Abstract Background and purpose Intravenous Thrombolysis (IVT) prior to Mechanical Thrombectomy (MT) for Acute Ischaemic Stroke (AIS) due to Large-Vessel Occlusion (LVO) remains controversial. Therefore, the authors performed a meta-analysis of the available real-world evidence focusing on the efficacy and safety of Bridging Therapy (BT) compared with direct MT in patients with AIS due to LVO. Methods Four databases were searched until 01 February 2023. Retrospective and prospective studies from nationwide or health organization registry databases that compared the clinical outcomes of BT and direct MT were included. Odds Ratios (ORs) and 95 % Confidence Intervals (CIs) for efficacy and safety outcomes were pooled using a random-effects model. Results Of the 12 studies, 86,695 patients were included. In patients with AIS due to LVO, BT group was associated with higher odds of achieving excellent functional outcome (modified Rankin Scale score 0-1) at 90 days (OR = 1.48, 95 % CI 1.25-1.75), favorable discharge disposition (to the home with or without services) (OR = 1.33, 95 % CI 1.29-1.38), and decreased mortality at 90 days (OR = 0.62, 95 % CI 0.56-0.70), as compared with the direct MT group. In addition, the risk of symptomatic intracranial hemorrhage did not increase significantly in the BT group. Conclusion The present meta-analysis indicates that BT was associated with favorable outcomes in patients with AIS due to LVO. These findings support the current practice in a real-world setting and strengthen their validity. For patients eligible for both IVT and MT, BT remains the standard treatment until more data are available. (IVT (MT (AIS LargeVessel Large Vessel LVO (LVO controversial Therefore metaanalysis meta analysis realworld real world (BT 0 2023 included ORs (ORs 9 CIs (CIs randomeffects random effects model 1 86695 86 695 86,69 modified 0-1 OR 148 48 1.48 1.251.75, 125175 1.25 1.75 , 25 75 1.25-1.75) services 133 33 1.33 1.291.38, 129138 1.29 1.38 29 38 1.29-1.38) 062 62 0.62 0.560.70, 056070 0.56 0.70 56 70 0.56-0.70) addition validity 202 8669 8 69 86,6 0- 14 4 1.4 251 1.251.75 12517 125 1.2 175 1.7 2 7 1.25-1.75 13 3 1.3 291 1.291.38 12913 129 138 1.29-1.38 06 6 0.6 560 0.560.70 05607 056 0.5 070 0.7 5 0.56-0.70 20 866 86, 1. 1.251.7 1251 17 1.25-1.7 1.291.3 1291 1.29-1.3 0. 0.560.7 0560 05 07 0.56-0.7 1.251. 1.25-1. 1.291. 1.29-1. 0.560. 0.56-0. 1.251 1.25-1 1.291 1.29-1 0.560 0.56-0 1.25- 1.29- 0.56-

RESUMO Objetivo Estudar os efeitos do trauma contuso e do exercício exaustivo na expressão dos fatores relacionados à degradação MuRF1 e MAFbx no músculo esquelético de ratos e descrever o mecanismo de reparo da lesão muscular esquelética. Métodos Quarenta e dois ratos SD machos foram divididos aleatoriamente em 7 grupos. Os ratos de cada grupo foram mortos em diferentes momentos (0h, 24h, 48h) após exercício exaustivo (E0, E24, E48) e trauma contuso (D0, D24, D48), respectivamente, e no estado de repouso no grupo controle (C). Os músculos gastrocnêmios direitos foram ressecados e divididos em duas partes, uma para os mRNAs de MuRF1 e MAFbx por PCR em tempo real e outra para a medição de proteínas a partir do Western blot. Resultados Em comparação com o grupo controle, o mRNA de MuRF1 e a expressão proteica do músculo esquelético no grupo E0 foram acentuadamente aumentados (P <0,05) e seguidos por uma tendência descendente nos grupos E24 e E48. Por outro lado, a expressão do mRNA de MuRF1 do músculo esquelético no grupo D24 foi significativamente regulada para cima (P <0,01), depois diminuiu no grupo D48 (P <0,01). Enquanto isso, em comparação com o grupo C, a expressão gênica do mRNA de MAFbx continuou regulada para cima em D24 e D48 (P <0,05), mas diminuiu em E24 e E48 (p<0,01). Por outro lado, os teores de proteína NF-κB do músculo esquelético nos grupos D0, D24 e D48, bem como no grupo E48, foram marcadamente regulados para baixo (P <0,05), e o do grupo E48 também foi notavelmente regulado para baixo (P <0,05). Conclusão NF-κB pode regular negativamente o processo de degradação da proteína pela via NF-κB / MuRF1. Nível de evidência III; Estudos terapêuticos que investigam os resultados do tratamento.

