

RESUMEN

Smart metal-metal oxide heterointerface construction holds promising potentials to endow an efficient electron redistribution for electrochemical CO2 reduction reaction (CO2RR). However, inhibited by the intrinsic linear-scaling relationship, the binding energies of competitive intermediates will simultaneously change due to the shifts of electronic energy level, making it difficult to exclusively tailor the binding energies to target intermediates and the final CO2RR performance. Nonetheless, creating specific adsorption sites selective for target intermediates probably breaks the linear-scaling relationship. To verify it, Ag nanoclusters were anchored onto oxygen vacancy-rich CeO2 nanorods (Ag/OV-CeO2) for CO2RR, and it was found that the oxygen vacancy-driven heterointerface could effectively promote CO2RR to CO across the entire potential window, where a maximum CO Faraday efficiency (FE) of 96.3% at -0.9 V and an impressively high CO FE of over 62.3% were achieved at a low overpotential of 390 mV within a flow cell. The experimental and computational results collectively suggested that the oxygen vacancy-driven heterointerfacial charge spillover conferred an optimal electronic structure of Ag and introduced additional adsorption sites exclusively recognizable for *COOH, which, beyond the linear-scaling relationship, enhanced the binding energy to *COOH without hindering *CO desorption, thus resulting in the efficient CO2RR to CO.

3.
BMC Med Genomics ; 17(1): 169, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38915017

RESUMEN

BACKGROUND: Distal hereditary motor neuropathy (dHMN) is a heterogeneous group of hereditary diseases caused by the gradual degeneration of the lower motor neuron. More than 30 genes associated with dHMN have been reported, while 70-80% of those with the condition are still unable to receive a genetic diagnosis. METHODS: A 26-year-old man experiencing gradual weakness in his lower limbs was referred to our hospital, and data on clinical features, laboratory tests, and electrophysiological tests were collected. To identify the disease-causing mutation, we conducted whole exome sequencing (WES) and then validated it through Sanger sequencing for the proband and his parents. Silico analysis was performed to predict the pathogenesis of the identified mutations. A literature review of all reported mutations of the related gene for the disease was performed. RESULTS: The patient presented with dHMN phenotype harboring a novel homozygous variant c.361G > C (p.Ala121Pro) in SORD, inherited from his parents, respectively. A121 is a highly conserved site and the mutation was categorized as "likely pathogenic" according to the criteria and guidelines of the American College of Medical Genetics and Genomics (ACMG). A total of 13 published articles including 101 patients reported 18 SORD variants. Almost all described cases have the homozygous deletion variant c.757delG (p.A253Qfs*27) or compound heterozygous state of a combination of c.757delG (p.A253Qfs*27) with another variant. The variant c.361G > C (p.Ala121Pro) detected in our patient was the second homozygous variant in SORD-associated hereditary neuropathy. CONCLUSION: One novel homozygous variant c.361G > C (p.Ala121Pro) in SORD was identified in a Chinese patient with dHMN phenotype, which expands the mutation spectrum of SORD-associated hereditary neuropathy and underscores the significance of screening for SORD variants in patients with undiagnosed hereditary neuropathy patients.


Asunto(s)
Mutación , Humanos , Masculino , Adulto , Secuenciación del Exoma , Neuropatía Hereditaria Motora y Sensorial/genética , Linaje , Fenotipo
4.
Small Methods ; : e2301778, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38741551

RESUMEN

With the rapid development and maturity of electrochemical CO2 conversion involving cathodic CO2 reduction reaction (CO2RR) and anodic oxygen evolution reaction (OER), conventional ex situ characterizations gradually fall behind in detecting real-time products distribution, tracking intermediates, and monitoring structural evolution, etc. Nevertheless, advanced in situ techniques, with intriguing merits like good reproducibility, facile operability, high sensitivity, and short response time, can realize in situ detection and recording of dynamic data, and observe materials structural evolution in real time. As an emerging visual technique, scanning electrochemical microscope (SECM) presents local electrochemical signals on various materials surface through capturing micro-current caused by reactants oxidation and reduction. Importantly, SECM holds particular potentials in visualizing reactive intermediates at active sites and obtaining instantaneous morphology evolution images to reveal the intrinsic reactivity of active sites. Therefore, this review focuses on SECM fundamentals and its specific applications toward CO2RR and OER, mainly including electrochemical behavior observation on local regions of various materials, target products and onset potentials identification in real-time, reaction pathways clarification, reaction kinetics exploration under steady-state conditions, electroactive materials screening and multi-techniques coupling for a joint utilization. This review undoubtedly provides a leading guidance to extend various SECM applications to other energy-related fields.

