Relationship of hemoglobin levels with outcomes in deceased donor kidney transplant: a retrospective cohort study / Relação dos níveis de hemoglobina com desfechos em transplante renal de doador falecido: um estudo de coorte retrospectivo

ABSTRACT Introduction: Anemia is frequent in patients undergoing replacement therapy for kidney failure. Anemia in the pre- and post-transplantation period might be related to kidney transplant outcomes. The current study therefore sought to assess the relationship between anemia, delayed allograft function (DGF), chronic kidney allograft dysfunction (CAD), and death from any cause following kidney transplantation from a deceased donor. Methods: This was a retrospective study with 206 kidney transplant patients of deceased donors. We analyzed deceased donors' and kidney transplant patients' demographic data. Moreover, we compared biochemical parameters, anemia status, and medicines between DGF and non-DGF groups. Afterward, we performed a multivariate analysis. We also evaluated outcomes, such as CAD within one year and death in ten years. Results: We observed a lower frequency of pre-transplant hemoglobin concentration (Hb) but higher frequency of donor-serum creatinine and red blood transfusion within one week after transplantation in the group with DGF. In addition, there was an independent association between Hb concentration before transplantation and DGF [OR 0.252, 95%CI: 0.159-0.401; p < 0.001]. There was also an association between Hb concentration after six months of kidney transplantation and both CAD [OR 0.798, 95% CI: 0.687-0.926; p = 0.003] and death from any cause. Conclusion: An association was found between pre-transplantation anemia and DGF and between anemia six months after transplantation and both CAD and death by any cause. Thus, anemia before or after transplantation affects the outcomes for patients who have undergone kidney transplantation from a deceased donor.

RESUMO Introdução: A anemia é frequente em pacientes submetidos à terapia substitutiva para insuficiência renal. A anemia nos períodos pré e pós-transplante pode estar relacionada aos desfechos do transplante renal. Portanto, o presente estudo buscou avaliar a relação entre anemia, função retardada do enxerto (FRE), disfunção crônica do enxerto renal (DCE) e óbito por qualquer causa após transplante renal de doador falecido. Métodos: Este foi um estudo retrospectivo com 206 pacientes transplantados renais de doadores falecidos. Analisamos dados demográficos de doadores falecidos e pacientes transplantados renais. Além disso, comparamos parâmetros bioquímicos, status de anemia e medicamentos entre os grupos FRE e não-FRE. Posteriormente, realizamos uma análise multivariada. Também avaliamos desfechos, como DCE em um ano e óbito em dez anos. Resultados: Observamos menor frequência de concentração de hemoglobina (Hb) pré-transplante, mas maior frequência de creatinina sérica do doador e transfusão de hemácias no período de uma semana após o transplante no grupo FRE. Além disso, houve associação independente entre a concentração de Hb antes do transplante e a FRE [OR 0,252; IC 95%: 0,159-0,401; p < 0,001]. Houve também associação entre a concentração de Hb após seis meses de transplante renal e ambos, DCE [OR 0,798; IC95%: 0,687-0,926; p = 0,003] e óbito por qualquer causa. Conclusão: Encontrou-se uma associação entre anemia pré-transplante e FRE e entre anemia seis meses após o transplante e ambos, DCE e óbito por qualquer causa. Assim, a anemia antes ou após o transplante afeta os desfechos de pacientes que foram submetidos a transplante renal de doador falecido.

Papel da Rigidez Aórtica na Previsão da Resposta aos Inibidores da Fosfodiesterase-5 no Tratamento da Disfunção Erétil / Role of Aortic Stiffness in Predicting Response to Phosphodiesterase-5 Inhibitors in the Treatment of Erectile Dysfunction

Resumo Fundamento: Sabe-se que a rigidez aórtica (RA) aumenta em pacientes com disfunção erétil (DE). Os inibidores da enzima fosfodiesterase tipo 5 (PDE-5) são usados no tratamento da DE, e as respostas dos pacientes a esse tratamento podem variar. Objetivos: Nosso objetivo foi investigar o papel da RA na previsão da resposta de pacientes planejados para tomar inibidores da enzima PDE-5 devido à DE. Métodos: Um total de 96 pacientes do sexo masculino com DE foram incluídos no estudo. O questionário do Índice Internacional de Função Erétil (IIEF) foi utilizado para avaliar a presença e gravidade da DE e a resposta ao tratamento. A ecocardiografia transtorácica foi utilizada para avaliar RA. Resultados: Houve diferença estatisticamente significativa entre os valores de deformação aórtica e distensibilidade aórtica dos grupos de estudo (p<0,001). O escore delta IIEF apresentou alto nível de correlação positiva com a deformação aórtica (p<0,01, r=0,758) e um nível moderado de correlação positiva com a distensibilidade aórtica (p<0,01, r=0,574). Conclusão: Determinamos que em pacientes com DE, a deformação aórtica e a distensibilidade aórtica medidas de forma não invasiva por meio de ecocardiografia transtorácica são parâmetros importantes na previsão da resposta dos pacientes à terapia com inibidores da PDE-5.

