Sleep problems of children with Down syndrome in northern China.

BACKGROUND: Limited research has looked at the present-day sleep problems among Chinese children with Down syndrome (DS). This study aimed to investigate the situation of the sleep problems of school-aged children with DS in northern China. METHODS: Parents of children with DS were a convenience sample recruited through the special education schools of Shandong Province in China. The Chinese version of the Children's Sleep Habits Questionnaire was applied to assess the sleep problems of children with DS. RESULTS: Parents of 334 children with DS reported the average sleep duration was 9.7 (9.3-10.2) hours per night, and 62.0% of children with DS were reported sleeping less than 10 h per night. Additionally, the total prevalence rate of sleep problems among children with DS was 69.8%. Sleep-disordered breathing (59.2%), sleep duration (33.8%) and bedtime resistance (32.0%) were the three most commonly reported sleeping problems. Younger children with DS (age 6-8 years) had severe problems with bedtime resistance, sleep anxiety and parasomnias than older children with DS (age 9-12 years) (all P < 0.05). CONCLUSION: Sleep problems are prominent among children with DS in northern China and are worthy of attention. Caregivers and health professionals should raise awareness of sleep problems in this group of children and implement targeted interventions to improve their sleep quality as early as possible.

MicroRNA-370-3p inhibits cell proliferation and induces chronic myelogenous leukaemia cell apoptosis by suppressing PDLIM1/Wnt/ß-catenin signaling.

Growing evidence has suggested that microRNA-370-3p (miR-370-3p) is downregulated and acts as a suppressor in several cancers. However, the role of miR-370-3p in chronic myeloid leukemia (CML) remains unknown. Here, the expression level and molecular mechanism of miR-370-3p in CML were investigated. Firstly, the expression of miR-370-3p has markedly decreased in the peripheral blood mononuclear cells (PBMCs) of patients with CML and in cell lines. Moreover, miR-370-3p in CML cells upregulated and downregulated proliferation and apoptosis, respectively. Notably, miR-370-3p directly targeted the 3'-untranslated region of PDZ and LIM domain protein 1 (PDLIM1). A negative correlation was observed between the levels of miR-370-3p and PDLIM1 in the PBMCs of patients with CML and healthy volunteers. PDLIM1 was shown to have an oncogenic role in CML cells by promoting proliferation and suppressing apoptosis. Finally, the miR-370-3p-PDLIM1-Wnt/ß-catenin signaling axis was indicated to play an important role in CML progression.

[Correlation between fasting plasma glucose, HbA1c and DNA methylation in adult twins].

OBJECTIVE: To explore the cytidine-phosphate-guanosine (CPG) sites associated with fas-ting plasma glucose (FPG) and glycated haemoglobin (HbA1c) in twins. METHODS: In the study, 169 pairs of monozygotic twins were recruited in Qingdao, Zhejiang, Jiangsu, Sichuan and Heilongjiang in June to December of 2013 and June 2017 to October 2018. The methylation was detected by Illumina Infinium HumanMethylation450 BeadChip and Illumina Infinium MethylationEPIC BeadChip. According to the Linear Mixed Effect model (LME model), fasting plasma glucose and HbA1c were taken as the main effects, the methylation level (ß value) was taken as the dependent variable, continuous variables, such as age, body mass index (BMI), blood pressure, components of blood cells, surrogate variables generated by SVA, and categorical variables, such as gender, smoking and drinking status, hypoglycemic drugs taking, were included in the fixed effect model as covariates, and the identity numbers (ID) of the twins was included in the random effect model. The intercept was set as a random. Regression analysis was carried out to find out the CpG sites related to fasting blood glucose or HbA1c, respectively. RESULTS: In this study, 338 monozygotic twins (169 pairs) were included, with 412 459 CpG loci. Among them, 114 pairs were male, and 55 pairs were female, with an average age of (48.2±11.9) years. After adjustment of age, gender, BMI, blood pressure, smoking, drinking, blood cell composition, and other covariates, and multiple comparison test, 7 CpG sites (cg19693031, cg01538969, cg08501915, cg04816311, ch.8.1820050F, cg06721411, cg26608667) were found related to fasting blood glucose, 3 of which (cg08501915, ch.8.1820050f, cg26608667) were the newly found sites in this study; whereas 10 CpG sites (cg19693031, cg04816311, cg01538969, cg01339781, cg01676795, cg24667115, cg09029192, cg20697417, ch.4.1528651F, cg16097041) were found related to HbA1c, and 4 of which(cg01339781, cg24667115, cg20697417, and ch.4.1528651f) were new. We found that cg19693031 in TXNIP gene was the lowest P-value site in the association analysis between DNA methylation and fas-ting plasma glucose and HbA1c (PFPG=2.42×10-19, FDRFPG<0.001; PHbA1c=1.72×10-19, FDRHbA1c<0.001). CONCLUSION: In this twin study, we found new CpG sites related to fasting blood glucose and HbA1c, and provided some clues that partly revealed the potential mechanism of blood glucose metabolism in terms of DNA methylation, but it needed further verification in external larger samples.