6.
JAMA ; 331(10): 840-849, 2024 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-38329440

RESUMEN

Importance: It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective: To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023. Interventions: Eligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures: The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results: Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance: Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability. Trial Registration: ChiCTR.org.cn Identifier: ChiCTR2100051729.


Asunto(s)
Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Femenino , Humanos , Anciano , Método Doble Ciego , Trombectomía/efectos adversos , Hemorragias Intracraneales , Metilprednisolona/efectos adversos
7.
Small ; 20(26): e2311130, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38247198

RESUMEN

Nuclear energy holds great potential to facilitate the global energy transition and alleviate the increasing environmental issues due to its high energy density, stable energy output, and carbon-free emission merits. Despite being limited by the insufficient terrestrial uranium reserves, uranium extraction from seawater (UES) can offset the gap. However, the low uranium concentration, the complicated uranium speciation, the competitive metal ions, and the inevitable marine interference remarkably affect the kinetics, capacity, selectivity, and sustainability of UES materials. To date, massive efforts have been made with varying degrees of success to pursue a desirable UES performance on various nanomaterials. Nevertheless, comprehensive and systematic coverage and discussion on the emerging UES materials presenting the fast-growing progress of this field is still lacking. This review thus challenges this position and emphatically focuses on this topic covering the current mainstream UES technologies with the emerging UES materials. Specifically, this review elucidates the causality between the physiochemical properties of UES materials induced by the intellectual design strategies and the UES performances and further dissects the relationships of materials-properties-activities and the corresponding mechanisms in depth. This review is envisaged to inspire innovative ideas and bring technical solutions for developing technically and economically viable UES materials.

8.
Nutr Rev ; 82(3): 361-373, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-37226405

RESUMEN

Despite intensive studies for decades, the common mechanistic correlations among the underlying pathology of diabetes mellitus (DM), its complications, and effective clinical treatments remain poorly characterized. High-quality diets and nutrition therapy have played an indispensable role in the management of DM. More importantly, tribbles homolog 3 (TRIB3), a nutrient-sensing and glucose-responsive regulator, might be an important stress-regulatory switch, linking glucose homeostasis and insulin resistance. Therefore, this review aimed to introduce the latest research progress on the crosstalk between dietary nutrition intervention and TRIB3 in the development and treatment of DM. This study also summarized the possible mechanisms involved in the signaling pathways of TRIB3 action in DM, in order to gain an in-depth understanding of dietary nutrition intervention and TRIB3 in the pathogenesis of DM at the organism level.


Asunto(s)
Diabetes Mellitus , Proteínas Serina-Treonina Quinasas , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Humanos , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Insulina/metabolismo , Glucosa/metabolismo , Dieta , Proteínas Represoras/metabolismo
9.
Antioxid Redox Signal ; 40(10-12): 598-615, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37265150