Abstract Background: It is known that aortic stiffness (AS) increases in patients with erectile dysfunction (ED). Phosphodiesterase type-5 (PDE-5) enzyme inhibitors are used in the treatment of ED, and patients' responses to this treatment may vary. Objectives: We aimed to investigate the role of AS in predicting the response of patients planned to take PDE-5 enzyme inhibitors due to ED. Methods: A total of 96 male patients with ED were included in the study. The International Index of Erectile Function (IIEF) questionnaire was used to evaluate the presence and severity of ED and the response to treatment. Transthoracic echocardiography was used to evaluate AS. Results: There was a statistically significant difference between the aortic strain and aortic distensibility values of the study groups (p<0.001). The delta IIEF score had a high level of positive correlation with aortic strain (p<0.01, r=0.758) and a moderate level of positive correlation with aortic distensibility (p<0.01, r=0.574). Conclusion: We determined that in patients with ED, aortic strain and aortic distensibility measured non-invasively using transthoracic echocardiography are important parameters in predicting patients' response to PDE-5 inhibitor therapy.

Remodelado del ventrículo izquierdo postinfarto: una mirada desde la perfusión miocárdica gated-SPECT / Left Ventricular Remodeling After Myocardial Infarction: A Perspective from Gated-SPECT Myocardial Perfusion Imaging

RESUMEN Introducción: El estudio gatillado de perfusión miocárdica con tomografía computarizada por emisión de fotón único, o gated-SPECT (por su denominación en inglés) es un método apropiado para cuantificar la magnitud de la escara necrótica y establecer su territorio. El análisis de pacientes con infartos de pequeña y mediana extensión que evolucionan con deterioro de la fracción de eyección ventricular izquierda (FEVI), podría arrojar luz acerca de los factores que influyen en la presencia de remodelado adverso y la consiguiente evolución a disfunción ventricular. Objetivos: a) evaluar la prevalencia de FEVI disminuida y factores asociados en una población de pacientes derivados para estudios de gated-SPECT, y b) definir la prevalencia de remodelado adverso y factores asociados en el subgrupo de pacientes con carga necrótica intermedia a baja. Material y métodos: Realizamos un análisis retrospectivo de pacientes consecutivos que se realizaron gated-SPECT durante el año 2017. Se excluyeron los pacientes con enfermedad valvular significativa o arritmias que produjeran alteración del gatillado. Se consideró remodelado adverso a la conjunción de FEVI disminuida (FEVI < 50%) y porcentaje de miocardio necrótico menor que 20 %. Resultados: Se incluyeron 1902 pacientes. La prevalencia de FEVI disminuida fue del 8 % (n =148). En el análisis multivariado, las variables independientes asociadas a disfunción ventricular fueron el género masculino (OR 2,50; IC 95% 1,30-4,90, p = 0,005), la diabetes (OR 1,83; IC 95% 1,12-3, p = 0,01), y compromiso necrótico mayor que 6,6 % (OR 39 IC 95% 25-61,28, p = 0,00001). En el subgrupo de pacientes con carga necrótica menor que 20% (n =197), la prevalencia de remodelado adverso fue del 25% (n =50). El análisis multivariado arrojó que la diabetes (OR 2,83; IC 95% 1,31 - 6,10 p = 0,007) y el género masculino (OR 5; IC 95% 1,10 - 22,9 p = 0,007) presentaron asociación independiente con el remodelado adverso. Conclusión: La gated-SPECT podría utilizarse en la valoración del remodelado adverso y factores asociados. Dicha valoración surge de la combinación de variables que no requieren un software adicional y se usan en la práctica diaria.

ABSTRACT Background: Gated single-photon emission computed tomography (gated-SPECT) myocardial perfusion imaging is a suitable technique for measuring the infarct scar size and defining its territory. Analyzing patients with small and medium myocardial infarctions that develop reduced left ventricular ejection fraction (LVEF) could provide additional information of the factors that contribute to adverse remodeling and its outcome. Objectives: a) To evaluate the prevalence of reduced LVEF and associated factors in a population of patients referred for gated-SPECT imaging, and b) to define the prevalence of adverse remodeling and associated factors in the subgroup of patients with intermediate to low necrotic burden. Methods: We conducted a retrospective analysis of consecutive patients undergoing gated-SPECT imaging during 2017. Patients with significant valvular heart disease or arrhythmias that could difficult adequate ECG gating were excluded from the study. Adverse remodeling was considered as the combination of reduced LVEF (LVEF < 50%) with percent myocardium scar < 20%. Results: A total of 1902 patients were included. The prevalence of reduced LVEF was 8% (n = 148). On multivariate analysis, the variables with independent association with ventricular dysfunction were male sex (OR 2.50; 95% CI 1.30-4.90, p = 0.005), diabetes (OR 1.83; 95% CI 1.12-3, p = 0.01), and percent myocardium scar > 6.6 % (OR 39; 95% CI 25-61.28, p = 0.00001). In the subgroup of patients with scar burden < 20 % (n = 197), the prevalence of adverse remodeling was 25 % (n = 50). On multivariate analysis, diabetes (OR 2.83; 95% CI 1.31 - 6.1 p = 0.007) and male sex (OR 5; 95% CI 1.1 - 22.9, p = 0.007) showed an independent association with adverse remodeling. Conclusion: Gated-SPECT could be used to assess adverse remodeling and its associated factors. This assessment is the result of combining variables used in daily practice which do not require any additional software.

