Swertiamarin attenuates paraquat-induced pulmonary epithelial-like cell apoptosis via NOX4-mediated regulation of redox and mitochondrial function

Abstract The aim of the present study was to investigate the effect of swertiamarin (STM) in attenuating paraquat (PQ)-induced human lung alveolar epithelial-like cell (A549) apoptosis and the underlying mechanisms. A549 cells were pretreated with different concentrations of STM for 2 hr and then cultured with or without PQ (700 µM) for 24 hr. Cell survival was determined using the CCK8 assay. Morphological changes, MDA content, inflammatory factors, fibrogenesis parameters, apoptosis rates, redox status and mitochondrial membrane potential (MMP) were evaluated. The expression of several genes involved in the modulation of redox status was measured by Western blotting. Cell viability and MMP were decreased, but the apoptosis rate and DCFH oxidation were elevated by PQ exposure. STM pretreatment notably increased cell viability and MMP and reduced the apoptosis rate and DCFH oxidation. Furthermore, TLR4- NOX4 signaling was significantly inhibited by STM. The downregulation of NOX4 by siRNA exerted the same protective effects as STM. This study provides the first evidence that STM attenuates PQ-induced pulmonary epithelial-like cell apoptosis via NOX4-mediated regulation of redox and mitochondrial function

Research progress on influencing factors of depressive symptoms in adolescents / 中国学校卫生

Abstract@#In recent years, mental health problems such as anxiety and depression among adolescents in China have attracted attention from all walks of life. Given that adolescence is a transitional and critical period for individual development, mental health affect the developmental opportunities. Therefore, in the review, the effects of environment, psychosocial factors and behavioral patterns on depressive symptoms are analyzed by combining with the characteristics of physical and mental development among adolescents. It is found that early adolescence and even childhood should be the key period for the prevention and intervention of depression. In order to formulate effective interventions and prevention strategies, it is proposed that future research should combine real situation in China with active exploration of protective factors and early predictors of depression.

Correlation between family environment and depressive symptoms among adolescents / 中国学校卫生

Objective@#To understand the relationship between family environment and depressive symptoms among adolescent, and to provide a reference for adolescent mental health promotion and intervention.@*Methods@#From September to December in 2021, a questionnaire survey on family environment and depressive symptoms was conducted among 8 102 middle school students by random cluster sampling method in Shanghai, Urumqi, Changsha and Kunming. The Chi square test was used to compare the depression status of students in different family environments. Multivariate Logistic regression analysis was used to explore the relationship between family environment and depressive symptoms.@*Results@#The detection rates of possible depression, likely depression and severe depression in adolescents were 11.2%, 5.9% and 8.4%, respectively. There were significant differences in the detection rate of depression by gender, academic period, urban and rural areas, family forms and only child statu( χ 2=87.60, 27.19, 6.65, 45.59, 4.78, P <0.05). Logistic regression analysis showed that adolescents in single parent families ( OR =1.45) and reorganized families( OR =1.69) were positively correlated with the occurrence of depressive symptoms compared with those in nuclear families( P <0.01).@*Conclusion@#Compared with nuclear families, the risks of adolescent depressive symptoms in single parent families and reorganized families are higher. Attention should be paid to the mental health education of teenagers from single parents and reorganized families to ensure the development of their physical and mental health.

Correlation between physical activity and depressive symptoms in adolescents / 中国学校卫生

Objective@#To analyze the correlation between physical activity and depressive symptoms in adolescents, so as to provide a reference for the early prevention of depression among adolescents.@*Methods@#Using a random cluster sampling method, 8 102 adolescents from Shanghai, Urumqi, Changsha and Kunming were investigated via the Physical Activity Assessment Questionnaire of Chinese Children and Adolescents aged 7 to 18 and the Center for Epidemiologic Studies Depression Scale (CES-D) for physical activity and depressive symptoms. Multivariate Logistic regression analysis was used to analyze the correlation between physical activity and depressive symptoms in adolescents.@*Results@#The proportion of adolescents who met moderate to vigorous physical activity (MVPA) standard was 37.0%, and the detection rate of depressive symptoms was 25.6%. The detection rate of depressive symptomsin compliant with MVPA standard group was significantly lower than that in non compliant group among different age and gender( χ 2=7.62-34.54, P <0.05). Adolescents with severe depressive symptoms had high light intensity physical activity(LPA) duration and low vigorous intensity physical activity(VPA) duration, while adolescents with mild depressive symptoms or asymptomatic adolescents had higher MVPA duration. There were differences in LPA and VPA among adolescents with different levels of depressive symptoms in the overall sample, and the differences were still significant among girls, middle school and statistically significant differences in LPA, moderate intensity physical activity(MPA), MVPA were also found among the high school subgroup. However, differences only in LPA were observed among boys with different levels of depression( H=46.48, 10.31, 25.02, 29.54, 30.25, 19.80, 22.20, 9.54, 8.62, 18.06, P <0.05). Multivariate Logistic regression model showed that gender and duration of MVPA were significantly related to risk of depressive symptoms( OR=1.56, 1.42, P <0.05).@*Conclusion@#Physical activity among adolescents is significantly related to depressive symptoms. MVPA may be an effective measure to reduce the degree of depressive symptoms.To improve the physical health and prevent depression among adolescents, it is important to choose appropriate physical activity types and effectively increase the duration of MVPA.

