OBJECTIVE: To analyze recurrence and progression patterns of primary central nervous system lymphoma (PCNSL) in patients without whole brain radiotherapy (WBRT) and assess the value of WBRT in PCNSL treatment. METHODS: This retrospective single-center study included 27 patients with PCNSL, who experienced recurrence/progression after achieving complete remission (CR), partial remission, or stable disease following initial treatments with chemotherapy but without WBRT. The patients were followed up regularly after the treatment for treatment efficacy assessment. By comparing the anatomical location of the lesions on magnetic resonance images (MRI) at the initial diagnosis and at recurrence/progression, we analyzed the patterns of relapse/progression in patients with different treatment responses and different initial status of the lesions. RESULTS: MRI data showed that in 16 (59.26%) of the 27 patients, recurrence/progression occurred in out-field area (outside the simulated clinical target volume [CTV]) but within the simulated WBRT target area in 16 (59.26%) patients, and within the CTV (in-field) in 11 (40.74%) patients. None of the patients had extracranial recurrence of the tumor. Of the 11 patients who achieved CR after the initial treatments, 9 (81.82%) had PCNSL recurrences in the out-field area but within WBRT target area; of the 13 patients with a single lesion at the initial treatment, 11 (84.62%) experienced PCNSL recurrence in the out-field area but within WBRT target area. CONCLUSIONS Systemic therapy combined with WBRT still remains the standard treatment for PCNSL patients, especially those who achieve CR after treatment or have a single initial lesion. Future prospective studies with larger sample sizes are needed to further explore the role of low-dose WBRT in PCNSL treatment.
Humans ; Lymphoma/radiotherapy* ; Central Nervous System Neoplasms/pathology* ; Retrospective Studies ; Prospective Studies ; Neoplasm Recurrence, Local/drug therapy* ; Combined Modality Therapy ; Brain/pathology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Methotrexate

Kaposiform lymphangiomatosis(KLA)is an aggressive subtype of generalized lymphatic anomaly. It is difficult to diagnose because of the lack of specificity of early symptoms. Moreover, there is still a lack of effective treatment, so the prognosis of this disease is generally poor, with a 5-year survival rate of 51% and an overall survival rate of only 34%. This article reviews the progress of the genetic studies related to the development of KLA and summarizes potential drug targets. A review of the literature found that the mutations potentially associated with KLA pathogenesis included NRAS gene mutations and CBL gene mutations. The signaling pathways involved were the PI3K-AKT-mTOR pathway and the RAS-MAPK-ERK pathway. Therefore, the key molecules PI3K/AKT/mTOR and RAS/MEK in the above signaling pathway may be used as targets for KLA-targeted therapy and develop specific treatments.

Kaposiform lymphangiomatosis(KLA)is an aggressive subtype of generalized lymphatic anomaly. It is difficult to diagnose because of the lack of specificity of early symptoms. Moreover, there is still a lack of effective treatment, so the prognosis of this disease is generally poor, with a 5-year survival rate of 51% and an overall survival rate of only 34%. This article reviews the progress of the genetic studies related to the development of KLA and summarizes potential drug targets. A review of the literature found that the mutations potentially associated with KLA pathogenesis included NRAS gene mutations and CBL gene mutations. The signaling pathways involved were the PI3K-AKT-mTOR pathway and the RAS-MAPK-ERK pathway. Therefore, the key molecules PI3K/AKT/mTOR and RAS/MEK in the above signaling pathway may be used as targets for KLA-targeted therapy and develop specific treatments.