RESUMEN

Aims: Obese patients are highly sensitive to adriamycin (ADR)-induced cardiotoxicity. However, the potential mechanism of superimposed toxicity remains to be elucidated. Sestrin 2 (SESN2), a potential antioxidant, could attenuate stress-induced cardiomyopathy; therefore, this study aims to explore whether SESN2 enhances cardiac resistance to ADR-induced oxidative damage in high-fat diet (HFD)-induced obese mice. Results: The results revealed that obesity decreased SESN2 expression in ADR-exposed heart. And, HFD mice may predispose to ADR-induced cardiotoxicity, which was probably associated with inhibiting protein kinase B (AKT), glycogen synthase kinase-3 beta (GSK-3ß) phosphorylation and subsequently blocking nuclear localization of nuclear factor erythroid-2 related factor 2 (NRF2), ultimately resulting in cardiac oxidative damage. However, these destructive cascades and cardiac oxidative damage effects induced by HFD/sodium palmitate combined with ADR were blocked by overexpression of SESN2. Moreover, the antioxidant effect of SESN2 could be largely abolished by sh-Nrf2 or wortmannin. And sulforaphane, an NRF2 agonist, could remarkably reverse cardiac pathological and functional abnormalities caused by ADR in obese mice. Innovation and Conclusion: This study demonstrated that SESN2 might be a promising therapeutic target for improving anthracycline-related cardiotoxicity in obesity by upregulating activity of NRF2 via AKT/GSK-3ß/Src family tyrosine kinase signaling pathway. Antioxid. Redox Signal. 40, 598-615.


Asunto(s)
Factor 2 Relacionado con NF-E2 , Proteínas Proto-Oncogénicas c-akt , Animales , Humanos , Ratones , Antioxidantes/metabolismo , Cardiotoxicidad , Dieta Alta en Grasa/efectos adversos , Doxorrubicina/toxicidad , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Ratones Obesos , Factor 2 Relacionado con NF-E2/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/etiología , Estrés Oxidativo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sestrinas/metabolismo
10.
World J Clin Cases ; 11(31): 7656-7662, 2023 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-38078131

RESUMEN

BACKGROUND: This report delves into the diagnostic and therapeutic journey undertaken by a patient with Sneddon's syndrome (SS) and cerebral venous sinus thrombosis (CVST). Particular emphasis is placed on the comprehensive elucidation of SS's clinical manifestations, the intricate path to diagnosis, and the exploration of potential underlying mechanisms. CASE SUMMARY: A 26-year-old woman presented with recurrent episodes of paroxysmal unilateral limb weakness accompanied by skin mottling, seizures, and cognitive impairment. Digital subtraction angiography revealed CVST. Despite negative antiphospholipid antibody results, skin biopsy indicated chronic inflammatory cell infiltration. The patient was treated using anticoagulation, antiepileptic therapy, and supportive care, which resulted in symptom improvement. The coexistence of SS and CVST is rare and the underlying pathophysiology remains uncertain. This case underscores the challenge in diagnosis and highlights the need for early clinical differentiation to facilitate accurate assessment and prompt intervention. CONCLUSION: This article has reported and analyzed the clinical data, diagnosis, treatment, and prognosis of a case of SS with CVST and reviewed the relevant literature to improve the clinical understanding of this rare condition.

11.
Medicine (Baltimore) ; 102(44): e35865, 2023 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-37933002

RESUMEN

RATIONALE: Isaacs syndrome is peripheral nerve hyperexcitability characterized by spontaneous muscle twitching and rigidity and is often associated with antibodies to CASPR2 (contactin-associated protein-like 2) and LGI1 (leucine-rich glioma-inactivated 1). But it is a rare Isaacs syndrome with LGI1 and CASPR2 antibodies after human papilloma virus (HPV) vaccination. PATIENT CONCERNS: The patient presented with limb pain, muscle twitching, numbness in the extremities and around the mouth, and hand rash after the second dose of HPV vaccine. DIAGNOSES: Laboratory tests indicated positive for LGI1 antibodies, CASPR2 antibodies, anti-phosphatidylserine/prothrombin antibodies and anti-sulfatide antibodies, TPO and ATG, IgG E. The patient post-M-wave discharges were seen on F-wave examination of the posterior tibial nerve in both lower limbs. We diagnosis the patient with Isaacs syndrome. INTERVENTIONS: Treatment with the intravenous immunoglobulin (IVIG) treatment, after 5 days of IVIG therapy (0.4 mg/kg/day), the rash on the hand disappeared, the pain was relieved, the sleep improved. OUTCOMES: After 3 Courses of treatment, the clinical manifestations of the nervous system disappeared and negative responsibility antibodies profile. LESSONS: This case report suggests a possible adverse reaction to HPV vaccination, which could be treated by attempting several periods of IVIG therapy. The underlying immune mechanisms need to be studied with further extensive data.