Correlation analysis between non suicidal self injury behavior and depressive symptoms in adolescents / 中国学校卫生

Objective@#To explore the correlation between non suicidal self injury(NSSI) behaviors and depressive symptoms in adolescents and to provide a theoretical basis for improvement of adolescent physical and mental health.@*Methods@#A total of 8 102 adolescents aged 12-17 years were selected by random cluster sampling method in Shanghai, Urumqi, Changsha and Kunming, using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Adolescent Non Suicidal Self Injurious Behavior Assessment Questionnaire. Depressive symptoms and the occurrence of NSSI behaviors were assessed. The relationship between NSSI behaviors and depressive symptoms was analyzed using Chi square test, one way analysis and Logistic regression analysis.@*Results@#The overall detection rate of NSSI in adolescents, 24.6%, with a significantly lower detection rate in boys (23.1%) than in girls (26.2%) ( χ 2=10.97, P <0.05), and 24.7%, 24.6% in the middle school and high school segments, respectively, but the difference was not statistically significant ( χ 2=0.01, P >0.05). The overall detection rate of adolescent depressive symptoms was 49.7 % in the group with NSSI and 17.7% in the group without NSSI, with statistically significant differences ( χ 2=808.80, P < 0.01 ). The detection rates of adolescent depressive symptoms in the group with NSSI (male:44.0%, female:54.7%, middle school:49.6%, high school:49.8%) and the group without NSSI (male:14.2%, female:21.4%, middle school:14.3%, high school: 21.0 %) were statistically significant by sex and age groups ( χ 2=385.58, 412.44, 520.60, 313.78, P ＜0.01). Logistic regression models, after adjusting for gender and age, the risk for depressive symptoms was 2.65 times (95% CI =2.27-3.09) and 7.28 times (95% CI = 6.34- 8.37) more frequently in adolescents with episodic self injurious behavior and frequent self injurious behavior, respectively, compared to those without self injurious behavior. The association between NSSI status and depressive symptoms did not show sex differences ( P >0.05).@*Conclusion@#Adolescent NSSI behavior is positively associated with depressive symptoms, the attention should be paid to adolescent physical and mental health to reduce the occurrence of NSSI.

Correlation between physical fitness condition and depressive symptoms in adolescents / 中国学校卫生

Objective@#To explore the relationship between adolescents physical fitness and depressive symptoms, and to provide reference for the early prevention and intervention of depressive symptoms and improvement of physical fitness in Chinese adolescents.@*Methods@#From September to December 2021, a total of 8 102 adolescents were selected by random cluster sampling method in Shanghai, Urumqi, Changsha and Kunming. The Center for Epidemiologic Studies Depression Scale(CES-D) was used to investigate the depressive symptoms, and completed grip strength, standing long jump, 50 m running, modified sitting forward flexion, 20 s repeated traverse, 30 s sit ups, 20 m round trip running (20 m SRT) test. χ 2 test, Goodman Kruskal Gamma and Logistic regression analysis were used to analyze the relationship between physical fitness index(PFI) and depressive symptoms.@*Results@#The overall detection rate of depressive symptoms in adolescents with high level PFI was 23.4%, and the detection rate of low level adolescents was 26.3%, with a statistically significant difference ( χ 2=6.73, P =0.01). There was a significant positive correlation between PFI and depressive symptoms in the high school group ( G=0.09, P <0.05) and the boy group ( G=0.12, P < 0.05 ), and there was no significant association between PFI and depressive symptoms in the junior high school group and the girl group ( P >0.05). After adjusting for gender and age in the Logistic regression model, compared with those with high PFI, the risk of depressive symptoms in those with low PFI was 1.18 times (95% CI =1.05-1.33).@*Conclusion@#There is a correlation between physical fitness and depressive symptoms in adolescents. Adolescents with low PFI are at higher risk of developing depressive symptoms than those with high PFI.