Pain Patterns of the Temporomandibular Joint Dysfunction and Implications of Stress-Related Behaviors: A Pilot Study / Patrones de Dolor de la Disfunción de la Articulación Temporomandibular e Implicaciones de los Comportamientos Relacionados con el Estrés: Un Estudio Piloto

SUMMARY: Temporomandibular joint dysfunction interferes with the quality of life and activities of daily living among patients. The symptoms of temporomandibular dysfunction, including pain and clicking and popping sounds, are worsened during stressful events, and patients report increased pain around the temporomandibular joint. Stress-related behaviors, such as teeth clenching and teeth grinding, are commonly reported as increasing during stress. The prevalence of temporomandibular dysfunction and stress-related behaviors is reported differently in the literature. Stress in higher education is common. The purpose of this pilot study was to investigate the prevalence of temporomandibular joint dysfunction and stress-related behaviors among staff members at a local University. The study also sought to explore pain patterns described by people experiencing temporomandibular joint dysfunction and the relationship between stress-related behaviors and pain symptoms experienced. Further, the impact of stress on symptoms experienced by people with temporomandibular dysfunction was investigated in this pilot study.

La disfunción de la articulación temporomandibular interfiere con la calidad de vida y las actividades de la vida diaria entre los pacientes. Los síntomas de la disfunción temporomandibular, incluidos el dolor y los chasquidos, empeoran durante los eventos estresantes, y los pacientes informan un aumento del dolor alrededor de la articulación temporomandibular. Los comportamientos relacionados con el estrés, como apretar y rechinar los dientes, suelen aumentar durante el estrés. La prevalencia de la disfunción temporomandibular y los comportamientos relacionados con el estrés se informa de manera diferente en la literatura. El estrés en la educación superior es común. El propósito de este estudio piloto fue investigar la prevalencia de la disfunción de la articulación temporomandibular y los comportamientos relacionados con el estrés entre los miembros del personal de una universidad local. El objetivo del estudio además fue explorar los patrones de dolor descritos por personas que experimentan disfunción de la articulación temporomandibular y la relación entre los comportamientos relacionados con el estrés y los síntomas de dolor experimentados. Además, en este estudio piloto se investigó el impacto del estrés en los síntomas que experimentan las personas con disfunción temporomandibular.

Inhibidores de la bomba de protones: el impacto en la salud cognitiva de los adultos mayores / Proton pump inhibitors: the impact on cognitive health in older adults

RESUMEN Los inhibidores de la bomba de protones (IBP) son los medicamentos más potentes para inhibir la secreción gástrica ácida, y se utilizan en el tratamiento de la mayor parte de las afecciones inflamatorias de la mucosa gástrica. Forman parte de los fármacos más recetados y sobreprescritos en todo el mundo; por ejemplo, en los Estados Unidos, según la Encuesta nacional de salud y nutrición, casi duplicaron su uso en los adultos de 40 años de un 4,9 % hasta un 8,3 %, entre los años 1999 a 2012. Aunque, en general, se consideran bien tolerados, algunos estudios epidemiológicos ―que extraen información a partir de grandes bases de datos― han reportado una serie de efectos adversos asociados con su uso prolongado, entre los cuales están el deterioro cognitivo, la enfermedad renal crónica, el infarto de miocardio, el accidente cerebrovascular, las fracturas óseas e incluso la muerte, entre otros. El objetivo fue realizar una revisión narrativa de la literatura acerca de los efectos del uso crónico de los IBP sobre el deterioro cognitivo en los adultos mayores. Se revisaron artículos a partir de una búsqueda en las bases de datos Pudmed, Scopus y Scielo con las palabras clave y términos Mesh/DeCS relacionados tanto en inglés como en español. Los efectos secundarios a nivel neurológico inducidos por el uso crónico de los IBP pueden estar relacionados indirectamente con la presencia de alteraciones sistémicas secundarias (deficiencia de magnesio y vitamina B12) o con efectos directos sobre el funcionamiento neuronal después de pasar a través de la barrera hematoencefálica. Si bien se han descrito varios mecanismos neurobiológicos por medio de los cuales los IBP podrían favorecer el desarrollo de la demencia ―que comprenden el funcionamiento de la proteína tau, la acumulación de beta amiloide (βA) y la deficiencia de cobalamina, entre otros―, la mayor parte de la evidencia clínica disponible no ha encontrado una asociación significativa entre el uso de los IBP y el riesgo de demencia o el deterioro cognitivo. Para establecer de una manera más clara los efectos clínicos adversos del uso crónico de los IBP, en especial, en el funcionamiento cerebral, se necesitan estudios de cohorte bien diseñados, con tamaños de muestra grandes y periodos de seguimiento prolongados, con un método confiable para ajustar los factores de confusión estandarizados y, además, realizar análisis por subgrupos.

