Mechanism of Bcl-2 BH4 selective inhibitor BDA-366 on NK/T cell lymphoma cells / 国际肿瘤学杂志

Objective:To investigate the inhibitory effect and killing mechanism of Bcl-2 BH4 selective inhibitor BDA-366 on NK/T cell lymphoma (NK/TCL) .Methods:Human NK cell leukemia cell line YT and human NK/TCL cell line NK92 cells were treated with 0, 0.05, 0.10, 0.20, 0.30, 0.40, 0.50 μmol/L BDA-366. CCK-8 assay was used to calculate the half inhibitory concentration (IC 50) value of BDA-366 on these cells. The apoptosis levels of cells in control group and IC 50 BDA-366 treated group were detected by flow cytometry. Western blotting was used to detect the expression levels of apoptosis-related proteins in cells of control group and 1/2 IC 50, IC 50, 2× IC 50 BDA-366 treated groups. TMRE and Fluo-3 fluorescent probe were used to detect mitochondrial membrane potential of control group and IC 50 BDA-366 treated group, and the intracellular Ca 2+ concentration of control group, IC 50, 2× IC 50 BDA-366 treated groups. NOD-SCID mice in control group and 10 mg/kg BDA-366 intraperitoneal injection group were weighed and HE staining was performed to evaluate the toxicity of BDA-366 in vivo. Results:The IC 50 of BDA-366 for YT and NK92 cells were 0.065 and 0.086 μmol/L respectively. The apoptosis rates of YT cells in the control group and 0.065 μmol/L BDA-366 group were (6.62±1.59) % and (34.60±3.06) % respectively. The apoptosis rates of NK92 cells in the control group and 0.086 μmol/L BDA-366 group were (5.57±0.88) % and (29.18±0.90) % respectively, both with statistically significant differences ( t=14.05, P<0.001; t=32.58, P<0.001). The relative expression of Bax in NK92 cells of the control group, 0.043, 0.086 and 0.172 μmol/L BDA-366 groups were 0.85±0.00, 1.26±0.04, 1.51±0.18, 1.15±0.10 ( F=20.70, P<0.001), the relative expression of Bax in BDA-366 groups were higher than that in the control group (all P<0.05). The fluorescence intensity of TMRE of YT cells in the control group and 0.065 μmol/L BDA-366 group were 8 372.00±330.47 and 6 419.67±311.34, and that of NK92 cells in the control group and 0.086 μmol/L BDA-366 group were 9 169.00±535.72 and 7 311.67±295.52 respectively, and there were statistically significant differences ( t=7.45, P=0.002; t=5.26, P=0.006). In YT cells, the intracellular Ca 2+ concentrations of 0.065 and 0.130 μmol/L BDA-366 groups were significantly higher than that of the control group (5 791.67±220.45, 6 729.33±585.39, 4 874.67±112.61, F=19.16, P=0.003) ( P=0.039; P=0.002). In NK92 cells, the intracellular Ca 2+ concentrations of 0.086 and 0.172 μmol/L BDA-366 groups were significantly higher than that of the control group (4 553.67±17.62, 4 740.33±254.50, 4 185.67±17.67, F=10.96, P=0.010) ( P=0.039; P=0.007). There was no statistically significant difference in body weight change on day 12 compared with day 0 of NOD-SCID mice between BDA-366 group and control group [ (3.18±0.01) g vs. (2.73±0.58) g, t=0.60, P=0.570], and HE staining showed no abnormal morphology of heart, liver, spleen, lung and kidney in BDA-366 group. Conclusion:BDA-366 promotes NK/TCL cells apoptosis in vitro, but does not cause weight loss and morphological changes of organs by HE staining in vivo. The inhibitory effect of BDA-366 on NK/TCL cells may be achieved by increasing Bax expression, inducing Ca 2+ release and reducing mitochondrial membrane potential.

Behavioural and emotional problems in Malaysian children and adolescents with type 1 diabetes mellitus: A cross-sectional study in a single centre / Journal of the ASEAN Federation of Endocrine Societies

Introduction@#Type 1 diabetes mellitus (T1DM) is an autoimmune disorder that requires a lifelong treatment regimen which may affect psychosocial development.@*Objective@#To identify behavioural and emotional problems in children and adolescents with T1DM.@*Methodology@#A cross-sectional study using the Child Behaviour Check List (CBCL) was conducted among all T1DM patients receiving treatment at the Paediatric Endocrine Unit, Hospital Tunku Azizah Kuala Lumpur, Malaysia.@*Results@#Forty T1DM patients were included. The mean age of the participants was 12.4 years (SD=2.69), with 52.5% males, and 75% Malay. The average duration of illness was 4.8 years, 9 were pre-pubertal, while mean HbA1c was 9.4%. Thirty-five percent of the respondents had parent-reported internalizing problems and 17.5% had parent-reported externalizing problems. Those >12 years old had more internalizing problems (p=0.004) compared to those ≤12 years old. The differences were in the anxious/depressed syndrome subscale (p=0.001) and withdrawn/depressed syndrome subscale (p=0.015). There were no statistically significant differences in the 3 main global scores by gender, glycaemic control, duration of illness and pubertal status by univariate analysis.@*Conclusion@#T1DM patients >12 years old were at higher risk of developing psychosocial difficulties. This highlighted the benefit of screening of behavioural and emotional issues in children and adolescents with T1DM.

