Objective To analyze the regulation of NEF3 expression in SH - SY5Y after RA induction. Methods The expression of NEF3 and Brg1 genes was individually detected by realtime RT - PCR and Western blot analyses. Then, the CAT reporter driven by 5' flanking region ofNEF3 gene (pBLCAT3 -2. 8k - NEF3) was co - transfccted with eukaryotic expression plasmids of pBJ5 - Brgl or pBJ5 - Brg1 - NTP into SH - SY5Y respectively. Promoter activity of the NEF3 gene was detected by competitive RT - PCR assay. Results Similar changes in the mRNA expression of NEF3 and Brg1 and that of the protein expression of Brgl were detected in Sh - SY5Y cells af-ter RA treatment for 12 -24h. Wild type Brgl can promote the expression of pBLCAT3 -2.8k -NEF3 promoter after RA induction, but not mutant Brg1. Conclusion Brgl helpes regulating the expression of NEF3 gene possibly via changes in chromatin conformation in the SH -SY5Y cells after RA induction.

Objective To evaluate the effect of exogenous wild PTEN gene stable transfected into human ovarian cancer cell line HO-8910 on phosphatidyl inositol 3-kinase( PI3K)/protein kinase B (Akt)siganal pathway and cells proliferation. Methods Wild-type PTEN recombinant eukaryotic expression plasmid was constructed and then was transfected into HO-8910 cells by lipofectamine 2000. The expression of PTEN, Akt1, Akt2, PI3K mRNA and protein of PTEN were tested by reverse transcription( RT)-PCR and Western blot. The proliferation of HO-8910 after wild PTEN gene transfected was measured by methyl thiazolyl tetrazolium(MTT). Results Wild-type PTEN gene was successfully transfected into HO-8910 cells. The results of RT-PCR and western bolt showed that there were the significant expression high level of PTEN mRNA and protein after infected by wild-PTEN plasmid than those in the control[ ( 17 372 ±23)vs.(39±1 )vs. (78 ±4)copies/ml,P ＜0. 05 ]. While the expression of mRNA of Akt1, Akt2 and PI3K were decreased clearly than those in the control [ (28 ± 2 ) vs. ( 115 ± 5 ), (7 ± 1 ) vs. ( 18 ± 2), (61 ± 2 ) vs.(84 ± 2)copies/ml , all P ＜ 0. 05 ]. The proliferation rate of HO-8910 cells was obviously slower than those in the control (90 158 ±47 vs. 148 251 ±65 vs. 250 115 ±62, P＜0.05). Conclusion Transfection of PTEN may increase the expression of PTEN and inhibit the proliferation of HO-8910 cells, in which PI3K/ Akt siganal pathway is inhibit significantly.

Establishment of quality management system (QMS) plays a critical role in the clinical data management (CDM). The objectives of CDM are to ensure the quality and integrity of the trial data. Thus, every stage or element that may impact the quality outcomes of clinical studies should be in the controlled manner, which is referred to the full life cycle of CDM associated with the data collection, handling and statistical analysis of trial data. Based on the QMS, this paper provides consensus on how to develop a compliant clinical data management plan (CDMP). According to the essential requirements of the CDM, the CDMP should encompass each process of data collection, data capture and cleaning, medical coding, data verification and reconciliation, database monitoring and management, external data transmission and integration, data documentation and data quality assurance and so on. Creating and following up data management plan in each designed data management steps, dynamically record systems used, actions taken, parties involved will build and confirm regulated data management processes, standard operational procedures and effective quality metrics in all data management activities. CDMP is one of most important data management documents that is the solid foundation for clinical data quality.