Objective:To explore the effects of IGF-1 on cognitive function in REM sleep deprivation model mice and its possible mechanism.Methods:C57BL/6J mice aged 8 weeks were randomly divided into 4 groups with 6 mice in each group.They were Normal control group (CC group), REM sleep deprivation 5d group (SD group), REM sleep deprivation 5d+ Intraperitoneal injection of IGF-1 group (SD+ IGF-1 group), and REM sleep deprivation 5d+ Intraperitoneal injection of PBS group (SD+ PBS group). The Morris water maze was used to test the cognitive function of all mice.The content of IGF-1 in mice hippocampus was detected by Elisa, and the expression level of TNF-α, IL-1β and IL-6 mRNA in mice in hippocampus was determined by RT-qPCR.Western blot was used to detect the protein expression levels of p-GSK3β, GSK3 beta, p-Akt, Akt, Bcl-2 and Caspase-9 in mice hippocampus of each group.Results:The time in the target quadrant and the number of times across the platform of the SD group ((11.87±1.67)s, (12.50±5.54) times, respectively)was lower than that of the CC group((19.40±1.75)s, (22.17±8.21) times, respectively), the difference was statistically significant( t=8.71, 2.26, both P<0.05). The time in the target quadrant and the number of times across the platform of the SD+ IGF-1 group ((18.11±1.12)s, (21.83±10.26) times), which were higher than those in the SD+ PBS group ((10.60±1.36)s, (11.50±3.94) times). The difference was statistically significant( t=8.69, 2.42, both P<0.05). The expression of IGF-1 protein in the hippocampus of SD group ((579.38±55.95) pg/mg) was lower than that of CC group ((729.13±79.46)pg/mg), and the difference was statistically significant ( t=3.83, P<0.05). The expression of IGF1 protein in the hippocampus of SD+ IGF-1 group((665.50±55.21)pg/mg) was significantly higher than that of SD+ PBS group ((563.40±76.33)pg/mg), the difference was statistically significant ( t=2.61, P<0.05). The expression of p-GSK3 beta protein (1.51±0.02) in mice hippocampus of SD group was higher than that of CC group (1.47±0.03), and the expression of p-Akt (0.92±0.04) was lower than that of CC group (1.18±0.05), The difference was statistically significant ( t=3.07, t=10.85, both P<0.05). The expression of Caspase-9 in mice hippocampus of SD group(0.65±0.03)was higher than that of CC group (0.60±0.02). The expression of Bcl-2 in mice hippocampus of SD group (0.93±0.03) was lower than that of CC group (1.00±0.04), and the difference was statistically significant ( t=3.65, 3.98, both P<0.05). The expression of p-Akt and p-GSK3β protein in mice hippocamps of SD+ IGF-1 group( (1.20±0.04), (1.57±0.03)) was increased compared with those of SD+ PBS group ((0.92±0.05), (1.51±0.03)), and the difference was statistically significant ( t=3.98, 11.49, both P<0.05). The expression of Caspase-9 in mice hippocamps of SD+ IGF-1 group (0.60±0.03) was decreased compared with that of SD+ PBS group (0.67±0.02). The expression of Bcl-2 in mice hippocampus of SD+ IGF-1 group (1.00±0.03) was increased compared with SD+ PBS group (0.93±0.02), and the difference was statistically significant ( t=5.19, 3.83, both P<0.05). The expression level of TNF-α, IL-1β, and IL-6 mRNA in mice hippocampus of SD group ((3.36±0.67), (2.00±0.40), (4.63±0.72)) were increased compared with CC group with statistically significant differences ( t=8.58, 6.15, 2.37, all P<0.05). The expression level of TNF-α, IL-1β, and IL-6 mRNA in mice hippocampu of SD+ IGF-1 group ((1.21±0.25), (1.08±0.33), (0.98±0.47)) were lower than those of SD+ PBS group ((3.86±0.79), (2.11±0.30), (4.43±0.67)), with statistically significant differences ( t=7.81, 5.76, 10.39, all P<0.05). Conclusion:The cognitive function of mice decreased after REM sleep deprivation and improved after IGF-1 supplementation, which may be related to the activation of PI3K / Akt signal pathway by IGF-1, thus reducing apoptosis related signal transduction and inflammatory factor expression.

Objective:To examine the prospective association of pubertal timing and tempo with depressive symptoms in adolescents.Methods:Since 2013, 2 084 students in grade 1-3 were selected from two primary schools in Bengbu, Anhui Province were selected by using convenience sampling method to establish the adolescence pubertal development cohort. Followed up for 6 years, physical examination, secondary sexual development evaluation (testicular volume for boys and breast development for girls) and depressive symptoms were evaluated biennially. Non-linear growth model was used to estimate pubertal timing and tempo for boys and girls respectively. Depressive symptoms were interviewed by using the Short Mood & Feeling Questionnaire (SMFQ) at baseline and Mood & Feeling Questionnaire (MFQ) during follow-up for students in grade 1-2. Children Depression Inventory (CDI) was used for students in grade 3 at baseline and during follow-up. Depressive symptom scores were standardized by using the Z-score method. Multivariate linear regression model was used to analyze the predictive effects of modeling pubertal timing and tempo on depressive symptoms of adolescence boys and girls. Results:There were 1 909 students with complete questionnaire and puberty development information, including 1 052 boys (59.19%) and 857 girls (43.81%), with average age about (13.94±0.87) years and 91.60 percent follow-up rate. The average modeling pubertal timing of girls (11.25 years) was earlier than that of boys (12.70 years), and the average pubertal tempo of girls about 1.47 Tanner stage/year was faster than that of boys about 1.28 Tanner stage/year. After controlling for depressive symptoms, maternal education and adverse childhood experiences at baseline and age, body mass index (BMI) classification and sleep time during follow-up, this predictive effect of pubertal timing and tempo on depressive symptoms was only significant among girls. Compared with girls with on time pubertal timing, girls in the delay timing group had a lower level of depressive symptoms (β=-0.19, 95% CI:-0.34,-0.01). Compared with girls in average pubertal tempo group, the fast tempo group associated with an increasing risk of depressive symptoms (β =0.23, 95% CI: 0.05, 0.40), while the slow tempo group associated with an decreasing risk of depressive symptoms (β =-0.21, 95％ CI:-0.39,-0.03). Insignificant effects were found in puberty timing and tempo on depressive symptoms of boys ( P>0.05). Conclusion:Fast pubertal tempo increases the risk of development of depressive symptoms of adolescent girls. There is no predictive effect of pubertal timing and tempo on depression symptoms of adolescent boys.