A Study on the Parenting Styles and Parental Stress of Parents of (Attention Deficit Hyperactivity Disorder) ADHD Children

Background: There are several steps involved in deciding if a child has ADHD. No single test is available to diagnose ADHD and many other problems such as depression, anxiety, sleep problems and certain types of learning disabilities can also have similar symptoms. One of the process involves doing a medical examination, including hearing and vision tests, to rule out other problems with symptoms like ADHD. Diagnosis of ADHD includes a checklist for rating ADHD symptoms and taking a history of the child from parents, teachers, and sometimes, the child itself. Aim & Objectives: To know the prevalence of psychiatric co-morbidities in ADHD and to assess parental stress and parenting style among parents of children having ADHD.Material & Methods:A total of 78 children (6 to 18 years of age) and their parents were selected for the completion this study. The study was carried out in the Department of Psychiatry, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi. Bivariate table and chi-square/Fisher Exact test were used. Correlation test has also been applied to know the association between demographic variables and their responses. Conclusions:We conclude that specific scales of the CBCL may help to identify specific comorbidities within ADHD cases in the primary care setting.

To study the usefulness of CBCL-TRF for assessment and screening of psychiatric morbidity in juvenile delinquent boys in an observation home.

Background: Given the growth of juvenile delinquent population, epidemiologic data on their psychiatric evaluation is becoming increasingly important. Rehabilitation for juvenile delinquent children is the key whether addressing healthcare, poverty, population control, unemployment or human rights issues. Therefore, the present study was undertaken to evaluate the usefulness of CBCL (Child Behaviour Checklist – TRF (Teacher Report Form) for assessment and screening of psychiatric morbidity in juvenile delinquent boys in an observation home. Method: The present cross-sectional study was conducted in an Observation Home for Boys. Prior to conducting the study, informed written permission was sought from the Superintendent of Observation Home for Boys. Study sample consisted of 50 boys aged between 6-16 years. The children were recruited through application of inclusion and exclusion criteria and after taking written informed permission from the Observation Home authorities. Results: Significant CBCL total score was found in 22 (44%) juveniles. Eighteen (36%) juveniles had high score on externalizing behaviour, and 14 (28%) on internalizing behaviour. The sensitivity of CBCL significant score was found to be 88.64% and specificity was 100%. This indicates the utility of CBCL in epidemiological studies and screening of juveniles. It is a simple tool for screening and as noted it has high sensitivity and specificity. Conclusion: In conclusion, the CBCL has implications for the training of manpower for strengthening of mental health services for these children. There is immediate need for multidisciplinary mental health services at each juvenile center.

Avaliação de aspectos emocionais e comportamentais de crianças com Transtorno do Espectro Autista / Evaluation of emotional and behavioral aspects in children with Autism Spectrum Disorder (ASD)

RESUMO O Transtorno do Espectro Autista (TEA) tem início precoce e é caracterizado predominantemente por prejuízos persistentes na comunicação social recíproca/interação social e por padrões restritos e repetitivos de comportamento, interesses ou atividades. Pesquisas apontam que indivíduos com TEA apresentam altas taxas de problemas emocionais e de comportamento. O objetivo do presente estudo é avaliar os aspectos emocionais e comportamentais através do Child Behavior Checklist (CBCL) em crianças que preencheram critérios para o diagnóstico de TEA. Trata-se de um estudo descritivo, quantitativo e retrospectivo. No CBCL/1½-5, contatou-se que a escala Problemas do Espectro Autista apresentou escore clínico. Quanto ao CBCL/6-18, as escalas Retraimento, Problemas de Pensamento, Problemas de Atenção e Problemas de Estresse (DSM) apresentaram sintomatologia clínica. Os achados desse estudo estão de acordo com outras pesquisas da área. Os resultados do presente estudo sugerem que o CBCL é útil para a identificação de sinais de alerta de TEA.

ABSTRACT Autism Spectrum Disorder (ASD) is a neurodevelopment disorder characterized by impairments in social interaction/communication and stereotyped behavior. The literature suggests that individuals with ASD often presents emotional and behavioral problems. The aim of this study was to examine emotional and behavioral aspects in patients who have been diagnosed with ASD after a psychological evaluation. The tool used for investigation was the Child Behavior Checklist (CBCL), in both versions (1½-5 and 6-18). This is a quantitative, descriptive and retrospective study. The CBCL/1½-5 profiles showed elevated scores in Withdrawn, Internalizing Problems and Autism Spectrum Problems scales. The CBCL/6-18 showed clinical scores for Withdrawn/Depressed, Thougt Problems, Attention Problems And Stress Problems. The pattern of elevations found in this study is consistent with prior studies. Although CBCL is not a diagnostic tool, it can be considered an useful instrument for detecting alarm signs of ASD.

