Objective To investigate whether the gamma-aminobutyric acid (GABAB) receptor genes,including gabbr1 gene and gabbr2 gene,are the susceptible genes for simple febrile seizures (sFS) by screening mutation of gabbr1 gene and gabbr2 gene and to study the possible association between sFS and the 2 genes.Methods All exons and flanking introns of gabbr1 gene and gabbr2 gene were amplified with polymerase chain reaction (PCR) and sequenced to screen the possible mutation on 60 children with sFS in the northern China in Han nationality population.One hundred and one healthy children from the same area were selected as controls,and the genotypes of single nucleotiole polymorphisms (SNPS) (rs29220,rs29230,rs29267 on gabbr1 gene and rs1000440,rs3205936,rs2304391 on gabbr2 gene) were typed by PCR-restriction fragment length polymorphism.EH1.20 software was used to estimate haplotype frequency to study the association with the haplotype as genetic marker between case group and control group.Results No mutation associated with sFS was found in the 60 sFS cases.In all sequenced regions,23 SNPs were identified in both genes:6 SNPs in gabbr1 gene and 17 SNPs in gabbr2 gene.The frequencies of the 6 SNPs were complied well with the Hardy-weinberg equilibrium in sFS group and normal group.Genotype proportions and allele frequencies of 6 SNPs were not significantly different between both groups.The haplotypes of 3 SNPs in gabbr1 gene and in gabbr2 gene distributions were not significantly different between 2 groups.Conclusions No mutations and associations were identified between sFS with both GABAB receptor genes(gabbr1 gene and gabbr2 gene).They may not be the susceptibility gene for simple febrile seizures in Han nationality population in northern China.

Interleukin 24 ( IL-24) has a good prospect in tumor therapy because it can specifically inhibit proliferation in a variety of tumor cells in vitro and in vivo and induce apoptosis of tumor cells without affecting normal cells .Gene therapies which use recombinant adenovirus as a vector have some limitations that restrict the clinical application of IL-24. In comparison, protein drugs have tremendous advantages .In this paper, the progress in research on IL-24 gene engineering protein is elaborated .

OBJECTIVE To explore the incidence rate,pathogen distribution and characteristics of drug resistance of ventilator-associated pneumonia(VAP) patients due to acute lung injury and acute respiratory distress syndrome(ALI/ARDS) after severe injury,and analyze impact factors on VAP.METHODS All 183 cases with ALI/ARDS after severe injury from Jan 2004 to Mar 2008,were admiitted and given mechanic ventilation over 48 hours in our ICU and EICU.RESULTS VAP was found in 98 cases,accounted for 53.56%.Among them,42 were early-onset VAP and the other 56 were late-onset VAP.Altogether 276 pathogens were isolated,and most of them were Pseudomonas aeruginosa,Staphylococci aureus,Klebsiella pneumoniae,Acinetobacter baumannii and Escherichia coli.In 41 cases only one pathogen was isolated,the other 57 cases were with two or above pathogens.The revealed important risk factors were coma,prolonged mechanical ventilation,tracheotomy,antiacid treatment,use of antimicrobial agents and low albumin.CONCLUSIONS The incidence rate of VAP due to ALI/ARDS is high,and most of the isolated pathogens are drug resistant.Mixed infections are found commonly in these cases.

Objective To evaluate the international prognostic index (IPI) in peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Methods From May 2005 to May 2008, 75 patients of PTCL--NOS were reviewed. All the patients were diagnosed again by immunohistochemical staining. According to IPI, they were divided into four groups:low risk (0-1), intermediate-low(2), intermediate-high(3), high risk (4-5), then the difference of treatment effectiveness and prognosis among them were analysed. Results IPI scoring of 75 patients were classified as low risk , 10 (13.3%); as intermediate-low, 14 (18.7%); as intermediate-high, 28 (37.3 %); as high risk, 23 (30.7%). There was a significant difference in complete remission rates with first line treatment(X2=16.677,P=0.001), and overall survival rates (P=0.0000) among four groups. Median survival time among 4 groups were 36+, 29.00, 17.00, 10.00 months. 1-year OS were 100.00 %, 89.05 %, 64.24 %, 15.73 %; 2-year OS were: 75.00 %, 53.01%, 34.42 %, 2.00 % respectively. Multivariate analysis showed that both complete remission rates of first line treatment(P=0.002) and IPI(P = 0.049) were independent prognostic factor for PTCL-NOS, while single index of IPI was not. Conclusion At a certain extent, IPI model was able to predict response of treatment effective and prognosis in PTCL-NOS.