[Bivariate heritability estimation of resting heart rate and common chronic disease based on extended pedigrees].

OBJECTIVE: To estimate the univariate heritability of resting heart rate and common chronic disease such as hypertension, diabetes, and dyslipidemia based on extended pedigrees in Fujian Tulou area and to explore bivariate heritability to test for the genetic correlation between resting heart rate and other relative phenotypes. METHODS: The study was conducted in Tulou area of Nanjing County, Fujian Province from August 2015 to December 2017. The participants were residents with Zhang surname and their relatives from Taxia Village, Qujiang Village, and Nanou Village or residents with Chen surname and their relatives from Caoban Village, Tumei Village, and Beiling Village. The baseline survey recruited 1 563 family members from 452 extended pedigrees. The pedigree reconstruction was based on the family information registration and the genealogy booklet. Univariate and bivariate heritability was estimated using variance component models for continuous variables, and susceptibility-threshold model for binary variables. RESULTS: The pedigree reconstruction identified 1 seven-generation pedigree, 2 five-generation pedigrees, 23 four-generation pedigrees, 186 three-generation pedigrees, and 240 two-generation pedigrees. The mean age of the participants was 57.2 years and the males accounted for 39.4%. The prevalence of hypertension, diabetes, dyslipidemia in this population was 49.2%, 10.0%, and 45.2%, respectively. The univariate heritability estimation of resting heart rate, hypertension, and dyslipidemia was 0.263 (95%CI: 0.120－0.407), 0.404 (95%CI: 0.135－0.673), and 0.799 (95%CI: 0.590－1), respectively. The heritability of systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was 0.379, 0.306, 0.393, 0.452, 0.568, 0.852, and 0.387, respectively. In bivariate analysis, there were phenotypic correlations between resting heart rate with hypertension, diabetes, diastolic blood pressure, fasting glucose, and triglyceride. After taking resting heart rate into account, there were strong genetic correlations between resting heart rate with fasting glucose (genetic correlation 0.485, 95%CI: 0.120－1, P<0.05) and diabetes (genetic correlation 0.795, 95%CI: 0.181－0.788, P<0.05). CONCLUSION: Resting heart rate was a heritable trait and correlated with several common chronic diseases and related traits. There was strong genetic correlation between resting heart rate with fasting glucose and diabetes, suggesting that they may share common genetic risk factors.

[Rethinking public health education and public health workforce development in China].

During the fighting against COVID-19, both the public health education and public health workforce of China have exposed important challenges. The present review discusses dilemmas and weakness that relate to the position of public health education in the higher education system, public health education system, curriculum system, teaching methods, practice-based teaching, training of highly qualified personnel in public health, public health teachers, remuneration and non-monetary honorable rewards for the public health workforce. Suggestions are also proposed for each of the challenges.

[Analysis of online education for public health and preventive medicine].

Since the outbreak of the Coronavirus Disease 2019 (COVID-19), universities have carried out online education for public health and preventive medicine courses under the policy of "Suspending Classes Without Stopping Learning" launched by the Chinese government. The Public Health and Preventive Medicine Committee of the Ministry of Education Steering Committee for Medical Education investigated the online teaching activities in the member universities. This study presents the survey results, discusses the existing problems, and proposes suggestions for further reforms on mixed teaching activities.

