O desmentido da privação como sintoma do discurso capitalista / Le déni de la privation comme symptôme du discours capitaliste / The denial of deprivation as a symptom of capitalist discourse

Na esteira das lógicas da economia psíquica e da economia política desenvolvidas por Freud e Lacan, tomamos como cerne um tipo de defesa que aparece em muitos casos da clínica contemporânea - o desmentido da privação - para colocar em evidência sua relação com o discurso capitalista pensado por Lacan. O desmentido da privação é um modo de defesa subjetivo que aparece como um índice do fracasso do pai privador na passagem do segundo para o terceiro tempo do complexo de Édipo. Trata-se de uma forma de se defender da castração buscando satisfação pulsional sem mediação simbólica ­ busca essa que é fracassada e extrapola o princípio de prazer. Conclui-se que esse desmentido contemporâneo é um sintoma do próprio discurso capitalista. Se a for aclusão da castração no discurso capitalista é uma promessa igualmente fracassada, o desmentido da privação aparece na subjetividade tentando solucionar esse fracasso. Ele é um sinal de que o discurso capitalista não cumpre sua promessa - e isso por sua própria engrenagem lógica.

Dans le sillage des logiques d'économie psychique et d'économie politique développées par Freud et Lacan, nous nous concentrons sur un type de défense qui apparaît dans de nombreux cas de pratique clinique contemporaine - le déni de la privation - pour mettre en évidence sa relation avec le discours capitaliste d' accord avec ce qui fut pensé par Lacan. Le déni de la privation est une défense subjective qui apparaît comme un indice de l'échec du père qui prive dans le passage du deuxième au troisième stade du complexe d'Œdipe. C'est une manière de se défendre de la castration en recherchant une satisfaction pulsionnelle sans médiation symbolique ­ une recherche qui échoue et dépasse le principe du plaisir. Nous concluons que ce déni contemporain est un symptôme du discours capitaliste lui-même. Si la for clusion de la castration dans le discours capitaliste est une promesse également ratée, le déni de la privation apparaît dans la subjectivité qui tente de résoudre cet échec. C'est le signe que le discours capitalistene tient pas ses promesses - et cela par sa propre logique.

Following the logics of psychic economy and political economy developed by Freud and Lacan, we target a type of defense that appears in many cases of contemporary clinical practice - the denial of deprivation - to highlight its relationship with the capitalist discourse as thought by Lacan. The denial of deprivation is a subjective defense that appears as an index of the failure of the depriving father in the transition from the second to the third stage of the Oedipus complex. It is a way of defending oneself from castration by seeking instinctual satisfaction without symbolic mediation ­ a search that fails and goes beyond the pleasure principle. The conclusion is that this contemporary denial is a symptom of capitalist discourse itself. If the foreclosure of castration in capitalist discourse is an equally failed promise, the denial of deprivation appears in subjectivity trying to resolve this failure. It is a sign that capitalist discourse does not fulfill its promise - and this by its own logical perspective.

Pharmacotherapy plan for metastatic hormone-sensitive prostate cancer：a network meta-analysis / 中国药房

OBJECTIVE To determine the optimal therapeutic plan for metastatic hormone-sensitive prostate cancer （mHSPC）， and to provide reference for clinical decision-making. METHODS Retrieved from Medline， Embase， BIOSIS preview， the Cochrane Library and ClinicalTrials. gov systematically， randomized controlled trials about mHSPC therapy， with overall survival （OS） and radiographic progression-free survival （rPFS） as efficacy outcomes and the incidence of serious adverse events （SAEs） as safety outcome， were collected during the inception-Mar. 2022. Two researchers independently screened the literature， extracted data， and evaluated the risk of bias for the included study before conducting a Bayesian network meta-analysis. RESULTS Eight studies with 9 437 patients were finally included. The effectiveness and safety of 7 therapy plans were compared [abiraterone acetate， apalutamide， darolutamide+docetaxel， docetaxel， enzalutamide， standard non-steroidal antiandrogen （SNA） in addition to ADT， and ADT alone]. In terms of efficacy index， the most beneficial regimen （except for ADT+SNA） for OS was ADT+darolutamide+docetaxel （HR＝0.54， 95%CI of 0.44-0.66）， followed by ADT+abiraterone acetate （HR＝0.64，95%CI of 0.57- 0.71）， apalutamide （HR＝0.65， 95%CI of 0.53-0.79）， enzalutamide （HR＝0.66， 95%CI of 0.53-0.82）； the least beneficial regimen for OS was ADT+docetaxel （HR＝0.79， 95%CI of 0.71-0.88）. The most beneficial regimen （except for ADT+SNA） for rPFS was ADT+enzalutamide （HR＝0.39， 95%CI of 0.30-0.50）， followed by ADT+apalutamide （HR＝0.48， 95%CI of 0.39- 0.60）， abiraterone acetate （HR＝0.57， 95%CI of 0.51-0.64）， docetaxel （HR＝0.62， 95%CI of 0.56-0.69）. The results of the tumor- loading subgroup analysis were the same. In terms of safety， ADT+darolutamide+docetaxel （OR＝25.86， 95%CI of 14.08-51.33）， and ADT+docetaxel （OR＝23.35， 95%CI of 13.26-44.81） were associated with markedly increased SAEs； the incidence of SAEs caused by ADT+abiraterone acetate （OR＝1.42，95%CI of 1.10-1.82） was slightly increased， and those of other therapy plans had no significant difference. CONCLUSIONS Compared with ADT alone， ADT+ darolutamide+docetaxel may provide the most significant OS benefit， but the incidence of SAEs is increased greatly； compared with ADT+docetaxel， ADT+abiraterone acetate， apalutamide or enzalutamide provide more OS benefits. ADT+enzalutamide provide optimal rPFS benefits with no increased SAEs.

