Association study between haplotypes of WNT signaling pathway genes and nonsyndromic oral clefts among Chinese Han populations / 北京大学学报(医学版)

OBJECTIVE@#To explore whether WNT signaling pathway genes were associated with non-syndromic oral clefts (NSOC) based on haplotypes analyses among 1 008 Chinese NSOC case-parent trios.@*METHODS@#The genome-wide association study (GWAS) data of 806 Chinese non-syndromic cleft lip with or without cleft palate (NSCL/P) trios and 202 Chinese non-syndromic cleft palate (NSCP) case-parent trios were drawn from the International Consortium to Identify Genes and Interactions Controlling Oral Clefts (ICOCs) study GWAS data set, whose Chinese study population were recruited from four provinces in China, namely Taiwan, Shandong, Hubei, and Sichuan provinces. The process of DNA genotyping was conducted by the Center for Inherited Disease Research in the Johns Hopkins University, using Illumina Human610-Quad v.1_B Bead Chip. The method of sliding windows was used to determine the haplotypes for analyses, including 2 SNPs haplotypes and 3 SNPs haplotypes. Haplotypes with a frequency lower than 1% were excluded for further analyses. To further assess the association between haplotypes and NSOC risks, and the transmission disequilibrium test (TDT) was performed. The Bonferroni method was adopted to correct multiple tests in the study, with which the threshold of statistical significance level was set as P < 0.05 divided by the number of tests, e.g P < 3.47×10-4 in the current stu-dy. All the statistical analyses were performed by using plink (v1.07).@*RESULTS@#After quality control, a total of 144 single nucleotide polymorphisms (SNPs) mapped in seven genes in WNT signaling pathway were included for the analyses among the 806 Chinese NSCL/P trios and 202 Chinese NSCP trios. A total of 1 042 haplotypes with frequency higher than 1% were included for NSCL/P analyses and another 1 057 haplotypes with frequency higher than 1% were included for NSCP analyses. Results from the TDT analyses showed that a total of 69 haplotypes were nominally associated with the NSCL/P risk among Chinese (P < 0.05). Another 34 haplotypes showed nominal significant association with the NSCP risk among Chinese (P < 0.05). However, none of these haplotypes reached pre-defined statistical significance level after Bonferroni correction (P>3.47×10-4).@*CONCLUSION@#This study failed to observe any statistically significant associations between haplotypes of seven WNT signaling pathway genes and the risk of NSOC among Chinese. Further studies are warranted to replicate the findings here.

Centromere protein U enhances the progression of bladder cancer by promoting mitochondrial ribosomal protein s28 expression

Bladder cancer is one of the most common types of cancer. Most gene mutations related to bladder cancer are dominantly acquired gene mutations and are not inherited. Previous comparative transcriptome analysis of urinary bladder cancer and control samples has revealed a set of genes that may play a role in tumor progression. Here we set out to investigate further the expression of two candidate genes, centromere protein U (CENPU) and mitochondrial ribosomal protein s28 (MRPS28) to better understand their role in bladder cancer pathogenesis. Our results confirmed that CENPU is up-regulated in human bladder cancer tissues at mRNA and protein levels. Gain-of-function and loss-of-function studies in T24 human urinary bladder cancer cell line revealed a hierarchical relationship between CENPU and MRPS28 in the regulation of cell viability, migration and invasion activity. CENPU expression was also up-regulated in in vivo nude mice xenograft model of bladder cancer and mice overexpressing CENPU had significantly higher tumor volume. In summary, our findings identify CENPU and MRPS28 in the molecular pathogenesis of bladder cancer and suggest that CENPU enhances the progression of bladder cancer by promoting MRPS28 expression.

Centromere protein U enhances the progression of bladder cancer by promoting mitochondrial ribosomal protein s28 expression

Bladder cancer is one of the most common types of cancer. Most gene mutations related to bladder cancer are dominantly acquired gene mutations and are not inherited. Previous comparative transcriptome analysis of urinary bladder cancer and control samples has revealed a set of genes that may play a role in tumor progression. Here we set out to investigate further the expression of two candidate genes, centromere protein U (CENPU) and mitochondrial ribosomal protein s28 (MRPS28) to better understand their role in bladder cancer pathogenesis. Our results confirmed that CENPU is up-regulated in human bladder cancer tissues at mRNA and protein levels. Gain-of-function and loss-of-function studies in T24 human urinary bladder cancer cell line revealed a hierarchical relationship between CENPU and MRPS28 in the regulation of cell viability, migration and invasion activity. CENPU expression was also up-regulated in in vivo nude mice xenograft model of bladder cancer and mice overexpressing CENPU had significantly higher tumor volume. In summary, our findings identify CENPU and MRPS28 in the molecular pathogenesis of bladder cancer and suggest that CENPU enhances the progression of bladder cancer by promoting MRPS28 expression.

