Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

Objective To prepare 4-sulfonylcalix[6]arene-modified cotton fibers for adsorption and removal of uranium based on the specific complexation of calix[6]arene with uranium (VI). Methods Chemical grafting was used for the modification of cotton, which reacted with α-bromoisobutyryl bromide, glycidyl methacrylate, and 4-sulfonylcalix[6]arene. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and infrared spectroscopy (FTIR) were used to characterize the structure of 4-sulfonylcalix[6]arene-modified cotton (Cotton S-C[6]a). A Franz diffusion cell was used to simulate uranium-contaminated skin. Laser fluorimetry was used to determine the uranium content. Results SEM, XPS, and FTIR showed that cotton fibers were successfully grafted with 4-sulfonylcalix[6]arene. The optimal conditions of Cotton S-C[6]a for the adsorption of uranium (VI) was pH 4.0, duration of 20 min, and 20 mg of adsorbent. The adsorption process fitted well with pseudo-secondary-order kinetics. The uranium removal efficiency of Cotton S-C[6]a was up to 78.46% in aqueous solution and 81.72% on skin. Conclusion The synthesized Cotton S-C[6]a is highly efficient in the removal of uranium (VI) in solution and on contaminated skin.

Objective To analyze the malignant tumor incidence and mortality in Heilongjiang province in 2013.Methods Tumor registration data of Heilongjiang province cancer registries in 2013 were collected.The malignant tumor incidence and mortality of registration data from 7 cancer registries were analyzed according to the criteria of quality control from National Central Cancer Registry (NCCR).Results The crude incidence rate of cancer in Heilongjiang province was 234.34/105.Age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population were 153.08/105 and 149.33/105 with the cumulative incidence rate (0-74 years old) of 17.17％.The cancer incidence and ASIRC were 258.42/105 and 157.00/105 in urban areas,whereas in rural areas,they were 190.95/105 and 145.44/105,respectively.The cancer mortality in Heilongjiang province was 147.62/10s.Age-standardized mortality rates by ASIRC and by world standard population were 92.22/105 and 91.41/105 with the cumulative incidence rate (0-74 years old) of 10.44％.The cancer mortality and ASIRC were 171.85/105 and 97.85/105 in urban areas,whereas in rural areas,they were 103.95/105 and 78.48/105,respectively.Lung cancer,breast cancer,liver cancer,colorectal cancer and gastric cancer were the high-incidence cancers in Heilongjiang province.Lung cancer,liver cancer,gastric cancer,colorectal cancer and breast cancer were the most death causes.Conclusion The morbidity and mortality of lung cancer are the highest in Heilongjiang province in 2013.Lung cancer and digestive system malignancies are the most common cancers in Heilongjiang province.Dynamic monitoring tumor morbi-dity and mortality in Heilongjiang province is the basis of the cancer prevention and control work.The active and effective comprehensive control measures should be taken to curb the rising trend of malignant tumor burden.

AIM: To investigate the role of transcription factor hairy and enhancer of split 1 (Hes1) in the malignant transformation of human bronchial epithelial cell line BEP2D induced by tobacco.METHODS: The BEP2D cells were chronically exposed to cigarette smoke condensate (CSC) at 1 cigarette per L until the 70th generation.The phenotype of malignant transformation of the cells induced by CSC was detected by soft agar clony formation assay.RT-PCR and Western blot were used to determined the expression of Hes1 at mRNA and protein levels in each generation of the cells.The proliferation and apoptosis of the BEP2D cells exposed to CSC were analyzed with the methods of MTT assay, flow cytometry and cell colony formation assay after treatment with Notch pathway bloker DAPT or liposome transfection with Hes1-siRNA.The expression of Hes1 in the peripheral small airway tissues of the smoking rats was evaluated by immunohistochemical staining.The expression of Hes1 in non-small-cell lung cancer and normal airway tissues was also detected by the methods of immunohistochemistry and RT-PCR.RESULTS: The BEP2D cells in the 70th generation had a malignant transformation phenotype.The expression of Hes1 in the BEP2D cells exposed to CSC for different time showed an increa-sing trend.DAPT and liposome transfection with Hes1-siRNA down-regulated the expression of Hes1, inhibited the cell proliferation and induced cell apoptosis.The expression of Hes1 in the airway mucosa of the rats exposed to cigarette smoke for 1 month and 6 months was significantly higher than that in control group.Cigarette smoking induced the expression of Hes1 in lung cancer and normal airway tissues.CONCLUSION: Hes1 may be involved in smoking-induced lung cancer by promoting the imbalance between apoptosis and proliferation.