Effect of Salvianolic Acid B Combined with Puerarin on Pyroptosis of SH-SY5Y Cells Injured by Oxygen-glucose Deprivation/Reoxygenation / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of salvianolic acid B combined with puerarin in protecting the SH-SY5Y cells from the damage by oxygen-glucose deprivation/reoxygenation （OGD/R） based on pyroptosis. MethodSH-SY5Y cells were used to establish the model of OGD/R， and cells were classified into the control， OGD/R， 10 μmol·L-1 salvianolic acid B， 100 μmol·L-1 puerarin， 10 μmol·L-1 salvianolic acid B + 100 μmol·L-1 puerarin， and 10 μmol·L-1 NOD-like receptor protein 3 （NLRP3） inhibitor MCC950 groups. Except the control group， other groups were rapidly reoxygenated for 12 h after 6 h OGD for modeling. The cell survival rate was determined by the methyl thiazolyl tetrazolium （MTT） assay. An optical microscope was used to observe the cell morphology. A spectrophotometer was used to determine the content of lactic dehydrogenase （LDH） in culture supernatant. Cell damage was measured by Hoechst/PI staining. The mRNA levels of NLRP3， cysteinyl aspartate specific proteinase-1 （Caspase-1）， gasdermin D （GSDMD）， apoptosis-associated speck-like protein （ASC）， and interleukin-1β （IL-1β） were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein activation of Caspase-1 and NLRP3 was detected by immunofluorescence. Western blot was employed to determine the protein levels of IL-1β， ASC， NLRP3， Caspase-1， and cleaved Caspase-1. ResultCompared with the control group， the OGD/R group showed decreased cell survival rate （P<0.01）， damaged cell morphology， increased leakage rate of LDH （P<0.01）， up-regulated mRNA levels of NLRP3， Caspase-1， GSDMD， ASC， and IL-1β （P<0.01）， and up-regulated protein levels of IL-1β， ASC， NLRP3， Caspase-1， and cleaved Caspase-1 （P<0.01）. Compared with the OGD/R group， salvianolic acid B， puerarin， and salvianolic acid B combined with puerarin improved cell survival rate （P<0.01）， and the combined treatment group outperformed salvianolic acid B and puerarin used alone （P<0.01）. Salvianolic acid B combined with puerarin and MCC950 both improved cell morphology， reduced the leakage of LDH （P<0.01）， alleviated cell damage， and down-regulated the mRNA levels of NLRP3， Caspase-1， GSDMD， ASC， and IL-1β （P<0.05， P<0.01） and also the protein levels of IL-1β， ASC， NLRP3， Caspase-1， and cleaved Caspase-1 （P<0.05， P<0.01）. ConclusionThe results indicated that salvianolic acid B combined with puerarin can alleviate the OGD/R-induced damage of SH-SY5Y cells by inhibiting pyroptosis.

Association between sleep duration and latency, nocturnal awakenings, and body mass index among infants / Associação entre duração e latência do sono, despertares noturnos e índice de massa corporal de lactentes

ABSTRACT Objective: To investigate the association between sleep duration, nocturnal awakenings, and sleep latency with body mass index (BMI) at six and 12 months of age. Methods: 179 children from a birth cohort were enrolled. At six and 12 months of age, anthropometric data were obtained using standardized techniques and infants' mothers answered the Brief Infant Sleep Questionnaire for sleep data. The association of BMI with the independent variables (sleep duration, latency, and nocturnal awakenings) was assessed by linear regression models. Analyses were adjusted for potential confounders and a p-value<0.05 was adopted to define statistical significance. Results: For each additional hour of sleep duration, BMI was reduced by 0.15 kg/m² (95% confidence interval [CI] -0.28; -0.01; p=0.03) and each additional minute of sleep latency increased BMI by 0.01 kg/m² (95%CI -0.00; 0.03; p=0.02). These associations were independent of gestational age, child sex, birth weight, duration of exclusive breastfeeding, smoking during pregnancy, and mother's BMI, education, and marital status. Nocturnal awakenings showed no association with the outcome. Conclusions: Our findings suggest that sleep duration and sleep latency time are associated with BMI in the first year of life. Insights into the influence of sleep early in life on weight status may be helpful to complement future nutritional recommendations and prevent and treat obesity.

