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Fetal alcohol spectrum disorder (FASD) encompasses neurodevelopmental disabilities and physical birth defects associated with prenatal alcohol exposure. Previously, we attempted to identify epigenetic biomarkers for FASD by investigating the genome-wide DNA methylation (DNAm) profiles of individuals with FASD compared to healthy controls. In this study, we generated additional gene expression profiles in a subset of our previous FASD cohort, encompassing the most severely affected individuals, to examine the functional integrative effects of altered DNAm status on gene expression. We identified six differentially methylated regions (annotated to the SEC61G, REEP3, ZNF577, HNRNPF, MSC, and SDHAF1 genes) associated with changes in gene expression (p-value < 0.05). To the best of our knowledge, this study is the first to assess whole blood gene expression and DNAm-gene expression associations in FASD. Our results present novel insights into the molecular footprint of FASD in whole blood and opens opportunities for future research into multi-omics biomarkers for the diagnosis of FASD.

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BACKGROUND: Vagus nerve stimulation has been suggested to affect immune responses, partly through a neuronal circuit requiring sympathetic innervation of the splenic nerve bundle and norepinephrine (NE) release. Molecular and cellular mechanisms of action remain elusive. Here, we investigated the therapeutic value of this neuromodulation in inflammatory bowel disease (IBD) by applying electrical splenic nerve bundle stimulation (SpNS) in mice with dextran sulfate sodium (DSS)-induced colitis. METHODS: Cuff electrodes were implanted around the splenic nerve bundle in mice, whereupon mice received SpNS or sham stimulation. Stimulation was applied 6 times daily for 12 days during DSS-induced colitis. Colonic and splenic tissues were collected for transcriptional analyses by qPCR and RNA-sequencing (RNA-seq). In addition, murine and human splenocytes were stimulated with lipopolysaccharide (LPS) in the absence or presence of NE. Single-cell RNA-seq data from publicly available data sets were analyzed for expression of ß-adrenergic receptors (ß-ARs). RESULTS: Colitic mice undergoing SpNS displayed reduced colon weight/length ratios and showed improved Disease Activity Index scores with reduced Tumor Necrosis Factor α mRNA expression in the colon compared with sham stimulated mice. Analyses of splenocytes from SpNS mice using RNA-seq demonstrated specific immune metabolism transcriptome profile changes in myeloid cells. Splenocytes showed expression of ß-ARs in myeloid and T cells. Cytokine production was reduced by NE in mouse and human LPS-stimulated splenocytes. CONCLUSIONS: Together, our results demonstrate that SpNS reduces clinical features of colonic inflammation in mice with DSS-induced colitis possibly by inhibiting splenic myeloid cell activation. Our data further support exploration of the clinical use of SpNS for patients with IBD.

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BackgroundRisk stratification of COVID-19 patients upon hospital admission is key for their successful treatment and efficient utilization of hospital resources. ObjectiveTo evaluate the risk factors associated with ventilation need and mortality. Design, setting and participantsWe established a retrospective cohort of COVID-19 patients from Mass General Brigham hospitals. Demographic, clinical, and admission laboratory data were obtained from electronic medical records of patients admitted to hospital with laboratory-confirmed COVID-19 before May 19th, 2020. Using patients admitted to Massachusetts General Hospital (MGH, derivation cohort), multivariable logistic regression analyses were used to construct the Ventilation in COVID Estimator (VICE) and Death in COVID Estimator (DICE) risk scores. MeasurementsThe primary outcomes were ventilation status and death. ResultsThe entire cohort included 1042 patients (median age, 64 years; 56.8% male). The derivation and validation cohorts for the risk scores included 578 and 464 patients, respectively. We found seven factors to be independently predictive for ventilation requirement (diabetes mellitus, dyspnea, alanine aminotransferase, troponin, C-reactive protein, neutrophil-lymphocyte ratio, and lactate dehydrogenase), and 10 factors to be predictors of in-hospital mortality (age, sex, diabetes mellitus, chronic statin use, albumin, C-reactive protein, neutrophil-lymphocyte ratio, mean corpuscular volume, platelet count, and procalcitonin). Using these factors, we constructed the VICE and DICE risk scores, which performed with C-statistics of at least 0.8 in our cohorts. Importantly, the chronic use of a statin was associated with protection against death due to COVID-19. The VICE and DICE score calculators have been placed on an interactive website freely available to the public (https://covid-calculator.com/). LimitationsOne potential limitation is the modest sample sizes in both our derivation and validation cohorts. ConclusionThe risk scores developed in this study may help clinicians more appropriately determine which COVID-19 patients will need to be managed with greater intensity.