[Association between family history of diabetes and incident diabetes of adults: a prospective study].

Objective: To evaluate the association betweew family history of diabetes and incident diabetes of adults. Methods: A total of 49 266 participants in the China Kadoorie Biobank (CKB) study from Wuzhong district of Suzhou city were included in the analysis, after the exclusion of those with heart disease, stroke, cancer and diabetes at baseline survey. The person-year of follow-up was calculated from the date on completion of baseline survey to the date on any firstly-occurred event, i.e., diabetes incidence, death, loss of follow-up, or December 31, 2013. Cox regression model was used to estimate the hazards ratios of the association between family history of diabetes and incident diabetes. Results: During 348 677 person-years of the follow-up (median 7.08 years), a total of 423 men and 791 women were diagnosed as having diabetes. Compared to those without diabetic family history, participants with family history of diabetes showed a higher risk of diabetes, with a HR (95%CI) of 1.90 (1.57-2.29), and the risk increased with the number of relatives suffering from diabetes (Pfor trend<0.05). The family history of maternal type, sibling type, and sibling and parental type had a statistically significant association with the risk of diabetes. The adjusted HR (95%CI) was 2.03 (1.45-2.77), 2.07 (1.56-2.68) and 2.39 (1.14-4.34), respectively. Modification effects of tobacco smoking, alcohol drinking, body mass index and physical activity on the association between diabetic family history and risk of diabetes were not observed in the study (Pfor interaction >0.05). Conclusions: Diabetic family history is associated with the increased incident diabetes, and the risk increased with the number of relatives suffering from diabetes.

Development and validation of an individualized nomogram to identify occult peritoneal metastasis in patients with advanced gastric cancer.

BACKGROUND: Occult peritoneal metastasis (PM) in advanced gastric cancer (AGC) patients is highly possible to be missed on computed tomography (CT) images. Patients with occult PMs are subject to late detection or even improper surgical treatment. We therefore aimed to develop a radiomic nomogram to preoperatively identify occult PMs in AGC patients. PATIENTS AND METHODS: A total of 554 AGC patients from 4 centers were divided into 1 training, 1 internal validation, and 2 external validation cohorts. All patients' PM status was firstly diagnosed as negative by CT, but later confirmed by laparoscopy (PM-positive n = 122, PM-negative n = 432). Radiomic signatures reflecting phenotypes of the primary tumor (RS1) and peritoneum region (RS2) were built as predictors of PM from 266 quantitative image features. Individualized nomograms of PM status incorporating RS1, RS2, or clinical factors were developed and evaluated regarding prediction ability. RESULTS: RS1, RS2, and Lauren type were significant predictors of occult PM (all P < 0.05). A nomogram of these three factors demonstrated better diagnostic accuracy than the model with RS1, RS2, or clinical factors alone (all net reclassification improvement P < 0.05). The area under curve yielded was 0.958 [95% confidence interval (CI) 0.923-0.993], 0.941 (95% CI 0.904-0.977), 0.928 (95% CI 0.886-0.971), and 0.920 (95% CI 0.862-0.978) for the training, internal, and two external validation cohorts, respectively. Stratification analysis showed that this nomogram had potential generalization ability. CONCLUSION: CT phenotypes of both primary tumor and nearby peritoneum are significantly associated with occult PM status. A nomogram of these CT phenotypes and Lauren type has an excellent prediction ability of occult PM, and may have significant clinical implications on early detection of occult PM for AGC.

Donor-derived marrow mesenchymal stromal cell co-transplantation following a haploidentical hematopoietic stem cell transplantation trail to treat severe aplastic anemia in children.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is associated with an increased risk of graft failure and severe graft-versus-host disease (GVHD). Recent studies have shown that mesenchymal stromal cells (MSCs) display potent immunosuppressive effects and can support normal hematopoiesis. In a multi-center trial, we co-transplanted culture-expanded donor-derived bone marrow MSCs (BM-MSCs) into 35 children with severe aplastic anemia (SAA) undergoing haplo-HSCT. All 35 patients (100%) achieved hematopoietic reconstitution and showed sustained full donor chimerism. The median time for myeloid engraftment was 14 days (range 10-22 days), while that for platelet engraftment was 18 days (range 9-36 days). The incidence of grade II-IV acute GVHD and chronic GVHD was 25.71 and 22.86%, respectively. The overall survival rate was 85.71% with a median of 22 months (range 3.5-37 months). The combined transplantation of haploidentical HSCs and BM-MSCs into children with SAA without an HLA-identical sibling donor is relatively safe and may represent an effective new therapy to improve survival rates and reduce the risk of graft failure.