RESUMO Objetivo: Investigar a associação entre duração do sono, despertares noturnos e latência do sono com o índice de massa corporal (IMC) aos seis e 12 meses de idade. Métodos: foram incluídas 179 crianças de uma coorte de nascimentos. Aos seis e 12 meses de idade, dados antropométricos foram obtidos por meio de técnicas padronizadas e as mães dos lactentes responderam ao Brief Infant Sleep Questionnaire para dados do sono. A associação do IMC com as variáveis independentes (duração do sono, latência e despertares noturnos) foi avaliada por modelos de regressão linear. As análises foram ajustadas para potenciais fatores de confusão e o p-valor<0,05 foi adotado para definir a significância estatística. Resultados: Para cada hora adicional de duração do sono, o IMC foi reduzido em 0,15 kg/m² (intervalo de confiança [IC]95% -0,28; -0,01; p=0,03) e cada minuto adicional no tempo de latência resultou em aumento de 0,01 kg/m² (IC95% -0,00; 0,03; p=0,02) no IMC. Essas associações foram independentes da idade gestacional, sexo da criança, peso ao nascer, duração do aleitamento materno exclusivo, tabagismo durante a gravidez e IMC, escolaridade e estado civil da mãe. Os despertares noturnos não apresentaram associação com o desfecho. Conclusões: Nossos achados sugerem que a duração e a latência do sono estão associadas ao IMC no primeiro ano de vida. Informações sobre a influência do sono no início da vida sobre o status do peso podem ser úteis para complementar futuras recomendações nutricionais e prevenir e tratar a obesidade.

Hunger in Brazil: Notes on the narratives in the Folha de São Paulo newspaper during the 2020 pandemic period / A fome no Brasil: notas sobre as narrativas no jornal Folha de São Paulo no período pandêmico de 2020

ABSTRACT Objective This survey aims atreviewing the journalistic narratives of the newspaper Folha de São Paulo (digital edition) about hunger in Brazil during the 2020 pandemic period. It is known that journalism plays an important role in keeping the public informed and in helping to contribute to the shaping of society's opinion. Despite hunger being a structural phenomenon in this country, little is published in the mainstream media discussing the magnitude of the problem and the articulation of measures taken in the three government spheres (federal, state and municipal), to ensure access to food to the most vulnerable populations. Method News excerpts addressing hunger as the main topic were selected from Folha de São Paulo daily newspaper and were highlighted based on reading keys (n=11, published between March and December 2020). Results In all the selected articles, the newspaper addressed the cause of hunger from the perspective of the pandemic (passing event and manifestation). Issues linked to the economic and social crisis experienced in the country were not emphasized. This form of covering hunger in news articles can enhance the idea that the poor are the result of the currently spreading fatality. Conclusion Finally, from these first results we could infer that the newspaper, when addressing hunger in Brazil in the first months of the COVID-19 pandemic, sought to construct a biased reality that hunger was derived from the health crisis, at the same time that it presents the hungry people narratives as a discursive strategy to sensitize the reader to Folha de São Paulo intentions.

RESUMO Objetivo A nota tem como objetivo examinar as narrativas jornalísticas do jornal Folha de São Paulo (digital) sobre a fome no Brasil, no período pandêmico de 2020, uma vez que se compreende que as narrativas jornalísticas têm um papel importante na formação de opinião da sociedade. Apesar da fome ser um fenômeno estrutural no país, pouco se vê nos grandes meios de comunicação o debate sobre a magnitude dos problemas e articulação de medidas governamentais nas três esferas de gestão (federal, estadual e municipal), que possam assegurar o acesso à alimentação adequada e saudável dos mais vulneráveis. Método Foram selecionadas notícias na Folha de São Paulo que tratavam da fome como pauta principal, sendo analisadas com base em chaves de leitura (n=11, divulgadas entre março e dezembro de 2020). Resultados Em todas as matérias selecionadas o jornal abordou a causa da fome a partir da perspectiva da pandemia (acontecimento e manifestação passageira). As questões vinculadas à crise econômica e social vivenciada no país não foram enfatizadas. A forma de acionar os famintos nas matérias pode reforçar a ideia de que os pobres são fruto da fatalidade que se propaga. Conclusão Por fim, os resultados iniciais permitem inferir que o jornal ao editar a fome no Brasil, no primeiro ano da pandemia de COVID-19, procurou construir uma realidade enviesada de que a fome é derivada de uma crise sanitária ao mesmo tempo que apresenta as narrativas dos famintos como estratégia discursiva para sensibilizar o leitor em relação às suas intenções.

Avaliação da qualidade do sono e sonolência diurna de um grupo de idosos / Assessment of sleep quality and daytime sleepiness in a group of elderly people

O objetivo do estudo foi avaliar a qualidade do sono e sonolência diurna de um grupo de idosos, verificar se há associação com prática de atividade física, presença de doença crônica, e Índice de Massa Corporal (IMC) e se há correlação com IMC, idade e qualidade de vida. Trata-se de um estudo transversal e descritivo. Para avaliação da qualidade do sono utilizou-se o Pittsburgh Sleep Quality Index (PSQI), para avaliação da sonolência diurna a Escala de Sonolência de Epworth (ESE) e para avaliação da qualidade de vida o WHOQOL-BREF. Foram avaliados 47 idosos com mediana (intervalo interquartil 25-75%) de 66 (62-70) anos de idade e IMC de 28,58 (26,21-30,44). 74,5% apresentaram sono ruim, 61,7% apresentaram Sonolência Diurna Normal e 97,8% classificados com boa qualidade de vida, com destaque para os domínios relações sociais (80%) e autoavaliação da qualidade de vida (80%). Apenas apresentou associação estatisticamente significativa a presença de qualidade de sono ruim com a prática de atividade física. Não houve associação entre presença de qualidade de sono ruim ou sonolência com IMC e presença de doença crônica. Houve uma correlação fraca, negativa e estatisticamente significativa apenas entre qualidade do sono com qualidade de vida (ρ=-0,466) e idade (ρ=-0,297). Conclui-se que os idosos apresentaram qualidade do sono ruim, sonolência diurna normal e qualidade de vida geral boa.

