Speech- and language-linked FOXP2 mutation targets protein motors in striatal neurons.

Human speech and language are among the most complex motor and cognitive abilities. The discovery of a mutation in the transcription factor FOXP2 in KE family members with speech disturbances has been a landmark example of the genetic control of vocal communication in humans. Cellular mechanisms underlying this control have remained unclear. By leveraging FOXP2 mutation/deletion mouse models, we found that the KE family FOXP2R553H mutation directly disables intracellular dynein-dynactin 'protein motors' in the striatum by induction of a disruptive high level of dynactin1 that impairs TrkB endosome trafficking, microtubule dynamics, dendritic outgrowth and electrophysiological activity in striatal neurons alongside vocalization deficits. Dynactin1 knockdown in mice carrying FOXP2R553H mutations rescued these cellular abnormalities and improved vocalization. We suggest that FOXP2 controls vocal circuit formation by regulating protein motor homeostasis in striatal neurons, and that its disruption could contribute to the pathophysiology of FOXP2 mutation/deletion-associated speech disorders.

Cytogenetic Characteristics of Childhood Acute Lymphoblastic Leukemia: A Study of 1541 Chinese Patients Newly Diagnosed between 2001 and 2014.

OBJECTIVE: Cytogenetic abnormalities have been proven to be the most valuable parameter for risk stratification of childhood acute lymphoblastic leukemia (ALL). However, studies on the prevalence of cytogenetic abnormalities and their correlation to clinical features in Chinese pediatric patients are limited, especially large-scale studies. METHODS: We collected the cytogenetics and clinical data of 1541 children newly diagnosed with ALL between 2001 and 2014 in four Chinese hospitals, and retrospectively analyzed their clinical features, prognosis and risk factors associated with pediatric ALL. RESULTS: All of these patients had karyotyping results, and some of them were tested for fusion genes by fluorescence in situ hybridization or reverse-transcription polymerase chain reaction. Overall, 930 cases (60.4%) had abnormal cytogenetics in this study, mainly including high hyperdiploidy (HHD, n=276, 17.9%), hypodiploidy (n=74, 4.8%), t(12;21)/TEL-AML1 (n=260, 16.9%), t(1;19)/E2A-PBX1 (n=72, 4.7%), t(9;22)/BCR-ABL (n=64, 4.2%), and t(v;11q23)/MLL rearrangements (n=40, 2.6%). The distribution of each cytogenetic abnormality was correlated with gender, age, white blood cell count at diagnosis, and immunophenotype. In addition, multivariate analysis suggested that t(v;11q23)/MLL rearrangements (OR: 2.317, 95%CI: 1.219-3.748, P=0.008) and t(9;22)/BCR-ABL (OR: 2.519, 95%CI: 1.59-3.992, P<0.001) were independent risk factors for a lower event-free survival (EFS) rate in children with ALL, while HHD (OR: 0.638, 95%CI: 0.455-0.894, P=0.009) and t(12;21)/TEL-AML1 (OR: 0.486, 95%CI: 0.333-0.707, P<0.001) were independent factors of a favorable EFS. CONCLUSION: The cytogenetic characteristics presented in our study resembled other research groups, emphasizing the important role of cytogenetic and molecular genetic classification in ALL, especially in B-ALL.

The Effect of Splenectomy on the Reversal of Cirrhosis: a Prospective Study.

BACKGROUND: Studies have demonstrated that liver fibrosis can be reversed by medication treatments. After splenectomy, cirrhosis patients have short-term changes in several serum markers for cirrhosis and liver stiffness. AIMS: To investigate the effect of splenectomy on the severity of cirrhosis. METHODS: A total of 62 patients with cirrhosis and portal hypertension receiving splenectomy from December 2014 to July 2017 were enrolled. The degree of cirrhosis was preoperatively and postoperatively evaluated by serum markers, including hyaluronan (HA), laminin, amino-terminal propeptide of type III procollagen (PIIINP), type IV collagen (C-IV), liver stiffness (FibroScan), and liver volume. RESULTS: HA levels significantly increased at 1 week and 1 month postoperation (both P < 0.05), whereas the levels of PIIINP and C-IV significantly decreased from 1 month to 12 months postoperation (all P < 0.05). In addition, elastography examination demonstrated that the FibroScan score significantly reduced from 1 month to 24 months postoperation as compared with the baseline level (all P < 0.05). CT scan showed that the liver volume significantly increased at 6 months postoperation (P < 0.05). Furthermore, the alteration trends of these serum markers and the FibroScan score were further confirmed by the multivariate linear regression. CONCLUSIONS: These observations suggested that splenectomy may result in long-term reversal of cirrhosis.

