ABSTRACT Purpose: Spontaneous intracerebral hemorrhage (ICH) is a major public health problem with a huge economic burden worldwide. Ulinastatin (UTI), a serine protease inhibitor, has been reported to be anti-inflammatory, immune regulation, and organ protection by reducing reactive oxygen species production, and inflammation. Necroptosis is a programmed cell death mechanism that plays a vital role in neuronal cell death after ICH. However, the neuroprotection of UTI in ICH has not been confirmed, and the potential mechanism is unclear. The present study aimed to investigate the neuroprotection and potential molecular mechanisms of UTI in ICH-induced EBI in a C57BL/6 mouse model. Methods: The neurological score, brain water content, neuroinflammatory cytokine levels, and neuronal damage were evaluated. The anti-inflammation effectiveness of UTI in ICH patients also was evaluated. Results: UTI treatment markedly increased the neurological score, alleviate the brain edema, decreased the inflammatory cytokine TNF-α, interleukin‑1β (IL‑1β), IL‑6, NF‑κB levels, and RIP1/RIP3, which indicated that UTI-mediated inhibition of neuroinflammation, and necroptosis alleviated neuronal damage after ICH. UTI also can decrease the inflammatory cytokine of ICH patients. The neuroprotective capacity of UTI is partly dependent on the MAPK/NF-κB signaling pathway. Conclusions: UTI improves neurological outcomes in mice and reduces neuronal death by protecting against neural neuroinflammation, and necroptosis.

RESUMO Objetivo: Determinar se os níveis séricos do anticorpo antirreceptor de acetilcolina (anti-AChR-Abs) estão relacionados aos parâmetros clínicos do blefaroespasmo (BSP). Métodos: Fora recrutados 83 adultos com BSP, 60 pacientes ambulatoriais com espasmo hemifacial (HFS) e 58 controles. Foi aplicado um questionário para registrar história pessoal, fatores demográficos, resposta à toxina botulínica tipo A (BoNT-A) e outras condições neurológicas. Os níveis de anti-AChR-Abs foram quantificados usando um ensaio imunoenzimático. Resultados: O nível de anti-AChR-Abs foi de 0,237 ± 0,022 unidades de densidade óptica (OD) no grupo BSP, significativamente diferente em comparação com o grupo HFS (0,160 ± 0,064) e o grupo controle (0,126 ± 0,038). O nível de anti-AChR-Abs se correlacionou com a idade e a duração da resposta à injeção de BoNT-A. Conclusão: Pacientes com BSP apresentaram títulos elevados de anti-AChR-Abs, o que sugere que a desimunidade desempenha um papel no surgimento de BSP. O aumento do título de anti-AChR-Abs pode ser um preditor de resposta insuficiente à BoNT-A em BSP.

ABSTRACT Objective: To determine whether serum levels of anti-acetylcholine receptor antibody (anti-AChR-Abs) are related to clinical parameters of blepharospasm (BSP). Methods: Eighty-three adults with BSP, 60 outpatients with hemifacial spasm (HFS) and 58 controls were recruited. Personal history, demographic factors, response to botulinum toxin type A (BoNT-A) and other neurological conditions were recorded. Anti-AChR-Abs levels were quantified using an enzyme-linked immunosorbent assay. Results: The anti-AChR Abs levels were 0.237 ± 0.022 optical density units in the BSP group, which was significantly different from the HFS group (0.160 ± 0.064) and control group (0.126 ± 0.038). The anti-AChR Abs level was correlated with age and the duration of response to the BoNT-A injection. Conclusion: Patients with BSP had an elevated anti-AChR Abs titer, which suggests that dysimmunity plays a role in the onset of BSP. An increased anti-AChR Abs titer may be a predictor for poor response to BoNT-A in BSP.

Resumo Fundamentos: A influência da anatomia da veia pulmonar (VP) na criocinética durante a ablação por criobalão (CB) não está clara. Objetivo: Investigar a relação entre a anatomia da VP e a criocinética durante a ablação com CB para fibrilação atrial (FA). Métodos: sessenta pacientes consecutivos foram matriculados. Foram avaliados em imagens de tomografia computadorizada multidetectora (TCMD) pré-procedimento a anatomia da VP, incluindo diâmetros dos óstios (longo, curto e corrigido), relação entre diâmetros curtos e longos, forma do óstio (redondo, oval, triangular e estreito) e padrão de drenagem (típico, com tronco comum, antro comum, ramo ostial e VP supranumerária). Os parâmetros criocinéticos [tempo de congelamento de balão de 0 a -30ºC (TCB), temperatura do nadir do balão (TNB) e tempo de aquecimento do balão de -30 a + 15ºC (TAB)] foram registrados durante o procedimento. Todos os valores de p são bicaudais, com valores de p < 0,05 considerados estatisticamente significativos. Resultados: o ciclo de congelamento foi realizado 606 vezes. Correlação negativa moderada foi documentada entre o TNB e o diâmetro VP corrigido (r = - 0,51, p < 0,001) ao usar CBs de 23 mm e correlação negativa leve (r = - 0,32, p = 0,001) foi encontrada ao usar 28- mm CBs. A análise de regressão logística multivariada revelou que o diâmetro corrigido do óstio da VP (OR, 1,4; p = 0,004) previu um TNB < -51ºC ao usar CB de 23 mm, enquanto a forma oval do óstio VP (OR, 0,3; p = 0,033) e as localizações da VP (VP inferior: OR, 0,04; p = 0,005; VP superior direito: OR, 4,3; p = 0,025) previram TNB < -51ºC ao usar CBs de 28 mm. Conclusões: A TCMD pode fornecer uma avaliação precisa da anatomia da VP antes da ablação por CB. A anatomia da VP está associada à criocinética durante a ablação.

Abstract Background: The influence of pulmonary vein (PV) anatomy on cryo kinetics during cryoballoon (CB) ablation is unclear. Objective: To investigate the relationship between PV anatomy and cryo kinetics during CB ablation for atrial fibrillation (AF). Methods: Sixty consecutive patients were enrolled. PV anatomy, including ostial diameters (long, short and corrected), ratio between short and long diameters, ostium shape (round, oval, triangular, and narrow), and drainage pattern (typical, with common trunk, common antrum, ostial branch and supernumerary PV) were evaluated on multi-detector computed tomography (MDCT) images pre-procedure. Cryo kinetics parameters [balloon freeze time from 0 to -30ºC (BFT), balloon nadir temperature (BNT) and balloon warming time from -30 to +15ºC (BWT)] were recorded during procedure. All p values are two-sided, with values of p < 0.05 considered to be statistically significant. Results: 606 times of freezing cycle were accomplished. Moderate negative correlation was documented between BNT and corrected PV diameter (r = -0.51, p < 0.001) when using 23-mm CBs, and mild negative correlation (r = - 0.32, p = 0.001) was found when using 28-mm CBs. Multivariate logistic regression analysis revealed that PV corrected ostial diameter (OR, 1.4; p = 0.004) predicted a BNT < -51ºC when using 23-mm CBs, while PV ostium oval shape (OR, 0.3; p = 0.033) and PV locations (left inferior PV: OR, 0.04; p = 0.005; right superior PV: OR, 4.3; p = 0.025) predicted BNT < -51ºC when using 28-mm CBs. Conclusions: MDCT can provide PV anatomy accurate evaluation prior CB ablation. PV anatomy is associated with cryo kinetics during ablation.