The objective of the study was to evaluate the quality of sleep and daytime sleepiness of a group of elderly people, checking whether there is an association with physical activity, presence of chronic disease, and Body Mass Index (BMI) and whether there is a correlation with BMI, age and quality of life. This is a cross-sectional and descriptive study. To assess sleep quality, the Pittsburgh Sleep Quality Index (PSQI) was used, the Epworth Sleepiness Scale (ESE) was used to assess daytime sleepiness, and the WHOQOL-BREF was used to assess quality of life. 47 elderly people were evaluated with a median (interquartile range 25-75%) of 66 (62-70) years of age and BMI of 28.58 (26.21-30.44). 74.5% had poor sleep, 61.7% had Normal Daytime Sleepiness and 97.8% classified as having a good quality of life, with emphasis on the domains of social relationships (80%) and self-assessment of quality of life (80%). There was only a statistically significant association between the presence of poor sleep quality and the practice of physical activity. There was no association between the presence of poor sleep quality or sleepiness with BMI and the presence of chronic disease. There was a weak, negative and statistically significant correlation only between sleep quality and quality of life (ρ=-0.466) and age (ρ=- 0.297). It is concluded that the elderly had poor sleep quality, normal daytime sleepiness and good general quality of life.

Background cardiovascular risk factors in patients of metastatic prostate cancer on androgen deprivation therapy: A retrospective observational study from a tertiary care hospital of Eastern India

Background: Androgen deprivation therapy (ADT) is indispensable part of treatment for metastatic prostate cancer (MPC) patients. There is documented association between ADT and adverse cardiovascular (CV) events, with variability between the different modes. However, there is dearth of evidence on the background CV risk factors of these group of patients at diagnosis. Aims and Objectives: We envisaged this retrospective observational study in the department of oncology to document the background CV risk factors of MPC patients at diagnosis, to help us better select the available ADTs based on their CV risks. Materials and Methods: Over a period of 2 years, all patients registered for treatment with a diagnosis of MPC, indicated for ADT, and available detailed history and background cardiological evaluation at presentation, were included in the study. As indirect indicators of CV risks, history of smoking, presence and treatment of dyslipidemia, and type 2 diabetes mellitus (T2DM), were documented. As direct indicators of CV risks, presence and treatment of hypertension, ischemic heart disease (IHD), congestive cardiac failure (CCF), ECG, and echocardiography changes suggesting cardiac morbidity were documented and the data were analyzed using descriptive statistical methods. Results: Indirect indicators: dyslipidemia, habit of smoking, and T2DM were found in 74%, 29.3%, and 13.3% patients, respectively. Direct indicators: Presence of hypertension, IHD, CCF, abnormalities in ECG, and echocardiography were found in 38.7%, 10.6%, 4%, 28%, and 34.6% patients, respectively. ST-T changes on ECG, low EF, and IHD on echocardiography were seen in 28.5%, 23%, and 26.9%, respectively. Conclusions: MPC patients have a substantial pre-existing CV risk at diagnosis. Our findings warrant a meticulous screening of all MPC patients for CV risk factors, to help in judicious selection of their ADT.

Changing Sleep Patterns and Anxiety due to Covid?19 Home Confinement among Working Population: A Cross?Sectional Study

Introduction: The COVID?19 pandemic took the entire world unawares and people were forced to stay indoors overnight. Due to this a drastic change ensued in lifestyle with many succumbing to various kinds of stresses and psychological problems. This study aims to study the changing sleep patterns and level of anxiety among the working population due to the COVID?19 Pandemic lockdown. Methodology: An online survey was conducted using a cloud?based website. The sleep patterns both prior to and during the lockdown period of the pandemic were assessed using a self?administered questionnaire. The level of anxiety during both these periods (before and during lockdown) amongst the working population was also assessed using the Generalized Anxiety Disorder Scores (GADS). Results: A total of 224 individuals participated in the study of which 52.7% were males and 47.3% were females. On analysis, the lifestyle and sleep deprivation scores showed that before the lockdown only 2.7% reported a low score out of total participants. However, this number was raised to 13.4% during the lockdown. The percentage of people reporting deteriorated sleep quality gradually increased with females reporting moderate to severe category of Generalized Anxiety Disorder scores as compared to Males. Conclusion: The study suggests that there has been a significant change in the sleep quality of the study participants due to Covid enforced lockdown which if unnoticed might lead to significant health problems. The effective use of programs like yoga, meditation, and deep breathing exercises, if followed timely could reduce psychological distress to some extent.