ABSTRACT Proton pump inhibitors (PPIs) are the most potent drugs to inhibit gastric acid secretion, being used in the treatment of most inflammatory conditions of the gastric mucosa. They are among the most prescribed and overprescribed medications worldwide; for example, in the United States, according to the National Health and Nutrition Examination Survey, they almost doubled their use in adults aged 40 years and older from 4.9 % to 8.3 % between 1999 and 2012. Although they are generally considered well tolerated, some epidemiological studies extracting information from large databases have reported a number of adverse effects associated with their prolonged use, including cognitive impairment, chronic kidney disease, myocardial infarction, stroke, bone fractures and even death, among others. The objective was to conduct a narrative review of the literature on the effects of chronic use of PPIs on cognitive impairment in older adults. Articles were reviewed based on a search in the PubMed, Scopus and SciELO databases using both English and Spanish keywords and related MeSH/DeCS terms. Neurological side effects induced by chronic PPI use may be indirectly related to secondary systemic disorders (magnesium and vitamin B12 deficiency) or to direct effects on neuronal functioning after passing through the blood-brain barrier. Although several neurobiological mechanisms by which PPIs could favor the development of dementia-which involve Tau protein function, beta-amyloid [βA] accumulation and cobalamin deficiency, among others-have been described, most of the available clinical evidence has not shown a significant association between PPI use and the risk of dementia or cognitive impairment. To establish the adverse clinical effects of chronic PPI use more clearly, especially on brain functioning, well-designed cohort studies with large sample sizes and long follow-up periods, with a reliable method to adjust for standardized confounders, as well as subgroup analyses are needed.

Correlato neurobiológico de los síntomas premotores del parkinson: el origen en la teoría de Braak / Neurobiological correlate of parkinson's premotor symptoms: the origin in Braak's theory / Correlação neurobiológica dos sintomas pré-motores de parkinson: a origem na teoria de Braak

El diagnóstico de enfermedad de Parkinson (ED) se basa en las principales manifestaciones motoras: bradicinesia en combinación con temblor en reposo, rigidez o ambos. Cuando se realiza el diagnóstico basado en la sintomatología motora clínica típica ya se han perdido hasta el 60 % de las neuronas dopaminérgicas de la sustancia negra pars compacta mesencefálica. La identificación de los síntomas premotores son un marcador temprano para sospechar la aparición futura de la enfermedad, así como su progresión y gravedad. La hipótesis sobre la patogénesis que mejor expone la progresión de la enfermedad es la teoría de Braak. Esta se basa en la aparición y presencia de cuerpos de Lewy en diferentes estructuras anatómicas, las cuales representadas en cada uno de sus seis estadios y podrían ser la explicación biológica de los síntomas premotores, motores y no motores. La detección temprana de los síntomas premotores puede tener repercusiones positivas en el enfoque, seguimiento, diagnóstico y tratamiento de la EP. El propósito de este artículo es identificar las aproximaciones neurológicas descritas por la teoría de Braak para los síntomas premotores de la enfermedad de Parkinson de acuerdo con la literatura publicada en los últimos 20 años.

The diagnosis of Parkinson's disease (PD) is based on the main motor manifestations: bradykinesia in combination with tremor at rest, rigidity, or both. When the diagnosis is made based on typical clinical motor symptoms, up to 60 % of the dopaminergic neurons of the mesencephalic substantia nigra pars compacta have already been lost. The identification of premotor symptoms is an early marker to suspect the future appearance of the disease, as well as its progression and severity. The hypothesis about the pathogenesis that best exposes the progression of the disease is Braak's theory. It is based on the appearance and presence of Lewy bodies in different anatomical structures, which are represented in each of its six stages and could be the biological explanation biological of premotor, motor, and non-motor symptoms. Early detection of premotor symptoms can have positive repercussions in the approach, follow-up, diagnosis and treatment of PD. The purpose of this article is to identify the neurological approaches described by Braak's theory for the premotor symptoms of Parkinson's disease according to the literature published in the last 20 years.