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OBJECTIVE：To investigate the effects of parecoxib sodium ，flurbiprofen axetil and lornoxicam combined with patient controlled intravenous analgesia （PICA） on postoperative analgesia in patients undergoing gynecological laparoscopic surgery and its effect on serum related factors. METHODS ：A total of 280 patients who underwent gynecologic laparoscopic surgery in the Second Affiliated Hospital of Hainan Medical University from Mar. 2017 to Mar. 2019 were randomly divided into control group （group C ），parecoxib sodium group （group P ），and flurbiprofen axetil group （group F ）and lornoxicam group （group L ）acording to random number table ，with 70 patients in each group. Four groups of patients received Sodium chloride injection 5 mL，Parecoxib sodium for injection 40 mg，Flurbiprofen axetil injection 50 mg and Lornoxicam for injection 8 mg （added 8 mg when the effect was not good ）intravenously at 30 min before the end of surgery. At the end of surgery ，they were given PICA of Sufentanil citrate injection and Dizosin injection for analgesia. The situation of pain and nausea symptom were evaluated at 6，12，24 and 48 h after surgery by using numerical rating scale （NRS）. The levels of serum CRP ，IL-6，SP and PGE 2 were detected by chemiluminescence method and ELISA. The times of pressing PICA pump and the dosage of analgesic were recorded in 4 groups within 24 h after surgery. The ADRs of patients within 48 h after surgery were recorded ，such as bloating ， dizziness，itchy skin ，respiratory depression and urinary retention. RESULTS ：At different time points ，the NRS scores of pain of group P ，F and L were significantly lower than those of group C ；and 48 h after surgery ，NRS score of pain of group L was significantly lower than those of group P and F （P＜0.05）. There was no statistical significance in the level of CRP ，IL-6，SP and PGE2 of 4 groups before surger （P＞0.05）. The CRP ，IL-6，SP and PGE 2 levels at each time point after surgery of group P ，F and L were significantly lower than those of group C ；compared with group P ，serum level of SP at 48 h after surgery as well as serum levels of PGE 2 at 12，24 and 48 h after surgery were significantly decreased in group F ，and serum level of IL- 6 at 48 h after surgery，serum levels of SP at 24 and 48 h after surgery ，serum levels of PGE 2 at 12，24，48 h after surgery were decreased significantly in group L ；compared with group F ，serum level of SP at 48 h after surgery as well as serum levels of PGE 2 at 12， 24，48 h after surgery were all decreased significantly in group L （P＜0.05）. There was no statistical significance in the incidence of anausea and vomiting among 4 groups（P＞0.05）. CONCLUSIONS ：Parecoxib sodium ，flurbiprofen axetil and lornoxicam combined with PICA can effectively relieve the pain of patients after gynecological laparoscopic surgery and reduce the levels of serum related factor ，and lornoxicam has the most obvious effect.

