Dissecting the causal relationship between neuroticism and osteoarthritis: a univariable and multivariable Mendelian randomization study.

Background: Mental health has been found to be associated with risk of osteoarthritis (OA), but the causal relationship was not fully clarified. Methods: Two-sample Mendelian randomization (MR) study was conducted to investigate the causal relationship between neuroticism (n = 329,821) and the two most frequently affected parts of osteoarthritis (OA) (knee OA: case/control =24,955/378,169; hip OA: case/control = 15,704/378,169) using large scale summary genome-wide association study (GWAS) data. Inverse variance weighted (IVW), weighted median, and MR-Egger were used to estimate the causal effects. Multiple sensitivity analyses were conducted to examine the robustness of the causal estimates. Multivariable MR analysis was used to estimate the direct effects of neuroticism on OA after accounting for the other OA risk factors. Two-step MR approach was employed to explore the potential mediators of the causal relationship. Results: Univariable MR analysis indicated that 1-SD increase in genetically predicted neuroticism score was associated with an increased risk of knee OA (IVW: OR, 1.17; 95% CI, 1.087-1.26; p = 2.72E-05) but not with hip OA. The causal effects remained significant after accounting for the effects of BMI, alcohol drinking, and vigorous physical activity but were attenuated with adjustment of smoking. Further mediation analysis revealed that smoking initiation mediated a significant proportion of the causal effects of neuroticism on knee OA (proportion of mediation effects in total effects: 22.3%; 95% CI, 5.9%-38.6%; p = 7.60E-03). Conclusions: Neuroticism has significant causal effects on knee OA risk. Smoking might partly mediate the causal relationship. Further studies were warranted to explore the underlying mechanisms and potential use of neuroticism management for OA treatment.

Cardiovascular control responses in high intensity exercise stress tests / Respostas de controle cardiovascular em testes de estresse de exercícios de alta intensidade / Respuestas de control cardiovascular en pruebas de estrés de ejercicios de alta intensidad

ABSTRACT Introduction: High intensity exercise is an important factor to achieve the best exercise effect, and is closely related to the patient's safety and rehabilitation. Objective: To investigate the effects of high intensity exercise on cardiovascular response and substance and energy metabolism. Methods: 50 male students at a university were selected. The average age of the subjects was 23 years old. Process of the experiment: Before the experiment, each subject took routine warm-up activities first, then put on the experimental equipment and began to run 100 meters. At the same time, the subjects' heart rate, blood oxygen parameters and exercise time were recorded. After passing the finish line, a period of heart rate recording and blood oxygen parameters were continued. Results: Anaerobic metabolism was the main activity in the 100m race. The first 7s after the start of the race, there is a non-lactic acid process without oxygen metabolism, and the muscle oxygen saturation curve presents little change. Conclusions: High intensity exercise in sports training and physical exercise can lead to reduced heart rate variability. The increased incidence of various arrhythmias should be based on the actual situation of the movement of the object, and a reasonable arrangement of exercise load intensity. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: Exercícios de alta intensidade são um importante fator para alcançar o melhor efeito de exercícios, e está estreitamente ligado a segurança e reabilitação do paciente. Objetivo: Investigar os efeitos de exercícios de alta intensidade na resposta cardiovascular e no metabolismo de substâncias e energia. Métodos: 50 estudantes do sexo masculino em uma universidade foram selecionados. A idade média dos sujeitos do estudo era de 23 anos. Processo do experimento: Antes de iniciar, primeiramente, cada estudante fez aquecimentos de rotina. Após, colocaram o equipamento experimental e começaram a correr 100 metros. Ao mesmo tempo, a frequência cardíaca, parâmetros de oxigenação do sangue e tempo do exercício foram registrados. Após passar a linha de chegada, continuou-se a registrar a frequência cardíaca e os parâmetros de oxigenação do sangue por um tempo. Resultados: O metabolismo anaeróbico foi a atividade principal na corrida de 100 metros. Nos sete segundos após o início da corrida, há um processo ácido não láctico sem a metabolização de oxigênio e a curva de saturação de oxigênio do músculo apresenta pouca alteração. Conclusões: Exercícios de alta intensidade no treinamento esportivo e o exercício físico pode levar à variabilidade reduzida de frequência cardíaca. O aumento na incidência de várias arritmias deve se basear na situação real de movimento do sujeito e um manejo razoável da intensidade da carga do exercício. Nível de evidência II; Estudos terapêuticos - investigação de resultados de tratamento.

Resumen Introducción: Ejercicios de alta intensidad son un importante factor en alcanzar el mejor efecto de ejercicio, y está estrechamente relacionado a la seguridad y rehabilitación del paciente. Objetivo: Investigar los efectos de ejercicios de alta intensidad en la respuesta cardiovascular y en el metabolismo de sustancias y energía. Métodos: Se seleccionó 50 estudiantes del sexo masculino en una universidad. La edad media de los sujetos del estudio era de 23 años. Proceso del experimento: Antes de empezar, primeramente, cada estudiante hizo calentamientos de rutina. Después, pusieron el aparato experimental y empezaron a correr 100 metros. Al mismo tiempo, se registró la frecuencia cardíaca, parámetros de oxigenación de la sangre y el tiempo del ejercicio. Después de pasar la línea de llegada, se continuó a registrar la frecuencia cardíaca y los parámetros de oxigenación de la sangre por un tiempo. Resultados: El metabolismo anaeróbico fue la actividad principal en la carrera de 100 metros. 7 segundos tras el comienzo de la carrera, hay un proceso ácido no láctico sin la metabolización de oxígeno y la curva de saturación de oxígeno del músculo presenta poca alteración. Conclusiones: Ejercicios de alta intensidad en el entrenamiento deportivo y el ejercicio físico puede llevar a la variabilidad reducida de frecuencia cardíaca. El aumento en la incidencia de varias arritmias debe basarse en la situación real de movimiento del sujeto y un manejo razonable de la intensidad de carga del ejercicio. Nivel de evidencia II; Estudios terapéuticos - investigación de resultados de tratamiento.

