Fatty acid composition and metabolic pathways in Arbacia dufresnii (Arbaciidae: Arbacioida) gametes: implications of shrimp byproducts in aquaculture feeds / Composición de ácidos grasos y vías metabólicas en los gametos de Arbacia dufresnii (Arbaciidae: Arbacioida) implicaciones de los subproductos de langostinos en los alimentos de acuicultura

Abstract Introduction: Care towards nutrition is essential for the quality of a sustainable aquaculture product. Since the balance in food affects the growth and production of gametes. The circular economy is made possible through the use of discarded materials. Objective: The aim of this research was to study the fatty acid composition and metabolic pathways in the gametes of Arbacia dufresnii, with a focus on the implications of incorporating shrimp byproducts into aquaculture feeds. Methods: Four different treatments were designed to maintain optimal nutritional quality, particularly in lipids and proteins, based on previous studies. The fatty acid profiles of the feeds and gametes were analyzed by using gas-chromatography, and statistical analyses were conducted to determine significant differences. Results: Significant differences were observed in the abundance (%) of omega-3 (ω-3) and omega-6 (ω-6) fatty acids. The (ω-3) metabolic pathway was more pronounced in the gametes of wild animals and those fed with the experimental feeds. In contrast, the (ω-6) metabolic pathway was less relevant in these groups. The (ω-3) /(ω-6) ratio was highest in the gametes of wild animals. Feeds enriched in fatty acids enhanced their bioaccumulation in the gametes reaching higher concentrations than wild animals. The availability of fatty acids in foods allowed their bioaccumulation in gametes, with concentrations equal to or higher than those observed in animals in their natural environment for certain fatty acids. Conclusions: Incorporating shrimp byproducts in aquaculture feeds demonstrated a promising strategy for resource utilization and organic input generation. The fatty acid composition in the gametes of A. dufresnii was influenced by the diet, highlighting the potential of balanced feeds to enhance the bioaccumulation of essential fatty acids. These findings provide valuable insights for the development of sustainable aquaculture practices and the production of nutritionally enriched seafood products.

Resumen Introducción: El cuidado hacia la nutrición es fundamental para la calidad de un producto acuícola sostenible. Ya que el balance en los alimentos afecta el crecimiento y producción de los gametos. A partir del aprovechamiento de materias de descarte se posibilita la economía circular. Objetivo: El objetivo de este estudio fue investigar la composición de ácidos grasos y las vías metabólicas en los gametos de Arbacia dufresnii, centrándose en las implicaciones de la incorporación de subproductos de camarones en los alimentos de acuicultura. Métodos: Se diseñaron cuatro tratamientos diferentes para mantener una calidad nutricional óptima, especialmente en lípidos y proteínas, basándose en estudios previos. Se analizaron los perfiles de ácidos grasos de los alimentos y los gametos mediante cromatografía de gases, y se realizaron análisis estadísticos para determinar diferencias significativas. Resultados: Se observaron diferencias significativas en la abundancia (%) de ácidos grasos omega-3 (ω-3) y omega-6 (ω-6). La vía metabólica de (ω-3) fue más pronunciada en los gametos de los animales en su entorno natural y aquellos alimentados con los piensos experimentales. Por el contrario, la vía metabólica de (ω-6) tuvo menos relevancia en estos grupos. La relación (ω-3) /(ω-6) fue más alta en los gametos de los animales en su entorno natural. La disponibilidad de ácidos grasos en los alimentos permitió su bioacumulación en los gametos, con concentraciones iguales o superiores a las observadas en los animales en su entorno natural para ciertos ácidos grasos. Conclusiones: La incorporación de subproductos de camarones en los alimentos de acuicultura demostró ser una estrategia prometedora para la utilización de recursos y la generación de insumos orgánicos. La composición de ácidos grasos en los gametos de A. dufresnii fue influenciada por la dieta, destacando el potencial de los alimentos balanceados para mejorar la bioacumulación de ácidos grasos esenciales. Estos hallazgos brindan información valiosa para el desarrollo de prácticas sostenibles en acuicultura y la producción de productos marinos enriquecidos nutricionalmente.

Transcriptional differential analysis of ocular surface ectoderm and surface ectoderm / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To identify transcriptional differences between the ocular surface ectoderm(OSE)and surface ectoderm(SE)using RNA-seq, and elucidate the OSE transcriptome landscape and the regulatory networks involved in its development.METHODS:OSE and SE cells were differentiated from human embryonic stem(hES)cells. Differentially expressed genes(DEGs)between OSE and SE were analyzed using RNA-seq. Based on the DEGs, we performed gene ontology(GO)analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis, and protein-protein interaction(PPI)network analysis. Transcription factors(TFs)and hub genes were screened. Subsequently, TF-gene and TF-miRNA regulatory networks were constructed using the NetworkAnalyst platform.RESULTS:A total of 4 182 DEGs were detected between OSE and SE cells, with 2 771 up-regulated and 1 411 down-regulated genes in OSE cells. GO-BP analysis revealed that up-regulated genes in OSE were enriched in the regulation of ion transmembrane transport, axon development, and modulation of chemical synaptic transmission. Down-regulated genes were primarily involved in nuclear division, chromosome segregation, and regulation of cell cycle phase transition. KEGG analysis indicated that up-regulated genes in OSE cells were enriched in signaling pathways such as cocaine addiction, axon guidance, and amphetamine addiction, while down-regulated genes were enriched in proteoglycans in cancer, ECM-receptor interaction, protein digestion and absorption, and cytokine-cytokine receptor interaction. Additionally, compared with SE, 204 TFs(including FOS, EGR1, POU5F1, SOX2, and PAX6)were up-regulated, and 80 TFs(including HAND2, HOXB6, HOXB5, HOXA5, and HOXB8)were down-regulated in OSE cells. Furthermore, we identified 6 up-regulated and 9 down-regulated hub genes in OSE cells, and constructed TF-gene and TF-miRNA regulatory networks based on these hub genes.CONCLUSIONS:The transcriptome characteristics of OSE and SE cells were elucidated through RNA-seq analysis. These findings may provide a novel insight for studies on the development and in vitro directed induction of OSE and corneal epithelial cells.