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Objective: From the economic point of view, this study was to systematically assess the status quo on lung cancer screening in the world and to provide reference for further research and implementation of the programs, in China. Methods: PubMed, EMbase, The Cochrane Library,CNKI and Wanfang Data were searched to gather papers on studies related to economic evaluation regarding lung cancer screening worldwide, from the inception of studies to June 30(th), 2018. Basic characteristics, methods and main results were extracted. Quality of studies was assessed. Cost were converted to Chinese Yuan under the exchange rates from the World Bank. The ratio of incremental cost-effectiveness ratio (ICER) to local GDP per capita were calculated. Results: A total of 23 studies (only 1 randomized controlled trial) were included and the overall quality was accepted. 22 studies were from the developed countries. Nearly half of the studies (11 studies) took 55 years old as the starting age of the screening program. Smoking history was widely applied for the selection of criteria on target populations (18). Low-dose computed tomography (LDCT) was involved in every study used to evaluate the economic effectiveness. Annual (17) and once-life time (7) screening were more common frequencies. 22 studies reported ICERs for LDCT screening, compared to no screening, of which 17 were less than 3 times local GDP per capita, and were considered as cost-effectiveness, according to the WHO's recommendation. 15 and 7 studies reported ICERs for annual and once-life time screening, of which 12 and 7 studies were in favor the results of their cost-effectiveness, respectively. Additionally, the cost-effectiveness of once-lifetime screening was likely to be superior to the annual screening. Differences of cost-effectiveness among the subgroups, by starting age or by the smoking history, might exist. Conclusions: Based on the studies, evidence from the developed countries demonstrated that LDCT screening programs on lung cancer, implemented among populations selected by age and smoking history, generally appeared more cost-effective. Combined with the local situation of health resource, the findings could provide direction for less developed regions/countries lacking of local evidence. Low frequency of LDCT screening for lung cancer could be adopted when budget was limited. Data on starting ages, smoking history and other important components related to the strategy of screening programs, needs to be precisely evaluated under the situation of local population.

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Objective: To explore the associations between maternal and prenatal depressive symptoms and children's behavioral problems at 2 years old. Methods: In the present study, a total of 491 mother-child pairs were selected from the Shanghai-Minhang Birth Cohort Study (S-MBCS) which was conducted in Maternal and Child Health Hospital of Minhang District in Shanghai between April and December, 2012. Data from the Center for Epidemiologic Studies on Depression was gathered to assess the maternal depressive symptoms in the second and third trimester of pregnancy, as well as at 6 months and 12 months postpartum. Neurodevelopment at 2 years was assessed, using the Child Behavior Checklist. We used generalized linear models with a log-link function and a Binomial distribution to estimate the risk ratios (RRs) and 95%CIs, on children's behavioral problems at 2 years of age. Sensitivity analyses were performed among participants without postpartum depressive symptoms. Results: After adjustment on factors as maternal age, gestation week, average monthly income per person, parental education and children's gender etc., maternal depression in second trimester of pregnancy was found associated with higher risk of both developing emotional (RR=2.61, 95%CI: 1.36-4.99) and internalizing problems (RR=1.94, 95%CI: 1.22-3.08). However, maternal depression in third trimester was found to be associated with higher risks of developing emotional (RR=6.46, 95%CI: 3.09-13.53), withdrawn (RR=2.42, 95%CI: 1.16-5.02), aggressive (RR=2.93, 95%CI: 1.45-5.94), internalizing (RR=1.79, 95%CI: 1.01-3.16) or externalizing problems (RR=2.56, 95%CI:1.49-4.42). In sensitivity analysis, antenatal maternal depression was found positively associated with children's emotional, internalizing and externalizing problems and the differences all statistically significant. Conclusions: Maternal depression during pregnancy might increase the risks of children's behavioral problems. In order to decrease the incidence of children's behavioral problems and promoting both maternal and child health status, monitoring program regarding maternal mental health care should be strengthened.