Molecular mechanism of sleep deprivation-induced body injury and traditional Chinese medicine prevention and treatment: a review / 中国中药杂志

Sleep occupies one-third of a person's lifetime and is a necessary condition for maintaining physiological function and health. With the increase in social and economic pressures, the growing use of electronic devices and the accelerated aging process of the population, insufficient sleep and its hazards have drawn widespread attention from researchers in China and abroad. Sleep deprivation refers to a decrease in sleep or a severe lack of sleep due to various reasons. Previous studies have found that sleep deprivation can cause extensive damage to the body, including an increased incidence and mortality rate of neuropathic diseases in the brain, cardiovascular diseases, imbalances in the gut microbiota, and other multi-organ diseases. The mechanisms underlying the occurrence of multi-system and multi-organ diseases due to sleep deprivation mainly involve oxidative stress, inflammatory responses, and impaired immune function in the body. According to traditional Chinese medicine(TCM), sleep deprivation falls into the category of sleepiness, and long-term sleepiness leads to Yin-Yang imbalance, resulting in the consumption of Qi and damage to the five Zang-organs. The appropriate treatment should focus on tonifying deficiency, reinforcing healthy Qi, and harmonizing Yin and Yang. TCM is characterized by a wide variety and abundant resources, and it has minimal side effects and a broad range of applications. Numerous studies have shown that TCM drugs and prescriptions not only improve sleep but also have beneficial effects on liver nourishment, intelligence enhancement, and kidney tonification, effectively preventing and treating the body injury caused by sleep deprivation. Given the increasing prevalence of sleep deprivation and its significant impact on body health, this article reviewed sleep deprivation-mediated body injury and its mechanism, summarized and categorized TCM compound prescriptions and single drugs for preventing and treating body injury, with the aim of laying the foundation for researchers to develop effective drugs for preventing and treating body injury caused by sleep deprivation and providing references for further exploration of the molecular mechanisms underlying the body injury caused by sleep deprivation.

Mechanism of astragaloside Ⅳ in regulating autophagy of PC12 cells under oxygen-glucose deprivation by medicating Akt/mTOR/HIF-1α pathway / 中国中药杂志

This study explored the protective effect of astragaloside Ⅳ(AS-Ⅳ) on oxygen-glucose deprivation(OGD)-induced autophagic injury in PC12 cells and its underlying mechanism. An OGD-induced autophagic injury model in vitro was established in PC12 cells. The cells were divided into a normal group, an OGD group, low-, medium-, and high-dose AS-Ⅳ groups, and a positive drug dexmedetomidine(DEX) group. Cell viability was measured using the MTT assay. Transmission electron microscopy was used to observe autophagosomes and autolysosomes, and the MDC staining method was used to assess the fluorescence intensity of autophagosomes. Western blot was conducted to determine the relative expression levels of functional proteins LC3-Ⅱ/LC3-Ⅰ, Beclin1, p-Akt/Akt, p-mTOR/mTOR, and HIF-1α. Compared with the normal group, the OGD group exhibited a significant decrease in cell viability(P<0.01), an increase in autophagosomes(P<0.01), enhanced fluorescence intensity of autophagosomes(P<0.01), up-regulated Beclin1, LC3-Ⅱ/LC3-Ⅰ, and HIF-1α(P<0.05 or P<0.01), and down-regulated p-Akt/Akt and p-mTOR/mTOR(P<0.05 or P<0.01). Compared with the OGD group, the low-and medium-dose AS-Ⅳ groups and the DEX group showed a significant increase in cell viability(P<0.01), decreased autophagosomes(P<0.01), weakened fluorescence intensity of autophagosomes(P<0.01), down-regulated Beclin1, LC3-Ⅱ/LC3-Ⅰ, and HIF-1α(P<0.05 or P<0.01), and up-regulated p-Akt/Akt and p-mTOR/mTOR(P<0.01). AS-Ⅳ at low and medium doses exerted a protective effect against OGD-induced autophagic injury in PC12 cells by activating the Akt/mTOR pathway, subsequently influencing HIF-1α. The high-dose AS-Ⅳ group did not show a statistically significant difference compared with the OGD group. This study provides a certain target reference for the prevention and treatment of OGD-induced cellular autophagic injury by AS-Ⅳ and accumulates laboratory data for the secondary development of Astragali Radix and AS-Ⅳ.

Stigmasterol protects human brain microvessel endothelial cells against ischemia-reperfusion injury through suppressing EPHA2 phosphorylation / 中国天然药物

Stigmasterol is a plant sterol with anti-apoptotic, anti-oxidative and anti-inflammatory effect through multiple mechanisms. In this study, we further assessed whether it exerts protective effect on human brain microvessel endothelial cells (HBMECs) against ischemia-reperfusion injury and explored the underlying mechanisms. HBMECs were used to establish an in vitro oxygen and glucose deprivation/reperfusion (OGD/R) model, while a middle cerebral artery occlusion (MCAO) model of rats were constructed. The interaction between stigmasterol and EPHA2 was detected by surface plasmon resonance (SPR) and cellular thermal shift assay (CETSA). The results showed that 10 μmol·L-1 stigmasterol significantly protected cell viability, alleviated the loss of tight junction proteins and attenuated the blood-brain barrier (BBB) damage induced by OGD/R in thein vitro model. Subsequent molecular docking showed that stigmasterol might interact with EPHA2 at multiple sites, including T692, a critical gatekeep residue of this receptor. Exogenous ephrin-A1 (an EPHA2 ligand) exacerbated OGD/R-induced EPHA2 phosphorylation at S897, facilitated ZO-1/claudin-5 loss, and promoted BBB leakage in vitro, which were significantly attenuated after stigmasterol treatment. The rat MCAO model confirmed these protective effects in vivo. In summary, these findings suggest that stigmasterol protects HBMECs against ischemia-reperfusion injury by maintaining cell viability, reducing the loss of tight junction proteins, and attenuating the BBB damage. These protective effects are at least meditated by its interaction with EPHA2 and inhibitory effect on EPHA2 phosphorylation.