[Mining Polo-Box domain of Polo-like kinase 1 as a new therapeutic target for cancer].

Polo-like kinase 1 (Plk1) is widely regarded as one of the most promising targets for cancer therapy due to its essential role in cell division and tumor cell survival. At present, most Plk1 inhibitors have been developed based on kinase domain, some of which are in clinical trial. However, inhibitors targeting kinase domain face off-target effect and drug resistance owing to the conserved nature and the frequent mutations in the ATP-binding pocket. In addition to a highly conserved kinase domain, Plk1 also contains a unique Polo-Box domain (PBD), which is essential for Plk1's subcellular localization and mitotic functions. Inhibitors targeting Plk1 PBD show stronger selectivity and less drug resistance for cancer therapy. Therefore, Plk1 PBD is an attractive target for the development of anti-cancer agents. In this review, we will summarize the up-to date drug discovery for targeting Plk1 PBD, including the molecular structure and cellular functions of Plk1 PBD. Small-molecule inhibitors targeting Plk1 PBD not only provide an opportunity to specifically inhibit Plk1 activity for cancer treatment, but also unveil novel biological basis regarding the molecular recognition of Plk1 and its substrates.

Muscle-Bone Interactions in Chinese Men and Women Aged 18-35 Years.

To characterize bone mineral density (BMD), bone strength, muscle and fat mass, and muscle strength and power in Chinese women (n = 25) and men (n = 28) classified as in the bone accrual phase (18-25 years) or in the peak bone mass phase (26-35 years). Calcium intakes, physical activity levels, and serum vitamin D were measured. Dual-energy X-ray absorptiometry (DXA) assessed body composition, lumbar spine, and hip areal BMD (aBMD) variables and peripheral quantitative computed tomography (pQCT) assessed cortical and trabecular volumetric BMD (vBMD) and bone strength. Muscle strength and power were assessed by grip strength, leg press, and vertical jump tests. Calcium, serum vitamin D, and physical activity levels were similar across age and sex groups. Significant sex differences (p < 0.05) were found for most body composition variables, hip aBMD, tibia variables, and muscle strength and power. Adjusting for height and weight eliminated most of the significant sex differences. Women showed stronger positive correlations between body composition and bone variables (r = 0.44 to 0.78) than men. Also, correlations between muscle strength/power were stronger in women vs. men (r = 0.43 to 0.82). Bone traits were better related to body composition and muscle function in Chinese women compared to Chinese men aged 18 to 35 years, and peak bone mass seems to be achieved by 25 years of age in both Chinese men and women since there were no differences between the two age groups.

[Clinical features and disease activity index of Behçet's disease].

OBJECTIVE: The clinical features and two disease activity assessment methods of Behçet's disease were evaluated in order to guide clinical management. METHODS: A total of 116 patients with Behçet's disease from China-Japan Union Hospital of Jilin University in 2007-2014 were analyzed retrospectively for the gender and age distribution as well as clinical features of multisystem involvement. The correlations of Behçet's Disease Current Activity Form (BDCAF) and electronic medical record (EMR)-based activity index (EMRAI) scoring systems with clinical data were compared in Chinese patients for the first time, and clinical suggestion was raised. RESULTS: Behçet's disease was commonly seen in young adults with age between 21-40 years old with mean course of four years.Males had longer duration than females (9.5 years vs 4.0 years, P<0.05), and vasculopathy was more commonly seen in males (11.9% vs 1.36%, P<0.05), while females had wider age distribution. BDCAF and EMRAI scoring systems were positively correlated with each other; the former was well associated with laboratory inflammatory indices, and the latter was simplified for application. CONCLUSIONS: The clinical manifestation of Behçet's disease varies with different gender; BDCAF and EMRAI scoring system well correlate with the laboratory inflammatory indices of patients, and can indicate the disease activity.

[Bone mineral density and disease activity in untreated systemic lupus erythematosus patients].

OBJECTIVE: To determine the effects of disease activity and other risk factors on bone mineral density (BMD) in untreated systemic lupus erythematosus (SLE). METHODS: Lumbar and hip BMD were determined by dual energy X-ray absorptiometry (DXA) in 50 healthy controls and 120 premenopausal SLE females from Department of Rheumatology & Immunology, Third Hospital of Medical College of Jilin University during the period of 2010 - 2012. The SLE patients were divided into 2 groups, i.e. untreated and treated with glucocorticoid and immunosuppressives. Simple and multiple linear regression analyses were performed to determine the associations between BMD and disease-related variables. To completely eliminate the influences of glucocorticoid treatment on the results, the untreated SLE patients were chosen to investigate the risk factors with regression analysis. RESULTS: In femoral neck, greater trochanter and total hip, both the treated and untreated SLE patients had significantly lower BMD than the healthy controls (P < 0.01). In greater trochanter, the treated SLE group had significantly lower BMD than the untreated group. The BMD of left and right femoral neck of the former were botj -0.06 while that of the later -0.11 and -0.12 respectively (P < 0.05). Regression analysis showed that long disease duration and high (SLE disease activity index) SLEDAI were the risk factors of low BMD (P < 0.05), especially high SLEDAI. CONCLUSION: SLE itself may result in low BMD, especially in patients with high SLEDAI. Hip joints are predominantly affected. Long disease duration is also closely associated with low BMD in SLE.