Expression of low-density lipoprotein receptor-associated protein 11 in colorectal cancer tissues and its effects on proliferation and apoptosis of SW480 cells / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨低密度脂蛋白受体相关蛋白11（LRP11）在结直肠癌（CRC）组织中的表达及其对结肠癌SW480细胞增殖与凋亡的影响。方法：利用生物信息学方法分析TCGA数据库中LRP11在CRC组织中的表达水平。用慢病毒感染技术分别将sh-LRP11及sh-NC质粒转染至SW480细胞，采用qPCR、WB法检测感染后各组细胞中LRP11的mRNA和蛋白的表达，CCK-8法、流式细胞术分别检测细胞的增殖活力、凋亡率及细胞周期分布情况，WB法检测SW480细胞中cyclin D1、BAX、Bcl-2、β-catenin、活化β-catenin等蛋白的表达水平。结果：TCGA数据库数据分析显示，LRP11 mRNA在CRC组织中的表达水平显著高于正常组织（P<0.05）。与sh-NC组比较，sh-LRP11组SW480细胞的增殖活力明显降低、细胞凋亡率显著升高（均P<0.01），细胞中BAX表达显著升高、Bcl-2表达显著降低（均P<0.01）；G0/G1期细胞增多、S期细胞明显减少（均P<0.01），cyclin D1的蛋白表达显著降低（P<0.01）；Wnt/β-catenin信号通路中β-catenin和活化β-catenin的蛋白表达均显著下降（均P<0.01）。结论：LRP11 mRNA在CRC组织中呈高表达，干扰LRP11表达可抑制结肠癌SW480细胞增殖并促进其凋亡，为CRC提供了一种潜在的治疗靶点。

Football player's training for improving physical function and health / Treino de jogadores de futebol americano para a melhoria de sua função física e saúde / Entrenamiento de jugadores de fútbol americano para la mejoría de su función física y salud

ABSTRACT Introduction: Due to the fierce confrontation, high intensity, long duration, and high technical and tactical requirements of modern football, this sport puts forward higher requirements on the physical function of the athletes. Objective: To further explore the importance of physical training based on expounding the concepts of physical fitness and physical training. Methods: The article uses literature research, expert interviews, questionnaires, observations, measurements, mathematical statistics, and other research methods to explore the physical characteristics and training of Chinese football players. Results: The physical training of football players should conform to the specific characteristics of football. This sport requires combining technical and tactical training, psychological training, and academic training of football matches, which must be developed simultaneously. Conclusion: The purpose of physical training is to improve the functional capabilities of athletes to a certain extent, exploit and develop the athlete's athletic potential, and effectively maintain this functional ability. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: Graças ao confronto físico agressivo, à intensidade elevada, à longa duração, e às exigências técnicas e táticas do futebol americano moderno, esse esporte exige muito da função física de seus atletas. Objetivo: Explorar mais à fundo a importância do treinamento físico baseado na utilização de conceitos de aptidão física e treinamento físico. Métodos: Este artigo utiliza pesquisa bibliográfica, entrevistas com especialistas, questionários, observações, mensurações, estatísticas matemáticas, e outros métodos de pesquisa para explorar as características físicas e o treinamento de jogadores de futebol americano chineses. Resultados: O treinamento físico de jogadores de futebol americano deve estar de acordo com as características específicas do esporte, que requer uma combinação de treino tático, técnico, psicológico e acadêmico, no que diz respeito a partidas de futebol americano, todos os quais devem ser desenvolvidos simultaneamente. Conclusão: O objetivo do treinamento físico é aprimorar a capacidade funcional de atletas até certo ponto, explorar e desenvolver o potencial físico do atleta e, efetivamente, manter sua habilidade funcional. Nível de evidência II; Estudos terapêuticos - investigação de resultados de tratamento.