Prevalence of attention deficit hyperactivity disorder, gender difference and its co morbidity among urban school children in a city of southern Rajasthan, India

Background: Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed disorders of childhood (3-5%). The main characteristics of attention deficit hyperactivity disorder are inattention, hyperactivity, and impulsivity. 'The Objective of this study was to study prevalence of ADHD in school aged children.Methods: A cross sectional descriptive school-based study was conducted in a private school of Udaipur from January 2017 to September 2018.' All eligible students were included. Total 1200 students were enrolled. They were assessed for the presence of ADHD using INCLEN diagnostic tool and those found positive were further assessed for the presence of co-morbid conditions using child behavior checklist (CBCL).Results: In present study out of total 1200 students 730(60.83%) were male and 470(39.17%) were female. 76 (6.3%) students out of 1200 were ADHD Positive. ADHD was more common in male students (73.7%), urban locality (57.89%), in age group 6 to 9 years (44.7%) and higher economic class (46.1%). Hyperactivity-Impulsivity type was most common type (51.32%). Male students had predominance of hyperactivity (60.7%) whereas in female student's inattention type was predominant (45%). Aggressive Behavior (19.6%) and rule breaking behavior (80.4%) was more common in male. Somatic complaints were more common in females (60%). Oppositional defiant disorder was observed in male (21.4%) and female (10%) students. 15.8% of ADHD students had learning disorder.Conclusions: Present study shows 6.3% prevalence of ADHD. Hyperactivity type of ADHD was more common in boys, while Inattention type was more common in girls. Among associated co morbid conditions - aggressive behavior, rule breaking behavior and oppositional defiant disorder (ODD) was found to be more prevalent in boys while anxious behavior, somatic complaints and social problems were more commonly found in girls. Thought problems, learning disorders and conduct disorders are also observed in ADHD students.

Mechanism underlying the anti-apoptotic activity of pORF5 plasmid protein in Chlamydia trachomatis via high-mobility group box 1 protein: a preliminary study / 中华皮肤科杂志

Objective To explore the molecular mechanism underlying the anti-apoptotic activity of pORF5 plasmid protein of Chlamydia trachomatis,so as to provide an experimental basis for further clarifying the pathogenesis of Chlamydia trachomatis.Methods HeLa cells were divided into two groups:carbonyl cyanide m-chlorophenyl hydrazone (CCCP,an apoptosis inducer) group was stimulated by CCCP for 30 minutes,and pORF5 + CCCP group was pretreated with pORF5 plasmid protein for 18 hours followed by CCCP for 30 minutes.Then,Western blot analysis was performed to determine the expression of apoptosisrelated proteins Bcl-2,Bax and caspase-3,JC-1 fluorescent probe was used to detect changes in the mitochondrial membrane potential in HeLa cells,and cytochrome c release from mitochondria was analyzed by indirect immunofluorescence assay.To analyze whether high-mobility group box 1 (HMGB1) protein participated in the anti-apoptotic role of pORF5 plasmid protein,HMGB 1 shRNA and control RNA were separately transfected into the HeLa cells,which were then stimulated by pORF5 plasmid protein and CCCP.Then,the protein expression of Bcl-2,Bax,activated caspase-3 was determined,and cytochrome c release was analyzed.Data were compared between two groups by using paired t test.Results pORF5 plasmid protein could antagonize the CCCP-induced decrease of mitochondrial membrane potential,and the red/green fluorescence intensity ratio was significantly lower in the CCCP group (0.4 ± 0.1) than in the pORF5 + CCCP group (1.7 ± 0.3;t =6.95,P ＜ 0.01).The protein expression of Bcl-2 in the HeLa cells in the pORF5 + CCCP group was 5.3 ± 0.6 times more than that in the CCCP group (t =8.62,P ＜ 0.01),while the protein expression of Bax and activated caspase-3 in the pORF5 + CCCP group significantly decreased by 79％ ± 10％ (t =9.23,P ＜ 0.01) and 75％ ± 8％ (t =4.26,P ＜ 0.05) respectively compared with the CCCP group.Compared with the control RNA transfection group,the HMGB1 shRNA transfection group showed significantly decreased mitochondrial membrane potential in the HeLa cells (t =11.23,P ＜ 0.01),increased cytochrome c release,decreased Bcl-2 expresson (t =7.19,P ＜ 0.05) and increased Bax expression (t =13.06,P ＜ 0.01) after stimulation with pORF5 and CCCP.Conclusion Chlamydia trachomatis plasmid protein pORF5 plays an anti-apoptosis role by blocking the mitochondrial apoptotic pathway through HMGB1 protein.