Short-term effects of household indoor- and outdoor-originating fine particulate matters on heart rate and heart rate variability in chronic obstructive pulmonary diseases patients, Beijing / 中华预防医学杂志

Objective@#To assess the associations of indoor fine particulate matter (PM2.5) from outdoor and indoor sources with heart rate (HR) and heart rate variability (HRV) in patients with chronic obstructive pulmonary disease (COPD) of Beijing.@*Methods@#A total of 40 male patients in a stable stage of COPD were recruited from a hospital in a panel study in Beijing with 5 consecutive days of measurement for each subject. General information and disease history of the participants from questionnaires were obtained prior to the study. HR and HRV were repeatedly examined using dynamic electrocardiograph. HRV included standard deviation of all NN intervals (SDNN), root mean square of successive differences between adjacent NN intervals (rMSSD), total power (TP) power in the low-frequency band (LF) and the high-frequency band (HF). Iron was used as tracer element to separate indoor-originated PM2.5 and outdoor-originated PM2.5. Mixed-effect models were applied to assess the associations of outdoor-originated PM2.5 or indoor-originated PM2.5 and health effects.@*Results@#The P50 (P25, P75) values of daily indoor PM2.5, indoor-originated PM2.5 and outdoor-originated PM2.5 were 50.9 (26.8, 122.7), 16.0 (1.9, 43.7) and 27.3 (13.5, 61.8) μg/m3, respectively. The mean±SD of concentrations of real-time indoor PM2.5, indoor-originated PM2.5 and outdoor-originated PM2.5 were (61.5±58.8), (25.3±39.1) and (36.2±42.7) μg/m3, respectively. Compared with outdoor-originated PM2.5, indoor-originated PM2.5 had significant associations with HRV and HR. Each 10 μg/m3 increase at 4 h indoor-originated PM2.5 and outdoor-originated PM2.5 moving average was associated with 3.4% (95%CI: -4.7%, -2.1%) and 0.6% (95%CI: -2.0%, -0.8%) reduction in TP (P<0.001). Each 10 μg/m3 increase at 12 h indoor-originated PM2.5 moving average was associated with 7.6% (95%CI: -10.1%, -5.1%), 4.7% (95%CI: -6.7%, -2.7%), 3.3% (95%CI: -4.2%,-2.4%) and 3.0% (95%CI: -4.5%, -1.5%) reduction in HF, LF, SDNN and rMSSD, respectively. Each 10 μg/m3 increase at 12 h outdoor-originated PM2.5 moving average was associated with 0.7% (95%CI: -2.7%, -1.4%), 0.2% (95%CI: -1.9%, 1.4%), 0.7% (95%CI: -1.4%, -0.1%) and 0.2% (95%CI: -1.3%, 0.9%) reduction in HF, LF, SDNN and rMSSD, respectively (P<0.001). Each 10 μg/m3 increase at 8 h indoor-originated PM2.5 and outdoor-originated PM2.5 moving average was associated with 0.7% (95%CI: 0.4%, 1.0%) and 0.4% (95%CI: 0.2%, 0.6%) increase in HR.@*Conclusion@#Exposure to indoor-originated PM2.5 was more strongly associations with HRV indices and HR compared with outdoor-originated PM2.5 in male COPD patients.

Effects of high-efficiency particulate air purifiers on indoor fine particulate matter and its constituents in a district of Beijing during winter / 北京大学学报(医学版)

OBJECTIVE@#To analyze the effect of domestic high-efficiency particulate air (HEPA) purifiers on the concentrations of indoor fine particulate matter (PM2.5) and its elementary constituents in 20 residences in a district of Beijing during winter.@*METHODS@#From November 2015 to January 2016, 20 residences in a district of Beijing were selected, where indoor and outdoor PM2.5 data were collected simultaneously in three time periods according to the operating of air purifiers (Group 0 h: 24 hours before operating; Group 24 h: 24 hours after operating; Group 48 h: 24 to 48 hours after operating). The content of 21 elements in PM2.5 samples were determined by inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma optical emission spectrometry (ICP-OES). Indoor/outdoor particle concentration ratio (I/O ratios) and ΔI/O ratios were used to describe the pollution levels and the variation range of PM2.5 and its 21 elementary constituents. One-way analysis of variance (ANOVA) for repeated measurement data was applied to compare the I/O ratios of PM2.5 and its elementary constituents among the different groups, and Bonferroni method was used for comparison in pairs. Wilcoxon signed rank test for paired-samples was used to compare ΔI/O ratios of 21 elementary constituents with that of PM2.5.@*RESULTS@#The median I/O ratios of PM2.5 in the three groups were 1.27 (P25-P75: 0.50-2.68), 0.45 (P25-P75: 0.27-1.03) and 0.36 (P25-P75: 0.28-2.48), respectively. Compared with Group 0 h, the I/O ratios of PM2.5 in Group 24 h (P=0.042) and Group 48 h (P=0.006) decreased significantly. However, there was no significant difference between Group 24 h and Group 48 h. Significant differences were found comparing ΔI/O ratios of aluminium, ferrum and titanium to that of PM2.5, in both Group 24 h and Group 48 h (P<0.05). No significant change was found in the I/O ratios of these three elements among the three groups before and after air purifier operating (P>0.05). Distances from residences to traffic arteries could affect I/O ratios of some elements from traffic-related source (P<0.05).@*CONCLUSION@#Domestic HEPA air purifiers could effectively reduce indoor PM2.5 concentration, and the pollution level of PM2.5 tend to be stable after the purifier operating for a time. The purifiers had different effects on different elements, among which most showed statistical significances.