ABSTRACT Objective To study the effects of contusion and exhaustive exercise on the expression of degradation-related factors MuRF1 and MAFbx in the skeletal muscle of rats and describe the repair mechanism of skeletal muscle injury. Methods Forty-two male SD rats were randomly divided into 7 groups. The rats in each group were killed at different time points (0h, 24h, 48h) after exhaustive exercise (E0, E24, E48) and contusion (D0, D24, D48), respectively, and in the resting state in control group (C). The right gastrocnemius muscles were resected and divided into two parts, one for the mRNAs of MuRF1 and MAFbx by real-time PCR, and the other for protein measurement by Western blotting. Results Compared with the control group, the MuRF1 mRNA and protein expression of the skeletal muscle in the E0 group was markedly increased (P <0.05) and followed by a downward trend in E24 the E48 groups. On the other hand, MuRF1 mRNA expression of the skeletal muscle in the D24 group was significantly upregulated (P <0.01), then decreased in the D48 group (P <0.01). Meanwhile, compared with the C group, MAFbx mRNA gene expression continued to be upregulated in D24 and D48 (P <0.05), but decreased in E24 and E48 (p<0.01). On the other hand, the NF-κB protein contents of the skeletal muscle in the D0, D24, and D48 groups, as well as in the E48 group, were markedly downregulated (P <0.05), and the one in E48 was also remarkably downregulated (P <0.05). Conclusion NF-κB may negatively regulate the process of protein degradation by the NF-κB / MuRF1 signal pathway. Level of evidence III; Therapeutic studies investigating the results of treatment.

RESUMEN Objetivo Estudiar los efectos de la contusión y del ejercicio exhaustivo sobre la expresión de los factores relacionados con la degradación MuRF1 y MAFbx en el músculo esquelético de ratas y describir el mecanismo de reparación de la lesión muscular esquelética. Métodos Cuarenta y dos ratas macho SD fueron divididas aleatoriamente en 7 grupos. Las ratas de cada grupo fueron sacrificadas en diferentes momentos (0h, 24h, 48h) después del ejercicio exhaustivo (E0, E24, E48) y de la contusión (D0, D24, D48), respectivamente, y en estado de reposo en el grupo de control (C). Se resecaron los músculos gastrocnemios derechos y se dividieron en dos partes, una para los ARNm de MuRF1 y MAFbx mediante PCR en tiempo real y la otra para la medición de proteínas mediante Western blot. Resultados En comparación con el grupo control, el ARNm de MuRF1 y la expresión proteica del músculo esquelético en el grupo E0 se incrementó notablemente (P <0,05) y fueron seguidos por una tendencia a la baja en los grupos E24 y E48. Por otra parte, la expresión del ARNm de MuRF1 del músculo esquelético en el grupo D24 fue significativamente regulada al alza (P <0,01), y luego disminuyó en el grupo D48 (P <0,01). Mientras tanto, en comparación con el grupo C, la expresión génica del ARNm de MAFbx permaneció regulada al alza en D24 y D48 (P <0,05), pero disminuyó en E24 y E48 (p<0,01). Por otro lado, el contenido de proteína NF-κB del músculo esquelético en los grupos D0, D24 y D48, así como en el grupo E48, se vio notablemente regulado a la baja (P <0,05), y el del grupo E48 también se vio notablemente regulado a la baja (P <0,05). Conclusión NF-κB puede regular negativamente el proceso de degradación de la proteína a través de la vía NF-κB / MuRF1. Nivel de evidencia III; Estudios terapéuticos que investigan los resultados del tratamiento.