Objective To investigate the expression of monocyte subsets and their chemokine,i.e.,monocyte chemoattractant protein (MCP-1) and fractalkine (FKN),in patients with acute coronary svndrome (ACS),and to analyze their correlation.Methods Patients with the syndrome of pectoralgia and to be inspected with coronary angiography (CAG) in our hospital from Sep.to Dec.,2016 were included.Patients' venous blood was collected on the operation day before operation,the level and proportion of monocyte (Mon) subsets,which was namely CD14 + CD16-Mon (Mon1),CD14+CD16 + Mon (Mon2) and CD14-CD16 + Mon (Mon3) according to the expression of cluster differentiation-14 (CD14) and CD16,were detected by flow cytometry (FCM).Patients' venous blood was collected on the operation day before operation and one day after operation,the concentrations of MCP-1 and FKN in plasma were measured by ELISA.We compared the expression levels of MCP-1-Mon1 and FKN-Mon3,and analyzed their relationship between each other respectively in different groups.Results Diagnosed according to the clinical symptoms,myocardial markers,electrocardiogram and CAG results,70 individuals were analyzed,including 30 patients with acute myocardial infarction (AMI group),25 patients with unstable angina pectoris (UAP group) and 15 patients with the chest pain symptoms and normal CAG results (control group).The percentage of Mon1 in the AMI group was higher than that in the other groups (P＜0.05);no difference was observed for Mon3 among the groups (P＞0.05).The Mon3/Mon1 ratio in the AMI group was lower than that in the control group (P＜0.05).Moreover,the levels of FKN and MCP-1 in the ACS group were greater than those in the control group.The level of red blood cell distribution width (RDW) was significantly increased in the AMI and UAP group than that in the control group (P＜0.05).There was a significant correlation between FKN and Mon3 (P＜0.05,R=0.650 2).Conclusions The monocyte subset of Mon1 and Mon3 increased in the early stage of ACS,with their chemokine (FKN and MCP-1) increasing at the same time.There is a significant correlation between FKN and Mon3,which indicates MCP-1-Mon1 and FKN-Mon3 may participate in the pathophysiological process of early ACS in patients.

Objective To evaluate the regulatory effects of psilocybin on social behavior of male C57BL/6J mice.Methods Adult male C57BL/6J mice were intraperitoneally injected with psilocybin(0.2,1 and 5 mg/kg,i.p.),and the effects of psilocybin on prosocial behavior were evaluated by the three-chamber test.Stressed mice undergoing chronic social defeat stress(CSDS)were given acute intraperitoneal injection of psilocybin(1 mg/kg)to evaluate the moderation of social novelty preference behavior using the modified two-chamber test.Results Intraperitoneal injection of psilocybin(1 mg/kg)promoted prosocial behavior and prolonged social time(P＜0.01),while intraperitoneal injection of psilocybin(0.2 mg/kg)had no apparent effect on the prosocial behavior of mice,and intraperitoneal injection of psilocybin(5 mg/kg)inhibited prosocial behavior before promoting it.Further studies showed that intraperitoneal injection of psilocybin(1 mg/kg)increased the social novelty exploration time in stressed mice undergoing CSDS.Conclusion This study shows that 1 mg/kg dose of psilocybin can promote the prosocial behavior in mice,and potentially ameliorate the deficit of social novelty preference behavior in CSDS mice.

Objective? To compare the reliability and validity of Intensive Care Delirium Screening Checklist (ICDSC) and Neelon and Champagne Confusion Scale (NEECHAM) when evaluating non-mechanical ventilation patients in Neurosurgery Department. Methods? A total of 100 non-mechanical ventilation patients in the Neurosurgery Department of a ClassⅢ Grade A hospital in Shanxi Province from August to December 2018 were selected. The non-operative patients were assessed on the third day after admission, and the operative patients were assessed on the third day after operation. Qualified nurses assessed the patients at 00:00—1:00, 8:00—9:00 and 16:00—17:00 with ICDSC and NEECHAM. Psychiatrists assess the patients at 16:30—17:30 on the same day by Richmond Agitation and Sedation Scale (RASS) and Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV). Using the results of DSM-IV as the gold standard, the curve of ROC was drawn, and the sensitivity and specificity of the two scales were compared. Results? Area under ROC Curve (ROCAUC) of ICDSC was 0.891 (95%CI: 0.826-0.956,P＜0.01). The ROCAUC of NEECHAM was 0.987 (95% CI: 0.970-0.999, P＜ 0.01). When the optimal threshold of ICDSC was 4.25, the sensitivity and specificity were 87.8% and 76.2% respectively. When the optimal threshold of NEECHAM was 23.5, the sensitivity and specificity were 98.0% and 92.9% respectively. Conclusions? The misdiagnosis rate of NEECHAM is lower than ICDSC, and the diagnostic efficacy, authenticity, reliability and diagnostic value of NEECHAM are higher than ICDSC. NEECHAM is more suitable for nurses to evaluate delirium in neurosurgery patients without mechanical ventilation.