Asociación entre síntomas depresivos del cuidador principal y problemas conductuales en una muestra de preescolares chilenos de 30 a 48 meses de edad / Association between primary caregiver depressive symptoms and behavioral problems in a sample of chilean preschool children age 30 to 48 months

Resumen Introducción: La salud mental del cuidador influye en el desarrollo de los niños; sin embargo, desconocemos si existe una asociación entre síntomas depresivos del cuidador y problemas conductuales en preescolares chilenos. El objetivo fue analizar la asociación entre los síntomas depresivos del cuidador principal y la presencia de problemas conductuales en preescolares usuarios de la red pública de salud chilena. Método: Estudio transversal. Muestreo por conglomerados estratificados bietápico. Muestra de 1.377 preescolares de 2,5-4 años y sus cuidadores principales. Con consentimiento informado se aplicó encuesta sociodemográfica y Child Behavior Checklist 1½-5. Los síntomas depresivos del cuidador se evaluaron mediante Entrevista Diagnóstica Internacional Compuesta abreviada. Resultados: Edad promedio del preescolar 40,95 ± 4,6 meses, 51,3% varones. 97,5% fueron cuidadoras mujeres, edad promedio 31,6 ± 10,2 años y escolaridad 9,5 años. Se encontró problemas conductuales de rango clínico en las tres escalas: total de problemas conductuales 21,4%, conductas internalizantes 23,1% y externalizantes 16,4%. Se encontró sintomatologia depresiva en 9,1% de los cuidadores, la que aumenta a 14,5,% y 16,1% en cuidadores de preescolares con conductas internalizantes y externalizantes respectivamente. En el análisis de regresión logística multinomial ajustando por variables confundentes, la asociación bivariada con los problemas conductuales internalizantes desaparece, sin embargo, se mantiene para el total de problemas conductuales y conductas externalizantes. Conclusiones: La asociación entre síntomas depresivos del cuidador y problemas conductuales en preescolares chilenos es consistente y modulada por otras variables médicas y psicosociales, esto sugiere la importancia de la identificación, prevención e intervención temprana de la díada y su entorno.

Introduction: The mental health of the caregiver influences the development of children; however we do not know if there is an association between depressive symptoms of the caregiver and behavioral problems in Chilean preschoolers. The objective was to analyze the association between primary caregiver depressive symptoms and behavioral problems in preschoolers users of the Chilean public health network. Method: Cross-sectional study. Two-stage stratified cluster sampling. Sample 1377 preschool children 2,5-4 years old and their primary caregivers. In order to assess child behavior, a sociodemographic survey and Child Behavior Checklist ½-5 we applied to each caregiver, under informed consent. Caregiver depressive symptoms were assessed using the International Diagnostic Composite Interview Short Form. Results: Preschool age was 40.95 ± 4.6 months, 51.3% were boys. 97.5% of caregivers were female, (ages 31.6 ± 10.2 yr, average schooling 9.5 years). Behavioral problems of clinical rank were found in the three scales: total behavioral problems 21.4%, internalizing 23.1%, and externalizing behaviors 16.4%. 9.1% of caregivers experienced depressive symptomatology. In preschool children with internalizing behavioral, caregivers showed depressive symptoms in 14,5% of cases, and 16,1% in those with an externalizing behavioral. In multinomial logistic regression analysis adjusted for confounding variables, bivariate association for internalizing behavioral problems was lost, but persisted for total behavioral problems and for externalizing behavioral. Conclusions: The association between caregiver's depressive symptoms and behavioral problems in Chilean preschool children is consistent and modulated by other medical and psychosocial variables, suggesting the importance of identification, prevention and early intervention of the dyad and their environment.

A study on psychosocial behavioral outcomes of microtia children and their parents after microtia reconstruction / 中华整形外科杂志

Objective@#To explore the psycho-social and behavioral outcomes of microtia children and psychological health of their parents after microtia reconstruction, and to observe the effects of microtia reconstruction on the psycho-social health of microtia children and their parents.@*Methods@#72 patients were recruited and investigated for their psycho-social behavioral problems with Achenbach′s Child Behavior Checklist (CBCL). Their parents were investigated for psychological health with symptom checklist 90 (SCL-90). The patients and their parents were both assessed with questionnaire before the after operation (6 to 12months post-operation).@*Results@#After microtia reconstruction, the scores of CBCL and SCL-90 decreased significantly.①As determined from CBCL, after operation the scores of activity and sociality ability of the patients increased with significant difference in statistics (P<0. 01). The behavioral problems raw scores were lower than that of pre-operation. The percentage of behavioral problems of the microtia children decreased significantly compared with that before operation, it was significant in statistics (P<0. 01). ②As determined from SCL- 90, it is found out that the general scores and the number of positive items of the parents with microtia children decreased with significant difference in statistics (P<0.01). The scores of SCL-90 factors decreased with a significant difference in statistics (P<0.05).@*Conclusions@#There was significant improvement in the psycho-social behavioral outcomes of microtia children and their patients after microtia reconstruction. There is a positive effect of microtia reconstruction on microtia children and their parents.

