[Correlation of carbon dioxide derived parameters during cardiopulmonary bypass with acute kidney injury after pediatric cardiac surgery].

Objective: To explore the correlation of the ratio of venous-arterial carbon dioxide (CO2) tension difference to arterial-venous O2 content difference (Pv-aCO2/Ca-vO2) and venous-arterial CO2 gradient (Pv-aCO2) during cardiopulmonary bypass (CPB) with acute kidney injury (AKI) after pediatric cardiac surgery. Methods: The clinical data of children (1 month ≤ age ≤ 3 years old) who underwent open heart surgery under CPB in West China Hospital of Sichuan University from March 2021 to August 2022 were retrospectively analyzed. All paired blood gases of the children during CPB (the sampling time interval of arterial and venous blood was within 10 minutes) were collected. According to the Failure, Loss, End-Stage Renal Disease (pRIFLE) diagnostic criteria, the children were divided into AKI group and non-AKI group. Multivariate logistic regression analysis was performed to identify the risk factors of postoperative AKI in pediatric cardiac surgery. Results: A total of 213 children were enrolled (101 males and 112 females), aged 12(6, 24) months, and 84 of them (39.4%) developed AKI. Three children died in AKI group, with a mortality of 3.6%. There were no deaths in non-AKI group. The incidence of postoperative low cardiac output syndrome (LCOS) was higher in AKI group [29.8% (25/84) vs 7.0% (9/129), P<0.001]. In addition, compared with the non-AKI group, children in AKI group had longer recovery time [15 (6, 78) h vs 6 (3, 19) h, P<0.001], mechanical ventilation time [17 (7, 97) h vs 6 (4, 20) h, P<0.001], intensive care unit (ICU) stay [6 (4, 11) d vs 3 (2, 5) d, P<0.001], and hospital stay [12 (9, 18) d vs 9 (8, 11) d, P<0.001]. A total of 317 arterial and venous blood gas pairs from 30 (n=207), 60 (n=75) and 90 min (n=35) after aortic clamping were included in the analysis. Univariate analysis showed that Pv-aCO2/Ca-vO2 (P=0.015) at 30 min after aortic clamping, Pv-aCO2 (P=0.041) and Pv-aCO2/Ca-vO2 (P=0.014) at 60 min after aortic clamping, peak Pv-aCO2 (P=0.009), peak Pv-aCO2/Ca-vO2 (P<0.001) and the average value of Pv-aCO2/Ca-vO2 (P=0.001) were higher in AKI group. Multivariate logistic regression analysis showed that longer duration of CPB (OR=1.013, 95%CI: 1.003-1.023, P=0.012), higher peak Pv-aCO2/Ca-vO2 (OR=1.337, 95%CI: 1.037-1.723, P=0.025) were risk factors for AKI. Conclusion: The occurrence of AKI after pediatric cardiac surgery is related to the short-term adverse clinical prognosis, and longer duration of CPB and higher peak Pv-aCO2/Ca-vO2 are independent risk factors for AKI.

[Analysis of the clinical efficacy and safety of bronchial thermoplasty in the treatment of patients with severe asthma and asthma-chronic obstructive pulmonary disease overlap].