Objective To perform a prenatal diagnosis for the second fetuses from 28 pedigrees with proband of mitochondrial disease due to mitochondrial DNA (mtDNA) mutation.Methods From April 2011 to November 2015,peripheral blood samples of 28 probands and their parents,urine samples of these probands and their mothers as well as amniotic fluid samples of the second fetuses from the 28 pedigrees were collected in Peking University First Hospital.DNA sequencing was used to identify mtDNA mutations.Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to verify mutation sites,calculate mutation loads,and further confirm the diagnosis after birth.Microsatellite maker analysis was also performed on five short tandem repeats located in nuclear genes to exclude maternal contamination.Statistical analysis was carried out using independent t-test.Results In the 15 pedigrees carrying A3243G mutation,13 mothers and nine fetuses carried A3243G mutation.Neither the other two mothers nor their fetuses were positive for A3243G mutation.Among the 12 pedigrees with T8993G mutation,there were eight mothers carrying T8993G mutation and all of their fetuses carried the same mutation;and the other four mothers and their fetuses were negative for T8993G mutation.T10191C mutation was only found in one proband and the second fetus of that pedigree,but not in the mother.None of the fathers had mtDNA mutation.Results of PCR-RFLP were consistent with those of DNA sequencing.Short tandem repeat analysis demonstrated that amniocyte samples were from fetuses without maternal contamination.No mtDNA mutations were found in the six newborns who were negative for mtDNA mutations in prenatal diagnosis.The mean mutation load in urine samples of the six mothers without A3243G mutation in amniocytes was significantly lower than that of the nine mothers with A3243G mutation [(10.1 ±4.8) ％ vs (28.2 ± 15.1) ％,t=2.290,P=0.043].Conclusions The lower the mtDNA mutation load in maternal urine samples,the less the possibility she bears a child with mtDNA mutation.However,prenatal diagnosis of mitochondrial disease is necessary.

Objectives To provide prenatal diagnosis and genetic counseling for four athigh-risk pregnant women with a suspected family or personal history of fragile X syndrome (FXS) by genetic screening of fragile X mental retardation (FMR1) gene.Methods This study was conducted on four pregnant women (No.l to 4) who received outpatient treatment in Peking University First Hospital from August 2014 to June 2016.Genomic DNA was extracted from peripheral blood samples of the pregnant women and six of their family members,four of which were suspected or confirmed FXS and the other two were FMR1 gene carriers.Amplide X kits were used to detect CGG repeat size in FMR1 gene.Two amniocytes and one chorionic villi samples were collected from three pregnant women to extract DNAs for FMR1 gene and karyotyping analyses.Results There were patients diagnosed with FXS in all the families by detecting CGG repeat numbers in FMR1 gene.The pregnant woman No.1 was a permutation carrier;No.2 carried normal FMR1 alleles while her brother had a mutation with over 20 CGG repeats in FMRI gene at chromosome X.No.3 and 4 were full mutation carriers with over 200 CGG repeats in FMR1 gene.After genetic counseling,No.3 decided to terminate the pregnancy due to abnormal fetal karyotype (47,XY,+21) and full mutation of FMR1 alleles.No.1 and 4 continued to pregnancy as their fetuses were normal in FMR1 alleles and karyotype.No.2 continued to pregnancy as her fetus was free of FXS risk.Conclusions Prenatal diagnosis and genetic counseling should be conducted on women at highrisk for FXS to avoid birth defects.People with a family history of FXS should be tested for FMR1 gene carrier status.

BACKGROUND:Lipoic acid, with a closed circle structure composed by sulphur and carbon atoms, exerts strong anti-oxidation, and has been extensively applied in the prevention and treatment of oxidative stress, diabetic cataract, diabetic neuropathy and cardiovascular diseases. OBJECTIVE:To investigate the protective effect of lipoic acid on peripheral nerve function during peripheral nerve ischemia/reperfusion injury. METHODS:Models of peripheral nerve ischemia/reperfusion injury were established in rabbits, and then rabbit models were then allotted to treatment and non-treatment groups. The treatment group was subdivided into experimental (injection of lippoic acid) and control groups according to the use of lipoic acid at 1, 3 and 6 hours after ischemia and before reperfusion. The ultrastructural changes of the sciatic nerve were observed under electron microscope, and the electrophysiological changes of the sciatic nerve were detected using evoked potential instrument. RESULTS AND CONCLUSION:With the ischemic time increasing, the number of vacuoles in the axon increased gradually, accompanied by axonal atrophy, and Waller's degeneration in the aggregated microfilaments. The myelin sheath thickening and dissolving were visible. All above phenomena became severest at 6 hours after ischemia. Compared with the control groups, lipoic acid reduced the number of the vacuoles in the axon and all eviated axonal atrophy, Waller's degeneration and demyelination. As the ischemic time increasing, the latency of sciatic nerve was significantly increased, and peaked at 6 hours of ischemia;while the amplitude was significantly decreased, and reached a minimum at 6 hours of ischemia. Compared with the control groups, in the experimental groups, the latency of sciatic nerve was significantly decreased, but the amplitude was significantly increased. These results suggest that lipoic acid provides neuroprotection against peripheral nerve ischemia/reperfusion injury.

