A Spacetime Odyssey of Neural Progenitors to Generate Neuronal Diversity / 神经科学通报·英文版

To understand how the nervous system develops from a small pool of progenitors during early embryonic development, it is fundamentally important to identify the diversity of neuronal subtypes, decode the origin of neuronal diversity, and uncover the principles governing neuronal specification across different regions. Recent single-cell analyses have systematically identified neuronal diversity at unprecedented scale and speed, leaving the deconstruction of spatiotemporal mechanisms for generating neuronal diversity an imperative and paramount challenge. In this review, we highlight three distinct strategies deployed by neural progenitors to produce diverse neuronal subtypes, including predetermined, stochastic, and cascade diversifying models, and elaborate how these strategies are implemented in distinct regions such as the neocortex, spinal cord, retina, and hypothalamus. Importantly, the identity of neural progenitors is defined by their spatial position and temporal patterning factors, and each type of progenitor cell gives rise to distinguishable cohorts of neuronal subtypes. Microenvironmental cues, spontaneous activity, and connectional pattern further reshape and diversify the fate of unspecialized neurons in particular regions. The illumination of how neuronal diversity is generated will pave the way for producing specific brain organoids to model human disease and desired neuronal subtypes for cell therapy, as well as understanding the organization of functional neural circuits and the evolution of the nervous system.

Clinical Diagnosis and Prenatal Screening of Hb Lepore-BW Associated with IVS-II-654 Heterozygous Mutation / 中国实验血液学杂志

OBJECTIVE@#To identify one case of rare Hb Lepore-BW associated with IVS-II-654 heterozygous mutation in Sichuan area.@*METHODS@#The blood routine examination and hemoglobin electrophoresis methods were used to analyze the blood routine parameters, HbA2 and HbF in the samples of peripheral blood in proband and his parents, as well as the cord blood of pregnant woman. The detection of thalassemia gene and Sanger sequencing methods were used to detect the hemoglobin mutations.@*RESULTS@#The result showed that the Hb Lepore-BW heterozygous mutation was detected in the father of the proband, while a rare Hb Lepore-BW with IVS-II-654 heterozygous mutation was detected in the proband, as well as his mother and cord blood were both detected as IVS-II-654 heterozygous mutation.@*CONCLUSION@#The study identified a rare Hb Lepore-BW with IVS-II-654 heterozygous mutation, which was characterized by intermediate β-thalassemia. It is necessary to hemoglobin electrophoresis combined with routine blood testing in prenatal screening.

Effect of parent-child cooperative music therapy on children with autism spectrum disorder and their mothers: a prospective randomized controlled study / 中国当代儿科杂志

OBJECTIVES@#To study the effect of parent-child cooperative music therapy on the core symptoms of children with autism spectrum disorder (ASD) and their mothers.@*METHODS@#In this prospective study, 112 children with ASD and their mothers were divided into a music therapy group and an applied behavior analysis (ABA) group using a random number table (n=56 each). The children in the ABA group were treated with ABA, and those in the music therapy group were given parent-child cooperative music therapy in addition to the ABA treatment. The duration of intervention was 8 weeks for both groups. Childhood Autism Rating Scale (CARS), Autism Behavior Checklist (ABC), Parenting Stress Index-Short form (PSI-SF), Family APGAR Index, and Herth Hope Index (HHI) were used to evaluate the core symptoms of children with ASD and the parenting stress, family APGAR index, and hope level of mothers before and after intervention.@*RESULTS@#A total of 100 child-mother dyads completed the whole study, with 50 child-mother dyads in each group. After intervention, the children in the music therapy group had significantly lower total score of ABC scale and scores of sensation, social interaction, and somatic movement, as well as a significantly lower total score of CARS than those in the ABA group (P<0.05). After intervention, compared with the mothers in the ABA group, the mothers in the music therapy group had significantly higher total score of PSI-SF and score of parent-child dysfunctional interaction, significantly higher total score of HHI and scores of each dimension, and significantly higher total score of APGAR and scores of cooperation and intimacy (P<0.05).@*CONCLUSIONS@#Parent-child cooperative music therapy combined with ABA can alleviate the core symptoms of children with ASD, reduce the parenting stress of their mothers, and improve family APGAR index and hope level.