RESUMEN Introducción: Gracias al confrontamiento físico agresivo, a la intensidad elevada, a la larga duración, y a las exigencias técnicas y tácticas del futbol americano moderno, este deporte exige mucho de la función física de sus atletas. Objetivo: Explorar más a fondo la importancia del entrenamiento físico basado en la utilización de conceptos de aptitud física y entrenamiento físico. Métodos: Este artículo utiliza investigación bibliográfica, entrevistas con especialistas, cuestionarios, observaciones, mediciones, estadística matemática y otros métodos de investigación para explorar las características físicas y el entrenamiento de jugadores chinos de fútbol americano. Resultados: El entrenamiento físico de jugadores de fútbol americano debe estar de acuerdo con las características específicas del deporte, que requiere una combinación de entrenamiento táctico, técnico, psicológico y académico, con respecto a partidos de futbol americano, que deben desarrollarse simultáneamente. Conclusión: El objetivo del entrenamiento físico es mejorar la capacidad funcional de atletas hasta cierto punto, explorar y desarrollar el potencial físico del atleta y, efectivamente, mantener su habilidad funcional. Nivel de evidencia II; Estudios terapéuticos - investigación de resultados de tratamiento.

Clinical relevance of miR-423-5p levels in chronic obstructive pulmonary disease patients

Abstract Objective: This study aimed to examine changes in miRNAs expression profile of COPD patients. Methods: Thirty-six COPD patients as well as thirty-three healthy volunteers were recruited. Total RNAs were collected from the plasma of each participant. The differentially expressed miRNAs in COPD were screened from the GEO database. RT-qPCR was carried out to detect miRNA expression. Results: In total, 9 out of 55 miRNAs were expressed differentially in COPD patients. Confirmed by RT-qPCR validation, 6 miRNAs increased while 3 miRNAs decreased. Further analysis of miR-423-5p, which has not been reported in COPD, showed that AUC for the diagnosis of COPD was 0.9651, and miR-423-5p levels was inversely correlated with the duration of smoking. Conclusion: The present study demonstrates that miR-423-5p is a potential marker for identifying COPD patients.

Sharing the WHO guideline on control and elimination of human schistosomiasis to achieve the goal of schistosomiasis elimination in China / 中国血吸虫病防治杂志

Currently, the national schistosomiasis control program of China is moving from transmission interruption to elimination, and there are multiple challenges during the stage moving towards the progression of schistosomiasis elimination, including a high difficulty in shrinking snail-infested areas, unstable achievements for infectious source control, imperfect surveillance system and a reduction in schistosomiasis control and administration. Based on the core suggestions proposed in the 2022 WHO guideline on control and elimination of human schistosomiasis, recommendations on schistosomiasis surveillance system building, development of novel diagnostics, adjustment of the schistosomiasis control strategy and maintaining and improvements of the schistosomiasis control capability are proposed for the national schistosomiasis control program of China in the new era according to the actual status of schistosomiasis control in China. Formulation of the national schistosomiasis control strategy and goal from One Health perspective, verification of transmission interruption and elimination of schistosomiasis, precision implementation of schistosomiasis control interventions with adaptations to local circumstances, development and application of highly sensitive and specific diagnostics are recommended for elimination of schistosomiasis in China. In addition, the implementation of the 2022 WHO guideline on control and elimination of human schistosomiasis may guide the elimination of schistosomiasis in China.

Decoding the evolution of preventive chemotherapy schemes for schistosomiasis in China to improve the precise implementation of the WHO guideline on control and elimination of human schistosomiasis / 中国血吸虫病防治杂志

Preventive chemotherapy is one of the pivotal interventions for the control and elimination of schistosomiasis, which is effective to reduce the morbidity and prevalence of schistosomiasis. In order to promote the United Nations' sustainable development goals and the targets set for schistosomiasis control in the Ending the neglect to attain the Sustainable Development Goals: a road map for neglected tropical diseases 2021-2030, WHO released the guideline on control and elimination of human schistosomiasis in 2022, with major evidence-based updates of the current preventive chemotherapy strategy for schistosomiasis. In China where great success has been achieved in schistosomiasis control, the preventive chemotherapy strategy for schistosomiasis has been updated several times during the past seven decades. This article reviews the evolution of the WHO guidelines on preventive chemotherapy and Chinese national preventive chemotherapy schemes, compares the current Chinese national preventive chemotherapy scheme and the recommendations for preventive chemotherapy proposed in the 2022 WHO guideline on control and elimination of human schistosomiasis, and proposes recommendations for preventive chemotherapy during the future implementation of the 2022 WHO guideline, so as to provide insights into schistosomiasis control among public health professionals engaging in healthcare foreign aid.