ObjectiveToexplorethedynamicchangesofoxidativestressandcytokinesinMongoliangerbilswith nonalcoholic fatty liver disease ( NAFLD) and their significance.Methods Forty-eight healthy male gerbils were randomly divided into normal group and model group , 24 in each group .Gerbils of the model group were fed with high fat diet while those of the normal group with normal diet .Eight gerbils in each group were killed at the end of 4 w, 8 w and 16 w, respectively .MDA content and SOD , GSH-PX and T-AOC activity in the liver tissue were detected by chemical method, and serum TNF-α, INF-γand IL-10 levels were determined using liquid suspension chip .Results With the development of NAFLD , MDA content in liver increased gradually , and the MDA contents were all significantly higher than those of the normal group ( P<0.01 ); T-AOC level slightly increased , and then decreased , the levels at 4 w and 16 w were markedly decreased compared with those of the normal group (P<0.05);SOD level was significantly increased and then markedly reduced, the level of the model group at 4 w was significantly increased (P<0.05), while that at 8 w and 16 w were significantly decreased (P<0.05, P<0.01).The level of GSH-PX was decreased gradually , the levels at 8 w and 16 w were significantly lower than those of the normal group (P<0.05).With the progression of NAFLD,serum TNF-αand IFN-γwere increased gradually , while the level of IL-10 decreased gradually , and the levels at 8 w and 16 w were significantly lower than those of the normal group ( P <0.05, P <0.01).Conclusions The oxidative stress-related indicators and inflammatory cytokines in the gerbil NAFLD models induced by high fat diet are significantly changed as simple fatty liver develops into steatohepatitis , liver fibrosis and cirrhosis , and participate in the development and progression of NAFLD .

Objective To explore the effect of high fat diet on serum biochemical parameters and histopathology of main organs in Mongolian gerbils.Methods Forty-eight healthy adult male Mongolian gerbils were randomly and equally divided into model and normal groups.The gerbils in the model group were fed with high fat diet while the normal group with standard diet.Eight gerbils in each group were killed at the end of 4th,8th and 16th week,respectively,and the body weight, serum levels of Glu, TG, CHOL, HDL-C, LDL-C, UA, CREA, BUN, TBil, TP, ALB, ALT, AST and AMS were determined.The histopathological changes of main organs were observed.Results Compared with the normal group,the blood lipid of the model gerbils was significantly increased, the liver function was impaired, the blood uric acid level was higher, and the blood glucose was decreased at the end of 16th week.The AMS was increased at the end of 16th week,but the renal function showed no significant changes.The liver tissue of the model group gradually showed steatosis, inflammation, fibrosis and cirrhosis, accompanied by splenomegalia. The lung tissue and myocardium showed fatty degeneration and obvious damages in the later period,the pancreatic islets were enlarged and the amount of endocrine cells was increased,and the small intestine and kidney didn’ t show any distinct changes.Conclusions A gerbil models of hyperlipidemia and nonalcoholic steatohepatitis and cirrhosis can be well established by high fat diet feeding,and may serve as good models for research of hyperlipidemia-related hyperuricemia, and lung and myocardial damages.

Objective To observe the expression of insulin-like growth factor 1 (IGF-1),insulin-like growth factor binding protein 3 ( IGFBP-3) in rats’ serum with non-alcoholic fatty liver disease ( NAFLD) and the impact of Polyene phosphatidyl choline .Methods NAFLD model was induced by feeding the SD rats with a high-fat diet, with Polyene phosphatidyl choline to intervene .Observe the pathological changes of the rats ’ liver tissue dynamically after HE staining . Detect the contents of IGF-1,IGFBP-3 in serum dynamically through the immuno radio metric assay ( IRMA).Results There were no obvious exception of the liver tissue pathology in the normal group at each time .With the extension of a high-fat diet,the liver tissue of the model group increased on fatty change ,the degree of inflammation ,the balloon sample change , the NAFLD activity score at 4,8,12weeks.IGF-1,IGFBP-3 in serum were decreased significantly ,and the model set was significantly lower than the normal group at the same phase .After the application of polyene phosphatidyl choline ,the degree of rat liver tissue inflammation and the NAFLD activity score were reduced significantly when compared with model group , while the level of IGF-1,IGFBP-3were significantly higher .Conclusion The levels of IGF-1,IGFBP-3 in the rats’ serum reduce in the development of non-alcoholic fatty liver disease .