Mechanism of Gastrodia elata active ingredient reducing oxygen-glucose deprivation/reoxygenation injury in rat neuron / 中国药房

OBJECTIVE To study the improvement effect and mechanism of Gastrodia elata active ingredient 3，4- dihydroxybenzaldehyde （3，4-DD） on oxygen-glucose deprivation/reoxygenation（OGD/R） injury in rat primary brain microvascular endothelial cells （BMECs）-rat adrenal chromaffin cells PC12 co-culture system. METHODS The co-culture model of BMECs and PC12 cells was replicated in the Transwell chamber， and divided into control group， model group， butylphthalide group （positive control group， 0.1 mmol/L） and 3，4-DD group （0.1 μmol/L）. OGD/R injury model of the co-culture system was induced in those groups except for the control group. After preventively intervention in BMECs with relevant medicine or culture medium for 24 h， cell transendothelial electronic resistance （TEER） value， lactate dehydrogenase （LDH） activity， brain-derived neurotrophic factor （BDNF） level and mRNA expressions of TrkB， Plc-γ， Map-2， GAP-43 in PC12 cells was detected. RESULTS Compared with the control group， TEER of the co-culture model， LDH activity and BDNF level of PC12 cells were decreased significantly in the model group （P＜0.01）， while mRNA expressions of TrkB， Plc-γ， Map-2 and GAP-43 in PC12 cells were increased significantly （P＜0.01）. Compared with the model group， TEER of the co-culture model， LDH activity， BDNF level， and the mRNA expressions of TrkB， Plc-γ， Map-2 and GAP-43 in PC12 cells were increased significantly in the 3，4-DD group and butylphthalide group （P＜0.05 or P＜0.01）. CONCLUSIONS 3，4-DD can relieve the damage of neuronal OGD/R by acting on BMECs， the mechanism of which may be associated with activating the BDNF/TrkB signaling pathway.

Effect of Huanglian Ejiaotang on 5-Hydroxytryptamine System and Gut Microbiota in Sleep-deprived Rats / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Huanglian Ejiaotang in intervening in insomnia based on 5-hydroxytryptamine （5-HT） system and gut microbiota. MethodFifty-five SPF-grade SD rats were randomly divided into normal group， model group， low-， medium-， and high-dose Huanglian Ejiaotang groups （1.925， 3.85， and 7.7 g·kg-1）， and Estazolam group （0.1 mg·kg-1）. Except for those in the normal group， the rats in the other five groups were subjected to sleep deprivation on a narrow platform for 12 hours daily for 21 consecutive days. After 14 days of drug intervention， the sleep， exploratory behavior， and depressive-like behavior of the rats were assessed using the pentobarbital sodium sleep synergistic test， the open field test， and the sugar preference test， respectively. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of 5-HT， 5-hydroxyindoleacetic acid （5-HIAA）， tryptophan hydroxylase （TPH）， and monoamine oxidase-A （MAO-A）. Real-time polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression of the 5-HT1A receptor （5-HT1AR） and 5-HT2A receptor （5-HT2AR）. Differences in gut microbiota among the groups were assessed using 16S rRNA sequencing， and the correlation between the 5-HT system and microbiota was revealed using redundancy analysis. ResultCompared with the normal group， the model group showed a prolonged sleep latency （P<0.05）， reduced sleep maintenance （P<0.01）， decreased central area activity time in the open field （P<0.01）， and reduced sugar preference rate （P<0.05）. Moreover， the model group also showed decreased levels of 5-HT， 5-HIAA， TPH， and MAO-A （P<0.01）， decreased 5-HIAA/5-HT ratio （P<0.01）， downregulated mRNA expression of 5-HT1AR （P<0.01）， and upregulated mRNA expression of 5-HT2AR （P<0.05）. The proportion of Firmicutes decreased， while that of Bacteroidetes increased， leading to a decreased Firmicutes/Bacteroidetes （F/B） ratio （P<0.05）. Compared with the model group， the high-dose Huanglian Ejiaotang group exhibited a shortened sleep latency （P<0.01）， and increased sleep maintenance （P<0.01）. The low-dose Huanglian Ejiaotang group showed increased central area activity time （P<0.01） and an increased sugar preference rate （P<0.05）. The high-dose Huanglian Ejiaotang group exhibited increased levels of 5-HT， 5-HIAA， TPH， and MAO-A （P<0.01）， increased 5-HIAA/5-HT ratio （P<0.05）， upregulated mRNA expression of 5-HT1AR （P<0.01）， and downregulated mRNA expression of 5-HT2AR （P<0.05）. The low-dose Huanglian Ejiaotang group displayed an increased proportion of Firmicutes and a decreased proportion of Bacteroidetes， resulting in an increased F/B ratio. At the phylum level， 5-HT， 5-HIAA， and MAO-A were positively correlated with Firmicutes and negatively correlated with Bacteroidetes. At the genus level， 5-HT， 5-HIAA， TPH， and MAO-A were negatively correlated with Prevotella and Lactobacillus and positively correlated with Blautia and Bacteroides. ConclusionHuanglian Ejiaotang can improve sleep deprivation-induced insomnia and depressive-like behavior by regulating the activity of the 5-HT system and the composition of gut microbiota.