[Study on the current status of postgraduates training in public health and preventive medicine in China in 2016].

To investigate the current status of postgraduates training in public health and preventive medicine in China. In this study, a questionnaire survey was conducted among directors of enrollment and teaching in 22 universities with postgraduate admission qualifications in corresponding disciplines nationwide. In 2016, full-time postgraduates were mainly academic masters. In addition to the graduate entrance examination, the common enrollment mode in colleges was to enroll a high qualified student with recommendations from relevant experts or institutions and an exemption from entrance examination (20/22). The emphasis on training contents between academic and public health master was different. Currently, the scale of public health postgraduate enrollment in public health and preventive medicine in China is stable, and the training program is reasonable, but there is an issue of monotonous model and uneven distribution of enrollment.

[Investigation on the current status of the cultivation of the master of public health (MPH) in colleges in China].

In order to understand the status of the cultivation of the masters of public health (MPH) in colleges in China and improve the cultivation model, an electronic questionnaire survey were conducted among 22 schools of public health in colleges. The result showed that the size and the enrolment scale of Chinese MPH students were relatively small, and the training objectives were still unclear. There was no obvious difference between the curriculum setting for MPH and academic master degree. The practical skill-oriented courses and emergency response ability of public health practice were insufficient. The cultivation model of MPH should be improved in future.

[Analysis of the contradiction between the supply and demand of Chinese graduate students' emergency professional ability in public health and preventive medicine in China].

In order to underst and the status of health emergency personnel training development and raising coping measures, electronic questionnaire surveys were conducted among 22 colleges and universities in different region of China. The result showed that colleges universities in China invested less in the training of emergency personnel. It is different and emphasized particularly for the cultivation of emergency professional ability among different types of public health students. Universities and employer hold relative evaluation of students' emergency professional ability with distinct regional differences.

[Correlation between blood pressure and DNA methylation in adult twins].

OBJECTIVE: To explore the DNA methylation sites correlated with blood pressure (systolic blood pressure, diastolic blood pressure, mean arterial pressure, pulse pressure) in adult twin population. METHODS: A total of 476 twins from the Chinese National Twin Registry were selected as the research population. Questionnaires were used to collect demographic characteristics, lifestyle, disease status and other information, and blood pressure, height, weight and other anthropometric indicators were measured. The genome-wide DNA methylation of whole blood samples was detected by using Infinium HumanMethylation450 BeadChip. The DNA methylation sites correlated with blood pressure were analyzed by constructing mixed effect model with adjusting potential confounding factors, and the significant level was false discovery rate <0.05. RESULTS: After data quality control, 465 twins (122 pairs of monozygotic twins, 104 pairs of dizygotic twins, 13 individuals from 13 pairs of twins) aged (44.8±13.2) years were finally enrolled. There were more males and more monozygotic twins, and the current smokers and current regular drinkers both accounted for more than 30%. No significant CpG site was found after multiple testing in the correlation study between genome-wide DNA methylation and blood pressure by using the collected twins. However, the cg07761116 located on chromosome 10 had low P value in the correlation analysis of 3 blood pressure indices (systolic blood pressure, diastolic blood pressure, mean arterial pressure), suggesting that this site might be correlated with blood pressure. The other 7 sites had low P value in the correlation analysis of the two blood pressure indices, respectively, which pointed to genes involved in neurological development, protein homeostasis, inflammatory reaction and other pathways. CONCLUSION: There is no sufficient evidence to support any DNA methylation site correlated with blood pressure, which may be caused by insufficient sample size and other reasons. This study could provide a reference for subsequent similar twin studies, and subsequent studies can focus on the cg07761116 located on chromosome 10 and other sites with low P values.

[Relationship between PD-L1 protein expression and gene amplification in gastric cancer tissues].