Correlação entre o perfil do sono e o comportamento em indivíduos com transtorno específico da aprendizagem / Correlation between sleep profile and behavior in individuals with specific learning disorder

RESUMO Objetivo Correlacionar o sono e o comportamento em indivíduos com transtorno específico da aprendizagem. Método Na análise do sono, foram utilizados o Questionário de Hábitos Gerais de Sono, o Diário de Sono e a Escala de Distúrbios do Sono em Crianças (EDSC) e, para análise do comportamento, foi utilizado o Child Behavior Checklist (CBCL). Resultados 65,5% dos indivíduos com transtorno específico de aprendizagem apresentaram indicativo de distúrbios de sono, sendo os mais frequentes os distúrbios de transição sono-vigília e escores totais para distúrbios de sono acima do aceitável. Além disso, os indivíduos com transtorno específico de aprendizagem apresentaram maior latência de sono que o respectivo grupo controle. Quanto ao comportamento, 72,4% dos indivíduos com transtorno específico de aprendizagem apresentaram quadro clínico de problemas comportamentais. No grupo controle, nenhum dos participantes apresentou indicativo de problemas de sono ou comportamento. No grupo transtorno específico de aprendizagem, os distúrbios de sono encontrados apresentaram correlação com os problemas comportamentais. Conclusão Indivíduos com transtorno específico da aprendizagem apresentaram altos índices de distúrbios de sono e alterações comportamentais. Quanto piores os distúrbios de sono, piores foram os aspectos comportamentais dos indivíduos com transtorno específico da aprendizagem.

ABSTRACT Purpose This study aimed to correlate sleep profile and behavior in individuals with Specific Learning Disorder (SLD). Methods The Sleep General Habits Questionnaire, Sleep Diary, and Sleep Disturbance Scale for Children (SDSC) were used in analysis of sleep, whereas the Child Behavior Checklist (CBCL) inventory was used in analysis of behavior. Results 65.5% of the individuals with SLD presented symptoms of sleep disorders, most frequently wakefulness-sleep transition and sleep disturbance total score, which showed values higher than acceptable. In addition, individuals with SLD presented higher sleep latency than those with typical development. Concerning behavior, 72.4% of the individuals with SLD presented clinical condition of behavior problems. In the control group, none of the participants showed symptoms of sleep or behavior problems. In the SLD group, correlation was observed between behavioral problems and sleep disturbance. Conclusion Individuals with SLD showed high rates of sleep disturbance and behavioral problems. The worse the sleep disturbance, the worse the behavioral aspects in these individuals.

Association between serotonin 2C receptor gene (HTR2C) polymorphisms and psychopathological symptoms in children and adolescents

Serotonin 2C receptors (5HT2C) are involved in serotonin-driven dynamic equilibrium adjustments responsible for homeostatic stability in brain structures that modulate behavior and emotions. Single nucleotide polymorphisms (SNPs) from the serotonin 2C receptor gene (HTR2C) have been associated with several neurological and mental disorders, including abnormalities in cognitive and emotional processes. The aim of this study was to evaluate the association between the rs6318 SNP of the HTR2C gene and behavioral characteristics exhibited by children and adolescents based on the Child Behavior Checklist (CBCL/6-18) inventory. Eighty-five psychiatric outpatients between 8 and 18 years of age underwent genotyping of the rs6318 SNP. The CBCL/6-18 scale was administered to their caregivers. The chi-squared test was used to assess differences in the frequency of C and G alleles of the rs6318 SNP relative to the grouped CBCL/6-18 scores; significance level was 5%. The presence of the G allele of rs6318 was found to be associated with characteristics of aggressive behavior and social problems, and aggressive behavior was found to be associated with heterozygosis in females. These findings contribute to the identification of mental and behavioral phenotypes associated with gene expression.

Hipercalcemia, peak monoclonal y leucemización como presentación de un linfoma de células B de alto grado, con reordenamiento de MYC, BCL-2 y BCL-6 (Triple Hit). Caso clínico / Hypercalcemia, monoclonal peak and leukemic presentation of a High-grade B-cell lymphoma with MYC, BCL-2 and BCL-6 translocations (triple hit). Report of one case

High-grade B-cell lymphomas with rearrangement of MYC, BCL-2 and/or BCL-6 were introduced by the update of the WHO classification of lymphoid neoplasms. They usually present unique morphological and molecular characteristics, with an aggressive clinical outcome and worse prognosis. We report a 48 year-old female patient presenting with B symptoms and enlarged lymph nodes. Blood count showed pancytopenia and peripheral blood smears showed large lymphoid cells, some with nuclei and vacuoles. LDH was 3524 g/L and serum calcium was 11.5 mg/dL. Flow cytometry immunophenotyping showed pathological mature B lymphocytes. Protein electrophoresis showed a slight monoclonal peak. The biopsy disclosed a triple expressor diffuse large B-cell lymphoma, arising from germinal center. FISH was positive for MYC, BCL-2 and BCL-6 (triple hit) with a clonal evolution. Conventional cytogenetics showed a complex karyotype. Chemotherapy was started with R-CHOP (Rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone). She developed impaired consciousness; the brain CT scan showed a large brain mass. The patient died within 3 weeks.