Abstract Character strengths could effectively prevent negative psychological outcomes in adults. However, there was little research conducted among early adolescents. The present study aimed to explore character strengths that were independently related to fewer behavior problems in early adolescents. In total, 521 early adolescents (mean age 10.92 ± 0.04, range 10–12 years) were recruited from primary schools in Sichuan, China. Character strengths were measured using the Values in Action Inventory of Strengths for Youth (VIA-Youth). Behavior problems were measured using the Conners Parent Symptom Questionnaire (PSQ). The results showed that behavior problems were negatively correlated with character strengths ( r = −0.14 to −0.3, p < 0.05 Bonferroni corrected). Character strengths explained a significant proportion of additional variance (14–22%) in five types of behavior problems after controlling the effect of demographic factors (residence, left-behind experiences, maternal education level). Moreover, several specific character strengths showed an independent contribution ( β = −0.34 to −0.14 for self-regulation, perseverance, zest, humility, and leadership; β = 0.21 to 0.34, for hope; all p < 0.05) to behavior problems. Our study revealed that character strengths were protective factors against behavior problems in early adolescents.

RESUMO Objetivo: Estudar os efeitos do exercício exaustivo e da contusão sobre a expressão dos fatores relacionados com a autofagia das proteínas Beclina 1, LC3 e PINK-1 no músculo esquelético de ratos. Métodos: Quarenta de dois ratos SD machos foram divididos randomicamente em 7 grupos com 6 ratos cada um: C, D0, D24, D48, E0, E24 e E48. Os ratos de cada um dos grupos foram submetidos à eutanásia e dissecados nos diferentes pontos de tempo de acordo com os grupos acima. Cada músculo quadríceps femoral dos membros posteriores esquerdos foi removido e dividido em duas partes, uma para RNAm de Beclina 1, LC3 e PINK-1 por PCR quantitativa fluorescente em tempo real e a outra para a proteína LC3 por Western blotting. Resultados: Em comparação com o grupo C, o teor de RNAm em Beclina 1, PINK-1 e LC3 no grupo exercício exaustivo imediato (E0) foi significativamente reduzido (p < 0,01). Contudo, os níveis de RNAm em PINK-1 e LC3 e a proteína LC3 em células do músculo esquelético aumentaram significativamente nas 48 horas pós-depleção (E48) (p < 0,05), sugerindo que a autofagia celular tendeu a aumentar durante o período de recuperação. Em comparação com o grupo C, o teor de RNAm de Beclina 1, RNAm de Pink-1 e RNAm de LC3 no grupo contusão imediata (D0) aumentou significativamente (p < 0,01) o que foi seguido por tendência de queda. Conclusão: Em geral, foram encontradas diferenças entre os modelos de contusão e de exercício exaustivo em cada fase de recuperação. A expressão gênica dos fatores relacionados com a autofagia não foi alta na fase de recuperação do exercício exaustivo inicial e, subsequentemente, seguiu tendência ascendente. Porém, os fatores acima aumentaram significativamente nas fases de recuperação imediata e inicial depois de contusão. O trauma contuso pode ser mais grave do que a lesão induzida por exercício exaustivo, de modo que a autofagia tem início mais cedo, de acordo com as mudanças nos fatores relacionados com a autofagia. Nível de Evidência III; Estudos terapêuticos -Investigação dos resultados do tratamento.

ABSTRACT Objective: To study the effects of exhaustive exercise and contusion on autophagy-related factors Beclin1, LC3 and PINK1 expression in the skeletal muscle of rats. Methods: Forty-two male SD rats were randomly divided into 7 groups, 6 rats in each group: C, D0, D24, D48, E0, E24, and E48. Each group of rats was killed and dissected at the different respective time points specified above. The whole quadriceps femoris of the left hind limbs were removed and divided into two parts, one for mRNAs of Beclin1, LC3 and PINK1 by real-time fluorescent quantitative PCR, and the other for LC3 protein by Western blotting. Results: Compared with group C, the contents of Beclin1 mRNA, PINK1 mRNA, and LC3 mRNA in the immediate exhaustive exercise group (E0) were significantly reduced p<0.01. However, the levels of PINK1 mRNA, LC3 mRNA, and LC3 protein in skeletal muscle cells increased significantly in the 48 hours after exhaustion (E48) p<0.05, suggesting that cell autophagy had an increasing trend during the recovery period. Meanwhile, compared with the C group, the contents of Beclin1 mRNA, PINK1 mRNA, and LC3 mRNA in the immediate blunt contusion group (D0) increased significantly p<0.01 and were followed by a downward trend. Conclusion: Generally, there were differences between the blunt contusion and exhausted exercise models at each recovery phase. The gene expression of the autophagy-related factors was not high in the early exhaustive exercise recovery phase and subsequently followed an upward trend. But the above factors increased significantly in the immediate and early recovery phases after blunt contusion. Injury from blunt contusion may be more severe than exhaustive exercise-induced-injury, so the autophagy starts earlier according to the changes in autophagy-related factors. Level of evidence III; Therapeutic studies investigating the results of treatment.