Expression and clinical significance of runt-related transcription factor 3 in children with bronchiolitis / 中国当代儿科杂志

OBJECTIVE@#To study the mRNA level of runt-related transcription factor 3 (RUNX3) in children with bronchiolitis and its clinical significance in bronchiolitis.@*METHODS@#A total of 54 young children with bronchiolitis were enrolled as the bronchiolitis group, among whom 28 with atopic constitution were enrolled in the atopic bronchiolitis group and 26 with non-atopic constitution were enrolled in the non-atopic bronchiolitis group. A total of 48 healthy young children were enrolled as the healthy control group, among whom 24 with atopic constitution were enrolled in the atopic healthy control group and 24 with non-atopic constitution were enrolled in the non-atopic healthy control group. Quantitative real-time PCR was used to measure the mRNA level of RUNX3 in peripheral blood mononuclear cells. ELISA was used to measure the serum levels of interleukin-4 (IL-4) and interferon gamma (IFN-γ).@*RESULTS@#The bronchiolitis group had a significantly lower mRNA level of RUNX3 than the healthy control group, and the atopic bronchiolitis group had a significantly lower mRNA level of RUNX3 than the non-atopic bronchiolitis, atopic healthy control, and non-atopic healthy control groups (P<0.05). The bronchiolitis group had a significantly higher serum level of IL-4 than the healthy control group, and the atopic bronchiolitis group had a significantly higher serum level of IL-4 than the non-atopic healthy control group (P<0.05). The bronchiolitis group had a significantly lower serum level of IFN-γ than the healthy control group, and the atopic bronchiolitis group had a significantly lower serum level of IFN-γ than the non-atopic bronchiolitis, atopic healthy control, and non-atopic healthy control groups (P<0.05). The correlation analysis showed that the mRNA level of RUNX3 was negatively correlated with the serum level of IL-4 and was positively correlated with the serum level of IFN-γ (P<0.05).@*CONCLUSIONS@#Measurement of RUNX3 gene expression in peripheral blood mononuclear cells has a certain value in identifying children with atopic constitution at high risk of asthma among children with bronchiolitis.

Risk Analysis of Catheter-related Bloodstream Infection and Thrombosis in Patients with Blood Diseases Undergoing Peripheral Introvascular Central Catheter (PICC) / 中国实验血液学杂志

OBJECTIVE@#To evaluate the effects of peripheral introvascular central catheters (PICC) on the catheter-associated bloodstream infections (CRBSI) and the formations of catheter-related bloodstream infections.@*METHODS@#Total of 483 patients with hematologic malignancies admitted in our hospital from January 2013 to December 2016 were enrolled in this study, and 612 PICC catheterization were conducted. The median time of catheterization was 101 d (48 ∼ 184 d) . The incidence rates of CRBSI and CRTC were observed, and the CRBSI and CRTC associated variables were also analyzed.@*RESULTS@#There were 47 cases of CRBSI (7.7%), and the incidence was 0.59‰ PICC days, and there were 16 cases of CRTC (2.6%), with the incidence of 0.20‰ PICC days. Meanwhile, no other related serious complications found. The Cox regression analysis of CRBSI and CRTC-associated variables showed that the acute leukemia was significantly related with a higher incidence of CRBSI as compared with the other type of disease, however, which was not significantly related with the CRTC.@*CONCLUSION@#Compared with the traditional CVAD catheterization, the PICC is more safe and effective for the patients with malignant tumors, thus which may become a alternative method for CVAD.