Analysis of the new WHO guideline to accelerate the progress towards elimination of schistosomiasis in China / 中国血吸虫病防治杂志

On February 2022, WHO released the evidence-based guideline on control and elimination of human schistosomiasis, with aims to guide the elimination of schistosomiasis as a public health problem in disease-endemic countries by 2030 and promote the interruption of schistosomiasis transmission across the world. Based on the One Health concept, six evidence-based recommendations were proposed in this guideline. This article aims to analyze the feasibility of key aspects of this guideline in Chinese national schistosomiasis control program and illustrate the significance to guide the future actions for Chinese national schistosomiasis control program. Currently, the One Health concept has been embodied in the Chinese national schistosomiasis control program. Based on this new WHO guideline, the following recommendations are proposed for the national schistosomiasis control program of China: (1) improving the systematic framework building, facilitating the agreement of the cross-sectoral consensus, and building a high-level leadership group; (2) optimizing the current human and livestock treatments in the national schistosomiasis control program of China; (3) developing highly sensitive and specific diagnostics and the framework for verifying elimination of schistosomiasis; (4) accelerating the progress towards elimination of schistosomiasis and other parasitic diseases through integrating the national control programs for other parasitic diseases.

Prescribing Pattern of Benzodiazepine Receptor Agonists (BZRA) and Factors Associated With Duration of BZRA Use in a Malaysian Psychiatry Outpatient Clinic

@#Introduction: Benzodiazepine receptor agonist (BZRA) are among the most frequently used psychotropic medications worldwide. We aim to understand the pattern of prescription of BZRA in the government healthcare facilities and identify factors affecting the likelihood of BZRA prescription and duration of use. Method: This is a retrospective study. Data was obtained from record of outpatient clinical notes. Medications studied were midazolam, alprazolam, lorazepam, bromazepam, clonazepam, diazepam and zolpidem. Mean duration per prescription, mean dosage per prescription and duration per patient per year were calculated for each sedative hypnotic. The likelihood of factors affecting duration of prescription were also analysed. Results: The prevalence of sedative hypnotic use in psychiatry outpatient clinic was 12.16%. Clonazepam was found to have the longest duration per patient per year (306.5 days). Insomnia and anxiety are the two most common reasons for sedative hypnotic prescription. Factors found to affect duration of prescription were unemployment, borderline personality disorder, alcohol and substance use disorders. Conclusion: Implementation of effective monitoring system on sedative hypnotic prescribing and increase use of non-pharmacological interventions for insomnia and anxiety are necessary to curb prolonged use of sedative hypnotic.

Endemic situation of schistosomiasis in national surveillance sites of Zhejiang Province from 2015 to 2019 / 中国血吸虫病防治杂志

Objective To analyze the endemic situation of schistosomiasis in national surveillance sites of Zhejiang Province, so as to provide the scientific evidence for formulating the new schistosomiasis surveillance program and consolidating schistosomiasis elimination achievements. Methods A total of 54 to 55 national surveillance sites and 6 risk monitoring sites were assigned in historical endemic regions of Zhejiang Province from 2015 to 2019, where the Schistosoma japonicum infections in humans, livestock, snails and wild feces were monitored. All data pertaining to the surveillance results were descriptively analyzed. Results There were 34 530 person-time local residents receiving serological screening for S. japonicum infections in national surveillance sites of Zhejiang Province from 2015 to 2019, and the seroprevalance of S. japonicum infections were 0.29% to 0.68%; however, no egg-positives were detected. During the period from 2015 to 2019, there were 62 086 person-time mobile populations receiving serological screening for S. japonicum infections in national surveillance sites of Zhejiang Province, and the seroprevalance of S. japonicum infections were 0.32% to 0.56%; additionally, there were 27 egg-positives identified, including 3 imported cases with schistosomiasis haematobia and one case with acute schistosomiasis japonica, indicating that the adjusted prevalence of Schistosoma infections were 0.01% to 0.07% among mobile populations. A total of 829 livestock were examined for S. japonicum infections, with no positives detected. There were 10.55 hm2 and 2.89 hm2 snail habitats found in national surveillance sites and risk monitoring sites of Zhejiang Province during the 5-year period, respectively; however, no S. japonicum infections were identified in snails. Moreover, a total of 305 wild feces were tested for S. japonicum infections, and no egg-positives were identified. Conclusions The schistosomiasis elimination achievement have been consolidated in Zhejiang Province; however, the risk factors of re-emerging schistosomiasis have not been completely eliminated, such as residual snails and imported schistosomiasis cases. Further surveillance and control activities of snails and the source of S. japonicum infections should be reinforced.