Research progress of NLRP3 inflammasome in the treatment of uveitis / 国际眼科杂志(Guoji Yanke Zazhi)

The NLRP3 inflammasome is a cellular multimeric protein complex that plays a crucial role in inflammation and immune responses. It consists of three main components: Nod-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein containing(ASC)and cysteine protease 1(caspase-1). Uveitis is a broad term encompassing a range of inflammatory diseases that primarily affect the iris, ciliary body, vitreous, retina and choroid. It is considered a major cause of blindness globally. Numerous studies have demonstrated the involvement of NLRP3 inflammasome in the onset and progression of uveitis, indicating its potential as a significant therapeutic target for uveitis in the future. This article provides an overview of the structure, biological functions and activation pathways of the NLRP3 inflammasome, as well as the current research progress on its association with different types of uveitis. Additionally, it discusses the application potential of the NLRP3 inflammasome in the treatment of uveitis.

Signaling Pathways Related to Renal Interstitial Fibrosis in Diabetic Kidney Disease Regulated by Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Diabetic kidney disease （DKD） is a common microvascular complication of diabetics mellitus （DM） and the leading cause of end-stage renal disease （ESRD）. Renal interstitial fibrosis （RIF） is the primary pathological basis for DKD progression to ESRD， which significantly increases the mortality rate of DKD patients and burdens patients and society， and it is thus a clinical problem that needs to be solved urgently. The pathogenesis of RIF is complex and mainly associated with excessive deposition of extracellular matrix （ECM）， epithelial-mesenchymal transition （EMT）， oxidative stress， inflammation， and autophagy. Multiple signaling pathways such as transforming growth factor-β1/Smad （TGF-β1/Smad）， nuclear transcription factor-κB （NF-κB）， p38 mitogen-activated protein kinase （p38 MAPK）， secretory glycoprotein/β-catenin （Wnt/β-catenin）， mammalian target of rapamycin （mTOR）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， neurogenic site-gap homologous protein （Notch）， and nuclear factor E2-associated factor 2 （Nrf2） mediate the development of RIF， which are currently novel targets for DKD therapy. Due to the complexity of its pathogenesis， the current Western medical treatment mainly focuses on essential treatment to improve metabolism， which has poor efficacy and is difficult to prevent the progression of DKD， so it is significant to find new treatment methods clinically. In recent years， many studies have proved that traditional Chinese medicine can alleviate oxidative stress， inhibit inflammatory response， and regulate cellular autophagy by modulating relevant signaling pathways， so as to treat RIF in DKD， which has the advantages of multi-pathway， multi-targeting， multi-linking， and significant therapeutic efficacy. However， there is still a lack of relevant summary. By reviewing the latest research reports in China and abroad， this article examines the roles of the signaling pathways mentioned above in the occurrence and development of RIF in DKD and the recent research progress in the intervention of RIF in DKD by traditional Chinese medicine via these pathways， aiming to provide new ideas and references for further scientific research and clinical practice.

Mechanism of Traditional Chinese Medicine in Treatment of Neurodegenerative Diseases by Regulating Polarization Balance of Microglia： A Review / 中国实验方剂学杂志

Neuroinflammation is a common pathological feature of neurodegenerative diseases （NDs）. Microglia （MG）， a resident macrophage in the brain with a unique developmental origin， is the core driver of neuroinflammation. It can participate in the occurrence and development of NDs through different polarization states and play a key role in regulating neurogenesis and synapse shaping and maintaining homeostasis. MG can be divided into M1 pro-inflammatory phenotype and M2 anti-inflammatory phenotype according to its function. The inflammatory mediators released by the M1 phenotype can lead to nerve degeneration and myelin sheath damage， while the activation of the M2 phenotype is required to inhibit the inflammatory response and promote tissue repair. With the advantages of multi-pathway， multi-target， and bidirectional regulation， traditional Chinese medicine can regulate the polarization balance of MG and has dual effects on NDs such as Alzheimer's disease， Parkinson's disease， and multiple sclerosis. The active components of traditional Chinese medicine and its compound can inhibit the activation of MG by regulating phosphatidylinositol-3-kinases/protein kinase B（PI3K/Akt）， NOD-like receptor thermal protein domain associated protein 3（NLRP3）， signal transducer and activator of transcription factor1（STAT1）， nuclear transcription factor kappa B（NF-κB）， and other pathways， promote the polarization of M1 phenotype to M2 phenotype， reduce the expression of interleukin（IL）-6， tumor necrosis factor-α（TNF-α）， and other pro-inflammatory factors， and increase the secretion of IL-10， arginase-1（Arg-1）， and other anti-inflammatory factors. It can also reduce β-amyloid deposition and tau protein expression in Alzheimer's disease， alleviate dopaminergic neuronal damage in Parkinson's disease， and relieve demyelination， inflammatory cell infiltration， and related clinical symptoms of multiple sclerosis. The bidirectional regulation of the M1/M2 polarization balance of MG by traditional Chinese medicine is a potential strategy for the treatment of NDs. This paper focused on the targets of the regulation of MG polarization balance by traditional Chinese medicine monomer and its compound in the treatment of NDs， so as to further study and summarize the existing research results and provide ideas and basis for the future treatment of NDs.