Objective: To investigate the relationship of PD-L1 protein expression and gene amplification in gastric cancer and their correlation with clinicopathologic factors. Methods: The cohort included 247 gastric cancer specimens with follow-up data and clinicopathologic data obtained from Shanxi Cancer Hospital in 2011. PD-L1 expression was detected by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Results: PD-L1 protein was expressed in 25.9% (64/247) of the tumor cells and 26.7% (66/247) of the tumor infiltrating immune cells (IC). There was a correlation between the two (P<0.01). The expression of PD-L1 in tumor cells correlated with the degree of differentiation and tumor diameter(P<0.05). The PD-L1 expression in IC correlated with vascular tumor thrombi(P<0.05). The amplification rate of PD-L1 gene detected by FISH was 19.0% (47/247), and was associated with age, large/small curvature of the stomach, tumor location, tumor diameter, and lymph node metastasis(P<0.05). The positive coincidence rate of the two methods was 25.0% (16/64), negative coincidence rate was 83.0% (152/183), and total coincidence rate was 68.0% (168/247), suggesting that the coincidence of IHC and FISH was poor (P=0.157). There was a negative correlation between PD-L1 protein expression on tumor cells and prognosis in gastric cancer. There was no significant correlation between PD-L1 protein expression on IC and PD-L1 gene amplification with prognosis. Vascular tumor thrombi, tumor diameter, depth of invasion, and lymph node metastasis were all poor prognostic factors of gastric cancer(P<0.05). Multivariate Cox regression analysis showed that PD-L1 protein expression, depth of invasion and lymph node metastasis were all independent prognostic risk factors for gastric cancer. Conclusions: Concordance between PD-L1 protein expression and gene amplification is poor. PD-L1 protein expression may signify poor prognosis. There is no significant correlation between PD-L1 gene amplification and prognosis of patients with gastric cancer.

[Mental health problems among female staff in a provincial maternal and child health hospital: an investigation of 647 individuals].

Objective: To investigate the current status of depression and anxiety among female staff in a maternal and child health hospital, and to provide a basis for developing related prevention and intervention measures and promoting the mental health of female staff. Methods: The female staff from a provincial maternal and child health hospital completed a psycho-health questionnaire survey on Internet from June to October, 2016. The questionnaires used in the survey consisted of Patient Health Questionnaire (PHQ-9) , Generalized Anxiety Disorder Scale (GAD-7) , and Symptom Checklist-90 (SCL-90) . The distribution features of mental health problems such as depression and anxiety were analyzed according to the results: of the questionnaire survey. Results Of all female staff surveyed, 42.04% showed depression symptoms, 28.90% showed anxiety symptoms, and 26.12% showed comorbid symptoms of depression and anxiety. Moderate or severe depression (anxiety) was mainly distributed among the female staff with comorbid symptoms (90.63% and 97.01%, respectively) . There were significant differences in the distribution of moderate or severe anxiety symptoms between the medical staff and nursing staff (χ(2)= 5.81, P=0.05) and between those with intermediate and junior professional titles (χ(2)=7.99, P=0.018) . As for SCL-90 results, the total score, total average score, and scores on factors of somatization, compulsion, interpersonal sensitivity, depression, and anxiety in the female staff with comorbid symptoms, moderate or severe depression, and moderate or severe anxiety were significantly higher than the national norm (P<0.01) , while the scores on paranoid and psychotic factors were significantly lower than the national norm (P<0.01) . The numbers of cases of positive factors were significantly higher in the female staff with comorbid symptoms than in the female staff with a single symptom and asymptomatic female staff (both P<0.01) , and positive cases were mainly distributed in depression, interpersonal sensitivity, compulsion, anxiety, and somatic factors. Conclusion: The prevalence of depression and anxiety is high among female staff in the maternal and child health hospital, mainly characterized by comorbid symptoms of moderate or severe depression and anxiety. Comorbidity is accompanied by mental health problems such as interpersonal sensitivity, obsessive compulsion, and physical discomfort. Corresponding measures are needed for the prevention and intervention of mental health problems among female staff in the maternal and child health hospital.

Expression profile of eukaryotic translation initiation factor and matrix metalloproteinase 9 in endometrial cancer tissue.