O diagnóstico da doença de Parkinson (DP) baseia-se nas principais manifestações motoras: bradicinesia combinada com tremor de repouso, rigidez ou ambos. Quando o diagnóstico é feito com base em sintomas clínicos motores típicos, até 60% dos neurônios dopaminérgicos da substância negra pars compacta mesencefálica já foram perdidos. A identificação de sintomas pré-motores é um marcador precoce para suspeitar do futuro aparecimento da doença, bem como da sua progressão e gravidade. A hipótese sobre a patogênese que melhor expõe a progressão da doença é a teoria de Braak. Isto se baseia no aparecimento e presença de corpos de Lewy em diferentes estruturas anatômicas, que estão representados em cada uma de suas seis etapas e podem ser a explicação biológica dos sintomas pré-motores, motores e não motores. A detecção precoce de sintomas pré-motores pode repercutir positivamente na abordagem, acompanhamento, diagnóstico e tratamento da DP. O objetivo deste artigo é identificar as abordagens neurológicas descritas pela teoria de Braak para os sintomas pré-motores da doença de Parkinson de acordo com a literatura publicada nos últimos 20 anos.

Application of Insect Medicines in Treatment of Coronary Microvascular Dysfunction Based on Comorbidity Theory of "Blood-Vessel-Cardiac Collaterals" / 中国实验方剂学杂志

Coronary microvascular dysfunction （CMD） is one of the important causes of myocardial ischemia and non-obstructive coronary artery ischemic symptoms. However， effective diagnostic methods and targeted treatment strategies for CMD are currently lacking. According to traditional Chinese medicine （TCM）， the comorbidity theory of "blood-vessel-cardiac collaterals" plays a central role throughout the entire development process of CMD. It suggests that in the clinical diagnosis and treatment of CMD， the treatment of blood， vessels， and cardiac collaterals should not be neglected. In light of this， insect medicines， known for their efficacy in promoting blood circulation， resolving stasis， and alleviating spasms， hold promise as a potential treatment for CMD. However， there is currently no research or summary on the use of insect medicines for the treatment of CMD. Therefore， this article took the comorbidity theory of "blood-vessel-cardiac collaterals" as the starting point and divided the pathogenesis of CMD into five evolution stages： Beginning in the blood （changes in blood components and hemorheology）， progressing in the vessels （atheromatous plaque formation and unstable plaques）， occurring in the cardiac collaterals （microvascular endothelial damage and microvascular constriction and spasms）， ending in the cardiac collaterals （microvascular remodeling）， and resulting in energy metabolism disorders throughout the process， so as to explore the pathogenesis and evolution of CMD. In addition， based on the modern pharmacological research on insect medicines， this article discussed the clinical application of insect medicines in the treatment of CMD from four aspects： Promoting blood circulation and removing blood stasis to relieve vessels' obstruction， relieving spasms to alleviate pain， combating poison with poison to disperse stagnation， and tonifying cardiac collaterals to nourish the heart， which aims to provide a theoretical basis for the use of TCM in treating CMD， broaden the scope of medication， and improve clinical efficacy.

Evaluation of asymptomatic ocular surface disorders in hospitalized patients with primary pterygium before surgery / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the preoperative ocular symptoms and the characteristics of asymptomatic ocular surface abnormalities in hospitalized patients with primary pterygium.METHODS: Cross-sectional study. Hospitalized patients diagnosed with primary pterygium and scheduled to receive pterygium excision surgery at the Xiamen Eye Center of Xiamen University from August 2022 to October 2022 were enrolled. Ocular surface disease index questionnaire(OSDI), six examinations including non-invasive tear film break-up time, Schirmer I test, tear meniscus height, lid margin abnormality, meibomian gland dropout and tear film lipid layer thickness, and anterior segment optical coherence tomography(AS-OCT)were performed and statistically analyzed.RESULTS: A total of 178 cases(178 eyes), with a mean age of 54.39±10.75 years old, were recruited, including 75 males(42.1%)and 103 females(57.9%). The average values of ocular surface parameters in these patients included OSDI: 11.47±9.69, tear film break-up time: 7.10±3.86 s; tear meniscus height: 0.16±0.07 mm, Schirmer I test values: 14.39±7.29 mm/5 min, and pterygium thickness: 504.74±175.87 μm. Totally 161 eyes(90.4%)presented with abnormal lid margin, 44 eyes(24.7%)presented with meibomian gland dropout score ≥4, 52 eyes(29.2%)presented with low lipid layer thickness. In the 6 objective examinations, abnormalities in at least 4 of these tests were found in 85.4% of eyes. Pterygium morphology was classified into four grades: 10 eyes(5.6%)of grade Ⅰ, 93 eyes(52.2%)of grade Ⅱ, 60 eyes(33.7%)of grade Ⅲ, and 15 eyes(8.4%)of grade Ⅳ. In patients with a higher grade of pterygium, the tear film break-up time was lower, and the proportion of abnormal lid margin was also significantly higher(P&#x0026;#x003C;0.05). The patients were further divided into two subgroups, including 121 eyes(68.0%)with normal OSDI &#x0026;#x003C;13 in the normal group and 57 eyes(32.0%)with OSDI ≥13 in the abnormal group. No significant difference was found in the proportion of meibomian gland dysfunction between the two groups of patients(71.9% vs. 71.9%, P=0.872). In addition, there were differences in the number of abnormal objective examinations(4.11±0.85 vs. 4.91±0.99, P&#x0026;#x003C;0.001).CONCLUSIONS: Asymptomatic ocular surface abnormalities were present preoperatively in patients hospitalized for primary pterygium. A comparable high incidence of structural or functional meibomian gland dysfunction existed in pterygium patients with or without apparent ocular discomfort. More attention should be paid to the ocular surface abnormalities in those asymptomatic patients before primary pterygium surgery.