Fractional anisotropy in degenerative cervical stenosis surgery prognostic: a systematic review / Anisotropia fracionada no prognóstico de cirurgia de estenose cervical degenerativa: revisão sistemática / Anisotropía fraccional en el pronóstico de cirugía de la estenosis cervical degenerativa: revisión sistemática

ABSTRACT Cervical spondylotic myelopathy (CSM) is a common disease with an increased anticipated burden to health systems worldwide. Methods to predict outcomes in these patients are needed so physicians can provide more effective care. Fractional anisotropy (FA) analysis is a promising technique used to quantify how preserved the diffusion is in neural pathways. A systematic review and meta-analysis were performed using the PRISMA guidelines. Full articles available online were searched for correlation coefficients between FA values and mJOA scores. Average FA values, preoperative mJOA, and postoperative mJOA scores were gathered to perform a correlation analysis. A total of 5 articles presented correlations between FA and mJOA change and were included in the correlation meta-analysis. Correlation coefficients varied from -0.42 and 0.55. The number of patients in each study varied from 15 to 95. The Random effects model resulted in a non-significant correlation coefficient of 0.1315 (95% CI: -0.2575 to 0.4839; p= 0.5124). Spearman's correlation analysis was significant for preoperative vs postoperative mJOA (r = 0.79, p = 0.02), while preoperative FA did not correlate significantly with preoperative or postoperative mJOA. At this point, the data available in the literature is insufficient to determine a real correlation between FA and mJOA scores. More studies are necessary for a better understanding of this matter. Level of Evidence III; Study Review.

Resumo: A mielopatia espondilótica cervical (CSM, pelas suas siglas em inglês) é uma doença comum com elevados gastos para os sistemas de saúde em todo o mundo. Métodos para prever resultados nesses pacientes são necessários para que a atenção médica seja mais eficaz. A análise de anisotropia fracionada (FA) é uma técnica promissora usada para quantificar a preservação da difusão nas vias neurais. Uma revisão sistemática e meta-análise foi realizada usando as diretrizes PRISMA. Artigos completos disponíveis online foram avaliados em busca de coeficientes de correlação entre valores de FA e escores de mJOA. Valores médios de FA, escores de mJOA pré-operatórios e pós-operatórios foram coletados para realizar uma análise de correlação. Um total de 5 artigos apresentaram correlações entre alteração de FA e mJOA e foram incluídos na meta-análise de correlação. Os coeficientes de correlação variaram entre -0,42 e 0,55. O número de pacientes em cada estudo variou de 15 a 95. O modelo de efeitos aleatórios resultou em um coeficiente de correlação não significativo de 0,1315 (95% CI: -0,2575 a 0,4839; p= 0,5124). A análise de correlação de Spearman foi significativa para mJOA pré-operatório vs. pós-operatório (r = 0,79, p = 0,02), enquanto a FA pré-operatório não apresentou correlação significativa com o mJOA pré-operatório ou pós-operatório. Os dados disponíveis na literatura neste momento são insuficientes para determinar uma correlação real entre os escores FA e mJOA. Mais estudos são necessários para uma melhor compreensão deste assunto. Nível de Evidência III; Revisão de Estudos.

Resumen: La mielopatía cervical espondilótica (CSM, por sus siglas en inglés) es una enfermedad común con una mayor carga anticipada para los sistemas de salud en todo el mundo. Se necesitan métodos para predecir los resultados en estos pacientes para que los médicos puedan brindar una atención más eficaz. El análisis de anisotropía fraccional (FA) es una técnica prometedora que se utiliza para cuantificar cuán preservada está la difusión en las vías neurales. Se realizó una revisión sistemática y un metanálisis utilizando las pautas PRISMA. Se buscaron artículos completos disponibles en línea para encontrar coeficientes de correlación entre los valores de FA y las puntuaciones de mJOA. Se recopilaron los valores promedio de FA, mJOA preoperatorios y mJOA postoperatorios para realizar un análisis de correlación. Un total de 5 artículos presentaron correlaciones entre el cambio de FA y mJOA y se incluyeron en el metanálisis de correlación. Los coeficientes de correlación variaron entre -0,42 y 0,55. El número de pacientes en cada estudio varió de 15 a 95. El modelo de efectos aleatorios resultó en un coeficiente de correlación no significativo de 0,1315 (IC 95%: -0,2575 a 0,4839; p= 0,5124). El análisis de correlación de Spearman fue significativo para la mJOA preoperatoria frente a la posoperatoria (r = 0,79, p = 0,02), mientras que la FA preoperatoria no presentó una correlación significativa con la mJOA preoperatoria o posoperatoria. Los datos disponibles en la literatura en este momento son insuficientes para determinar una correlación real entre las puntuaciones de FA y mJOA. Son necesarios más estudios para una mejor comprensión de este asunto. Nivel de Evidencia III; Revisión de Estudios.

Central auditory processing and aphasia: A scoping review / Processamento auditivo central e afasia: uma revisão de escopo

ABSTRACT Purpose: to report scientific evidence on the impact of aphasia on central auditory processing and map the contribution of auditory training to aphasic individuals. Methods: a scoping review approaching national and international databases (SciELO, LILACS, PubMed, Scopus, and Cochrane Library) and the gray literature (Google Scholar and Open Grey). The inclusion criteria covered articles that addressed the interface between central auditory processing and aphasia, excluding duplicates, literature reviews, and scientific abstracts. Literature Review: the review comprised 13 articles that met the eligibility criteria for this study. Seven of the selected articles assessed central auditory processing, four used electrophysiological examinations (such as auditory brainstem response and long-latency auditory evoked potentials) to assess the auditory pathway, and only one analyzed the intervention in aphasic individuals with auditory training. Conclusion: scientific evidence points to an important change in aphasic people's central auditory processing, with impaired figure-ground, auditory closure, temporal resolution and ordering, and binaural integration. Moreover, it is relevant to assess auditory processing, given the contribution of auditory training in speech-language-hearing therapy for a better prognosis in the rehabilitation of aphasia.