The aim of the present study was to provide a novel method for the diagnosis, prevention and treatment of endometrial cancer by the determination of the characteristic expression of the eukaryotic translation initiation factor 4E (eIF4E) and the enzyme matrix metalloproteinase 9 (MMP9) in endometrial cancer tissue. Three types of endometrial tissue specimens were selected (including 20 cases of normal endometrial tissue specimens, 15 cases of hyperplastic endometrial tissue specimens and 45 cases of endometrial cancer tissue specimens). The expression of eIF4E and MMP9 in the specimens was examined by immunohistochemistry and their corresponding levels were statistically analyzed. The positive expression rates of eIF4E and MMP9 in endometrial cancer specimens were 64.44% and 66.67% respectively, which were higher than those noted in hyperplastic endometrial tissue specimens and normal endometrial tissue specimens (p less than 0.05). The comparisons between the groups indicated that the expression levels of eIF4E and MMP9 in the endometrial cancer specimens were increased compared with those noted in the normal endometrial tissue specimens (p less than 0.0167). In endometrial cancer specimens, the positive expression rates of eIF4E and MMP9 were related to the endometrial cancer stages as determined by the International Federation of Gynecology and Obstetrics (FIGO), tumor cell differentiation degree and lymphatic metastasis (p less than 0.05) classifications. eIF4E expression was positively related to MMP9 expression in endometrial cancer specimens. High expression levels of eIF4E and MMP9 proteins were noted in endometrial cancer specimens, which were correlated with FIGO stages, histological grade and degree of lymphatic metastasis. Thus, endometrial cancer and malignant biological behavior may be connected to the high expression of eIF4E and MMP9. The positive correlation between eIF4E and MMP9 expression in endometrial cancer specimens suggests their potential up-regulation during carcinogenesis.

Expression and clinical significance of ARTN and MMP-9 in endometrial carcinoma.

The aim of this study was to detect the differential expression of Artemin (ARTN) and matrix metallopeptidase protein 9 (MMP-9) in endometrial carcinoma (EC) and to assess their clinical significance in order to provide insight into the pathological mechanism of tumor infiltration and metastasis in EC. A total of 48 patients who had undergone surgery for EC at the School of Medicine and Affiliated Hospital of HeBei University of Engineering between July 2015 and July 2016 were included in the study. The 48 patients were classified into 3 groups according to tumor stage: 27 patients with EC stage I, 12 patients with EC stage II and 9 patients with EC stage III. The samples collected from each patient included fresh normal endometrial tissue, endometrial simple hyperplastic tissue and endometrial atypical hyperplastic tissue. The transcription levels of ARTN and MMP-9 mRNA in each group were investigated using RT-PCR. The expression levels of ARTN and MMP-9 protein in each group were examined using Western blotting. Spearman’s correlation analysis was used to analyze the correlation between the expression levels of ARTN and MMP-9 proteins and EC tissue type. RT-PCR and Western blotting assays revealed that the expression levels of ARTN and MMP-9 were increased in normal endometrial tissue, simple hyperplastic tissue, atypical hyperplastic tissue and EC of stages I, II and III. The differences noted were statistically significant (P less than 0.05). Furthermore, Western blot analysis indicated that the expression levels of ARTN and MMP-9 proteins in lymphatic metastatic tissues were higher than those in non-lymphatic metastatic tissues (P less than 0.05). The expression levels in the infiltration tissues of the deep muscular layer were higher than those noted in the light muscular layer (P less than 0.05). The expression levels of ARTN and MMP-9 proteins were positively correlated (P less than 0.05). The data suggest that ARTN and MMP-9 are involved in the occurrence, development, invasion and metastasis of EC, and play a synergistic role in the development of EC and lymphatic metastasis.

[Clinical significance of serum resistin in patients with generalized myasthenia gravis].