Expert consensus on the strategy and measures to interrupt the transmission of schistosomiasis in China / 中国血吸虫病防治杂志

Since 2015 when the transmission of schistosomiasis was controlled in China, the country has been moving towards elimination of schistosomiasis, with the surveillance-response as the main interventions for schistosomiasis control. During the period of the 13th Five-Year Plan, the transmission of schistosomiasis had been interrupted in four provinces of Sichuan, Jiangsu, Yunnan and Hubei and the prevalence of schistosomiasis has been at the historically lowest level in China. As a consequence, the goal set in The 13th Five-Year National Schistosomiasis Control Program in China is almost achieved. However, there are multiple challenges during the stage moving towards elimination of schistosomiasis in China, including the widespread distribution of intermediate host snails and complicated snail habitats, many types of sources of Schistosoma japonicum infections and difficulty in management of bovines and sheep, unmet requirements for the current schistosomiasis control program with the currently available tools, and vulnerable control achievements. During the 14th Five-Year period, it is crucial to consolidate the schistosomiasis control achievements and gradually solve the above difficulties, and critical to provide the basis for achieving the ultimate goal of elimination of schistosomiasis in China. Based on the past experiences from the national schistosomiasis control program and the challenges for schistosomiasis elimination in China, an expert consensus has been reached pertaining to the objectives, control strategy and measures for The 14th Five-Year National Schistosomiasis Control Program in China, so as to provide insights in to the development of The 14th Five-Year National Schistosomiasis Control Program in China.

The harm and protective measures of facial occupational exposure of dental medical and nursing personnel / 口腔疾病防治

@#There are many kinds of medical facial protective equipment with different functions. However, due to the lack of recognition of the hazards of facial occupational exposure, an incomplete understanding of the functions and effects of protective equipment and a lack of awareness, the proportion of staff that wear protective equipment in the Department of Stomatology is low. In this paper, the harmful and protective effects of face occupational exposure of dental staff were reviewed. A literature review showed that with the increasing prevalence of infection with AIDS, hepatitis B, hepatitis C and multidrug resistant bacteria in recent years, the occupational infection rate of medical staff in the Department of Stomatology has increased. The noise generated during oral treatment and the light from photosensitive curing lamps and treatment or surgical lasers can also cause occupational damage to hearing and vision. Face protection measures lack comprehensive functioning, and there is a lack of products that can be easily worn, indicating that the functions of face protection products need to be improved and strengthened. To minimize occupational infection and injury, we should not only improve the existing protective equipment but also improve personal protection awareness through advertising and education and comprehensively explore effective measures to improve occupational safety to ultimately achieve safe and high-quality medical services.

Anti-tumor Efficacy and Safety of Zeylenone on Acute T Lymphoblastic Leukemia / 中国实验方剂学杂志

Objective:To investigate the anti-tumor efficacy, mechanism and safety of zeylenone on acute T lymphocytic leukemia. Method:In vitro, Molt-4 cells were treated with various concentrations of zeylenone (0.2, 0.4, 0.8, 1.6, 3.2 μmol·L-1) for 48 h, and the cell viability was measured with cell counting kit-8 (CCK-8) assay. nonobese diabetic-severce combined immunodeficient mice（NOD/SCID） mice were randomly divided into six groups: normal group, model group, vincristine group (1 mg·kg-1), low-dose zeylenone group (12.5 mg·kg-1), medium-dose zeylenone group (25 mg·kg-1), high-dose zeylenone group (50 mg·kg-1). With the exception of normal group, mice were pre-irradiated with 60Co and inoculated subcutaneously with Molt-4 cells to establish the Molt-4 xenograft model. Then NOD/SCID mice were sacrificed after 13 days of administration. The tumor inhibition rates, relative tumor growth rates and organ indexes were calculated. Hematoxylin and eosin (HE) staining was used to observe the pathological changes of liver and spleen tissues in mice. The expressions of phosphorylation signal transducer and activator of transcription (p-STAT3), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and cysteine aspartate-specific protease-3 (Caspase-3) were detected in tumor tissues by Western blot. Result:In vitro, zeylenone had an obvious inhibitory effect on Molt-4 cells. IC50 values of zeylenone was 1.49 μmol·L-1. In vivo, compared with the model group, medium and high-dose zeylenone groups had significant tumor inhibition effects, with the inhibition rates of 50.24% and 60.75%, respectively (P<0.01). Additionally, liver and spleen injuries were slight in the above mentioned two groups compared with the vincristine group, indicating that zeylenone was safe. Western blot analysis showed that medium and high-dose zeylenone groups showed significant declines in proteins p-STAT3, Caspase-3 and Bcl-2, and marked increases in pro-apoptotic protein Bax compared with the model group (P<0.05, P<0.01). Conclusion:zeylenone could obviously inhibit the proliferation and induce the apoptosis of Molt-4 cells; and its mechanism may be related to the down-regulation of p-STAT3, Caspase-3, Bcl-2 and the up-regulation of Bax expressions. In addition, zeylenone had less damage to liver and spleen, and was safer than vincristine.