RESUMO Objetivo: reportar as evidências científicas do impacto da afasia no Processamento Auditivo Central e mapear a contribuição do Treinamento Auditivo para a população afásica. Métodos: trata-se de uma revisão de escopo realizada nas bases de dados nacionais e internacionais: Scielo, Lilacs, Pubmed, Scopus, Cochrane Library e com uma busca adicional à literatura cinzenta no Google Scholar e Open Grey. Os critérios de inclusão abrangeram artigos que abordassem a interface do processamento auditivo central e afasia, excluindo-se as duplicações, artigos de revisão da literatura e resumos científicos. Revisão de Literatura: selecionaram-se 13 artigos que cumpriram os critérios de elegibilidade deste estudo. Dos artigos selecionados, sete apresentaram a avaliação do Processamento Auditivo Central, quatro apresentaram os exames eletrofisiológicos - como os exames de Potencial Evocado Auditivo de Tronco Encefálico (PEATE) e Potencial Evocado Auditivo de Longa Latência (PEALL) - para avaliação da via auditiva e apenas um estudo analisou a intervenção dos indivíduos afásicos por meio do treinamento auditivo. Conclusão: as evidências científicas apontam importante alteração no Processamento Auditivo Central dos afásicos, apresentando prejuízos nas habilidades auditivas de figura-fundo, fechamento auditivo, resolução e ordenação temporal e integração binaural. Ainda, demonstra-se como relevante a avaliação do processamento, devido à contribuição do Treinamento Auditivo nas terapias fonoaudiológicas para um melhor prognóstico na reabilitação das afasias.

Aplicação das regras de vinculação da Classificação Internacional de Funcionalidade, Incapacidade e Saúde com a Avaliação Geriátrica Ampla / Linking the content of the Comprehensive Geriatric Assessment of a reference center for the health of the elderly with the International Classification of Functioning, Disability and Health

Objetivo: Vincular o conteúdo da Avaliação Geriátrica Ampla (AGA) de um centro de referência na saúde da pessoa idosa com a Classificação Internacional de Funcionalidade, Incapacidade e Saúde (CIF) e apresentar seu Conjunto Básico de categorias da CIF. Método: A AGA foi vinculada à CIF por dois especialistas, treinados de acordo com as regras de vinculação estabelecidas. A concordância entre os especialistas foi determinada com base no índice kappa de Cohen. Resultados: A concordância entre os especialistas foi considerada perfeita para cada domínio da CIF (k= 0,91; p<0,00; concordância= 93,32%). A AGA continha 419 itens, sendo que 106 não puderam ser vinculados à CIF, por estarem associados a condições de saúde ou não se enquadrarem nas categorias da CIF. Foi verificado que 313 estavam ligados aos domínios da CIF e que 181 (60,13%) estavam relacionados às funções do corpo, 18 (5,98%) às estruturas do corpo, 73 (24,258%) à atividade e participação, 30 (9,97%) a fatores ambientais e 11 (3,51%) aos fatores pessoais. Conclusões: A CIF pode ser inserida em contextos específicos dos serviços de saúde sendo viável a vinculação da CIF com formulários elaborados pelos próprios serviços de saúde. A correspondência entre um instrumento de avaliação geriátrico e a CIF potencializa discussões de casos, planos terapêuticos e cuidado continuado. A dinâmica do processo de cuidado padronizado pela CIF pode facilitar a ampliação do cuidado e estabelecimento de metas terapêuticas que ultrapassem o contexto do serviço e alcancem a esfera familiar e social.

Objective: Linking the content of the Comprehensive Geriatric Assessment (CGA) of a reference center for the health of the elderly with the International Classification of Functioning, Disability and Health (ICF) and present its Basic Set of ICF codes. Method: The AGA were linked to the ICF by two specialists, trained according to the established linking rules. Agreement between the health professionals was determined based on Cohen's kappa index. Results: The agreement between the two health professionals was considered perfect for each ICF domain (k= 0.91; p<0.00; agreement= 93.32%). The AGA contained 419 items, 106 of which could not be linked to the ICF, as they were associated with health conditions or did not fit into any category. It was found that 313 were linked to the ICF domains and that 181 (60.13%) were related to body functions, 18 (5.98%) to body structures, 73 (24.258%) to activity and participation, 30 (9.97%) to environmental factors and 11 (3.51%) to personal factors. Conclusions: The ICF can be inserted in specific contexts of health services, making it feasible to link the ICF with forms prepared by the health services themselves. The correspondence between a geriatric assessment instrument and the ICF enhances case discussions, therapeutic plans and continued care. The dynamics of the care process standardized by the ICF can facilitate the expansion of care and the establishment of therapeutic goals that go beyond the context of the service and reach the family and social sphere.

Validation of qrs-polarity algorithm with special emphasis in parahisian pathways / Validación del algoritmo de la polaridad del qrs con especial énfasis en vías parahisianas

Abstract Background: In 1996 Iturralde et al. published an algorithm based on the QRS polarity to determine the location of the accessory pathways (AP), this algorithm was developed before the massive practice of invasive electrophysiology. Purpose: To validate the QRS-Polarity algorithm in a modern cohort of subjects submitted to radiofrequency catheter ablation (RFCA). Our objective was to determinate its global accuracy and its accuracy for parahisian AP. Methods: We conducted a retrospective analysis of patients with Wolff-Parkinson-White (WPW) syndrome who underwent an electrophysiological study (EPS) and RFCA. We employed the QRS-Polarity algorithm to predict the AP anatomical location and we compared this result with the real anatomic location determined in the EPS. To determine accuracy, the Cohen's kappa coefficient (k) and the Pearson correlation coefficient were used. Results: A total of 364 patients were included (mean age 30 years, 57% male). The global k score was 0.78 and the Pearson's coefficient was 0.90. The accuracy for each zone was also evaluated, the best correlation was for the left lateral AP (k of 0.97). There were 26 patients with a parahisian AP, who showed a great variability in the ECG features. Employing the QRS-Polarity algorithm, 34.6% patients had a correct anatomical location, 42.3% had an adjacent location and only 23% an incorrect location. Conclusion: The QRS-Polarity algorithm has a good global accuracy; its precision is high, especially for left lateral AP. This algorithm is also useful for the parahisian AP.