Asunto(s)
Síndrome de Isaacs , Vacunas contra Papillomavirus , Humanos , Autoanticuerpos , Exantema , Inmunoglobulinas Intravenosas/uso terapéutico , Péptidos y Proteínas de Señalización Intracelular , Síndrome de Isaacs/inducido químicamente , Síndrome de Isaacs/diagnóstico , Proteínas de la Membrana , Proteínas del Tejido Nervioso , Dolor , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/efectos adversos , Vacunación/efectos adversos
12.
Epilepsy Res ; 197: 107245, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37864968

RESUMEN

OBJECTIVE: To investigate the initial treatment of patients with convulsive status epilepticus (CSE) in a resource-limited region of China, and to discuss the difference of in-hospital outcomes and economic costs between those with guideline-recommended initial treatment and those without. METHODS: In this retrospective study, we screened adult patients discharged with the diagnosis of CSE in four centers in west China. Individuals with different exposure to the initial drug were divided into benzodiazepine (BDZ) and non-BDZ group for outcome comparison. The primary outcomes were seizure control, and the ratio of patients who developed refractory SE. The secondary outcomes included in-hospital mortality, the modified Rankin Scale (mRS) score at discharge, in-hospital respiratory support rate, length, and cost of the stay. RESULTS: Three-hundred and thirteen patients (127, 40.6% were women) with CSE were included. The median age was 43 (range 16-92). There were 152 (48.6%) patients initially treated with BDZ. Among the 36 who received midazolam as initial treatment, twenty-six received an insufficient dose. The other 116 (76.3%) patients in the BDZ group chose diazepam as initial treatment. Fifteen of them (12.9%) were treated underdose. In the non-BDZ group (161, 51.4%), antiseizure medications (ASMs) and/or coma-induced drugs were used as initial treatment. Among those initially administrated ASMs, intramuscular phenobarbital (38,37.6%) and valproate (46, 52.3%) were most frequently seen. There was a significant difference in the time latency to initial treatment and etiology between BDZ and non-BDZ group. The non-BDZ group reported a higher cessation rate after initial treatment compared to the BDZ group (P = 0.012). No significant difference in other primary and secondary outcomes. SIGNIFICANCE: Non-adherence and underdosing of the initial treatment of SE were common in China. However, the non-BDZ group showed a better seizure control rate. The effect came from early aggressive medication, that is, the combination of ASMs and anesthesia. Non-BDZ group was not inferior to BDZs in terms of seizure control, the occurrence of in-hospital death, and poor outcome at discharge. More robust evidence is needed in developing settings when choosing the initial treatment.


Asunto(s)
Anticonvulsivantes , Estado Epiléptico , Adulto , Humanos , Femenino , Masculino , Anticonvulsivantes/uso terapéutico , Estudios Retrospectivos , Mortalidad Hospitalaria , Estado Epiléptico/diagnóstico , Estado Epiléptico/tratamiento farmacológico , Estado Epiléptico/etiología , Convulsiones/tratamiento farmacológico , Convulsiones/complicaciones , China
13.
Nutrients ; 15(9)2023 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-37432408

RESUMEN

Quercetin is a natural flavonoid widely found in natural fruits and vegetables. Recent studies have shown that quercetin mediates multiple beneficial effects in a variety of organ damage and diseases, and is considered a healthcare supplement with health-promoting potential. Male infertility is a major health concern, and testicular damage from multiple causes is an important etiology. Previous studies have shown that quercetin has a protective effect on reproductive function. This may be related to the antioxidant, anti-inflammatory, and anti-apoptotic biological activities of quercetin. Therefore, this paper reviews the mechanisms by which quercetin exerts its pharmacological activity and its role in testicular damage induced by various etiologies. In addition, this paper compiles the application of quercetin in clinical trials, demonstrating its practical effects in regulating blood pressure and inhibiting cellular senescence in human patients. However, more in-depth experimental studies and clinical trials are needed to confirm the true value of quercetin for the prevention and protection against testicular injury.


