Diabetes mellitus is poly-genetic inherited disease, which is influenced by both genes and environment. The environment may increase the susceptibility of diabetes mellitus via epigenetic way. While those from the same paternal and maternal imprinted genes in the role of offspring are not identical. Adverse intrauterine environment can be regarded as an integral part of the environment, therefore, intrauterine growth retardation may cause fetal epigenetic changes, which are also called imprinted genes. This paper will introduce the latest researches of the diabetes mellitus or insulin resistance-related imprinted genes,for example,GLUT4, IGF-2/H19,PGC-1 α and so on, to explore the relevant therapeutic targets of diabetes mellitus or insulin resistance at the level of epigenetics.

Objective To construct the recombinant plasmid that highly expressed human subcellular PTEN,in order to provide a basis for further study on its anti-tumor effect. Methods PTEN cDNA was amplified by RT-PCR based on mRNA of placenta.The PCR product was ligated into T-vector,and transfected into E.coli;the obtained T-PTEN plasmid was identified with restrictive digestion and sequencing.PCR was used to incorporte nuclear signal of localization(NSL) into PTEN when T-PTEN was used as template.Then the PCR product was ligated into T-vector,and transfected into E.coli,and T-NSL-PTEN plasmid was obtained.pcDNA3.1 and T-NSL-PTEN were ligated after digested with EcoRⅠand BamHⅠ,and transfected into E.coli,the recombinant vector pcDNA3.1-NSL-PTEN was obtained,and identified with digestion and sequcncing.Results The recombinant expression vector DUM-PTEN and PUM-NSL PTEN were identified by restrictive digestion and DNA sequencing.As expected,by EcoRⅠ and BamHⅠ digestion,it showed the band of 1 200 bp.The sequencing result showed the NSL was incorporated successfully.The recombinant pcDNA3.1-PTEN was obtained with 1 200 bp,the sequencing result showed that its sequence was same as target gene;the recombinant pcDNA3.1-NSL-PTEN was comfirmed by restrictive digestion and sequencing,and the NSL was incorporated successfully. Conclusion The recombinant expression plasmid pcDNA3.1-NSL-PTEN is constructed successfully which can highly express human subcellular PTEN.

Objective To investigate the risk factors to acute lung injury based on multiple trauma to provide a theoretical basis for early intervention .Methods The emergency surgical patients with multiple trauma in our hospital from March 2006 to March 2011 were selected .The patients meeting the diagnostic criteria for acute lung injury were taken as the study group and the others as the control group .All patients were enrolled for evaluating the injury severity score (ISS) ,acute physiology and chronic health Ⅱ(APACHE Ⅱ) score and recording smoking ,alcohol abuse ,diabetes mellitus ,number of organ damage ,gastrointestinal bleeding , pulmonary contusion ,diffuse intravascular coagulation (DIC ) ,vomiting ,traumatic shock ,time to correct shock ,blood transfusion . The polymorphism of rs3788853 ,rs13306087 ,rs12709426 of angiotensin-converting enzyme(ACE) gene were analyzed .Results In the study group and the control group ,there were statistical differences in 6 influencing factors of the ISS ,APACHE Ⅱ score ,blood transfusion ,DIC ,traumatic shock ,time to correct shock>6 h(P<0 .05);the gene and genotype frequencies of ACE between the two groups had no statistical difference (P>0 .05);the 6 kinds of influencing factors were risk to acute lung injury based on multi-ple trauma by Logistic regression analysis .Conclusion The ISS ,APACHE Ⅱ score ,blood transfusion ,DIC ,traumatic shock ,long time to correct shock are the risk factors to acute lung injury based on multiple trauma .

Objective To investigate the levels of serum surfactant protein D (SP-D) and mannosebinding lectin (MBL) in infants with cytomegalovirus (CMV) pneumonia with the severity of disease.Methods A total of 101 hospitalized infants with CMV pneumonia were enrolled from January 2011 to December 2012.These patients were divided as the severe pneumonia group (n =48) and the mild pneumonia group (n =53) according to physical sign of lung and complication.Another 55 infants who were hospitalized in the same period with non-infectious diseases were used as the control group.Serum levels of SP-D and MBL were detected by enzyme-linked immunosorbent assay.Blood gas analyzer was used to measure arterial partial pressure of oxygen (PaO2) of the blood in severe patients.Results The mean serum SP-D levels in the severe pneumonia group [(150.08 ±52.59)ng/ml] and the mild pneumonia group [(109.67 ±31.39)ng/ml] were significantly higher than those in control group [(41.33 ± 16.42) ng/ml] (P ＜ 0.01), and higher in the severe pneumonia group than in the mild pneumonia group (P ＜ 0.01).However, there was no significant difference in serum MBL between all groups (P ＞ 0.05).In severe patients, serum SP-D levels were negatively correlated with PaO2 (r =-0.565, P ＜ 0.01).Conclusion Serum SP-D is associated with the severity of CMV pneumonia, but MBL shows no relation.The serum SP-D levels has an important clinical significance in judgment the sererity of infants with CMV pneumonia.