Spicy food consumption is associated with cognition and cerebrospinal fluid biomarkers of Alzheimer disease / 中华医学杂志(英文版)

BACKGROUND@#Recent studies suggest that a healthy diet helps to prevent the development of Alzheimer disease (AD). This study aimed to investigate whether spicy food consumption is associated with cognition and cerebrospinal fluid (CSF) biomarkers of AD in the Chinese population.@*METHODS@#We enrolled 55 AD patients and 55 age- and gender-matched cognitively normal (CN) subjects in a case-control study, as well as a cohort of 131 participants without subjective cognitive decline (non-AD) in a cross-sectional study. Spicy food consumption was assessed using the Food Frequency Questionnaire (FFQ). Associations of FFQ scores with cognition and CSF biomarkers of AD were analyzed.@*RESULTS@#In the case-control study, spicy food consumption was lower in AD patients than that in CNs (4.0 [4.0-8.0] vs. 8.0 [4.5-10.0], P < 0.001); FFQ scores were positively associated with Mini-Mental Status Examination scores in the total sample (r = 0.218, P = 0.014). In the cross-sectional study, the association between spicy food consumption and cognition levels was verified in non-AD subjects (r = 0.264, P = 0.0023). Moreover, higher FFQ scores were significantly associated with higher β-Amyloid (1-42) (Aβ42) levels and lower phospho-tau/Aβ42 and total tau/Aβ42 ratios in the CSF of non-AD subjects (P < 0.05).@*CONCLUSION@#Spicy food consumption is closely related to higher cognition levels and reversed AD biomarkers in the CSF, suggesting that a capsaicin-rich diet might have the potential to modify the cognitive status and cerebral pathologies associated with AD.

Association of Polygenic Risk Score with Age at Onset and Cerebrospinal Fluid Biomarkers of Alzheimer's Disease in a Chinese Cohort / 神经科学通报·英文版

To evaluate whether the polygenic profile modifies the development of sporadic Alzheimer's disease (sAD) and pathological biomarkers in cerebrospinal fluid (CSF), 462 sAD patients and 463 age-matched cognitively normal (CN) controls were genotyped for 35 single-nucleotide polymorphisms (SNPs) that are significantly associated with sAD. Then, the alleles found to be associated with sAD were used to build polygenic risk score (PRS) models to represent the genetic risk. Receiver operating characteristic (ROC) analyses and the Cox proportional hazards model were used to evaluate the predictive value of PRS for the sAD risk and age at onset. We measured the CSF levels of Aβ42, Aβ42/Aβ40, total tau (T-tau), and phosphorylated tau (P-tau) in a subgroup (60 sAD and 200 CN participants), and analyzed their relationships with the PRSs. We found that 14 SNPs, including SNPs in the APOE, BIN1, CD33, EPHA1, SORL1, and TOMM40 genes, were associated with sAD risk in our cohort. The PRS models built with these SNPs showed potential for discriminating sAD patients from CN controls, and were able to predict the incidence rate of sAD and age at onset. Furthermore, the PRSs were correlated with the CSF levels of Aβ42, Aβ42/Aβ40, T-tau, and P-tau. Our study suggests that PRS models hold promise for assessing the genetic risk and development of AD. As genetic risk profiles vary among populations, large-scale genome-wide sequencing studies are urgently needed to identify the genetic risk loci of sAD in Chinese populations to build accurate PRS models for clinical practice.