Asunto(s)
Flavonoides , Quercetina , Humanos , Masculino , Quercetina/farmacología , Quercetina/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Presión Sanguínea , Senescencia Celular
15.
Nutrients ; 15(10)2023 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-37242146

RESUMEN

Doxorubicin (DOX) is a highly effective chemotherapeutic drug, but its long-term use can cause cardiotoxicity and drug resistance. Accumulating evidence demonstrates that p53 is directly involved in DOX toxicity and resistance. One of the primary causes for DOX resistance is the mutation or inactivation of p53. Moreover, because the non-specific activation of p53 caused by DOX can kill non-cancerous cells, p53 is a popular target for reducing toxicity. However, the reduction in DOX-induced cardiotoxicity (DIC) via p53 suppression is often at odds with the antitumor advantages of p53 reactivation. Therefore, in order to increase the effectiveness of DOX, there is an urgent need to explore p53-targeted anticancer strategies owing to the complex regulatory network and polymorphisms of the p53 gene. In this review, we summarize the role and potential mechanisms of p53 in DIC and resistance. Furthermore, we focus on the advances and challenges in applying dietary nutrients, natural products, and other pharmacological strategies to overcome DOX-induced chemoresistance and cardiotoxicity. Lastly, we present potential therapeutic strategies to address key issues in order to provide new ideas for increasing the clinical use of DOX and improving its anticancer benefits.


Asunto(s)
Cardiotoxicidad , Proteína p53 Supresora de Tumor , Humanos , Cardiotoxicidad/etiología , Cardiotoxicidad/tratamiento farmacológico , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Doxorrubicina/efectos adversos , Apoptosis , Miocitos Cardíacos , Estrés Oxidativo
16.
N Engl J Med ; 388(22): 2025-2036, 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37256974

RESUMEN

BACKGROUND: The effects of the glycoprotein IIb/IIIa receptor inhibitor tirofiban in patients with acute ischemic stroke but who have no evidence of complete occlusion of large or medium-sized vessels have not been extensively studied. METHODS: In a multicenter trial in China, we enrolled patients with ischemic stroke without occlusion of large or medium-sized vessels and with a National Institutes of Health Stroke Scale score of 5 or more and at least one moderately to severely weak limb. Eligible patients had any of four clinical presentations: ineligible for thrombolysis or thrombectomy and within 24 hours after the patient was last known to be well; progression of stroke symptoms 24 to 96 hours after onset; early neurologic deterioration after thrombolysis; or thrombolysis with no improvement at 4 to 24 hours. Patients were assigned to receive intravenous tirofiban (plus oral placebo) or oral aspirin (100 mg per day, plus intravenous placebo) for 2 days; all patients then received oral aspirin until day 90. The primary efficacy end point was an excellent outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. Secondary end points included functional independence at 90 days and a quality-of-life score. The primary safety end points were death and symptomatic intracranial hemorrhage. RESULTS: A total of 606 patients were assigned to the tirofiban group and 571 to the aspirin group. Most patients had small infarctions that were presumed to be atherosclerotic. The percentage of patients with a score of 0 or 1 on the modified Rankin scale at 90 days was 29.1% with tirofiban and 22.2% with aspirin (adjusted risk ratio, 1.26; 95% confidence interval, 1.04 to 1.53, P = 0.02). Results for secondary end points were generally not consistent with the results of the primary analysis. Mortality was similar in the two groups. The incidence of symptomatic intracranial hemorrhage was 1.0% in the tirofiban group and 0% in the aspirin group. CONCLUSIONS: In this trial involving heterogeneous groups of patients with stroke of recent onset or progression of stroke symptoms and nonoccluded large and medium-sized cerebral vessels, intravenous tirofiban was associated with a greater likelihood of an excellent outcome than low-dose aspirin. Incidences of intracranial hemorrhages were low but slightly higher with tirofiban. (Funded by the National Natural Science Foundation of China; RESCUE BT2 Chinese Clinical Trial Registry number, ChiCTR2000029502.).