Evaluating the effect of WNT pathway genes considering interactions on the risk of non-syndromic oral clefts among Chinese populations / 北京大学学报(医学版)

OBJECTIVE@#In this study, we used genome-wide association study (GWAS) data to explore whether WNT pathway genes were associated with non-syndromic oral clefts (NSOC) considering gene-gene interaction and gene-environment interaction.@*METHODS@#We conducted the analysis using 806 non-syndromic cleft lip with or without cleft palate (NSCL/P) case-parent trios and 202 non-syndromic cleft palate (NSCP) case-parent trios among Chinese populations selected from an international consortium established for a GWAS of non-syndromic oral clefts. Genotype data and maternal environmental exposures were collected through DNA samples and questionnaires. Conditional Logistic regression models were adopted to explore gene-gene interaction and gene-environment in teraction using trio package in R software. The threshold of significance level was set as 3.47×10-4 using Bonferroni correction.@*RESULTS@#A total of 144 single nucleotide polymorphisms (SNPs) in seven genes passed the quality control process in NSCL/P trios and NSCP trios, respectively. Totally six pairs of SNPs interactions showed statistically significant SNP-SNP interaction (P < 3.47×10-4) after Bonferroni correction, which were rs7618735 (WNT5A) and rs10848543 (WNT5B), rs631948 (WNT11) and rs556874 (WNT5A), and rs631948 (WNT11) and rs472631 (WNT5A) among NSCL/P trios; rs589149 (WNT11) and rs4765834 (WNT5B), rs1402704 (WNT11) and rs358792 (WNT5A), and rs1402704 (WNT11) and rs358793 (WNT5A) among NSCP trios, respectively. In addition, no significant result was found for gene-environment interaction analysis in both of the NSCL/P trios and NSCP trios.@*CONCLUSION@#Though this study failed to detect significant association based on gene-environment interactions of seven WNT pathway genes and the risk of NSOC, WNT pathway genes may influence the risk of NSOC through potential gene-gene interaction.

Exploring parent-of-origin effects for non-syndromic cleft lip with or without cleft palate on PTCH1, PTCH2, SHH, SMO genes in Chinese case-parent trios / 北京大学学报(医学版)

OBJECTIVE@#Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect, affecting 1.4 per 1 000 live births, and multiple genetic and environmental risk factors influencing its risk. All the known genetic risk factors accounted for a small proportion of the heritability. Several authors have suggested parent-of-origin effects (PoO) may play an important role in the etiology of this complex and heterogeneous malformation. To clarify the genetic association between PTCH1, PTCH2, SHH and SMO in hedgehog (HH) pathway and NSCL/P, as well as testing for potential PoO effects in Chinese case-parent trios.@*METHODS@#We tested for transmission disequilibrium tests (TDT) and PoO effects using 83 common single nucleotide polymorphic (SNP) markers of HH pathway genes from 806 NSCL/P case-parent trios. These trios were drawn from an international consortium established for a genome-wide association studies (GWAS) of non-syndromic oral clefts of multiple ethnicities. DNA samples were collected from each trio. Single marker and haplotype based analysis were performed both in TDT tests and PoO effects. SNPs were excluded if they (ⅰ) had a call rate of < 95%, (ⅱ) had a minor allele frequency (MAF) of < 0.05, (ⅲ) had Mendelian errors over all trios of >5%, (ⅳ) had a genotype distribution in the parents that deviated from the Hardy-Weinberg equilibrium (HWE) (<i>P</i> < 0.000 1). The process was done using Plink (version 1.07, <a href="http://pngu.mgh.harvard.edu/~purcell/plink/data.shtml" target="_blank">http://pngu.mgh.harvard.edu/~purcell/plink/data.shtml</a>). TDT test was performed in Plink v1.07. A log-linear model was used to explore PoO effects using Haplin v6.2.1 as implemented in R package v3.4.2. Significance level was assessed using the Bonferroni correction.@*RESULTS@#A total of 18 SNPs were dropped due to low MAF, thus leaving 65 SNPs available for the analysis. Thus the Bonferroni threshold was 7.7×10-4 (0.05/65). Nominal significant association with NSCL/P was found at a SNP (rs4448343 in PTCH1, P=0.023) and six haplotypes (rs10512249-rs4448343, rs1461208-rs7786445, rs10512249-rs4448343, rs16909865-rs10512249-rs4448343, rs1461208-rs7786445-rs12698335, and rs288756-rs288758-rs1151790, P < 0.05). A total of six haplotypes (rs288765-rs1233563, rs12537550-rs11765352, rs872723-rs288765-rs1233563, rs288765-rs1233563-rs288756, rs6459952-rs12537550-rs11765352, and rs12537550-rs11765352-rs6971211) showed PoO effect (P < 0.05). None of the results remained significant after the Bonferroni correction (P>7.7×10-4).@*CONCLUSION@#Neither significant association between SNPs within HH pathway and the risk of NSCL/P nor PoO effects was seen in this study.