Performance of Automatic Blood Cell Analysis Parameters for Differential Diagnosis of Myelodysplastic Syndromes and Aplastic Anemia / 现代检验医学杂志

Objective To evaluate the performance of automated blood cell analysis parameters for differential diagnosis of myelodysplastic syndromes (MDS) and aplastic anemia (AA).Methods Data of automatic blood cell analysis parameters at diagnosis of confirmed patients with MDS and AA from December 2002 to February 2011 in Peking University Shenzhen Hospital were retrospectively reviewed.Results 33 cases of MDS and 36 cases of AA were recruited in this study.Based on the evaluable data,mean corpuscular hemoglobin concentration (MCHC) (328.58 ± 17.24 g/L vs 342.47±18.75 g/L,n=33/36) was significantly lower (P=0.002 1),while monocyte percentage (MONO％) (11.48±9.99 vs 6.94±2.50,n=32/34),platelet distribution width (PDW％) (13.51±4.24 vs 10.62±3.68,n=20/22) and platelet hematocrit (PCT％)(0.11 ±0.10 vs 0.04±0.07,n=11/15) were markedly higer (all P＜0.05) in patients with MDS than that of AA.No significantly differences for other blood cell analysis parameters were seen between patients with MDS and AA.Under the condition of best cut-off value,areas under the ROC curve of MCHC,MONO％,PDW and PCT were 0.706 (95％ confidence interval:0.584～0.809),0.666 (0.540～0.778),0.668 (0.506～0.805) and 0.745 (0.538～0.894) respectively.MONO％ and MCHC had high specificities (97.06％ and 88.89％) and positive predictive values (93.3％ and 80.0％) for differential diagnosis of MDS from AA.Conclusion MONO％ and MCHC may be used as simple indicators for differential diagnosis of MDS and AA.

Extraction of sperm DNA from mixed stain by the modified differential lysis method combined with silicon bead method / 法医学杂志

OBJECTIVE@#To extract sperm DNA from mixed stain by the modified differential lysis method combined with silicon bead method and to evaluate its application value.@*METHODS@#Fifty-two mixed stains containing female STR genotypes detected by differential lysis method were collected. The sperm DNA was extracted by the modified method combined with silicon bead method, then genotyped with the Identifiler Kit, and compared with the results of genotyping by the conventional differential lysis method as control.@*RESULTS@#Of the 52 samples, 38 samples with sole male STR genotypes in all loci were detected. The detection rate of male STR genotypes was 98.08% through the modified method combined with silicon bead method.@*CONCLUSION@#The modified differential lysis method combined with silicon bead method can be used in extraction of sperm DNA from mixed stain.