Objective:To examine the prospective association of pubertal timing and tempo with depressive symptoms in adolescents.Methods:Since 2013, 2 084 students in grade 1-3 were selected from two primary schools in Bengbu, Anhui Province were selected by using convenience sampling method to establish the adolescence pubertal development cohort. Followed up for 6 years, physical examination, secondary sexual development evaluation (testicular volume for boys and breast development for girls) and depressive symptoms were evaluated biennially. Non-linear growth model was used to estimate pubertal timing and tempo for boys and girls respectively. Depressive symptoms were interviewed by using the Short Mood & Feeling Questionnaire (SMFQ) at baseline and Mood & Feeling Questionnaire (MFQ) during follow-up for students in grade 1-2. Children Depression Inventory (CDI) was used for students in grade 3 at baseline and during follow-up. Depressive symptom scores were standardized by using the Z-score method. Multivariate linear regression model was used to analyze the predictive effects of modeling pubertal timing and tempo on depressive symptoms of adolescence boys and girls. Results:There were 1 909 students with complete questionnaire and puberty development information, including 1 052 boys (59.19%) and 857 girls (43.81%), with average age about (13.94±0.87) years and 91.60 percent follow-up rate. The average modeling pubertal timing of girls (11.25 years) was earlier than that of boys (12.70 years), and the average pubertal tempo of girls about 1.47 Tanner stage/year was faster than that of boys about 1.28 Tanner stage/year. After controlling for depressive symptoms, maternal education and adverse childhood experiences at baseline and age, body mass index (BMI) classification and sleep time during follow-up, this predictive effect of pubertal timing and tempo on depressive symptoms was only significant among girls. Compared with girls with on time pubertal timing, girls in the delay timing group had a lower level of depressive symptoms (β=-0.19, 95% CI:-0.34,-0.01). Compared with girls in average pubertal tempo group, the fast tempo group associated with an increasing risk of depressive symptoms (β =0.23, 95% CI: 0.05, 0.40), while the slow tempo group associated with an decreasing risk of depressive symptoms (β =-0.21, 95％ CI:-0.39,-0.03). Insignificant effects were found in puberty timing and tempo on depressive symptoms of boys ( P>0.05). Conclusion:Fast pubertal tempo increases the risk of development of depressive symptoms of adolescent girls. There is no predictive effect of pubertal timing and tempo on depression symptoms of adolescent boys.

Objective: To investigate the longitudinal association between peer bullying victimization and internalizing symptoms, and to examine whether parental warmth buffers against this effect,so as to provide a reference for improving the mental health of the special group of children. Methods: Students in grade 4 and grade 5 from three primary schools in Ma’anshan, Anhui Province were selected in Oct. 2017 with informed consent. Height, weight and pubertal development were objectively assessed. Internalizing symptoms and peer bullying victimization were evaluated at baseline and 1-year follow-up by using the MacArthur Health and Behavior Questionnaire-Child. Children were classified into three groups as non-bullying, non-consistent and consistent bullying victimization group. Multiple linear regression model was used to analyze whether the association between peer bullying victimization and internalizing symptoms varied across different parental warmth groups. Results: Compared with non-bullying victimization group, consistent-and non-consistent bullying victimization had higher internalizing symptoms at baseline and 1-year follow-up(P<0.01). Students reported consistent, non-consistent bullying victimization under moderate parental warmth had lower internalizing symptoms at baseline and 1-year follow-up than those reported under low parental warmth group(P<0.01). Multiple liner regression showed that consistent bullying victimization [β=0.66(95%CI=0.33-0.99), 0.37(95%CI=0.15-0.59), 0.58(95%CI=0.31-0.84), P<0.05] and non-consistent bullying victimization[β=0.33(95%CI=0.18-0.47), 0.28(95%CI=0.13-0.41), 0.29(95%CI=0.08-0.51),P<0.05] were associated with higher 1-year follow-up internalizing symptoms in non-consistent, moderate-and low parental warmth group, while such association was not observed in consistent parental warmth group. Abstract The experience of peer bullying victimization increases the risk of internalizing symptoms and this finding suggests that parental warmth help to buffer children from the internalizing symptoms associated with bullying victimization.