Effect of sleep on brain clearing metabolites: thinking based on lymphoid system / 中华神经科杂志

Disruption of the structure of regular sleep is a common cause of neurodegenerative diseases such as Alzheimer′s disease and Parkinson′s disease, and its pathogenesis may be related to the deposition of waste products in the central nervous system. The glymphatic pathway, which is essentially a periarterial cerebrospinal fluid inflow pathway and peripheral venous clearance pathway, is functionally dependent on interstitial bulk flow coupling supported by aquaporin-4 on the astrocyte end-foot, also known as the lymphoid glial system. The glymphatic pathway, which removes waste proteins from the brain, is active primarily during sleep, and sleep quality declines with age, while the glymphatic pathway system also deteriorates with age, suggesting a relationship between sleep disturbances and symptom progression in neurodegeneration, and glymphatic system as a link closely links the two. The interaction of sleep, aging, metabolic waste and glymphatic pathway reticulation provides new clues to the pathogenesis of central nervous system degenerative diseases, and the glymphatic pathway may constitute a new target on treatment. The recent research progress on the effects of sleep and sleep disorders on the circulation of the glymphatic system, and proposes the possibility of sleep intervention to slow down the impairment of the lymphoid system function or even restore the function of the lymphoid system and thus improve the disease development process were reviewed in this paper.

Melatonin attenuates bone resorption induced by acute sleep deprivation in growing rats / 中华内分泌代谢杂志

Objective:To explore the changes of bone turnover markers induced by sleep deprivation (SD) and the effect of melatonin supplementation on the bone turnover status.Methods:Six-week-old Wistar male rats were divided into SD, normal control (NC), and melatonin supplementation (SD+ MT) groups. Acute SD model was established using a modified multi-level bench method. The bone turnover markers, corticosterone, and melatonin in serum as well as Cathepsin K(CTSK) mRNA expression in bone tissue were tested.Results:Acute SD disrupted the balance between bone formation and bone absorption evidenced by rapid decreased serum procollagen type Ⅰ N-terminal propeptide (PⅠNP) levels and increased β cross-linked C-telopeptide of type Ⅰ collagen (β-CTX) levels ( P=0.003) from 24 h to 72 h. The exogenous melatonin treatment decreased β-CTX [(512.4±95.8) ng/mL vs (696.0±76.5) ng/mL, P=0.004] and the osteoclast-related gene CTSK mRNA level after 72 h SD. Conclusions:Acute SD accelerates bone resorption, which could be partially alleviated by melatonin supplementation.

Role of Homer1a/mGluR5 signaling pathway in cognitive dysfunction induced by sleep deprivation in aged rats / 中华麻醉学杂志

Objective:To evaluate the role of Homer1a/metabotropic glutamate receptor 5 (mGluR5) signaling pathway in sleep deprivation-induced cognitive dysfunction in aged rats.Methods:One hundred and four SPF healthy male Sprague-Dawley rats, aged 22-24 months, weighing 320-360 g, were divided into 4 groups ( n=26 each) using a random number table method: normal control group (group Control), sleep deprivation+ vehicle group (group SD+ Vehicle), sleep deprivation+ mGluR5 forward allosteric agent CDPPB group (group SD+ CDPPB), and sleep deprivation+ mGluR5 antagonist MPEP group (group SD+ MPEP). A 48-h sleep deprivation model was developed by sleep-deprived rod method. At the beginning of developing the model and 24 h after developing the model, CDPPB 10 mg/kg, MPEP 10 mg/kg and the equal volume of 1% Tween 80 were intraperitoneally injected in group SD+ CDPPB, group SD+ MPEP and group SD+ Vehicle, respectively.Morris water maze and novel object recognition tests were conducted to evaluate cognitive function after development of the model. The expression of Homer1a and mGluR5 in the hippocampus was detected by Western blot, the dendritic spine density in the hippocampal CA1 region was detected by Golgi staining, and the field excitatory postsynaptic potential (fEPSP) slope in the hippocampal CA1 region was detected by isolated electrophysiology. Results:Compared with Control group, the number of crossing the original platform, time of staying at the target quadrant, and novel object recognition index at 1 and 24 h after training were significantly decreased, the expression of Homer1a in the hippocampus was up-regulated, the expression of mGluR5 in the hippocampus was down-regulated, and the density of dendritic spine and fEPSP slope in the hippocampal CA1 region were decreased in group SD+ Vehicle ( P<0.05). Compared with group SD+ Vehicle, the number of crossing the original platform, time of staying at target quadrant, and novel object recognition index at 1 and 24 h after training were significantly increased, the expression of mGluR5 in hippocampus was up-regulated, and the density of dendritic spines and fEPSP slope in the hippocampal CA1 region were increased in group SD+ MPEP( P<0.05), and no statistically significant change was found in the parameters mentioned above in group SD+ CDPPB ( P>0.05). Conclusions:Sleep deprivation impairs the synaptic plasticity of hippocampal neurons by regulating Homer1a/mGluR5 signaling pathway, and thus mediating the process of cognitive dysfunction in aged rats.