Objective To study the expression of NF-κB p50 in nodal peripheral T-cell lymphomasunspecified (PTCL-U),and investigated the relationship between NF-κB and PTCL-U's complex biological behavior. Methods 51 patients with nodal PTCL-U were analysed by detecting the expression of NF-κB p50, p170 by immunohistochemistry and correlation between them and PTCL-U' s clinical feature, treatment effectiveness and prognosis were also studied. Results 11 patients(21.6 %, 11/51) and 31patients (60.8 %,31/51) were respectively positive for N F-κB p50 and p 170 expression. Expression of NF-κB were significantly correlated with p170 expression, poor performance status (PS＞2) and non-complete remission in first line treatment(Spearman correlation= 0.459, 0.313, 0.284; P = 0.001, 0.025, 0.044). Overall survival rate of NFκB p50-positive PTCL-U was significantly lower than that of NF-κB p50-negative patients by Log-Rank test (P =0.0451). Multivariate analysis showed poor performance and higher Ki-67 were independent prognostic factor for PTCL-U, while NF-κB p50 was not. Conclusion The expression of NF-κB pS0 was correlated with muhidrug resistance and poor prognosis in nodal PTCL-U.

Objective:To summarize the prenatal diagnostic characteristics of monogenic global developmental delay/intellectual disability(GDD/ID) pedigrees.Methods:This study retrospectively collected the prenatal molecular diagnostic results of 43 pedigrees that were affected with monogenic GDD/ID in the genetic counseling clinic of Peking University First Hospital from January 2015 to June 2019. The results of prenatal molecular tests were validated after birth or pregnancy termination. Pregnancy outcomes and healthy condition of the offspring were followed up. All data were analyzed by descriptive statistical analysis.Results:Among the 43 pedigrees, 24 were affected with autosomal recessive inheritance (AR) GDD/ID, in which six (25%) fetuses were found to carry two pathogenic variants; 13 (55%) had only one pathogenic variant; five (20%) did not harbor any variant. GDD/ID inherited in an autosomal dominant inheritance (AD) pattern was found in 13 pedigrees, in which 11 fetuses carried no variants while the other two fetuses had the same variants as the proband had (in one pedigree, a low-level variant was detected in the peripheral blood sample of the father while absent in peripheral blood samples of parents in the other pedigree, so it was suspected that the variants of these two affected fetuses were inherited from parental mosaicism). In the other six pedigrees with X-linked inheritance (XL) of GDD/ID, one male fetus was found to harbor the pathogenic variant, while no variants were detected in the others. Maternal contamination was excluded in all prenatal samples using short tandem repeat for linkage analysis. Postnatal validations were consistent with the prenatal tests. All nine affected fetuses were terminated, and the other thirty-four children were delivered and in good health.Conclusions:Prenatal molecular diagnostic test is an effective method to detect pathogenic variants during the first and second trimesters for pedigrees affected by monogenic GDD/ID. For pedigrees affected with AD or XL patterns caused by de novo mutations, potential parental mosaicism should be noted and prenatal diagnostic tests are also recommended.

Background The operation mode of automobile manufacturing industry (AMI) makes workers have different degrees of occupational stress and burnout, which may lead to negative emotions and depressive symptoms. Objective To study the relationship between occupational stress, job burnout, and depressive symptoms in AMI workers. Methods In this study, 1300 workers from a Guangzhou AMI company were selected as subjects by cluster random sampling method. Occupational stress, job burnout, and depressive symptoms of the workers were assessed by using the Effort-Reward Imbalance (ERI) questionnaire, the Maslach Burnout Inventory general survey questionnaire, and the Patient Health Questionnaire-9, respectively. Hierarchical regression was used to analyze the effects of occupational stress and job burnout on depressive symptoms in AMI workers. Mediating effect model was used to analyze the mediating effect of job burnout on the relationship between occupational stress and depressive symptoms. Results There were 1300 questionnaires distributed, 1228 valid questionnaires collected, with a 94.5% recovery rate. The ERI ratio of 1228 AMI workers was 1.06±0.72, and the positive rate of occupational stress was 37.3% (458/1228). The score of job burnout was 2.18±1.37, and the positive rate of job burnout was 62.6% (769/1228). The score of depressive symptoms was 10.27±6.42, and the positive rate of depressive symptoms was 47.1% (578/1228). The dimensional scores of effort and over-commitment in occupational stress as well as emotional exhaustion and depersonalization in job burnout of AMI workers were positively correlated with the depressive symptom scores (r_s=0.415, 0.571, 0.573, 0.593, P＜0.05). The dimensional scores of reward and personal achievement were negatively correlated (r_s=−0.454, −0.339, P＜0.05). The percentages of variance in depressive symptoms score explained by occupational stress and job burnout were 26.7% and 16.6%, respectively. Job burnout had a partial mediating effect between the three dimensions of occupational stress and depressive symptoms, and the mediating effect values were −0.2832 (95%CI: −0.3250– −0.2434), 0.3553 (95%CI: 0.3071–0.4041), and 0.4193 (95%CI: 0.3681–0.4725), respectively. Conclusion AMI workers' occupational stress affects job burnout, but also indirectly affects depressive symptoms. Job burnout partially mediates the association between occupational stress and depressive symptoms. Reducing occupational stress and burnout levels of AMI workers may alleviate depressive symptoms.