Resumen Antecedentes: En 1996 Iturralde y colaboradores publicaron un algoritmo basado en la polaridad del QRS para determinar la ubicación de las vías accesorias (VA), este algoritmo fue desarrollado antes de la práctica masiva de la electrofisiología invasiva. Objetivo: Validar el algoritmo de la polaridad del QRS en una cohorte moderna de sujetos sometidos a ablación con catéter por radiofrecuencia (ACRF). Nuestro objetivo fue determinar su precisión global y su precisión para las VA parahisianas. Métodos: Realizamos un análisis retrospectivo de pacientes con síndrome de Wolff-Parkinson-White (WPW) a los que se les realizó estudio electrofisiológico (EEF) y ACRF. Empleamos el algoritmo de la polaridad del QRS para predecir la ubicación anatómica de la VA y comparamos este resultado con la ubicación anatómica real determinada en el EEF. Para determinar la precisión se utilizaron el coeficiente kappa de Cohen (k) y el coeficiente de correlación de Pearson. Resultados: Se incluyeron un total de 364 pacientes (edad media 30 años, 57 % varones). La puntuación k global fue de 0,78 y el coeficiente de Pearson de 0,90. También se evaluó la precisión para cada zona, la mejor correlación fue para las VA laterales izquierdas (k de 0.97). Hubo 26 pacientes con VA parahisianas, que mostraron una gran variabilidad en las características del ECG. Empleando el algoritmo de la polaridad del QRS, el 34,6 % de los pacientes tenía una ubicación anatómica correcta, el 42,3 % tenía una ubicación adyacente y solo el 23 % una ubicación incorrecta. Conclusión: El algoritmo de la polaridad del QRS tiene una buena precisión global; su precisión es alta, especialmente para VA lateral izquierdo. Este algoritmo también es útil para la VA parahisiana.

Network-based Toxicogenomics Approach to Unraveling the Influence of Lead and Cadmium Mixture on the Development and Progression of Hypertension

Heavy metals, generally characterized by high densities and atomic weights, are ubiquitous in the environment and are a public health concern due to the several health issues they pose to humans. Of all heavy metals, lead and cadmium among others are known to be capable of inducing multiple health effects even at a low rate of exposure. Hypertension (HYP), a major cause of death and a risk factor for other cardiovascular diseases, is known to be caused by both lead and cadmium. While the mechanism underlying the development of HYP induced by independent exposure to lead and cadmium has been well studied, the mechanism underlying the induction and progression of HYP upon lead and cadmium co-exposure remains mildly explored. Hence, this study aimed to elucidate the mechanism using a toxicogenomic approach. The set of genes affected by both heavy metals was identified using the comparative toxicogenomics database (CTD) while HYP targets were retrieved from the Gene Cards database. The shared genes between the heavy metals and the disease were identified and subjected to further analysis. The results of our analysis revealed the signaling pathways that are dysregulated by lead and cadmium co-exposure while oxidative stress, inflammation, and endothelial dysfunction were revealed as processes pertinent to the induction and progression of HYP by lead and cadmium co-exposure. Biomarkers that could be used for prognosis evaluation were also identified. Ultimately, this study supports and advances the growing body of finding on the roles played by lead and cadmium co-exposure in inducing HYP.

Preoperative clinical management of patients who are candidates for facial transplantation / Manejo clínico pré-operatório de pacientes candidatos ao transplante facial

Introduction: Face transplantation has gained recognition, changing the clinicalsurgical scenario for restoring complex facial defects, as it attributes functional and aesthetic recovery to patients who have suffered serious accidents. At the time of writing this article, in official publications, 43 patients had already undergone facial transplantation worldwide. Face transplantation has numerous pieces of evidence that can irrefutably provide improvements to the patient. For this, preoperative care for the patient must be carefully established so that there is good surgical performance. Case Report: Male patient, 46 years old, reports that, at the age of 6, he had burns due to exposure to gasoline, with 72% of his body surface burned, showing sequelae of burns and surgical reconstructions on the face, with redundant and ptotic skin flap on the left cheek, absence of upper and lower lip and exposure of lower teeth. Conclusion: It is important to publicize this innovative procedure in different medical specialties and preoperative care through a thorough investigation, which attributes better surgical effectiveness, allowing the rescue of their facial identity, once stigmatized.

Introdução: O transplante de face adquiriu reconhecimento, alterando o panorama clínico-cirúrgico para a restauração de defeitos faciais complexos, visto que atribui recuperação funcional e estética a pacientes que sofreram acidentes graves. Até o momento da redação deste artigo, em publicações oficiais, 43 pacientes já haviam realizado o transplante facial em todo mundo. O transplante de face possui inúmeras evidências que podem fornecer melhorias ao paciente de forma irrefutável. Para isso, cuidados pré-operatórios ao paciente devem ser cuidadosamente estabelecidos para que haja um bom desempenho cirúrgico. Relato de Caso: Paciente sexo masculino, 46 anos, relata que, aos 6 anos de idade, teve queimadura por exposição à gasolina, com 72% de superfície corporal queimada, apresentando sequelas de queimaduras e reconstruções cirúrgicas na face, com retalho cutâneo redundante e ptótico em bochecha esquerda, ausência de lábio superior e inferior e exposição dos dentes inferiores. Conclusão: Ressalta-se a importância da divulgação desse procedimento inovador em diferentes especialidades médicas e dos cuidados pré-operatórios através de uma investigação minuciosa, que atribuem uma melhor eficácia cirúrgica, possibilitando o resgate de sua identidade facial, uma vez estigmatizada.