OBJECTIVETo analyze two Chinese pediatric patients with multiple malformations and growth and development delay.

METHODSBoth patients were subjected to targeted gene sequencing, and the results were analyzed with Ingenuity Variant Analysis software. Suspected pathogenic variations were verified by Sanger sequencing.

RESULTSHigh-throughput sequencing showed that both patients have carried heterozygous variants of the CHD7 gene. Patient 1 carried a nonsense mutation in exon 36 (c.7957C>T, p.Arg2653*), while patient 2 carried a nonsense mutation of exon 2 (c.718C>T, p.Gln240*). Sanger sequencing confirmed the above mutations in both patients, while their parents were of wild-type for the corresponding sites, indicating that the two mutations have happened de novo.

CONCLUSIONTwo patients were diagnosed with CHARGE syndrome by high-throughput sequencing.

CHARGE Syndrome ; genetics ; DNA Helicases ; genetics ; DNA-Binding Proteins ; genetics ; Genetic Testing ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Male ; Mutation

Objective: To investigate the association between etheno-DNA adduct and the promoter of DNA methylation levels of cyclin dependent kinase inhibitor 2A (P16), Ras association domain family 1 (RASSF1A) and O-6-methylguanine-DNA methyltransferase (MGMT) in workers with occupational exposure to diesel engine exhaust (DEE). Methods: We recruited 124 diesel engine testing workers as DEE exposure group and 112 water pump operator in the same area as control group in Henan province in 2012 using cluster sampling. The demographic data were obtained by questionnaire survey; urine after work and venous blood samples were collected from each subject. The urinary etheno-DNA adducts were detected using UPLC-MS/MS, including 1,N6-etheno-2'-deoxyadenosine (εdA) and 3,N4-etheno-2'-deoxycytidine(εdC). The DNA methylation levels of P16, RASSF1A, and MGMT were evaluated using bisulfite-pyrosequencing assay. The percentage of methylation was expressed as the 5-methylcytosine (5mC) over the sum of cytosines (%5mC). Spearman correlation and multiple linear regression were applied to analyze the association between etheno-DNA adducts and DNA methylation of P16, RASSF1A, and MGMT. Results: The median (P₂₅-P₇₅) of urinary εdA level was 230.00 (98.04-470.91) pmol/g creatinine in DEE exposure group, and 102.10 (49.95-194.48) creatinine in control group. The level of εdA was higher in DEE exposure group than control group (P<0.001). DNA methylation levels of P16, RASSF1A and MGMT were 2.04±0.41, 2.19 (1.94-2.51), 2.22 (1.94-2.46)%5mC in exposure group, and 2.19±0.40, 2.41 (2.11-2.67), 2.44 (2.15-2.91)%5mC in control group. DNA methylation levels were lower in exposure group (P values were 0.005, 0.002 and 0.001, respectively). Spearman correlation analysis showed that DNA methylation levels of P16, RASSF1A, and MGMT were negative associated with urinary εdA level (r values were -0.155, -0.137, and -0.198, respectively, P<0.05). No significant correlation was observed between the εdC level and any measured DNA methylation levels (P>0.05) . Multiple linear regression confirmed the negative correlation between εdA and DNA methylation levels of P16, RASSF1A, and MGMT in non-smoking group (β (95%CI) was -0.068 (-0.132--0.003), -0.082 (-0.159--0.004) and -0.048 (-0.090--0.007), P values were 0.039, 0.039 and 0.024, respectively). Moreover, εdC was negative associated with DNA methylation level of MGMT in non-smoking group (β (95%CI) was -0.094 (-0.179--0.008), P=0.032). Conclusion DEE exposure could induce the increased of εdA and decreased of DNA methylation levels of P16, RASSF1A and MGMT.