Exploring the association between SPRY gene family and non-syndromic oral clefts among Chinese populations using data of a next-generation sequencing study / 北京大学学报(医学版)

OBJECTIVE@#To explore the association between SPRY gene family and the risk of non-syndromic oral clefts among Chinese populations, in respect of single nucleotide polymorphisms (SNPs) association and parent-of-origin effects.@*METHODS@#Based on case-parent design, this study used the data of SPRY gene family in a next generation sequencing study of 183 non-syndromic cleft lip with or without cleft palate (NSCL/P) case-parent trios (549 participants) recruited from 2016 to 2018, to analyze the effects of SNP association and parent-of-origin. The sequencing study adopted a two-stage design. In the first stage, whole exome sequencing was conducted among 24 NSCL/P trios with family history to explore potential signals. Then in the second stage, another 159 NSCL/P trios were used as validation samples to verify the signals found in the first stage. The data of general information, disease features and parental environmental exposures for participants were collected through questionnaires. Blood samples were collected from each participant for DNA extraction and sequencing. Transmission disequilibrium tests (TDT) were conducted to test for the association between SNPs and NSCL/P, while Z score tests were applied to analyze parent-of-origin effects. The analyses were performed using Plink (v1.07). TRIO package in R (v3.5.1). Besides, famSKAT analyses were conducted in the first stage to combine the effect of SNPs located on the same gene, using famSKAT package in R(V3.5.1). Bonferroni method was adopted to correct multiple tests in the second stage.@*RESULTS@#Twenty-two SNPs in SPRY gene family were included for analyses after the quality control process in the first stage. Based on the variants annotation, functional prediction and statistical analysis, rs1298215244 (SPRY1) and rs504122 (SPRY2) were included in the second verification stage. TDTs in the verification stage revealed that rs1298215244: T>C, rs504122: G>C and rs504122: G>T were associated with the risk of NSCL/P after Bonferroni corrections, where rs504122: G>T was a rare variation. Although the test for parent-of-origin effect of rs1298215244: T>C reached nominal significance level, no SNP showed significant association with NSCL/P through parent-of-origin effect after Bonferroni corrections.@*CONCLUSION@#This study found that SNPs (including both common and rare variants) among the SPRY gene family were associated with the risk of NSCL/P among Chinese populations. This study failed to detect parent-of-origin effects among the SPRY gene family.

Epidemiological investigation of welder's pneumoconiosis in two container manufacturing industries in Guangdong province / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the incidence of welder's pneumoconiosis in container manufacturing industries in Guangdong province and present some preventive and curative strategy.</p><p><b>METHODS</b>Occupational epidemiology study methods were used to study the incidence of welder's pneumoconiosis in two container manufacturing enterprises (enterprise A and enterprise B).</p><p><b>RESULTS</b>Before 2004, the rate of up-to-standard of weld fume concentration in the workplaces was relatively low (< or = 40%), and the maximum value of time weighted average (TWA) was 26.7 mg/m(3). After 2004, with the system of dust control, the rate of up-to-standard was 85% in the enterprise A. Of the 813 weld workers examined, 19 were diagnosed as welder's pneumoconiosis (stage I was 15, while I (+) was 4 ) and the incidence was 2.34% (19/813). The age of electric welders suffering from welder's pneumoconiosis and the duration of dust exposure were (33.45 + 4.64) and (8.04 + 1.97) years respectively. Chest radiographic examination showed mainly small round opacities "p". The value of MVV, FEF25%, FEF50% and FEF75% in lung function tests were significantly lower than those of the control group (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>The main features of welder's pneumoconiosis in container manufacturing industries are the short duration of dust exposure, and small round opacities "p" in the chest radiographs. Therefore, it should be the key point of the prevention and treatment of occupational diseases in this industry to control the harmful weld fume.</p>