Trajetórias assistenciais de usuários com COVID-19: das medidas preventivas à reabilitação / Trayectorias asistenciales de usuarios con el COVID-19: de las medidas preventivas a la rehabilitación / Care trajectories of COVID-19 patients: from preventive measures to rehabilitation

O objetivo deste trabalho é analisar as trajetórias assistenciais, relativas ao uso e acesso às redes de atenção à saúde (RAS), de usuários diagnosticados, internados e em reabilitação decorrente da COVID-19. Foi realizado estudo avaliativo, qualitativo, com base em entrevistas com usuários, no Município de Niterói, Rio de Janeiro, Brasil. As trajetórias assistenciais, a partir da análise temática, foram reconstituídas em três momentos que expressam as experiências com a rede de saúde e apoio durante a pandemia: medidas de prevenção, apoio e diagnóstico; a experiência da internação; cuidados, reabilitação e apoio pós-COVID-19. Os resultados apontam que a principal fonte de informação sobre a doença foram os telejornais; as medidas preventivas de higienização, as mais adotadas; e a família foi a principal rede de apoio. Não houve tempos de espera para internação no hospital municipal de referência. A internação foi muito bem avaliada em função do acolhimento, cuidado multiprofissional, visitas virtuais e contato diário do médico com os familiares. Identificou-se, porém, "vácuo assistencial" pós-alta, com ausência de seguimento pela atenção primária à saúde (APS) e demais serviços públicos. Foi frequente a busca espontânea por planos populares e pagamento direto para acesso aos serviços especializados no pós-COVID-19, até a implantação do serviço de reabilitação. Em síntese, trajetórias assistenciais solitárias e descontínuas de indivíduos e famílias revelam diversos desafios ao sistema de saúde, entre os quais a garantia de acesso e coordenação dos cuidados pela APS, ampliação da oferta de serviços públicos especializados e de reabilitação em redes, alinhados aos princípios do cuidado humanizado, além da manutenção das medidas de apoio social.

Este artículo tiene por objetivo analizar las trayectorias asistenciales de usuarios diagnosticados, hospitalizados y en rehabilitación por el COVID-19 en cuanto al uso y acceso a las redes de atención a la salud (RAS). Se realizó un estudio cualitativo, evaluativo, a partir de entrevistas con usuarios en el municipio de Niterói, Rio de Janeiro, Brasil. A partir del análisis temático, las trayectorias asistenciales se reconstituyeron en tres momentos que expresan las experiencias con la red de salud y de apoyo durante la pandemia: las medidas de prevención, apoyo y diagnóstico; la experiencia de hospitalización; y los cuidados, rehabilitación y apoyo post-COVID-19. Los resultados muestran que los telediarios fueron la principal fuente de información sobre el COVID-19. Las medidas preventivas más adoptadas fueron las de higiene. La familia fue la principal red de apoyo. No hubo tiempo de espera para el ingreso en el hospital municipal de referencia. La hospitalización fue muy bien evaluada debido a la recepción, atención multidisciplinaria, visitas virtuales y contacto diario del médico con los familiares. Se identificó un "vacío asistencial" posterior al alta, sin seguimiento por parte de la atención primaria de salud (APS) y otros servicios públicos. Hubo una frecuente búsqueda espontánea de planes populares y pago directo para acceder a servicios especializados post-COVID-19 hasta la implementación del servicio de rehabilitación. Por lo tanto, las trayectorias asistenciales solitarias y discontinuas de individuos y familias revelan varios desafíos para el sistema de salud, entre ellos la garantía de acceso y coordinación de la atención por parte de la APS, la ampliación de la oferta de servicios públicos especializados y la rehabilitación en redes, combinada con los principios de cuidado humanizado, además del mantenimiento de las medidas de apoyo social.

This study aims to analyze the care trajectories of patients diagnosed with COVID-19 who were hospitalized and are currently undergoing rehabilitation regarding their use of and access to the healthcare network (HN). An evaluative, qualitative study was carried out based on interviews with patients in the city of Niterói, Rio de Janeiro State, Brazil. The care trajectories were reconstructed at three different occasions that express their experiences with the healthcare and support network during the pandemic: prevention, support and diagnosis measures; hospitalization; post-COVID-19 care, rehabilitation and support. The results indicate that the main source of information about COVID-19 was TV newscasts. Preventive hygiene measures were the most widely adopted. The family was the main support network. There was no waiting time for admission to the municipal referral hospital. Hospitalization was very well evaluated in terms of user embracement, multidisciplinary care, virtual visits and daily contact between doctor and family members. A post-discharge "care vacuum" was identified, with no follow-up by primary health care (PHC) and other public services. Low-cost health insurance plans and private specialized post-COVID-19 services were frequently and spontaneously sought until the implementation of the rehabilitation service. In summary, solitary and discontinuous care trajectories of individuals and families shed light on several challenges to the health system, including guaranteed access to coordinated PHC and expanded offer of specialized public services and rehabilitation, aligned with the principles of humanized care, in addition to the maintenance of social support measures.

Ebola outbreak in Guinea, 2021: Clinical care of patients with Ebola virus disease