Association of TET2, LMTK2 and FAM84B gene expression with prostate cancer risk in Chinese patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the association between the common variations of TET2 (rs7679673, A), MTK2 (rs6465657, T) and FAM84B (rs12543663, C) genes and prostate cancer (Pca) risk in Chinese population in Beijing, and to understand the relationship between genotypes and phenotypes including clinical characteristics and life style, etc. in patients with prostate cancer.</p><p><b>METHODS</b>Based on a case-control study, 124 patients with prostate cancer and 138 age-matched control subjects were recruited. Information of clinical phenotype and life style, etc. in the prostate cancer patients was collected. We compared the differences of allele and genotype frequencies of TET2 (rs7679673, A), LMTK2 (rs6465657, T) and FAM84B (rs12543663, C) gene expressions between the two groups for the allele and genotype frequencies, and explored the relationship between different genotypes and clinical features such as patient age, BMI, Gleason score, PSA level and tumor stage, by Chi-square test in patients with PCa. Multifactor dimensionality reduction was used to detect the gene-gene interactions.</p><p><b>RESULTS</b>The FAM84B (rs12543663, C) C carriers frequency had significant difference between the case group and the control group (χ(2) = 3.980 P = 0.046; OR = 1.883; 95%CI = 1.006-3.526). The allele and genotype frequencies of TET2 gene (rs7679673, A) and LMTK2 gene (rs6465657, T) were not significantly different between the case group and the control group (P > 0.05). Analysis of the genotypes and clinical phenotypes showed that the genetic type of FAM84B C carriers [CX (CC + CA)] were significantly associated with cancer stage (χ(2) = 9.585; P = 0.002; OR = 3.740; 95%CI = 1.580 - 8.853). Association between three loci and 12 kind of relevant outcomes was found in TET2 A carriers and the smoking and drinking patients (all P < 0.05). Significant correlation was also found between LMTK2 (rs6465657, T) TX carriers and surgery (χ(2) = 8.612; P = 0.003; OR = 0.174; 95%CI 0.049 - 0.620). No significant correlation was seen with other covariates (P > 0.05). Dendrogram analysis among the three loci showed that the best model consisted of the three sites (P = 0.0270), cross validation consistency: 10/10, and testing balanced accuracy: 0.5120. There may be gene-gene interaction among TET2 (rs7679673, A), LMTK2 (rs6465657, T), and FAM84B (rs12543663, C).</p><p><b>CONCLUSIONS</b>There may be obvious association of FAM84B (rs12543663, C) gene with prostate cancer risk and the stages, and the synergistic effects of TET2 (rs7679673, A), LMTK2 (rs6465657, T) and FAM84B (rs12543663, C) genes may have an association with prostate cancer risk in Chinese population.</p>

Impact of laparoscopic colorectal surgery on the peritoneal microstructural injury and expression of t-PA/PAI-1 / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To assess the influence of laparoscopic colorectal cancer resection on the peritoneal microstructure injury and expression of t-PA/PAI-1 molecules.</p><p><b>METHODS</b>A total of 50 patients with colorectal cancer were prospectively enrolled between June 2011 and February 2012 in the Shanxi Provincial Hospital and were assigned into laparoscopic group (LO, n=27) and conventional laparotomy group (CO, n=23) based on patients expectancy and surgeon decision. Optical microscope and scanning electron microscope were employed for comparison of the postoperative peritoneal injury between LO and CO. Before and after surgery, t-PA and PAI-1 of peritoneal tissue were determined by ELISA in both groups.</p><p><b>RESULTS</b>Optical microscope and scanning electronic microscopy scan indicated less serosal injury in LO group than that in CO group with regard to serosa integrity, continuity of covering adipocytes and mesothelial cells, and the aggregation level of inflammatory cells (P<0.01). The injury score was 38.22 in CO in and 14.67 in LO and the difference was statistically significant (P<0.01). No significant differences were found between LO and CO in terms of postoperative t-PA in the omentum, t-PA and PAI-1 in the intestinal serosa tissue (P>0.05), however PAI-1 in the omentum was significantly lower in LO group compared to CO group (P<0.05).</p><p><b>CONCLUSION</b>Laparoscopic radical resection for colorectal cancer causes less peritoneal structural injury and less influence on the fibrinolytic capacity, which may contribute to less postoperative adhesion.</p>

Association of prostate cancer with PDLIM5, SLC22A3 and NKX3-1 in Chinese men / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the association of prostate cancer (PCa) with PDLIM5 (rs17021918, T), SLC22A3 (rs9364554, C) and NKX3-1 (rs1512268, A) in Chinese men.</p><p><b>METHODS</b>We included 124 PCa patients and 138 normal controls in this study, compared the alleles and genotypes of PDLIM5 (rs17021918, T) , SLC22A3 (rs9364554, C) and NKX3-1 (rs1512268, A) of the two groups, and explored the association of each of the genes with the age, body mass index (BMI), Gleason score, PSA level and tumor stage of the patients. We analyzed the gene-gene interaction using the multifactor dimensionality reduction method (MDR).</p><p><b>RESULTS</b>There were no statistically significant differences in the frequency distribution of the risk alleles and genotypes of PDLIM5, SLC22A3 and NKX3-1 between the case and control groups (P > 0.05), nor were the three gene loci significantly associated with the age, Gleason score, PSA level and pathological grade of the PCa patients (CP < 0.05). MDR analysis showed no interaction between PDLIM5 and NKX3-1, but tree-diagram analysis revealed a possible synergistic action of the two polymorphism loci.</p><p><b>CONCLUSION</b>PCa might not be associated with PDLIM5 (rs17021918,T), SLC22A3 (rs9364554,C) and NKX3-1 (rs1512268,A) in Chinese men. However, PDLIM5 and NKX3-1 might have a synergistic action on the risk PCa.</p>