Asunto(s)
Fibrinolíticos , Accidente Cerebrovascular Isquémico , Tirofibán , Humanos , Aspirina/efectos adversos , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/etiología , Fibrinolíticos/efectos adversos , Fibrinolíticos/uso terapéutico , Hemorragias Intracraneales/inducido químicamente , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/etiología , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Tirofibán/efectos adversos , Tirofibán/uso terapéutico , Resultado del Tratamiento , Enfermedades Arteriales Cerebrales/tratamiento farmacológico , Enfermedades Arteriales Cerebrales/etiología
17.
J Stroke Cerebrovasc Dis ; 32(6): 107139, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37105014

RESUMEN

BACKGROUND AND OBJECTIVE: Risk factors and predictors of malignant cerebral edema (MCE) after successful endovascular thrombectomy (EVT) were not fully explored. This study aimed to evaluate the incidence and risk factors of MCE after successful reperfusion. METHODS: We retrospectively analyzed consecutive ischemic stroke patients who underwent EVT in our institution from November 2015 to April 2022. Patients who failed to achieve successful reperfusion (modified thrombolysis in cerebral infarction [mTICI]<2b) were excluded. Based on multivariate logistic models, the best-fit monogram was established. The discriminative performance was assessed by the receiver operating characteristics curve (ROC). RESULTS: A total of 307 patients were included and 48 (15.6%) were diagnosed with MCE after successful reperfusion. Patients with MCE after successful reperfusion had a lower 3-month favorable outcome (15.2% versus 59.6%; p<0.001), a lower 3-month good outcome (17.4% versus 68.4%; p<0.001), and a higher rate of mortality at 3-month (54.3% versus 8.8%; p<0.001) compared with patients without MCE. Predictors of MCE after successful reperfusion included admission glucose level, baseline National Institutes of Health Stroke Scale (NIHSS) score, stroke etiology, occlusion site and puncture-to-reperfusion (PTR) time>120 min. The area under the curve (AUC) of the nomogram was 0.805 (95% CI, 0.756-0.847). CONCLUSIONS: MCE after successful reperfusion is associated with poor outcome and mortality. A nomogram containing admission glucose level, baseline NIHSS score, stroke etiology, occlusion site and PTR time>120 min may predict the risk of MCE after successful reperfusion in patients with acute ischemic stroke and treated successfully with EVT.


Asunto(s)
Edema Encefálico , Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Estudios Retrospectivos , Accidente Cerebrovascular Isquémico/etiología , Edema Encefálico/diagnóstico por imagen , Edema Encefálico/etiología , Edema Encefálico/terapia , Resultado del Tratamiento , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/terapia , Trombectomía/efectos adversos , Reperfusión/efectos adversos , Glucosa , Procedimientos Endovasculares/efectos adversos , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/terapia
18.
Medicine (Baltimore) ; 102(7): e32956, 2023 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-36800611

RESUMEN

The purpose of this study was to assess the demographic data, clinical manifestations, cerebrospinal fluid (CSF), hematology, brain magnetic resonance imaging, electroencephalograms, and therapy and prognosis related to anti-gamma-aminobutyric acid B (anti-GABABR) encephalitis. We retrospectively examined the demographic data, clinical manifestations, laboratory results, brain magnetic resonance imaging, electroencephalograms, and therapy and prognosis of 6 patients with anti-GABABR encephalitis. We used the clinical data of patients with anti-GABABR encephalitis admitted to the Department of Neurology of Mianyang Central Hospital obtained from January 2017 to September 2020. Six patients with anti-GABABR encephalitis were included. Generalized tonic-clonic seizure was the first clinical symptom in 5 patients, while 1 patient first showed behavior disorder. After the first clinical symptom attack, 2 patients developed a memory deficit, 4 cases showed cognitive decline, 3 cases showed behavior disorder, 1 patient developed status epilepticus and only 1 patient returned to normal. CSF testing indicated normal intracranial pressure in 5 patients and elevated pressure in only 1 patient. Additionally, the cerebrospinal fluid tests revealed slight leukocytosis in all patients and elevated protein levels in 5 patients. The anti-GABABR antibody was positive in both serum and CSF in all patients. Brain magnetic resonance imaging showed limbic system lesions in 4 patients. Long-term electroencephalograms revealed abnormal waves in half of the patients. All patients were treated with high dosages of methylprednisolone, which was combined with intravenous immunoglobulin in 2 patients; symptoms were improved in 4 patients, 1 patient showed no significant change and 1 patient with status epilepticus died of severe pneumonia during hospitalization. Epilepsy is the most common initial symptom in patients of anti-GABABR encephalitis. Many patients are also affected by tumors. Early immunotherapy can achieve excellent effects, the long-term prognosis is good for most patients.