Objective: To explore the impact of adverse childhood experiences on pubertal development,and to provide a reference for conducting the targeted intervention in the early stage. Methods: A cluster sampling method was used to randomly select students of grades 3 to 4 from three primary schools in Ma’anshan municipality of Anhui province in October 2017. Self-reported childhood adverse experiences (ACEs), including physical, emotional and sexual abuse, as well as physical and emotional neglect were collected. Testicular volume and breast Tanner stage were assessed. A follow-up survey was conducted one year later to assess ACEs and pubertal development. ACEs of each dimension were divided into non-exposure group, transient exposure group and sustained exposure group according to ACEs exposure at baseline and follow-up. Multivariate linear regression model was used to analyze the relationship between ACEs exposure and pubertal development after 1-year follow-up. Results: Sustained emotional abuse was positively associated with increased breast Tanner stage and testicular volume (breast: β=0.36, 95%CI=0.09-0.63, P<0.01; testicular volume: β=1.07, 95%CI=0.47-1.66, P<0.01); sustained physical abuse was positively associated with decreased testicular volume (β=-0.83, 95%CI=-1.58--0.08, P<0.05); sustained and transient sexual abuse were significant positively associated with decreased breast Tanner stages (sustained: β=-1.43, 95%CI=-2.86--0.02, P<0.05; transient: β=-0.45, 95%CI=-0.73--0.19, P<0.05); sustained emotional neglect was positively associated with increased breast Tanner staging (β=0.33, 95%CI=0.06-0.61, P<0.05) and decreased testicular volume (β=-0.19, 95%CI=-1.38--0.19, P<0.01). Conclusion Sustained emotional abuse was associated with early pubertal development in boys and girls,and the specitic mechanisam differences of different ACES puberty development effects and the gender differences of the same ACES puberty development effects need to be furthur explored.

Objectives To explore the association between the single nucleotide polymorphism (SNP) rs2239669 in makorin ring-finger protein 3 (MKRN3) gene and the susceptibility to central precocious puberty (CPP). Methods A case-control study including 246 children with CPP and 269 healthy children was performed.The genotype and MKRN3 expression levels of patients were analyzed by PCR-HRM and RT-PCR,respectively. Results SNP rs2239669 genotype (TT,TC,CC) and allele frequencies (T and C) were different between cases and controls,with higher CC genotype in CPP patients. Under recessive model (CC/TT+TC),CC genotype was higher in CPP group and associated with higher risk of CPP (95%CI:1.062-2.143,P=0.021). MKRN3 expression levels were different among patients with different genotypes,of which TT genotype had the highest level followed by TC and CC (0.376±0.094, 0.330±0.068, 0.250±0.072, P=0.041). Conclusions MKRN3 SNP rs2239669 was associated with increased risk of CPP, and patients with TT genotype had higher MKRN3 levels.

Objective: To determine possible relations between early adiposity rebound and adolescent development. Methods: Prospective children cohort from 2 kindergartens selected through clustering convenience sampling method in Anhui Province was established since Sep. 2010. Participants were classified as Cohort 1 (2010), Cohort 2 (2011) and Cohort 3 (2012) according to the recruiting year. Till Sep. 2015, a toal of 802 girls were included in this study, and received follow-up till primary school. During kindergarten period, physical examination was carried out every 3 months, 8 times in total. In primary school, physical examination was carried out annually; till Sep.2015, the cohort 1, 2, 3 took physical examination for 12, 11, 10 times, respectively. Information on household economic status and child physical activity was acquired through parents questionnaire survey, and breast development were assessed through visual inspection and palpation. Adiposity rebound was determined according to Rolland-Cachera's method for each girl. Differences between early adiposity rebound and normal adiposity rebound groups were compared by using t test and χ² test. Multivariate regression analysis was applied to explore the association between early adiposity rebound and breast development. Results: The average age of participants was (8.90±0.87) years old and the BMI was (17.48±2.70) kg/m². The average age at adiposity rebound was (6.16±0.90) years old and the BMI was (15.33±1.82) kg/m². Premature breast development was found significantly higher in girls in early adiposity rebound group (27.8%, 54/802) than it in normal adiposity rebound group (13.7%) (P<0.001). After current adiposity, age, household economic status, childhood physical activity adjusted, the OR of premature beast development in early adiposity rebound group was 2.41(95%CI: 1.41-4.12). Conclusion Early adiposity rebound increases the risk of premature puberty in girls.