Effects of delayed mild hypothermia based on different time windows on the expressions of Bcl-2, Bax and Caspase-3 after traumatic brain injury in rats / 天津医药

Objective To explore the effects of delayed mild hypothermia (MHT) in different time windows on the expressions of Bcl-2, Bax and Caspase-3 in brain tissue of model rats with traumatic brain injury (TBI). Methods Thirty-six clean adult male SD rats were randomly divided into NT group (normal temperature), MHT 15 min group, MHT 2 h group and MHT 4 h group. TBI rat model was established by electronical controlled cortical injury device. The rats in the NT group were treated with normothermia (37℃) and the rats in the three hypothermia groups were implemented with low temperature (33.0±1.0)℃at 15 min, 2 h and 4 h for 6 h respectively after establishment of TBI model. The modified neurological senerity scores (mNSS), morphological changes in hippocampal CA1 areas, immunohistochemical staining and Western blot assay for Bcl-2, Bax and Caspase-3 were compared 3 days after TBI between the four groups. Results The neurological behavioral deficits were found in each group. Compared with the NT group, the mNSS were decreased in the three hypothermia groups (P<0.01). The results of HE staining showed that the structure of neurons was regular and arranged neatly, and the number of neurons decreased with alleviated nuclear fragmentation and dissolution in hypothermia groups. Compared with the NT group, the expression of Bcl-2 was upregulated, and the expressions of Bax and Caspase-3 were downregulated in three hypothermia groups (P<0.05). The above experimental results were superior in MHT15 min group to MHT 2 h group, and the therapeutic effect in MHT 2 h group was similar to MHT 4 h group. Conclusion The proper delayed mild hypothermia treatment could inhibit neuronal apoptosis and alleviate brain damage.

Prognostic significance of proteins expression by immunohistochemical method in diffuse large B cell lymphoma / 中华血液学杂志

Objective@#To analyze the prognostic significance of TP53, Bcl-2, Bcl-6, Myc proteins expression by immunohistochemical method (IHC) in diffuse large B cell Lymphoma (DLBCL) .@*Methods@#Clinical and pathologic data of 223 patients with DLBCL hospitalized in Zhejiang First Hospital from March 2009 to June 2015 were retrospectively analyzed.@*Results@#The 223 cases, a median age of 56 years old with a male predominance, had shown a 39.0% of TP53 positive expression, 38.6% of Myc, 69.1% of Bcl-2, 56.5% of Bcl-6, and 22.7% of Myc/Bcl-2 double expression. According to Hans’ classification, 27.4% were GCB and 72.6% were non-GCB. With a median follow-up of 38 (2-97) months, the 3 and 5 years survival rates were 70% and 66% , respectively. By multivariate analysis, TP53 over-expression and Myc/Bcl-2 double expression were independently associated with poor outcomes. 3-year and 5-year overall survival were 59% and 57% for patients with TP53 positive, 77% and 71% for patients with TP53 negative expression. Patients with non-GCB subtype receiving chemotherapy combined with rituximab had a higher OS than those without rituximab. But rituximab did not improve the prognosis of patients with TP53 positive.@*Conclusion@#Myc/Bcl-2 double expression and TP53 over-expression are poor prognosis for DLBCL patients. Patients with Myc/Bcl-2 double expression have shorter OS. Patients with non-GCB subtype who received chemotherapy combined with rituximab have a better OS than those without rituximab. But rituximab does not improve the prognosis of patients with TP53 positive.

Percepção de mães brasileiras e espanholas sobre os problemas de comportamento dos filhos com TDAH / Perception of Brazilian and Spanish mothers about behavior problems in children with ADHD / Percepción de madres brasileñas y españolas acerca de los problemas de conducta en hijos con TDAH

Compreendendo a gravidade que os problemas de comportamento podem acarretar no desenvolvimento da criança ao longo da vida, o principal objetivo deste estudo foi comparar a percepção de mães em relação aos problemas de comportamentos listados no CBCL (Child Behavior Checklist) em duas amostras clínicas compostas de crianças brasileiras e espanholas com o diagnóstico de TDAH. O estudo é do tipo exploratório-descritivo, documental, retrospectivo, transversal, de caráter quantitativo dos prontuários de pacientes atendidos entre janeiro de 2010 a abril de 2015 no Hospital Universitário Virgen de la Arrixaca ­ Murcia/Espanha, e no Hospital Universitário Bettina Ferro de Souza ­ Belém/Brasil. Em comparação com as mães espanholas, as mães brasileiras relataram escores significativamente mais altos em quatro escalas, sendo elas: Internalização; Retraimento/Depressão; Queixas Somáticas e Problemas de Pensamento. Enquanto que, nas demais escalas, os escores foram relativamente similares em ambas as culturas. Estudos transculturais têm sido imprescindíveis para a melhor compreensão das semelhanças e diferenças das percepções de pessoas que vivem em culturas distintas.