RESUMEN Objetivo: Estudiar los efectos del ejercicio exhaustivo y de la contusión sobre la expresión de los factores relacionados a la autofagia de las proteínas Beclina 1, LC3 y PINK-1 en el músculo esquelético de ratones. Métodos: Cuarenta y dos ratones SD machos fueron divididos aleatoriamente en 7 grupos con 6 ratones cada uno: C, D0, D24, D48, E0, E24 y E48. Los ratones de cada uno de los grupos fueron sometidos a eutanasia y disecados en los diferentes puntos de tiempo de acuerdo con los grupos encima. Cada músculo cuádriceps femoral de los miembros posteriores izquierdos fue removido y dividido en dos partes, una para RNAm de Beclina 1, LC3 y PINK-1 por PCR cuantitativa fluorescente en tiempo real y la otra para la proteína LC3 por Western blotting. Resultados: En comparación con el grupo C, el tenor de RNAm en Beclina 1, PINK-1 y LC3 en el grupo ejercicio exhaustivo inmediato (E0) fue significativamente reducido (p < 0,01). Con todo, los niveles de RNAm en PINK-1 y LC3 y la proteína LC3 en células del músculo esquelético aumentaron significativamente en las 48 horas post-depleción (E48) (p < 0,05), sugiriendo que la autofagia celular tendió a aumentar durante el período de recuperación. En comparación con el grupo C, el tenor de RNAm de Beclina 1, RNAm de Pink-1 y RNAm de LC3 en el grupo contusión inmediata (D0) aumentó significativamente (p < 0,01) lo que fue seguido por tendencia de caída. Conclusión: En general, fueron encontradas diferencias entre los modelos de contusión y de ejercicio exhaustivo en cada fase de recuperación. La expresión génica de los factores relacionados con la autofagia no fue alta en la fase de recuperación del ejercicio exhaustivo inicial y, subsecuentemente, siguió tendencia ascendente. Sin embrago, los factores encima aumentaron significativamente en las fases de recuperación inmediata e inicial después de contusión. El trauma contuso puede ser más grave que la lesión inducida por ejercicio exhaustivo, de modo que la autofagia tiene inicio más temprano, de acuerdo con los cambios en los factores relacionados a la autofagia. Nivel de Evidencia III; Estudios terapéuticos - Investigación de los resultados del tratamiento.

The objective of this study was to investigate the inhibitory effect of miR-135a in regulating JAK/STAT signaling pathway on airway inflammation in asthmatic mice. An asthma model was established by sensitization and stimulation with ovalbumin (OVA), and the corresponding drug intervention was given from the day of stimulation by means of nasal drops. Airway hyperresponsiveness was tested. The content of miR-135a in the lung tissue of mice was detected by RT-PCR. The pathological changes of lung tissue were evaluated by HE staining. Tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-5, and eotaxin in bronchoalveolar lavage fluid (BALF) and lung tissue were detected by ELISA and immunohistochemistry, respectively. The expression of JAK/STAT signaling pathway-related protein in lung tissue was detected by western blot. To further validate the effect of miR-135a overexpression on the JAK/STAT signaling pathway, pathway activators and inhibitors were added. Compared with the OVA group, the airway hyperresponsiveness of the mice was significantly decreased after treatment with the miR-135a agonist. The expression of miR-135a was significantly increased in the lung tissue and the pathological changes of the lung tissue were alleviated. The contents of TNF-α, IL-6, IL-5, and eotaxin in BALF and lung tissues were decreased. The expression of JAK/STAT signaling pathway-related proteins p-JAK3/JAK3, p-STAT1/STAT1, and p-STAT3/STAT3 were significantly reduced in lung tissue (P<0.05). Addition of JAK inhibitor AG490 reduced airway inflammation in asthmatic mice. miR-135a agonists inhibit airway inflammation in asthmatic mice by regulating the JAK/STAT signaling pathway.