Background: Experience from the Zaire Ebolavirus epidemic in the eastern Democratic Republic of the Congo (2018­2020) demonstrates that early initiation of essential critical care and administration of Zaire Ebolavirus specific monoclonal antibodies may be associated with improved outcomes among patients with Ebola virus disease (EVD). Objectives: This series describes 13 EVD patients and 276 patients with suspected EVD treated during a Zaire Ebolavirus outbreak in Guinea in 2021. Method: Patients with confirmed or suspected EVD were treated in two Ebola treatment centres (ETC) in the region of N'zérékoré. Data were reviewed from all patients with suspected or confirmed EVD hospitalised in these two ETCs during the outbreak (14 February 2021 ­ 19 June 2021). Ebola-specific monoclonal antibodies, were available 2 weeks after onset of the outbreak. Results: Nine of the 13 EVD patients (age range: 22­70 years) survived. The four EVD patients who died, including one pregnant woman, presented with multi-organ dysfunction and died within 48 h of admission. All eight patients who received Ebola-specific monoclonal antibodies survived. Four of the 13 EVD patients were health workers. Improvement of ETC design facilitated implementation of WHO-recommended 'optimized supportive care for EVD'. In this context, pragmatic clinical training was integrated in routine ETC activities. Initial clinical manifestations of 13 confirmed EVD patients were similar to those of 276 patients with suspected, but subsequently non confirmed EVD. These patients suffered from other acute infections (e.g. malaria in 183 of 276 patients; 66%). Five of the 276 patients with suspected EVD died. One of these five patients had Lassa virus disease and a coronavirus disease 2019 (COVID-19) co-infection. Conclusion: Multidisciplinary outbreak response teams can rapidly optimise ETC design. Trained clinical teams can provide WHO-recommended optimised supportive care, including safe administration of Ebola-specific monoclonal antibodies. Pragmatic training in essential critical care can be integrated in routine ETC activities. Contribution: This article describes clinical realities associated with implementation of WHO-recommended standards of 'optimized supportive care' and administration of Ebola virus specific treatments. In this context, the importance of essential design principles of ETCs is underlined, which allow continuous visual contact and verbal interaction of health workers and families with their patients. Elements that may contribute to further quality of care improvements for patients with confirmed or suspected EVD are discussed.

Biological Functions of CD24 in Malignant Tumor and its Application as a Novel Anti-tumor Target / 中国生物化学与分子生物学报

CD24 is a highly glycosylated protein that is linked to the plasma membrane via a glycosylphosphatidylinositol anchor. As a universally expressed protein on immune cells, CD24 is also overexpressed in nearly 70% of human cancers including hepatocellular carcinoma, lung cancer and bladder cancer et al. Studies revealed that CD24 is involved in regulating cell proliferation, migration and invasion in cancer cells by interacting with P-selectin, activating Wnt and MAPK signaling pathway or other signaling molecules. Therefore, CD24-targeted siRNA or antibody has a great potential to exert anti-tumor effects by blocking the interaction. There are currently several agents or regiments targeting CD24 for the treatment of patients with various kinds of cancers that are undergoing assessment in the preclinical study at present. Recent studies revealed that CD24 was able to interact with the inhibitory receptor sialic-acid-binding Ig-like lectin 10 (Siglec-10), which located on the surface of macrophages, to compose a novel immune checkpoint. The binding of CD24 to Siglec-10 elicits an inhibitory signaling cascade, limits macrophage phagocytosis, evades immune surveillance, and promotes tumor growth, which suggested that CD24 may be a potential target in anti-tumor immunotherapy. In this review, we introduced the structure and function of CD24 and its role in cancer progression and anti-tumor immunity. Moreover, the progression in developing novel anti-cancer drugs or treatment strategies with the target of CD24 was summarized, which aims to provide a new insight in CD24-targeting therapy.

Platelet-endothelial aggregation receptor 1 and its mediated signalling pathway Advances in the study of the role of platelets and endothelial cells / 中国临床药理学与治疗学

Platelet-aggregation receptor 1 (PEAR1) is a transmembrane receptor identified in 2005 and expressed mainly on platelets and endothelial cells. PEAR1 is a receptor protein that contacts platelets with each other and plays an important role in platelet activation and aggregation. Endothelial cells play an important role in maintaining vascular tone and vascular repair, and PEAR1 regulates the process of tumourigenesis and development by affecting their proliferation and associated neovascularisation. In recent years, PEAR1 has gradually been recognized as a potential target for antithrombotic drugs. This review focuses on elucidating the mechanisms of platelet endothelial aggregation receptor 1 and related signaling pathways in platelets and endothelial cells, and provides new ideas for the study of drug therapy for tumour-associated thrombosis.

Effects and mechanism of Ginseng Yixin granules (QSYXG) for heart failure with preserved ejection fraction based on the network pharmacology and molecular docking strategy / 中国临床药理学与治疗学

AIM: To study the mechanism of Ginseng Yixin granules (QSYXG) in treating ejection fraction preserved heart failure (HFpEF) based on network pharmacology. METHODS: Effective chemical composition information of QSYXG particles was collected through TCMSP database; DisGeNET, GeneCards, OMIM database for obtaining HFpEF related targets; Metascape GO and KEGG enrichment analysis of the intersection targets of HFpEF; STRING Construction and analysis of the database PPI network; Cytoscape3.7.2 Software construction network diagram; Docking of the major active components to the core target with the AutoDock Vina software molecules, the results were visualized and analyzed with pymol. RESULTS: A total of 66 components and corresponding targets were obtained, HFpEF corresponds to 1 931 targets, The intersection of 127 targets, the main active ingredients are quercetin, kaempferol, β-sitosterol, etc.; TNF, AKT1, IL-6, P53 and JUN as the core targets, Good docking of the key components with the core targets; Mainly involving the positive regulation of gene expression, signal transduction, negative regulation of apoptotic process, positive regulation of cell proliferation and senescence, hypoxia response, negative regulation of gene expression, inflammatory response and so on, PI3K-Akt, AGE-RAG, MAPK, TNF, IL-17, and HIF-1 are the main associated signaling pathways. CONCLUSION: QSYXG may treat HFpEF by activating targets of TNF, AKT1, IL-6, P53, JUN, and regulating apoptotic process, cell proliferation, hypoxia response, and inflammatory response.