Serum- and glucocorticoid-inducible kinase 3 is a potential oncogene in nasopharyngeal carcinoma / Quinase 3 sérica induzida por glicocorticoide é um potencial oncogene no carcinoma nasofaríngeo

Abstract Introduction: Serum- and glucocorticoid-inducible kinase 3, a serine/threonine kinase that functions downstream of the PI3K signaling pathway, plays a critical role in neoplastic processes. It is expressed by various tumors and contributes to carcinogenesis. Objective: The objective was to investigate serum- and glucocorticoid-inducible kinase 3 expression in nasopharyngeal carcinoma, to study the anti-tumor effects of serum- and glucocorticoid-inducible kinase 3 shRNA by inhibiting its expression in nasopharyngeal carcinoma cells and to discuss the potential implications of our findings. Methods: Serum- and glucocorticoid-inducible kinase 3 protein expression in nasopharyngeal carcinoma cell lines (CNE-1, CNE-2, HNE-1, HONE-1, and SUNE-1) and the human immortalized nasopharyngeal epithelium cell line NP69 were assayed by western blotting. Serum- and glucocorticoid-inducible kinase 3 expression in 42 paraffin-embedded nasopharyngeal carcinoma tissues were performed by immunohistochemistry. MTT assay, flow cytometry, and scratch tests were performed after CNE-2 cells were transfected with the best serum- and glucocorticoid-inducible kinase 3 shRNA plasmid selected by western blotting using lipofectamine to study its effect on cell proliferation, apoptosis, and migration. Results: Serum- and glucocorticoid-inducible kinase 3 was overexpressed in human nasopharyngeal carcinoma tissues and cells. Serum- and glucocorticoid-inducible kinase 3 expression decreased markedly after CNE-2 cells were transfected with the serum- and glucocorticoid-inducible kinase 3 shRNA, leading to strong inhibition of cell proliferation and migration. In addition, the apoptosis rate increased in CNE-2 cells after serum- and glucocorticoid-inducible kinase 3 knockdown. Conclusion: Serum- and glucocorticoid-inducible kinase 3 expression was more frequently observed as the nasopharyngeal epithelium progresses from normal tissue to carcinoma. This suggests that serum- and glucocorticoid-inducible kinase 3 contributes to the multistep process of NPC carcinogenesis. Serum- and glucocorticoid-inducible kinase 3 represents a target for nasopharyngeal carcinoma therapy, and a basis exists for the further investigation of this adjuvant treatment modality for nasopharyngeal carcinoma.

Resumo Introdução: A quinase 3 sérica induzida por glicocorticoide, uma serina/treonina quinase que funciona downstream da via de sinalização PI3K, desempenha um papel crítico nos processos neoplásicos. É expressa por vários tumores e contribui para a carcinogênese. Objetivo: Investigar a expressão de quinase 3 sérica induzida por glicocorticoide no carcinoma nasofaríngeo, estudar os efeitos antitumorais do shRNA da quinase 3 sérica induzida por glicocorticoide, que inibem sua expressão em células de carcinoma nasofaríngeo, e discutir as implicações potenciais de nossos achados. Método: A expressão de proteína quinase 3 sérica induzida por glicocorticoide em linhagens de células de carcinoma nasofaríngeo (CNE-1, CNE-2, HNE-1, HONE-1 e SUNE-1) e a linhagem de células humanas imortalizadas do epitélio nasofaríngeo NP69 foram avaliadas por Western blot. A expressão da quinase 3 sérica induzida por glicocorticoide em 42 tecidos de CNF embebidos em parafina foi feita por imuno-histoquímica. Testes com MTT, citometria de fluxo e testes de raspagem foram feitos após as células CNE-2 terem sido transfectadas com o melhor plasmídeo shRNA da quinase 3 sérica induzida por glicocorticoide selecionado por Western blot, com o uso de lipofectamina para estudar seu efeito na proliferação, apoptose e migração celular. Resultados: Foi observada uma sobre-expressão da quinase 3 sérica induzida por glicocorticoide em tecidos e células de carcinoma nasofaríngeo humanas. A expressão de quinase 3 sérica induzida por glicocorticoide diminuiu acentuadamente após as células CNE-2 terem sido transfectadas com o shRNA da quinase 3 sérica induzida por glicocorticoide, conduzindo a forte inibição de proliferação e migração celular. Além disso, a taxa de apoptose aumentou nas células CNE-2 após o knockdown da quinase 3 sérica induzida por glicocorticoide. Conclusão: A expressão de quinase 3 sérica induzida por glicocorticoide foi observada com maior frequência à medida que o epitélio nasofaríngeo progride de tecido normal para carcinoma. Isso sugere que a quinase 3 sérica induzida por glicocorticoide contribui para o processo multietapas da carcinogênese do carcinoma nasofaríngeo. A quinase 3 sérica induzida por glicocorticoide representa um alvo para a terapia do carcinoma nasofaríngeo e há uma base para a investigação adicional dessa modalidade de tratamento adjuvante para o carcinoma nasofaríngeo.