Studies on the microwave leakage of the interphone / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To assay and study the microwave leakage of 4 types of interphones.</p><p><b>METHODS</b>The radiation intensities of four types of 199 interphones were determined by the microwave leakage measure instrument of model ML-91 made in China.</p><p><b>RESULTS</b>The average intensities of microwave leakage at a distance of 5 cm from aerial part and other parts of interphones during launching [(1 316.0 +/- 144.3), (971.0 +/- 131.6) microW/cm(2) respectively] were significantly higher than during waiting [(14.4 +/- 5.3), (13.2 +/- 4.9) microW/cm(2) respectively] (P < 0.01). The average intensities of microwave leakage at a distance of 50 cm from different parts were (357.3 +/- 27.8) microW/cm(2). The daily average intensity of microwave leakage to which the head, chest and abdomen exposed was (945.5 +/- 447.1) microW.h/cm(2) in total, that exceeded the hygienic standard of microwave in China (400 microW.h/cm(2)), during the normal communication by interphones.</p><p><b>CONCLUSION</b>The microwave leakage was higher during launching than during waiting, and was the highest at the aerial part of the interphones. The microwave radiation of most interphones was higher than the current national standard. It may lead to potential effects on the owner of interphone, so protection against it should be made.</p>

Effect of whole-period psychiatric rehabilitation on outpatients with schizophrenia / 中国康复理论与实践

@#ObjectiveTo investigate the effect of whole-period psychiatric rehabilitation on outpatients with schizophrenia.Methods90 outpatients with schizophrenia were randomly divided into the study group and control group with 45 cases in each group. All cases in two groups received pharmacotherapy, but cases of study group were added with whole-period psychiatric rehabilitation. Assessments were performed before and after study. All subjects were evaluated with the Brief Psychiatric Rating Scale (BPRS) and Social Disability Screening Schedule (SDSS).ResultsThe outcome of the study group was significantly superior to the control group on overall improvement according to the reductions of BPRS score, Anergia factor score, thought disturbance factor score, suspiciousness factor score and SDSS score(P<0.05-0.01).ConclusionThe whole-period psychiatric rehabilitation may play an important role in controlling symptoms and improving social function to outpatients with schizophrenia.

Epigenetic modifications and its impact on animal cloning / 生物工程学报

Despite recent successes in cloning various mammals and amphibians, the low efficiency of animals production and abnormal symptoms in many cloned animals are crucial problems in cloning technology. To overcome these problems, scientists focus on mechanisms of cloning. A possible cause of the low success frequency of cloning is the insufficient dedifferentiation and the inadequate reprogramming of the high differentiated adult somatic nucleus in enucleated oocytes, which caused by incomplete methylation and premature de novo remethylation of donor DNA. In cloned embryos the methylation level is higher than normal embryos, and this may cause aberrant expression of several important genes, especially imprinting genes. Study on these mechanisms is very important to improve the rate of successful cloned animals.

Isolation and identification of reprogramming genes related to the development of the rabbit reconstructed embryos / 生物工程学报

By the method of single preimplantation embryos differential display polymerase chain reaction (SPEDDRT-PCR), 25 reprogramming cDNA fragments were obtained from single 2-cell, 8-cell embryos and blastula. After cloning and sequencing, five of them were identified by reverse-Northern and characterized with stage-specific expression during reconstructed embryo development. This results will help to isolate full length reprogramming genes and study their function during embryonic development.

Behavior Therapy for relieving the symptoms of outpatients with schizophrenia / 中国康复理论与实践

@#ObjectiveTo study the effects of the Behavior Therapy on outpatient with schizophrenics in relieving symptoms, insight, and attitude to treatment. Methods96 outpatients with schizophrenia were randomly assigned to the Behavior Therapy group and the control group. The Behavior Therapy courses were given to the Behavior Therapy group for six months. All the subjects were evaluated with Positive and Negative Syndrome Scale(PANSS) and Insight and Therapeutic Attitude questionaire(ITAQ). Results94 cases completed the trial. The scores of PANSS, the Negative Subscale, the General Psychopathology Subscale of the Behavior Therapy group decreased significantly after treatment(P<0.01). The score of ITAQ of the Behavior Therapy group increased significantly after treatment(P<0.01).The reductions of PANSS, the Positive Subscale, the Negative Subscale, the General Psychopathology Subscale and ITAQ between two groups were significant different(P<0.05-P<0.01). Conclusions The Behavior Therapy may play an important role in augmenting optimal pharmacotherapy for outpatients with schizophrenia and it is effective in improving symptoms, insight and therapeutic attitude.