Understanding the severity of the behavior problems can result in the development of the child throughout life, the aim of this study was to compare the perception of mothers in relation to behavior problems listed in the CBCL (Child Behavior Checklist) in two clinical samples composed of Brazilian and Spanish children diagnosed with ADHD. Method: The study is an exploratorydescriptive, documental, retrospective, cross-sectional, quantitative nature of the medical records treated between 2010 to April 2015 at the Hospital Universitario Virgen de la Arrixaca ­ Murcia/Spain, and the Hospital Universitário Bettina Ferro de Souza ­ Belém/Brasil. Results: The Brazilian mothers reported significantly higher scores on four scales compared to the Spanish mothers, and in the other, the scores were relatively similar in both cultures. Conclusion: cross-cultural studies have been essential to a better understanding of the similarities and differences in perceptions of people living in different cultures.

Comprendiendo la gravedad que los problemas de conducta pueden causar en el desarrollo del niño durante toda la vida, el objetivo de este estudio fue comparar la percepción de las madres en relación con los problemas de conducta que figuran en el CBCL (Child Behavior Checklist) en dos muestras clínicas compuestas de niños brasileños y españoles diagnosticados con TDAH. Método: El estudio es un documental-exploratorio descriptivo, transversal, de naturaleza cuantitativa retrospectiva de los informes de pacientes asistidos entre 2010 y abril de 2015 en el Hospital Universitario Virgen de la Arrixaca ­ Murcia/España, y en el Hospital Universitario de Bettina Ferro de Souza ­ Belém/Brasil. Resultados: Las madres brasileñas tuvieron puntuaciones significativamente mayores en cuatro escalas en comparación con las madres españolas, y en las demás, las puntuaciones fueron relativamente similares en ambas culturas. Conclusión: los estudios transculturales han sido esenciales para una mejor comprensión de las similitudes y diferencias en las percepciones de las personas que viven en las diferentes culturas.

Problemas de comportamento em crianças e adolescentes com falta de controle urinário noturno / Behavioral problems in children and adolescents with nocturnal enuresis

A enurese é um problema que aflige muitas crianças. O objetivo deste estudo foi investigar a associação entre a falta de controle urinário noturno e problemas de comportamento. Participaram 774 pais de crianças e adolescentes de 5 a 18 anos, respondendo ao Child Behavior Checklist - CBCL. Foi selecionado o item “meu filho faz xixi na cama”, que foi comparado com os demais itens do instrumento e seus resultados. Verificou-se que 8,91% dos pais assinalaram positivamente este item. Houve associação entre falta de controle urinário noturno e idade, escolaridade - os mais novos, os que estudam nas séries iniciais do Ensino Fundamental e os com defasagem idade-série escolar -, e problemas de comportamento medidos pelo CBCL. Observou-se que ‘molhar a cama’ é um problema comum e pode levar a importantes distúrbios sociais e psicológicos. A implementação de uma triagem para problemas psicológicos pode contribuir para um melhor tratamento da enurese noturna.

Enuresis (bedwetting) is a problem that affects a large number of children. The aim of the present study was to investigate associations with bedwetting and behavioral problems. A total of 774 parents of children and adolescents aged five to 18 years responded to the Child Behavior Checklist. The item “my child wets the bed” was selected and compared to the other items on this checklist. A total of 8.91% of the parents checked the item in question. Nocturnal enuresis was associated with age (younger children), schooling (those in early years of elementary school and those behind in school for their age) and behavioral problems measured by the checklist. Bedwetting is a common problem that can lead to social and psychological disorders. The implementation of a screening protocol for psychological problems could contribute to better treatment in cases of nocturnal enuresis.

Effects of Early Childhood Peer Relationships on Adolescent Mental Health: A 6- to 8-Year Follow-Up Study in South Korea

OBJECTIVE: Peer relationships are one of the important factors in children's development. The present study examines the relationship between the effects of early peer relationships and adolescent psychological adjustment. METHODS: The first survey took place from 1998 to 2000, and a follow-up assessment obtained data in 2006, as the original participants reached 13-15 years of age. The first assessment used the Korean version of the Child Behavior Checklist (K-CBCL) and simple questions about peer relationships to evaluate the participants. The follow-up assessment administered the Korean Youth Self Report (K-YSR). RESULTS: Children's peer relationships have longitudinal effects on mental health and adjustment. Children who had qualitative peer-relation problems were more likely to exhibit internalizing problems as adolescents. CONCLUSION: Children who have poor peer relationships might become more vulnerable to emotional problems and social adjustment as adolescents.