Research progress of AMPK regulating ferroptosis related signaling pathway / 中国药理学通报

Energy imbalance is eonsidered an important driver of human diseases. As an important energy sensor, AMPK plays a central role in maintaining energy homeostasis, making it a key target for disease prévention and treatment. As a new type of cell death, ferroptosis is related to the pathophysiologieal process of many diseases, and AMPK-related signaling pathway is an important way to regulate iron death. Understanding which pathway AMPK induces or inhibits ferroptosis will provide new ideas for the treatment of diseases in the future and provide new targets for new drug research. In this paper, we review the related litera-tures and explore the signaling pathways of AMPK regulating ferroptosis, wïth a brief description of the application of AMPK-mediated ferroptosis related signaling pathways in diseases, hoping to provide reference for later research.

Effect of acid sphingomyelinase on nonalcoholic fatty liver disease via PPARα- PGC-1α pathway / 中国药理学通报

Aim To investigate the effects of acid sphingomyelinase(ASMase)on high-fat induced nonalcoholic fatty liver disease in mice and its regulation of PPARα- PGC-1α pathway. Methods ASMase knockout mice based on C57BL/6 background were constructed. Closed group heterozygotes were obtained through hybridized with wild-type mice(ASMase+/-),together with the littermate WT mice were prepared for NAFLD model in this study. The experiment was divided into four groups:WT+Chow:the WT mice were fed with normal diet for 12 weeks; WT+HFD:the WT mice were fed with high-fat diet for 12 weeks; ASMase+/-+Chow:the ASMase+/- mice were fed with normal diet for 12 weeks; ASMase+/- +HFD:the ASMase+/- mice were fed with high fat diet for 12 weeks. Biochemical method was used to detect serum TC,TG and liver TC,TG contents and liver function such as ALT and AST. Oil red staining,HE staining,Masson staining and Sirius red staining were performed to detect liver lipid accumulation,hepatocyte morphology and liver fibrosis. AmplexTM red sphingomyelinase kit was applied to detect ASMase activity. Western blot was performed to detect protein expressions of ASMase,PPARα,PGC-1α and CPT1. Results WT+HFD group displayed hypercholesterolemia and liver dysfunction. Levels of liver triglyceride(TG)were significantly higher than those in WT+Chow group(P<0.05 or P<0.01). Meanwhile,the hepatocytes showed marked steatosis,balloon-like changes,and fibrosis. Protein expression and activity of ASMase in liver increased significantly(P<0.01 or P<0.001),whereas CPT1,PPARα and PGC-1α expressions were not statistically significant compared with matched control group. Heterozygously ASMase-deficient mice reduced the elevated liver TG induced by HFD,as well as improving balloon-like changes and liver fibrosis. Furthermore,the expressions of PPARα,PGC-1α and CPT1 were up-regulated in ASMase+/- +HFD mice compared with WT+Chow group.Conclusions ASMase promotes hepatic steatosis and fibrosis,which may be related to its inhibition of PPARα-PGC-1α pathway.

Research progress on regulatory mechanism of long non-coding RNA CYTOR in human cancer / 中国药理学通报

Cancer is difficult to cure because of its heterogeneity, drug resistance and easy recurrence and metastasis. Revealing the molecular mechanism of cancer genesis and development, identifying new diagnostic markers and molecular therapeutic targets are undoubtedly effective strategies to solve the problems of early diagnosis, treatment and improvement of prognosis of cancer patients. More and more studies have shown that long non-coding RNA (IncRNA) is specifically expressed in human cancer and is a key regulator of cancer occurrence and development. Cytoskeleton regulator RNA (CYTOR) is a carcinogenic lncRNA found in recent years. CYTOR is highly expressed in many types of cancer and regulates the development of cancer through a variety of pathways, which may be an effective biomarker for early cancer diagnosis, molecular targeted therapy and prognosis assessment. This paper reviews the molecular regulatory mechanism and related biological characteristics of CYTOR in human cancer, in order to provide new scientific reference for clinical cancer diagnosis and treatment.

Identification of metabolites in different parts of Juandan Baihe (Lilium lancifolium) by UPLC-Q-TOF-MS and their hypoglycemic activities / 数字中医药（英文）

Objective @#To identify the main components in the extracts of different parts of Juandan Baihe (Lilium lancifolium) by ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) technology and investigate their hypoglycemic activities.@*Methods@#The MS fragmentation pathways of the main types of compounds in Juandan Baihe (Lilium lancifolium) were studied, and the main components in the extracts were systematically identified using MS fragmentation pathways combined with MS mining technology. Based on the hyperglycemia male mouse model [specific pathogen free (SPF)-grade Kunming mice] induced by streptozotocin (intragastric administration of 80 mg/kg for 3 d), the hypoglycemic effects of extracts of Juandan Baihe (Lilium lancifolium) roots, stems, corms, leaves, and flowers were evaluated by measuring the changes of blood glucose, daily water consumption, daily food intake, and body weight.@*Result@#The MS fragmentation pathways of regalosides, dioscins, phenylpropanoids, flavonoids, and chlorogenic acids in Juandan Baihe (Lilium lancifolium) were clarified, and a mining method for compounds in this plant was constructed. A total of 58 compounds, including 6 chlorogenic acids, 14 regalosides, 13 phenylpropanoids, 5 flavonoids, and 20 dioscins, were identified from the roots, stems, corms, leaves, and flowers of Juandan Baihe (Lilium lancifolium). Among them, 30 compounds were reported for the first time from this plant. The root and corm extracts demonstrated significant hypoglycemic activities by reducing blood glucose levels from 23.76 ± 1.21 and 24.29 ± 1.35 mmol/L to 17.21 ± 1.23 and 18.78 ± 1.49 mmol/L, respectively (P < 0.05). The roots and corms extracts could also attenuate the symptoms of polydipsia (P < 0.01), polyphagia (P < 0.05), and weight loss caused by diabetes.@*Conclusion@#This study clarifies that the roots of Juandan Baihe (Lilium lancifolium) are rich in regalosides and dioscins for the first time, and have significant hypoglycemic activities, providing the foundation for the comprehensive utilization of this plant and the development of hypoglycemic drugs.