Optimization of the formulation of ranolazine hydrochloride sustained-release tablet and its pharmacokinetics in dogs / 药学学报

Ranolazine hydrochloride sustained-release tablet (RH-ST) was prepared and its release behavior in vitro was studied. The pharmacokinetic characteristics and bioavailability in six Beagle dogs after oral administration of RH-ST and ranolazine hydrochloride common tablets (RH-CT) as reference were compared. Three kinds of matrix, hydroxypropylmethylcellulose (HPMC K4M), ethylcellulose (EC 100cp) and acrylic resins (Eudragit RL100) were selected as functional excipients to keep ranolazine hydrochloride (RH) release for 12 hours. Through orthogonal designs, the polymers were quantified and the optimized cumulative release profile was obtained. The single oral dose of RH-ST 500 mg and RH-CT 333.3 mg was given to six dogs using a two way crossover design. Plasma levels were determined by LC-MS and the absorption fractions were calculated according to Loo-Riegelman formula. The steady-state concentration of RH in plasma of six dogs and its pharmacokinetics behaviors after continuous oral administration of RH-ST and RH-CT at different time intervals were studied by LC-MS. The steady-state pharmacokinetic parameters were computed by software program BAPP2.0. With the increase of the amount of the matrix, the drug release was decreased. The most important factor influencing drug release is the quantity of HPMC K4M. Drug release within the period (from 0 h to 12 h) fitted well into Higuchi model. The correlation coefficient (r) between the dissolution in vitro in release media of the distilled water and the absorptin fraction in vivo was 0.9550. To compare with RH-CT, RH-ST in vivo has a steady and slow release behavior, Tmax was obviously delayed (3.00 +/- 0.50) h and the relative bioavailability was over 80 percentage. The combined use of multiple polymers can decrease the tablet weight effectively, and the drug release rate can be decreased both in vitro and in vivo.

Prevalence of metabolic syndrome among rural adult residents in Ningxia / 中华流行病学杂志

Objective To describe the prevalence of metabolic syndrome(MS) among rural adult residents in Ningxia, under IDF2005 ATP Ⅲ 2005 AHA and CDs2004 definition. Methods Stratified cluster sampling methods was used and the participants were interviewed by trained health workers under a structured questionnaire. The number of research subjects was 1612. Fasting plasma glucose (FPG), blood lipids, body mass index (BMI) and blood pressure (BP) of all samples (1612 subjects) were measured, and related data was analysed by IDF2005, ATP Ⅲ 2005 AHA, as well as CDs2004 definition of MS. Results The age-standardized prevalence of MS was 15.00% by ATP Ⅲ 2005 AHA definition and 11.80%by IDF 2005 definition and 6.71% by CDs 2004 definition, respectively. Based on IDF 2005 and ATP Ⅲ 2005 AHA definition, women had higher prevalence than men (16.3% vs. 5.4%, 18.9% vs. 8.9%, P<0.01), but there was no significant difference (P>0.05) between them according to the CDs definition. MS prevalence among Hui (Muslim) ethnic group was higher than Han ethnic group(P<0.05). The prevalence of MS increased with age in all samples and the prevalence of MS started at age of 35 in Hui ethnic group, higher than in Han ethnic group. There was no significant difference in the prevalence rates of MS between male Hui ethnic group and male Han ethnic group (P>0.05). The prevalence of MS in female Hui ethnic group was higher than Han ethnic group females (P<0.05). Conclusion The prevalence of MS was high in the rural adult residents, in Ningxia. Clusters of MS components were commonly seen, and the main disorder appeared in lipid abnormalities and abnormal glucose metabolism. It is necessary to discuss that the cut off point of central obesity for the waist circumference diagnostic criteria of MS in different ethnic groups in China. Big differences on the components of MS were seen in different ethnic groups. It is important to choose suitable MS definition for prevention of MS and to reduce the incidence of cardiovascular disease.