A rapid and cost-effective method for genotyping apolipoprotein E gene polymorphism.

BACKGROUND: Apolipoprotein E (ApoE) is a major cholesterol carrier and plays an important role in maintaining lipid homeostasis both in the periphery and brain. Human APOE gene is polymorphic at two single nucleotides (rs429358 and rs7412) resulting in three different alleles (ε2, ε3 and ε4). ApoE isoforms modulate the risk for a variety of vascular and neurodegenerative diseases; thus, APOE genotyping is crucial for predicting disease risk and designing individualized therapy based on APOE genotype. RESULTS: We have developed an APOE genotyping method that is based on allele-specific PCR methodology adapted to Real Time PCR monitored by TaqMan probe. Rather than using TaqMan probes specific for the two polymorphic sites, only one TaqMan probe is used as the polymorphic alleles are recognized by site-specific PCR primers. Each genotyping assay can be completed within 90 minutes and is applicable to high-throughput analysis. Using this protocol, we genotyped a total of 1158 human DNA samples and obtained a 100% concordance with the APOE genotype determined by sequencing analysis. CONCLUSION: The APOE genotyping assay we have developed is accurate and cost-effective. In addition, our assay can readily be applied to genotyping large sample numbers. Therefore, our APOE genotyping method can be used for assessing the risk for a variety of vascular and neurodegenerative diseases that have been reported to be associated with APOE polymorphism.

Community-based evaluation of the reliability and validity of Chinese version of Composite International Diagnostic Interview-3.0 / 中国心理卫生杂志

Objective:To evaluate the test-retest reliability and validity of Chinese version of World Health Organization Composite International Diagnostic Interview version 3.0(CIDI-3.0)by community-based study.Methods:Among 202 subjects from Dalian city,with the clinician-administered Structured Clinical Interview for DSM-IV(SCID),102 patents were diagnostic as mood disorder,anxiety disorder,schizophrenia or psychotic disorder and so on.All of the patients and the other 100 subjects without mental disorders as the control group were interviewed blindly by CIDI-3.0 to test the validity of CIDI-3.0.Ten patients among them were interviewed twice independently in a 7-day interval to evaluate the reliability of CIDI-3.0.Results:(1)For the screen section,the sensitivity values of different mental disorders ranged from 60.4% to 93.1%,while the specificity values from 33.6% to 92.7%.The positive predictive values were from 60.1% to 95.1%,and the negative predictive values were from 68.1% to 93.7%.(2)For different mental disorders,the specificity values ranged from 97.1% to 98.9%,while the sensitivity values were from 33.3% to 70.3%.Positive predict values were from 66.7% to 95.7%,and negative predictive values were from 87.7% to 95.4%.(3)The consistency was 0.78 in any mental disorder.(4)For test-retest reliability,kappa values ranged from 0.737 to 1.0.Conclusion:By clinical reappraisal,the Chinese version of CIDI-3.0 has satisfied validity and reliability.The screen section has high sensitivity,while the diagnostic sections have high specificities.That indicates that CIDI-3.0 is acceptable as a validated instrument for community survey on mental disorders.

[The influence of abscisic acid treatment on desiccation tolerance in Dendrobium candidum protocorm-like bodies].

Effect of ABA on desiccation tolerance in the protocorm-like bodies (PLBs) of D. candidum was studied. The best result was obtained while ABA precultured at 5 micromol/L for 24 h (Fig.2). PLBs vitality rate was 10 times of the control after 2 h desiccation (Table 1). Detection of cytoplasmic osmoticums showed that ABA preculture could not induce the accumulations of soluble sugar, proline, etc (Tables 3, 4 and 7). But the content of soluble polysaccharide rose conspicuously (Table 5). So we think that the accumulation of soluble polysaccharide may play an important role in desiccation tolerance induced by ABA preculture.