Effects of sinomenine on hind limb ischemia-reperfusion injury and expression of Bcl-2 and Bax in skeletal muscle cells of rats / 中华麻醉学杂志

Objective To investigate the effects of sinomenine on hind limb ischemia?reperfusion ( I∕R) injury and expression of Bcl?2 and Bax in skeletal muscle cells of rats. Methods Fifty?four healthy adult male Wistar rats, aged 6-8 weeks, weighing 180-220 g, were divided into 3 groups ( n=18 each) using a random number table: sham operation group ( group S) , group I∕R and sinomenine group ( group SIN) . The rats were subjected to 4 h of ischemia on the proximal part of the right hind limb using elastic rubber bands followed by reperfusion in I∕R and SIN groups. Sinomenine 60 mg∕kg was injected intraperito?neally at 30 min before reperfusion in group SIN, and the equal volume of normal saline was given instead of sinomenine at 30 min before reperfusion in S and I∕R groups. Immediately after onset of reperfusion and at 4 and 24 h of reperfusion, blood samples were collected from the cardiac apex to measure the concentra?tions of serum lactate dehydrogenase ( LDH) and creatine kinase ( CK) . The animals were sacrificed imme?diately after blood sampling, and the gastrocnemius specimens of the hind limb were immediately removed for determination of the wet to dry weight ratio ( W∕D ratio) and expression of Bcl?2 and Bax in gastrocnemi?us cells ( by immunohistochemistry) and for examination of the pathological changes after haematoxylin and eosin staining. The Bcl?2∕Bax ratio was calculated. Results Compared with group S, the gastrocnemius W∕D ratio and concentrations of serum LDH and CK were significantly increased, the expression of Bcl?2 was significantly down?regulated, the expression of Bax was significantly up?regulated, and the Bcl?2∕Bax ratio was significantly decreased in I∕R and SIN groups ( P<0?05) . Compared with group I∕R, the gastroc?nemius W∕D ratio and concentrations of serum LDH and CK were significantly decreased, the expression of Bcl?2 was significantly up?regulated, the expression of Bax was significantly down?regulated, and the Bcl?2∕Bax ratio was significantly increased in group SIN ( P<0?05) . The pathological changes of the gastrocne?mius were significantly attenuated in group SIN as compared with group I∕R. Conclusion Sinomenine can attenuate hind limb I∕R injury, and the mechanism may be related to maintenance of the balance between Bcl?2 and Bax and to inhibition of apoptosis in skeletal muscle cells of rats.

Study on the inhibitory effect of the black garlic extract on the growth of hela cells / 中国医师杂志

Objective To explore the effect of black garlic extract on HeLa cells and its possible molecular mechanisms.Methods Inhibitory rate of HeLa cells was detected with methyl thiazolyl tetrazolium(MTT).Flow cytometry annexin V-fluorescein isothiocyanate/propidium iodide (V-FITC/PI) was used to detect tumor cell apoptosis.Flow cytometry was used to measure cell-cycle changes.Immunohistochemistry method was used to detect expressions of tumor proteins bax and Bcl-2.Results Black garlic extract significantly inhibited the growth of HeLa cells.Black garlic extract significantly induced apoptosis of HeLa cells.The apoptosis rate was (53.26 ± 1.78)％ in the black garlic high-dose group,and (3.68 ±0.11)％ in the control group.Black garlic extract affected cell cycle,upregulated bax expression,and downregulated bcl-2 expression.Conclusions Black garlic extract significantly induced the apoptosis of HeLa cells.This effect might be caused through increasing G2/M cells or changing expressions of bax and bcl-2.

Effect of berberine on the proliferation and apoptosis of a human skin squamous cell carcinoma cell line A431 / 中华皮肤科杂志

Objective To estimate the effect of berberine on the proliferation of and expressions of apoptosisrelated factors Bax and Bcl-2 in a human skin squamous cell carcinoma cell line A431.Methods A431 cells were cultured in vitro,and classified into various groups to be treated with berberine at different concentrations (12.5,25,5,100 mg/L) or cisplatin at 250 mg/L (positive control group) for different durations (12,24,48 and 72 hours).The A431 cells remaining untreated served as the negative control group.Subsequently,methyl thiazolyl tetrazolium (MTT) assay was performed to evaluate cell growth,and inverted microscopy to observe cell morphology.Real time quantitative reverse transcription-PCR and an immunofluorescence assay were conducted to measure the mRNA and protein expressions of Bax and Bcl-2 respectively.Statistical analysis was done by multi-way analysis of variance (ANOVA) using the software SPSS 13.0.Results MTr assay showed that berberine inhibited the growth of A431 cells,and the inhibitory effect increased with the increase in concentration (F =1118.312,P ＜ 0.001) and treatment duration (F =510.927,P ＜ 0.001) of berberine.Moreover,there was a significant interaction between the concentration and treatment duration of berberine (F =70.239,P ＜ 0.001).Inverted microscopy revealed that when the concentration of berberine increased,cell density was reduced,and cell morphology changed from polygonal to round with cell body shrinkage.The ratio of bax to Bcl-2 mRNA was elevated with the increase in treatment duration and concentration of berberine,and there were significant differences in the mRNA ratio among cells treated with berberine for different time durations at same concentrations (F =226.231,1300.636,4325.139 for berberine at 25,50 and 100 mg/L respectively,all P＜ 0.001).Immunofluorescence staining indicated that the fluorescence intensity of Bax was enhanced,while that of Bcl-2 was weakened after berberine treatment.Conclusions Berberine inhibits the growth of A431 cells in a dose-and timedependent manner,and may induce the apoptosis of A431 cells via regulating the expressions of Bax and Bcl-2.