Objective:To analyze the effects of HIV non-occupational post-exposure prophylaxis (nPEP) in men who have sex with men (MSM) in Nanning and Liuzhou, Guangxi Zhuang Autonomous Region.Methods:Participants were recruited through community publicity and advocacy under a "Trinity" approach among non-governmental organizations (NGO), CDCs/hospitals and pharmacies. Basic information, drug taking and follow-up tests of participants who had enrolled for 28 days of the research were collected. Descriptive statistics were used for data analysis.Results:From September 2017 to March 2019, a total of 213 MSM cases consulted for nPEP service, 159 of them were eligible for nPEP, and 154 were enrolled in the study for drug taking. For 132 cases enrolled in the study for 28 days and above, 118 completed the 28-day course of antiretroviral therapy (ART), while 10 failed to complete the 28-day course of ART, and 4 could not be confirmed whether completed the full course of ART due to loss of contact. For those who completed 28-day course of ART, 94.1% (111/118) and 75.4% (89/118) respectively received HIV tests at 4-6 weeks and 3 months after exposure, the results were all HIV negative.Conclusion:Under the "Trinity" approach, taking antiviral drugs earlier after HIV non-occupational exposure can effectively reduce the risk of HIV infection and to some extent, reduce the new infection cases.

Objective:To analyze the correlation between the changes of lung function and serum proinflammatory cytokines in workers occupationally exposed to toluene diisocyanate (TDI), and to explore the evaluation index of respiratory toxicity of TDI.Methods:In October 2014, 61 male workers engaged in TDI synthesis process, purification process, packaging process and the above production process in a TDI factory in western China were selected as TDI exposure group; 62 male enterprise managers who were not exposed to TDI and other known allergenic chemicals were selected as control group, which were matched at the age of workers in exposure group. The questionnaire survey obtained information such as gender, length of service, age, occupational history, exposed length of service and so on. The lung function indexes [forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC] and serum levels of interleukin (IL)-1 β, IL-6, IL-8, tumor necrosis factor (TNF)-α, macrophage inflammatory factor-1 β, monocyte chemoattractant factor-1 and vascular endothelial growth factor were measured. The urine was collected after the weekend shift, and the concentration of (TDA), the metabolite of TDI, was determined as the index of internal exposure. Spearman rank correlation was used to analyze the correlation between cytokines and lung function indexes, and multivariate linear regression was used to analyze the changes of lung function indexes and cytokines with TDI exposure concentration and time.Results:The median age ( P5- P95) of the exposed group and the control group was 36.5 (24.0-51.0) and 38.0 (24.0-50.0) years, respectively. In the exposed group, the median length of service ( P5- P95) was 6.94 (0.97-26.33) years, and the median concentration of TDA in urine was 15.56 (2.28-112.16) ng/ml. The three indexes of lung function, FVC, FEV1, FEV1/FVC and the levels of serum IL-8 and TNF-α were significantly lower than those in the control group ( P<0.01). With the increase of exposure concentration and exposure time, the level of serum TNF-α, FVC and FEV1 decreased, and showed a good dose-effect and time-effect relationship (all Ptrend values< 0.05). Serum IL-8 and TNF-α were positively correlated with FVC, FEV1 and FEV1/FVC (all P values<0.01). Conclusion:The levels of serum inflammatory factors IL-8 and TNF-α in worker exposed to TDI are related to lung function indexes, which can be used as early evaluation indexes of respiratory toxicity induced by TDI.