Earthworm Protein Protects Vascular Endothelial Function in Spontaneously Hypertensive Rats via PI3K/Akt/Nrf2 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of earthworm protein on the expression of phosphatidylinositol 3-kinase/protein kinase B/nuclear factor E2-related factor 2 （PI3K/Akt/Nrf2） pathway in the aorta of spontaneously hypertensive rats （SHR） and explore mechanism of earthworm protein in treating hypertensive vascular endothelial dysfunction （VED）. MethodTen 10-week-old Wistar Kyoto （WKY） rats and fifty SHR rats were selected for a week of adaptive feeding. WKY rats were selected as the normal group， and fifty SHR rats were randomized according to body weight into model， valsartan （8×10-3 g·kg-1·d-1）， and high-， medium-， and low-dose （0.2， 0.1， 0.05 g·kg-1·d-1， respectively） earthworm protein groups. The normal and model groups were administrated with equal volume of double distilled water by gavage. During the drug intervention period， the general situations of rats in each group were observed and their blood pressure was monitored at specific time points every other week before and after administration. After 8 weeks of drug intervention， enzyme-linked immunosorbent assay was employed to measure the levels of angiotensin-Ⅱ （Ang-Ⅱ） and endothelin-1 （ET-1） in the serum of rats in each group. The corresponding kits were used to determine the levels of nitric oxide （NO）， malondialdehyde （MDA）， glutathione peroxidase （GPX）， superoxide dismutase （SOD）， and ferrous ion （Fe2+）. Hematoxylin-eosin （HE） staining was employed to observe the changes in the intima of the aorta. Fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA levels of PI3K， Akt， Nrf2， heme oxygenase-1 （HO-1）， and glutathione peroxidase 4 （GPX4） in the aortic tissue. Western blotting was used to determine the protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the thoracic aorta. ResultCompared with the normal group， the model group had decreased body mass， increased irritability， severe endothelial damage， elevated blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe2+ （P<0.01）， lowered NO level （P<0.01）， and down-regulated mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the aortic tissue （P<0.01）. Compared with the model group， drug intervention caused no significant change in the body mass， calmed the rats， alleviated the endothelial damage， lowered blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe2+ （P<0.01）， elevated the NO level （P<0.05）， and up-regulated the mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 （P<0.05）. ConclusionThe earthworm protein can exert antihypertensive effects by ameliorating VED in SHR. Specifically， it may regulate the PI3K/Akt/Nrf2 signaling pathway to inhibit oxidative stress and ferroptosis.

Biological principles for "homotherapy for heteropathy" / 药学学报

Non-infectious chronic diseases in human including diabetes, non-alcoholic fatty liver disease (NAFLD), atherosclerosis (AS), neurodegenerative diseases, osteoporosis, as well as malignant tumors may have some common pathogenic mechanisms such as non-resolved inflammation (NRI), gut microbiota dysfunction, endoplasmic reticulum stress, mitochondria dysfunction, and abnormality of the mammalian target of rapamycin (mTOR) pathway. These pathogenic mechanisms could be the basis for "homotherapy for heteropathy" in clinic. Some commonly used clinical drugs, such as metformin, berberine, aspirin, statins, and rapamycin may execute therapeutic effect on their targeted diseases,and also have the effect of "homotherapy for heteropathy". The mechanisms of the above drugs may include anti-inflammation, modulation of gut microbiota, suppression of endoplasmic reticulum stress, improvement of mitochondria function, and inhibition of mTOR. For virus infectious diseases, as some viruses need certain commonly used replicases, the inhibitors of the replicases become examples of "homotherapy for heteropathy" for antiviral therapy in clinic (for example tenofovir for both AIDS and HBV infection). Especially, in case of outbreak of new emerging viruses, these viral enzyme inhibitors such as azvudine and sofibuvir, could be rapidly used in controlling viral epidemic or pandemic, based on the principle of "homotherapy for heteropathy". In this review article, we show the research progress of the biological basis for "homotherapy for heteropathy" and the possible mechanisms of some well-known drugs, in order to provide insights and new references for innovative drug R&D.

Advances in Neuromuscular Electrical Stimulation in Post-Stroke Movement Disorders / 中山大学学报(医学科学版)

In recent years， the incidence of stroke patients in China is increasing， and the motor dysfunction caused by it often seriously affects the quality of daily life of the patients， Neuromuscular electrical stimulation （NMES）， as an emerging rehabilitation therapy， is widely used in the treatment of motor dysfunction in stroke patients. This paper summarizes the parameters and mechanisms of the role of NMES in motor function rehabilitation after stroke and its use in clinical practice. In the future， the specific mechanism of NMES action and efficient and safe therapeutic options should be further explored.