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Objective: To assess the association and intensity of baseline TC level with the incidence of lung cancer in men in China. Methods: Since May 2006, all the male workers, including the employees and the retirees in Kailuan Group were recruited in the Kailuan male dynamic cohort study. Information about demographics, medical history, anthropometry and TC level were collected at the baseline interview, as well as the information of newly-diagnosed lung cancer cases during the follow-up period. According to guidelines for blood lipids in Chinese adults and the distribution in the population, TC level was classified into five groups as followed: <160, 160-, 180-, 200- and ≥240 mg/dl, with the second quintile group (160- mg/dl) serving as the referent category. Cox proportional hazards regression model and restricted cubic spline (RCS) model were used to evaluate the association and the nonlinear association between baseline TC level and the risk of lung cancer in the men. Results: By December 31, 2014, for the 109 884 men, a follow up of 763 819.25 person-years was made with a median follow-up period of 7.88 years. During the follow up, 808 lung cancer cases were identified. After adjustment for age, education level, income level, smoking status, alcohol consumption level, history of dust exposure, FPG level and BMI, HR (95%CI) of lung cancer for men with lower TC level (<160 mg/dl) and higher TC level (≥240 mg/dl) were 1.34 (1.04- 1.72) and 1.45 (1.09-1.92), respectively, compared with men with normal TC level (160- mg/dl). The results didn't change significantly after exclusion of newly diagnosed cancer cases within 2 years of follow up and subjects with the history of hyperlipidemia. Conclusion: Our results showed that TC might be associated with higher risk of lung cancer. Men with lower TC level or higher TC level had higher risk for lung cancer. Keep moderate TC level might be one of the effective precaution for the prevention of lung cancer.

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Objective: To investigate the changes of proportion on both consistent condom use and syphilis infection among low-fee female sex workers aged 35 and above (LFSW), in order to provide evidence for targeted intervention strategies. Methods: A total of six cities-Liuzhou city and Pingnan couty of Guigang city of Guangxi Zhuang Autonomous Region, Jinghong city of Xishuangbanna Dai autonomous prefecture and Dali city of Dali Bai autonomous prefecture of Yunnan province, Zhangjiajie city and Jianghua Yao autonomous county of Yongzhou city Hunan province were involved in this study, with 60 eligible participants needed in each city, estimated through a pre-study. The first cross-sectional survey was completed from October 2012 to January 2013. Face-to-face questionnaire interview was carried out to collect information on socio-demography, work-related information and condom use situation. Blood was collected for syphilis testing. The second cross-sectional survey was carried out from June to September, 2015 under the same procedure. Results: A total of 371 and 403 eligible participants were included in the first and second survey, respectively. When comparing the two surveys, we noticed that the average age showed a slight change, from 42.4 years to 43.8 years old (t=3.537, P<0.001) and the average price for every commercial sex exchange increased from 36.8 RMB to 49.5 RMB (t=11.961, P<0.001). In the first survey, 46.9% (174/371) of the participants had more than two years of experience working as LFSW, compared to 61.3% (247/403) in the second survey (χ(2)=16.125, P<0.001). Also, 46.9% (174/371) of the participants consistently used condoms with clients in the past month in the first survey versus 64.3% (259/403) (χ(2)=23.641, P<0.001) in the second one. Rates of syphilis infection were found from 15.9% (59/371) in the first survey reduced to 7.2% (29/403) in the second survey (χ(2)=14.533, P<0.001). Conclusion: Compared with the first survey, the proportion of consistent condoms use showed an increase. Although the proportion of syphilis infection decreased in the second survey, the scope did not meet the criteria on syphilis, set by the government. Targeted intervention strategies on condom promotion and syphilis control should be implemented consistently in this population.

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Objective: To investigate the association between alcohol consumption and lung cancer risk in Chinese males. Methods: Information on alcohol consumption and outcomes were collected on a biennial basis among males in Kailuan Cohort (2006-2015). In addition, electronic databases of hospitals affiliated to Kailuan Community, Insurance Systems of Kailuan Community and Tangshan were also used for supplementary information retrieval. Cox proportional hazards regression models were used to evaluate the hazard ratio (HR) and 95%CI of baseline frequency and type of alcohol consumption associated with lung cancer risk in males. Non-drinkers were used as control group. Results: A total of 101 751 males were included and 913 new lung cancer cases were identified in the Kailuan male cohort study, with a total follow-up time of 808 146.56 person-years and a median follow-up time of 8.88 years by 31 December 2015. After adjusting for potential confounding factors, the HR of former drinkers, occasional drinkers (<1/day) and drinkers (≥1/day) were 1.30 (95%CI: 0.90-1.88), 0.80 (95%CI: 0.64-1.01) and 1.04 (95%CI: 0.85-1.27), respectively, compared with non-drinkers. In addition, drinking beer/red wine (HR=0.91, 95%CI: 0.69-1.20) and white wine (HR=0.99, 95%CI: 0.83-1.19) showed no significant association with lung cancer. The results were similar when stratified analysis were conducted. Conclusion: Our study results don't support the hypothesis that alcohol consumption is significantly associated with the risk of lung cancer in males.