Objective To study the mechanism of chemotherapy resistance caused by interleukin-6 (IL-6) in ovarian cancer cells and its related signal pathways. Methods Ovarian cancer cell lines A2780(IL-6 receptor positive, while non-IL-6-expressing and cisplatin/paclitaxel-responsive) and SKOV3 cell lines( overexpressing of IL-6 receptor and IL-6 and cisplatin/paclitaxel-resistant) were suitable models for this study. The effect of exogenous (a short period of treatment with recombination IL-6) and endogenous IL-6(by transfecting with plasmid encoding for sense IL-6 ) in A2780 cells or deleting of endogenous IL-6expression in SKOV3 cells (by transfecting with plasmid encoding for antisense IL-6) on the sensitivity to cisplatin and paclitaxel was investigated. Meanwhile, the mechanism of chemotherapy resistance caused by IL-6 in ovarian cancer cells and its related signal pathways were also analyzed. Results We found that both exogenous and endogenous IL-6 induce cisplatin and paclitaxel resistance in non-IL-6-expressing A2780 cells (the resistance multiple to cisplatin and paclitaxel was: exogenous, 6. 25 and 7.31; endogenous, 7. 13 -8. 34 and 7. 61 - 10. 70), while deleting of endogenous IL-6 expression in IL-6-overexpressing SKOV3 cells promotes its sensitivity to anticancer drugs ( the resistance multiple to cisplatin and paclitaxel was 0. 15 and 0. 10, 0. 10 and 0. 08). IL-6 significantly up-regulated the expression levels of mRNA and protein of drug resistance-associated genes, MDR1 and GST-π, and apoptosis-inhibiting genes, bcl-2, bcl-xL and XIAP in a dose-dependent manner in A2780 cells. In accordance with this finding, the mRNA and protein levels of MDR1 and GST-π enhanced in sense IL-6-transfected A2780 cells, and reduced in antisense IL-6-transfected SKOV3 cells compared with the corresponding parental and control vector-transfected cells, which had no difference. It was found that PD98059 [ mitogen-activated protein kinase-extracellular signalregulated kinase (MEK) inhibitor ] and wortmannin [ phosphatidylinositol 3-kinase (PI3K) inhibitor ]significantly antagonized IL-6-induced phosphorylation of extracellular signal-regulated kinase ( ERK ) and protein kinase B (Akt), respectively, and both of them blocked IL-6-induced cisplatin and paclitaxel resistance and the inhibitory effects of PD98059 and wortmannin were dependent on its concentration.Conclusions These data suggest that IL-6-induced chemoresistance may be associated with increase of both drug resistance-associated genes ( MDR1 and GST-π) and apoptosis-inhibiting genes ( bcl-2, bcl-xL and XIAP), and activation of MEK/ERK and PL3K/Akt. Therefore, modulation of IL-6 expression or its related signaling pathway may be a promising strategy of treatment for drug-resistant ovarian cancer.

Objective To explore the clinical characteristics of tuberous sclerosis complex (TSC). Methods The clinical data of one child with TSC were collected. The clinical features and gene mutation were analyzed. Results A 36-day-old girl had abnormal nodules found by echocardiography, which was considered multiple cardiac rhabdomyomas. There were multiple hypomelanotic macules distributed over the skin surface of the trunk and legs. Cranial MRI showed cortical nodules, subependymal nodules and cerebral white matter radial migration line. A mutation in the TSC2 gene (c.4541-4544delCAAA) was found by second generation high-throughput sequencing technology and tuberous sclerosis complex was confirmed. Conclusion Gene detection is helpful in the early diagnosis of tuberous sclerosis complex.