Research on the dynamic changes of neurological dysfunction and cognitive function impairment in traumatic brain injury / 解剖学报

Objective To explore the dynamic changes and mechanisms of neurological and cognitive functions in mice with traumatic brain injury (TBI). Methods Totally 60 12⁃month⁃old Balb/ c mice were divided into control group (10 in group) and TBI group (50 in group). TBT model mice were divided into 5 subgroups according to the time of model construction, including model 1 day, model 1 day, model 3 day, model 7 day, model 14 days and model 28 days group with 10 in each group. At the 29th day of the experiment, neurological scores and step down tests were carried out. After the test, the mice were sacrificed for brains which were detected by immunohistochemistry staining, inflammatory cytokine tests and Western blotting. Results Compared with the control group, the neurological scores of mice in TBI group increased, and then decreased after the 7th day when the scores reached the peak. However, the latency of step down errors was lower than control group, and the number of step down errors was higher than control group which had no changes. Compared with the control group, the expression of lonized calcium⁃binding adapter molecule 1(IBA1), chemokine C⁃X3⁃C⁃motif ligand1 (CX3CL1), C⁃X3⁃C chemokine receptor 1(CX3CR1), NOD⁃like receptor thermal protein domain associated protein 3 (NLRP3), and phosphorylation nuclear factor(p⁃NF)⁃κB in TBI group increased and reached to the peak at the 7th day, and then started to decrease. At the same time, the levels of inflammatory cytokines interleukin⁃6(IL⁃6) and tumor necrosis factor⁃α(TNF⁃α) first increased to the peak, and then began to decrease. However, compared with the control group, the expression of amyloid β(Aβ) protein and p⁃Tau protein in the model group continued to increase at all time. Conclusion The TBI model caused continuous activation of microglia along with inflammatory response, which first increased and then decreased, resultsing in neurological scores changes. In addition, the inflammatory response may act as a promoter of Aβ protein deposition and Tau protein phosphorylation, leading to cognitive impairment in mice.

Research progress of targeted pulmonary vascular endothelial dysfunction in treatment of pulmonary hypertension / 中国药理学通报

Pulmonary hypertension (PH) is a progressive and fatal disease. The dysfunction of pulmonary artery endothelial cells (PAECs) is one of its important pathogenic factors. PAECs are monolayer flat epithelial cells, which play an important role in maintaining pulmonary vascular homeostasis. Studies have found that PAECs show damage and apoptosis at the early stage of PH development, while PAECs show anti-apoptotic characteristics at the late stage of PH development. The transition of PAECs into mesenchymal cells induced by hypoxic and inflammatory factors is also involved in the pathogenesis of PH. Carcinoid metabolism and mitochondrial dysfunction, bone mor- phogenic type 2 receptor mutation, epigenetic changes and inflammation of PAECs are the main pathogenesis of pulmonary vascular endothelial dysfunction in PH patients. New therapeutic measures targeting PAECs dysfunction are expected to play an important role in the treatment of PH in the future.

Advances of pathogenesis and drug development in amyotrophic lateral sclerosis / 中国药理学通报

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons. ALS patients develop progressive muscle atrophy, muscle weak and paralysis, finally died of respiratory failure. ALS is characterized by fast aggression and high mortality. What' s more, the disease is highly heterogeneous with unclear pathogenesis and lacks effective drugs for therapy. In this review, we summarize the main pathological mechanisms and the current drugs under development for ALS, which may provide a reference for the drug discovery in the future.

Related factors of post-stroke depression in patients with cerebral infarction during hospitalization in rehabilitation department / 中国康复理论与实践

ObjectTo explore the risk factors related to the intensity of post-stroke depression in patients with cerebral infarction during hospitalization in the rehabilitation department. MethodsThe hospital consultation records of cerebral infarction patients in Beijing Bo'ai Hospital from December, 2019 to February, 2023 were reviewed from the hospital information system, and those who were diagnosed as depression visited the department of psychology were selected. It was collected including general information of sexes, ages, education levels, matrimony; medical features of course, location, affected side, sensory disorders, aphasia, agrypnia, dysphagia, hand-shoulder syndrome, constipation; functioning of muscle strength and Brunnstrom stages; and scores of Mini-Mental State Examination (MMSE), National Institutes of Health Stroke Scale (NIHSS), Fugl-Meyer Assessment (FMA), Fugl-Meyer Assessment-Balance (FMA-B), modified Barthel Index (MBI) and Hamilton Depression Scale (HAMD). Patients with HAMD scores ≤ 20 were as the low group, and those > 20 were as the high group. ResultA total of 2 403 hospitalized stroke patients were included, out of which 269 patients with cerebral infarction were diagnosed as depression and visited the department of psychology; while 103 cases were in the low group and 166 cases were in the high group. The incidence of constipation was less, and the incidence of dysphagia and shoulder-hand syndrome was higher in the high group (χ2 > 5.379, P < 0.05), with weaker strength of iliopsoas muscle and quadriceps muscle, earlier of Brunnstrom stage of lower extremities and hands, and worse scores of NIHSS, MMSE, FMA, FMA-B and MBI (|Z| > 2.020, t > 2.171, P < 0.05). Logistic regression showed that constipation (OR = 0.435), quadriceps muscle strength (OR = 0.782) and dysphagia (OR = 2.602) related to the intensity of post-stroke depression in convalescent patients (P < 0.05). ConclusionPost-stroke dysphagia and poor quadriceps muscle strength may exacerbate post-stroke depression; however, constipation may not.