Comparison of effects of desflurane versus sevoflurane anesthesia on sleep quality of sleep-deprived mice / 中华麻醉学杂志

Objective:To compare the effects of desflurane and sevoflurane anesthesia on the sleep quality of sleep-deprived mice.Methods:Thirty-two clean-grade healthy male C57BL/6 mice, aged 10 weeks, weighing 20-25 g, were divided into 4 groups ( n=8 each) by the random number table method: control group (C group), sleep deprivation group (SD group), sleep deprivation+ sevoflurane group (SD+ SEV group), and sleep deprivation+ desflurane group (SD+ DES group). In the four groups, EEG-EMG electrodes were implanted for recording EEG and EMG, and sleep deprivation model was developed by the gentle stimulation method with a brush for 12 h (6: 00-18: 00) after 7 days of adaptation. The 6 h after sleep deprivation was divided into 2 time periods: T 1 period (18: 00-20: 00) and T 2 period (20: 00-24: 00). T 1 period In SD group, mice were allowed ad libitum recovery sleep after sleep deprivation. C group and SD group were exposed to 60% oxygen 1.5 L/min. In SD+ DES group and SD+ SEV group, mice were exposed to 6% desflurane and 2.5% sevoflurane, respectively, for 2 h in 60% oxygen 1.5 L/min following sleep deprivation. T 2 period Four groups were allowed ad libitum recovery sleep with the EEG-EMG signal recording. The percentages and number of wakefulness time, rapid eye movement time and non-rapid eye movement time during each time period were calculated using Lunion Data software. Results:Compared with C group, the percentage of non-rapid eye movement time and the percentage of rapid eye movement time were significantly decreased, and the percentage of wakefulness time was increased during 12 h sleep deprivation in SD group, SD+ SEV group and SD+ DES group ( P<0.05). Compared with T 1 period, the percentage of non-rapid eye movement time was significantly increased, and the percentage of wakefulness time and percentage of rapid eye movement time were decreased in T 2 period in SD group ( P<0.05). Compared with SD group, the percentage of non-rapid eye movement time and percentage of rapid eye movement time were significantly decreased, and the percentage of wakefulness time was increased in T 2 period in SD+ SEV group and SD+ DES group ( P<0.05). There was no significant difference in the percentage of non-rapid eye movement, rapid eye movement and wakefulness time in T 2 period between SD+ SEV group and SD+ DES group ( P>0.05). Compared with SD+ SEV group, the number of non-rapid eye movement in T 2 period was significantly reduced in SD+ DES group ( P<0.05). Conclusions:The effect of desflurane anesthesia in improving sleep quality is better than sevoflurane anesthesia in sleep-deprived mice.

Research progress of three techniques for hepatic hyperplasia / 中华肝胆外科杂志

Surgical resection is one of the important means to achieve long-term survival for patients with liver malignant tumor. However, most of the liver malignant tumor has been diagnosed in the middle and late stage, and lose the chance of surgical treatment. For these patients who have lost the chance of surgery, some surgeons have proposed the concept of planned liver resection, which is to reduce tumor stage and increase future liver remnant (FLR) in a planned way, so as to improve the safety of surgery and prolong the survival time of patients after surgery. For patients with FLR insufficiency after prior evaluation or/and treatment, the technique of hepatic hyperplasia is an important part of planned hepatectomy, that is, to effectively increase FLR in a short period of time by various means. Portal vein ligation (PVL) and portal vein embolization (PVE), associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and liver venous deprivation (LVD) are three main techniques for hepatic hyperplasia. This article reviews the principle, effect and safety of three liver augmentation techniques.

The efficacy analysis of moderately hypofractionated IMRT combined with androgen deprivation therapy for locally advanced prostate cancer / 中华放射医学与防护杂志

Objective:To investigate the efficacy and adverse reactions of moderately hypofractionated intensity modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT) for locally advanced prostate cancer (LAPC).Methods:This study retrospectively analyzed the medical records of 40 LAPC patients who were admitted in The Second Hospital of Dalian Medical University during 2014-2020. The planning gross target volume (PGTV) dose for prostate gland and seminal vesicle gland was 64.8-70.0 Gy/25-28 f, 2.4-2.8 Gy/f and the dose of PGTVnd in 20 cases with positive pelvic lymph nodes was 60.0-64.4 Gy/25-28 f, 2.3-2.4 Gy/f. The dose of planning target volume (PTV) for the drainage area of pelvic lymph nodes was 45.0-50.4 Gy/25-28 f. The enrolled patients were treated with long-term ADT, including neoadjuvant, simultaneous, and adjuvant therapies. The efficacy and adverse reactions were evaluated. The prognostic factors affecting the biochemical failure-free survival (BFFS) were analyzed.Results:The median follow-up time was 31 months. The 2- and 3-year overall survival (OS) rates were 100% and 96.9%, respectively. The 1-, 2-, and 3-year BFFS rates were 90%, 76.8% and 72%, respectively. The 1-, 2-, and 3-year distant metastasis-free survival (DMFS) rates were 92.2%, 82.8% and 75.1%, respectively. Gleason (GS) score ( χ2=10.00, P < 0.05) and adjacent tissue invasion ( χ2=8.85, P<0.05) were prognostic factors related to BFFS for LAPC. Adjacent tissue invasion and GS 9-10 were independent poor prognostic factors. The incidence of acute urinary adverse reaction and rectal injury (grade≥2) was 7.5% and 20%, respectively. The incidence of late urinary adverse reaction and rectal injury (grade≥2) was 12.5% and 17.5%, respectively. Adverse reactions at grade 3-4 did not occur. Conclusions:The moderately hypofractionated IMRT combined with ADT is feasible for LAPC treatment, achieving satisfactory survival effects. 70 Gy/25-28 f, 2.5-2.8 Gy/f is a safe and effective moderate hypofraction scheme. Adjacent tissue invasion and GS score are prognostic factors related to BFFS for LAPC.