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Objective: To understand the survival of HIV/AIDS patients after receiving antiretroviral therapy for 10 year in Henan province and related factors. Methods: The database of national integrated management system of HIV/AIDS was used to collect the basic information and follow-up information of HIV/AIDS patients who received antiretroviral therapy between 2003 and 2005 in Henan province. Software SPSS 23.0 was used to analyze the patients' survival and related factors based on the life-table method and Cox proportional hazards model. Results: Among the 2 448 HIV/AIDS patients who started antiretroviral therapy during 2003-2005, the men accounted for 53.5%, and women accounted for 46.5%. Up to 70.1% of the patients were aged 40-59 years and 95.5% of the patients had blood borne infections. The patients were observed for 10 years after antiviral treatment, and 719 cases died from AIDS related diseases, with a mortality rate of 3.78/100 per year (719/19 010 per year). The cumulative survival rates of patients within 1-year, 3 years, 5 years and 10 years were 0.94, 0.86, 0.78, 0.69 respectively. Compared with the patients aged <40 years, the HRs of the patients aged 40-, 50-, 60- and ≥70 years were 1.417 (95%CI: 0.903-2.222), 1.834 (95%CI: 1.174-2.866), 2.422 (95%CI: 1.539-3.810) and 3.424 (95%CI: 2.053-5.709) respectively. Compared with patients with baseline CD(4+)T lymphocyte >350 unit/ul, the HRs of the patients with CD(4+)T lymphocyte <50 unit/μl, 50-199 unit/ul and 200-350 unit/ul were 7.105 (95%CI: 5.449-9.264), 4.175 (95%CI: 3.249-5.366) and 2.214 (95%CI: 1.691-2.900) respectively. Compared with the women, the HR of the men was 1.480 (95%CI: 1.273-1.172). Compared with the patients who received second line ART therapy, the HR of patients receiving no second line therapy was 11.923 (95%CI: 9.410-15.104). Conclusions: The cumulative survival rate the HIV/AIDS patients after 10 years of antiretroviral therapy reached 0.69 in Henan. Male, old age, low basic CD(4+)T lymphocyte count and receiving no second line therapy were the risk factors for long-term survival of AIDS patients.

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The process of globalization increases the risk of global transmission of infectious diseases, resulting in pressure for country's prevention and control of imported infectious disease. Based on the risk assessment of disease importation and local transmission, a strategy that conducting importation prevention and routine prevention and control before the importation of disease and taking emergency control measures after the importation of disease was developed. In addition, it is important to take part in global infectious disease response action, aid the countries with outbreak or epidemic to actively decrease the risk of disease importation.

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OBJECTIVE: The authors report their experience about the endoscopic treatment of pancreatic pseudocysts (PP). DESIGN: Report of 8 cases; evaluation of effectiveness, morbidity and mortality. SETTING: Operative Unit of General and Thoracic Surgery, Department of Surgical, Anatomical and Oncological Disciplines. Policlinico, University of Palermo. INTERVENTIONS: endoscopic drainage in all 8 patients. RESULT: 88% successful (7/8). CONCLUSION: Endoscopic drainage of PP is a safe and simple treatment, with high rates of success and low rate of morbility.

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A single-tube reverse transcriptase-polymerase chain reaction (RT-PCR) using a fluorogenic real-time PCR detection method is described for the quantitation of equine infectious anemia virus (EIAV) RNA in the plasma of equids. To compensate for variations inherent in sample preparation a multiplex real-time RT-PCR system was developed that permitted the simultaneous calculation of the nucleic acid recovery rate along with the copy number of viral RNA molecules. Detection of EIAV RNA was linear from 10(9) to 10(1) molecules with intra- and inter-assay variability of less than 1% at 10(8), 10(6), 10(4) and 10(2) molecules.

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