Effect of early postoperative comprehensive rehabilitation on children and youth with supracondylar fracture of humerus complicated with ulnar nerve injury / 中国康复理论与实践

ObjectiveTo observe the therapeutic effect of early postoperative comprehensive rehabilitation on elbow joint dysfunction and ulnar nerve injury in children and adolecents with supracondylar fracture of humerus complicated with ulnar nerve injury. MethodsA total of 49 children with supracondylar fracture of humerus complicated with ulnar nerve injury after operation were selected from January, 2016 to December, 2021 in Wangjing Hospital, which were randomly divided into control group (n = 24) and treatment group (n = 25). The control group accepted wax therapy and acupuncture, and the treatment group accepted medicine fumigation, joint mobilization and electromyographic biofeedback, for twelve weeks. They were assessed with The Hospital for Special Surgery Elbow score (HSS) and Medical Research Neurotrauma Society Report (MCRR) before and after treatment. ResultsAfter treatent, the HSS scores increased in both groups (|t| > 8.345, P < 0.001). The HSS score was significantly higher in the treatment group than in the control group (t = 4.536, P < 0.001). The d-value of HSS scores before and after treatment was significantly higher in the treatment group than in the control group (t = 3.717, P < 0.05). The rate of excellent recovery of ulnar nerve function was significantly higher in the treatment group than in the control group (χ2 = 5.975, P < 0.05). ConclusionEarly postoperative comprehensive rehabilitation could romote the recovery of elbow function and ulnar nerve injury in children and youth with supracondylar fracture of humerus complicated with ulnar nerve injury.

Clinical management of chronic hepatitis B virus infection comorbid with metabolic dysfunction / 临床肝胆病杂志

With the rapid growth of metabolic dysfunction （MD） worldwide， there is also a gradual increase in the number of patients with chronic hepatitis B virus （HBV） infection and MD. Comorbidity with metabolic disorders such as hyperglycemia， hypertension， and dyslipidemia may increase the risk of adverse liver outcomes and cardiovascular events in patients with chronic HBV infection and affect the response to anti-HBV therapy. The standardized management of patients with chronic HBV infection and MD has become a challenge at present， and further in-depth research on the interaction between MD and HBV and targeted management strategies will help to optimize the clinical management of patients with chronic HBV infection.

Epidemiology and clinical outcome of chronic hepatitis B virus infection and metabolic dysfunction / 临床肝胆病杂志

Chronic hepatitis B virus （HBV） infection is a worldwide public health issue and a leading cause of liver fibrosis， liver cirrhosis， liver failure， and primary liver cancer in China. The incidence rate of nonalcoholic fatty liver disease （NAFLD） is gradually increasing with the improvement in the living standards of people and the changes in dietary structure. Population-based studies have found that HBV infection can influence the development of NAFLD， but the mechanism remains unknown. Hepatic steatosis can also influence the expression of HBV serum pathogenic indicators， and its combination with NAFLD and other metabolic dysfunction diseases can increase the risk of liver fibrosis， liver cirrhosis， and liver cancer. Chronic HBV infection is closely associated with metabolic dysfunction， and more studies are needed in the future to better understand related mechanisms， so as to provide a theoretical foundation for clinical diagnosis and treatment.

Chronic hepatitis B virus infection and metabolic associated fatty liver disease： The known and unknown aspects / 临床肝胆病杂志

Chronic hepatitis B virus （HBV） infection is the main cause of the disease burden of viral hepatitis worldwide， and meanwhile， due to changes in lifestyle and dietary habits， the incidence rate of metabolic associated fatty liver disease （MAFLD） is constantly increasing， making MAFLD the leading chronic liver disease around the world. Chronic HBV infection comorbid with MAFLD is becoming more and more common in clinical practice. Metabolic factors， rather than viral factors， are the main cause of chronic HBV infection comorbid with MAFLD. During disease progression， steatohepatitis and fibrosis， rather than steatosis， are the main influencing factors for the progression to liver cirrhosis and hepatocellular carcinoma. For patients with chronic HBV infection and MAFLD， integrated management of virus and metabolic factors is of great importance. This article reviews the tissues regarding the interaction， prognosis， and clinical management of chronic HBV infection and MAFLD.