Objective To investigate the phagocytosis function of cigarette smoke extracts (CSE)on the NR8383 cells. Methods The concentration of CSE and the optimal time was defined by cell counting kit-8 assay, Annexin V/PI cell apoptosis assay and CFSE cell proliferation assay. The cell was gained after exposed to the different concentration of CSE for 24 h and mixed with fluorescein-labeled Escherichia coli in 37℃ for 2 h. The fluorescence intensity was used to assay the phagocytosis function of NR8383 cells.Results The phagocytosis function of NR8383 cells may be changed by the concentration of CSE. In the concentration of 100 μg/ml, the phagocytosis function of NR8383 was enhanced 0.5 times than the normal cell when NR8383 cell was exposed to CSE, and the specific activity is the highest. When NR8383 cells were exposed to CSE and LPS, the phagocytosis function of NR8383 cells was enhanced 2 times than the normal cell. In the concentration of 200 μg/ml, the phagocytosis function of NR8383 cells was damaged, the rate of apoptosis is the 54. 1%. Conclusion Low concentration of CSE enhanced the phagocytosis function of NR8383 cells, but high concentration of CSE damaged the phagocytosis function of NR8383 cells. This study reveals a new role of CSE as an activator of macrophage function.

Objective To investigate the distribution of uranium in rats after inhalation with depleted uranium aerosols. Methods The depleted uranium aerosols were inhaled by Wistar rats. At 30, 90, 180, 270, 360, and 540 d after inhalation, the rata were sacrificed and tissue samples were collected. The contents of uranium in lung, kidney, liver, heart, brain, thighbone, spleen and thymus were measured by laser time-dependent spectroscopy analysis. Resulits The uranium contents of lung increased in the high-dosc and low-dose groups [(499833.3 ± 14214.8) ng/g and (25 424.0 ± 6193.4)ng/g, respectively] after inhalation, and significantly differed from the control (28.8 ± 13.9)ng/g, (P < 0.05).At 30 d after inhalation, the contents of uranium in lung, kidney and thighbone were higher than those of control, and then decreased time-dependently. At 60 d, the contents of uranium in liver, heart, brain, spleen and thymus were higher than those of control. Curve of the eontenta were biphasie, whieh went up first, reached at peak value and then went down. The contents of uranium were high in lung, thighbone, brain and thymus. Conclusions After inhalation of depleted uranium aerosols, lung and thighbone are the primary reservoirs for uranium redistributed, and accumulations in brain and thymus suggest other two organs for unanticipated injury by depleted uranium.

ObjectiveTo evaluate the effect of lifestyle intervention on high-risk individuals for hypertension. MethodsOne hundred and four prehypertensive adults who received physical examination during October 2005 and October 2007 and showed at least 2 hypertension risk factors were randomly assigned to the experimental or control group.A muhicomponent behavioral intervention,including health education(e.g.awareness of disease),metary gmdance,physical.exercise,and psychologtcat improvement,Was conducted for 2 years.The awareness of disease,blood pressure,bedy weight,and the change of risk factors were compared.ResultsAt 2 years,the awareness of disease in the experimental group wag significantly improved,and the blood pressure,body weight,and risk factors were obviously reduced.Although the awareness of disease and the risk factors in the control group were improved,the blood pressure and body weight were increased.The difference in average systolic blood pressure,average diastolic blood pressure,body weight,and the awareness of disease between the two groups were 13 mm Hg(1 mm Hg=0.133 kPa),7.9 nlnl Hg,3.7 kg,and 37.6%,respectively(all P<0.05).ConclusionThe lifestyle intervention among high-risk individuals for hypertension could effectively reduce blood pressure and body weight. Improved lifestyle would result in less risk factors.