Objective To investigate the nutritional status of vitamin D in preterm infants after birth and further explore its possible influencing factors, so as to guide clinical vitamin D therapy and to screen the preterm infants who are at high risk of vitamin D deficiency.Methods Retrospective analysis was conducted in the neonatal department of our hospital from April 21st, 2014 to February 5th, 2016.The serum 25(OH)D level in preterm infants were measured 2 weeks after birth.Data including gender, season of birth, time to initiation of breastfeeding were collected.According to the 25(OH)D levels[25(OH)D≤37.5 nmol/L, 37.5 nmol/L≤50.0 nmol/L, and 25(OH)D>50.0 nmol/L], all the preterm infants were divided into three groups: vitamin D deficiency, insufficiency, and sufficiency groups.The influencing factors of vitamin D in preterm infants were screened by using statistical method.Results The mean 25(OH)D level of 172 preterm infants was (43.1±16.7)nmol/L.In vitamin D deficient, insufficient, and sufficient groups, there were 68 (40％), 50 (29％) and 54(31％) cases of preterm babies, respectively.The mean values of 25(OH)D in these three groups were (27.8±16.7)nmol/L, (42.4±3.4)nmol/L, and (63.0±11.7)nmol/L, respectively.Only the season of birth had significant difference among three groups (P=0.013): 44.2％ of the preterm infants born in winter had vitamin D deficiency, which was higher than those in spring (41.7％), summer(33.3％), and autumn (38.1％);44.2％ of the preterm infants born in winter had vitamin D insufficiency, which was much higher than those in spring (30.6％), summer (25.1％), and autumn (19.0％);furthermore, only 11.6％ of the preterm infants born in the winter had vitamin D sufficiency, which was much lower than those in spring (27.8％), summer (41.2％), and autumn (42.9％) (OR=4.655, 95％ CI=1.716-12.627, P=0.003).Conclusion Vitamin D deficiency in preterm infants 2 weeks after birth is prevalent, and winter birth is a risk factor of vitamin D deficiency and insufficiency in preterm infants.

Objective Discussing the approach to design and implementation of ethical review information management system in clinical research involving human subject.Methods Systematic design and implementation based on ICH GCP,Chinese GCP,Ethical review of biomedical research involving human subjects,Standard Operating Procedure compliant with Asia Pacific SIDCER certification standards,as well as the working experiences of author group.Results According to the specific working procedures in Beijing e-plugger Support Technology Co.Lyd,We implement ethical management system with real-time online interactive work model among investigators,ethical committee secretariat and ethical reviewers,which is prepared for further system optimization and upgrade.Conclusions The application of ethical review information management system make the ethical management work more reliable,efficient,and also improve the quality of ethical review,which helps a lot in safeguarding the development of medical science.

Objective Ethical review is an important safeguard for the development of human subject research.The post approval review during the research process is particularly vital because it is the core method in the ethical review to protect participants' safety and right.In this article,current problems about post approval review were analyzed deeply to explore how to improve the mechanism of post approval review from the combination of management and technical aspect,particularly for the plan of not-for-cause visit.Methods According to the work experiences,literature review,identifying problems,to explore the collaboration to strengthen post approval review with experts,pharmacological institutions and scientific research management department.Results There are more and more frequent ethical issues during the implementation process,besides continuing strengthen the passive continuing review,continuing review guidelines and more detailed active continuing review screening and implementation mechanism should be developed.Conclusions It will prevent the occurrence of injury through establishing more optimal post approval review mechanism and a forehand active prevention strategy,which play an important role in the ethical review of human subject research.

Objective:To collect and analyze the non-compliance/protocol violation or deviation reported to the hospital Ethics Committee from 2017 to 2019, to explore the pattern of such events, as well as the causes and related logic. Empirical data evidence, lessons learned and preliminary advice were proposed to improve the understandings, management and implementation of clinical trials regarding to the non-compliance/protocol violation or deviations.Methods:The chi-square test and non-parameter test were conducted using SPSS 22.0.A total number of 754 reports received were analyzed, compared and summarized to provide the preliminary advice.Results:From 2017 to 2019, 754 reports on non-compliance/protocol violation or deviation, which covered 219 projects from 29 clinical departments, were received. 88% of these projects were drug/medical device clinical trials, while other 12% were investigator initiated trials. The reportrd events could be divided into 7 categories. The distribution of project resources, trial types and clinical specialties are significantly different. Meanwhile, the reports submitted by investigators have a lot of space for improvement.Conclusions:There were significant differences in the type and number of reported events on non-compliance/protocol violation or deviation between different trial types, as well as clinical trial specialties. The application report of protocol violation is generally poor. Combined with the working practice, the common reasons for the protocol violation are " the low overall compliance of the subjects" and " the insufficient compliance of the researchers" . Preliminary suggestions for management reform, such as increasing the training for researchers, improving the reporting mode, and regularly issuing follow-up and review research reports are recommended.