Objective: To detect the serum resistin levels in patients with generalized myasthenia gravis (GMG) and evaluate the clinical values of resistin. Methods: We detected the serum resistin levels in 58 patients with GMG and 58 healthy controls (HC) from January 2013 to December 2015 in Tianjin medical university general hospital.Then we analyzed the correlation of the serum resistin levels with the clinical features. Results: The serum resistin levels in patients with GMG, (8.26±4.27) ng/ml, was significantly higher than in HC, (4.12±1.36) ng/ml, (P<0.001). There was no statistical difference of the serum resistin levels between female or male patients with GMG (P=0.589). The serum resistin levels in patients with GMG was positively correlated with the quantitative MG score for disease severity (QMG) (r=0.446, P<0.001), but not correlated with age (r=0.168, P=0.206). The patients with higher resistin levels took higher risk of combining with thymoma (P=0.002), 56.5%, and these patients had higher QMG, 11(5) (P=0.001); and the ratio and QMG in the patients with lower resistin levels were 17.1%, 7(5), respectively.The GMG patients with thymoma (TGMG+ ) had remarkably higher serum resistin levels, (10.7±5.3) ng/ml (P=0.010) and the QMG score, 11(5) (P<0.001) than the GMG patients without thymoma (TGMG-) with (7.0±3.1) ng/ml and 8(5). Conclusion: Resistin is probably associated with the severity of the disease of MG, and maybe a potential biomarker of MG combined with thymoma.

[Mendelian randomization analysis of the relationship between obesity and DNA methylation].

Objective: To explore the association between DNA methylation and body mass index (BMI) using Mendelian randomization analysis. Methods: A total of 469 participants were selected from the Chinese National Twin Registry in 2013, who were living in Shandong, Jiangsu, Zhejiang, and Sichuan provinces, and at least 18 years of age. A questionnaire survey and physical examination were conducted to collect demographic, clinical, and behavioral information. Peripheral blood cells were collected to detect genotype and methylation status. Association analyses between DNA methylation and BMI and between CpGs and cis-SNP were conducted. With rs748212 as the instrumental variable, the association between cg15053022 and BMI was explored using the Mendelian randomization method. Results: A total of 469 participants were selected. The mean age of participants was (44.8±13.2) years and the BMI was (25.0±3.8) kg/m(2). Nine BMI-related DNA methylation sites were found and DNA methylation site cg15053022 in the ATP4A gene was negatively associated with cis-SNP rs748212 (ß=-0.020); the mean methylation level of AA, AC, and CC were 0.212±0.025, 0.242±0.024, and 0.264±0.028, respectively. rs748212 was associated with BMI (ß=0.04, P=0.007) and closely related to cg15053022 (F=237.66, P=0.143). Mendelian randomization analysis showed lower methylation levels at cg15053022 were associated with higher BMI (ß=-1.97, P<0.001). Conclusion: This study supported the impact of cg15053022 methylation in the ATP4A gene on BMI using Mendelian randomization analysis and provided the basis for using Mendelian randomization analysis in methylation studies.

Effects of an inducible aiiA gene on disease resistance in Eucalyptus urophylla × Eucalyptus grandis.

N-acyl-homoserine lactones (AHLs) are metabolites of mostly gram-negative bacteria and are critical signaling molecules in bacterial quorum-sensing systems. At threshold concentrations, AHLs can activate the expression of pathogenic genes and induce diseases. Therefore, reducing AHL concentrations is a key point of disease control in plants. AHL-lactonase, which is expressed by aiiA, is widespread in Bacillus sp and can hydrolyze AHLs. In the present study, we cloned aiiA from Bacillus subtilis by PCR. A plant expression vector of aiiA was constructed and name Pcam-PPP3-aiiA, in which expression of aiiA was controlled by the pathogen-inducible plant promoter PPP3. The recombinant plasmid was transferred into Eucalyptus × urophylla × E. grandis by an Agrobacterium-mediated transformation. PCR and Southern blotting showed that aiiA was successfully integrated into the E. urophylla × E. grandis genome and its expression was induced by Ralstonia solanacearum 12 h after inoculation, as shown by reverse transcription-PCR. The transcription efficacy of aiiA increased 43.88-, 30.65-, and 18.95-fold after inoculation with R. solanacearum, Erwinia carotovora ssp. zeae (Sabet) and Cylindrocladium quinqueseptatum, respectively as shown by RT-real-time PCR. Transgenic E.urophylla × E.grandis expressing the AIIA protein exhibited significantly enhanced disease resistance compared to non-transgenic plants by delaying the onset of wilting and reducing the disease index.