Asunto(s)
Encefalitis , Estado Epiléptico , Humanos , Estudios Retrospectivos , Receptores de GABA-B , Encefalitis/diagnóstico , Encefalitis/tratamiento farmacológico , Pronóstico , Anticuerpos , Autoanticuerpos
19.
BMC Neurol ; 23(1): 50, 2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36721101

RESUMEN

BACKGROUND AND OBJECTIVE: Liver fibrosis has been considered a predictor of cardiovascular disease. This study aimed to evaluate whether the degree of liver fibrosis is related to post-stroke depression (PSD) at 3 months follow-up. METHODS: We prospectively and continuously enrolled patients with first-ever ischemic stroke from June 2020 to January 2022. Liver fibrosis was measured after admission by calculating the Fibrosis-4 index (FIB-4) and stratified into two categories (< 2.67 versus ≥ 2.67). Patients with a 17-item Hamilton Depression Scale score > 7 were further evaluated using the Chinese version of the structured clinical interview of DSM-IV, for diagnosing PSD at 3 months. RESULTS: A total of 326 patients (mean age 66.6 years, 51.5% male) were recruited for the study. As determined by the FIB-4 score, 80 (24.5%) patients had advanced liver fibrosis. During the follow-up, PSD was observed in 91 patients, which accounted for 27.9% (95% confidence interval [CI] 25.5%-30.5%) of the cohort. The prevalence of advanced liver fibrosis was higher in PSD patients than those without PSD (40.0% versus 24.0%; P = 0.006). After adjustment for covariates in the multivariate logistic analysis, advanced fibrosis was significantly associated with PSD (odds ratio [OR], 1.88; 95% CI, 1.03-3.42; P = 0.040). Similar results were found when the FIB-4 was analyzed as a continuous variable. CONCLUSIONS: This study found that advanced liver fibrosis was associated with an increased risk of 3-month PSD. FIB-4 score may be valuable for screening depressive symptoms in ischemic stroke patients.


Asunto(s)
Depresión , Accidente Cerebrovascular Isquémico , Cirrosis Hepática , Anciano , Femenino , Humanos , Masculino , Depresión/epidemiología , Depresión/etiología , Accidente Cerebrovascular Isquémico/complicaciones , Accidente Cerebrovascular Isquémico/epidemiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/epidemiología
20.
Small ; 19(16): e2207074, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36670067

RESUMEN

High-capacity metal oxides based on non-toxic earth-abundant elements offer unique opportunities as advanced anodes for lithium-ion batteries (LIBs). But they often suffer from large volumetric expansion, particle pulverization, extensive side reactions, and fast degradations during cycling. Here, an easy synthesis method is reported to construct amorphous borate coating network, which stabilizes conversion-type iron oxide anode for the high-energy-density semi-solid-state bipolar LIBs. The nano-borate coated iron oxide anode has high tap density (1.6 g cm-3 ), high capacity (710 mAh g-1 between 0.5 - 3.0 V, vs Li/Li+ ), good rate performance (200 mAh g-1 at 50 C), and excellent cycling stability (≈100% capacity resention over 1,000 cycles at 5 A g-1 ). When paired with high-voltage cathode LiCoO2 , it enables Cu current collector-free pouch-type classic and bipolar full cells with high voltage (7.6 V with two stack layers), achieving high energy density (≈350 Wh kg-1 ), outstanding power density (≈6,700 W kg-1 ), and extended cycle life (75% capacity retention after 2,000 cycles at 2 C), superior to the state-of-the-art high-power LIBs using Li4 Ti5 O12 anode. The design and methodology of the nanoscale polyanion-like coating can be applied to other metal oxides electrode materials, as well as other electrochemical materials and devices.

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