Effects of silencing chloride intracellular channel 1 gene expression on the proliferation and invasion of mouse hepatocellular carcinoma cell lines / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the effects of silencing CLIC1 gene expression on the proliferation and invasion of Hca-F cells.</p><p><b>METHODS</b>The mouse CLIC1 cDNA sequence was retrieved from NCBI. Three shRNA sequences were designed and cloned into pGPU6/GFP/Neo plasmids. The plasmids were transfected into Hca-F cells with Lipofectamine 2000. Cell Counting-8 (CCK-8) kit and transwell chamber were used to study the effects of CLIC1 on the proliferation and invasion of Hca-F cells.</p><p><b>RESULTS</b>The pGPU6/GFP/Neo-shRNA-3 plasmid effectively repressed the expression of CLIC1 mRNA. Inhibition of CLIC1 gene expression led to decreased cell proliferation and reduced invasion.</p><p><b>CONCLUSION</b>CLIC1 is essential for the proliferation and invasion of Hca-F cells.</p>

Controlled study on the needling method for regulating the spleen and stomach for treatment of diabetic retinopathy / 中国针灸

<p><b>OBJECTIVE</b>To probe clinical therapeutic effect of acupuncture on diabetic retinopathy and the mechanism.</p><p><b>METHODS</b>One hundred and twenty cases of diabetic retinopathy were randomly divided into an observed group and a control group, 60 cases in each group. On the basis of routine diabetic treatment, the observation group were treated with the acupoints for regulating the spleen and stomach, and the control group with the acupoints around eye mainly. Clinical therapeutic effect was evaluated by eye fundus condition, blood glucose, blood lipids, nitric oxide (NO) and endothelin (ET) levels.</p><p><b>RESULTS</b>The needling method for regulating the spleen and stomach not only can improve the eye fundus condition, but also has benign regulative action on metabolism of blood glucose and blood lipids, and NO and ET levels, with significant differences as compared with those in the control group (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>The needling method for regulating the spleen and stomach is an effective therapy for diabetic retinopathy, and the mechanism is possibly related with the regulation of levels of vascular active substances, NO and ET.</p>

Mutation detection of ADPKD PKD1 gene in Hans by denaturing high-performance liquid chromatography / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To develop a screening system for more rapid and sensitive mutation detection of autosomal dominant polycystic kidney disease (ADPKD) gene 1 (PKD1) by using denaturing high-performance liquid chromatography (DHPLC) protocol.</p><p><b>METHODS</b>Using genomic DNA as templates extracted from blood samples of 19 Han pedigrees with 67 family members, the complete codon areas were amplified by long-range PCR and nested PCR in succession, and then the PCR products were analyzed by DHPLC. The mutations from screened abnormal PCR products were confirmed by DNA sequencing, and then compared with the mutations identified by single strand conformation polymorphism (SSCP) before.</p><p><b>RESULTS</b>There were 14 mutations found in this study, including 10 missense, 1 insertion, 1 deletion and 2 nonsense mutations. Besides 12 mutations identified before, mutations nt32819G>A and nt37137T>C were the novel mutations found. The mutation detection ratio was 73.7%.</p><p><b>CONCLUSION</b>This developed system via DHPLC can be used as a more effective approach for mutation detection of autosomal dominant polycystic kidney disease PKD1 in Hans.</p>