Objective: To investigate the clinical efficacy and safety analysis of bronchial thermoplasty (BT) in the treatment of severe asthma and asthma-chronic obstructive pulmonary disease overlap. Methods: The clinical data of 49 patients with asthma-COPD overlap who received BT in the University of Chinese Academy of Sciences Shenzhen Hospital from January 2016 to December 2018 and 50 patients with severe asthma who received BT in the same period were retrospectively analyzed. Patients were divided into overlap group and asthma group, and the baseline data of two groups were recorded. The pulmonary function before and after treatment (including forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1 as a percentage of predicted value (FEV1% pred)), hormone consumption, asthma control test (ACT) score, asthma quality of life questionnaire (AQLQ) score, asthma control questionnaire (ACQ) score, the overlap group before and after treatment COPD assessment test (CAT) score, modified British Medical Research Council (mMRC) score and postoperative respiratory adverse events in the next 3 weeks were comparatively analyzed. Results: The general baseline characteristics of the two groups are compared. The patients in the overlap group were older than those in the asthma group, and the course of disease and smoking history were longer than those in the asthma group. The inhaled hormone dosage in asthma group was greater than those in the overlap group ((64±11) years vs (48±11) years; 10.00 (10.00, 25.00) years vs 9.00 (1.75, 20.00) years; 20.00(2.00, 40.00) years vs 0 (0, 10.00) years; 320 (320, 640) µg/d vs 960 (320, 960) µg/d) (all P<0.05). The predicted values of lung function indexes FVC, FEV1, FEV1% pred in the overlap group before treatment were all lower than those in the asthma group (1.98 (1.43, 2.43) L vs 2.54 (2.02, 3.15) L; 0.92 (0.61, 1.26) L vs 1.69(1.17, 2.16) L; (50±16) L vs (65±14) L) (all P<0.05). There were no significant differences in ACT, ACQ, and AQLQ scores between the two groups before treatment (all P>0.05). Within 3 months after treatment, except for no significant improvement in FEV1% predicted value and inhaled hormone dosage in the overlap group (all P>0.05), other indexes in both groups were improved compared with those before treatment (all P<0.05). After 1 year of treatment, all indexes of the two groups were significantly improved than those before treatment, and all indexes of the asthma group were better than those of the overlap group (all P<0.05). In terms of respiratory adverse events occurring within 3 weeks after the operation, the incidence of cough and bloody sputum in the overlap group was higher than that in the asthma group, while the incidence of sputum and short-term wheezing was lower than that in the asthma group (all P<0.05). There were no statistically significant differences in the incidence of chest tightness, chest pain, segmental atelectasis and pneumonia between the two groups (all P>0.05), and the postoperative adverse reactions could be effectively controlled in a short period of time. Conclusion: BT treatment could not only improve the lung function, clinical symptoms and quality of life of asthmatic patients, but was also effective for asthma-COPD overlap patients. However, BT treatment had more benefits for asthmatic patients without serious adverse events occurred.

[Analysis of the safety and efficacy of bronchial thermoplasty for severe asthma with the first second forced expiratory volume (FEV(1)) as a percentage of the predicted value (FEV(1)%pred)<60].

Objective: To investigate the efficacy and safety of bronchial thermoplasty (BT) in severe asthma patients with the first second forced expiratory volume (FEV(1)) as a percentage of the predicted value (FEV(1)%pred) <60%. Methods: A retrospective analysis was performed on 75 patients with asthma who were treated with BT at Shenzhen University Hospital of the Chinese Academy of Sciences from January 2016 to January 2018. The patients were divided into two groups based on the FEV(1)%pred before treatment: FEV(1)%pred <60% group (39 cases) and FEV(1)%pred ≥60% group (36 cases). Comparative analysis of glucocorticoid consumption, times of acute attack, asthma control test (ACT) score, changes in lung function, and adverse reactions at 3 weeks after treatment were performed between the two groups of patients. Results: Before BT treatment, the consumption of oral prednisone, the amount of budesonide inhaled, and the times of acute attack [M (Q(1), Q(3))] in the FEV(1)%pred <60% group were significantly greater than those in the FEV(1)%pred ≥60% group, and the ACT score was significantly lower than the FEV(1)%pred ≥60% group [10.00 (0, 20.00) vs 0(0, 3.75) mg/d, 960 (320, 960) vs 320 (320, 640) µg/d, 5(4, 8) vs 4 (4, 5) times/year, 13 (9, 15) vs 17 (13, 19) scores] (all P<0.05). Except that the oral prednisone dosage in the FEV(1)%pred<60% group was still higher 1 year after treatment [0 (0, 5.00) vs 0 (0, 0) mg/d] (P=0.009), there was no significant difference in the remaining indicators between the two groups 1 year after treatment and 2 years after treatment (all P>0.05). After 1 year and 2 years of treatment, all indicators in the two groups were better than before treatment (all P<0.05). The inhaled budesonide amount and the times of acute exacerbation in the FEV(1)%pred <60% group 2 years after treatment were less than those 1 year after treatment [320 (320, 320) vs 320 (320, 640) µg/d, 0 (0, 0) vs 0(0, 1) times/year] (all P<0.05), and there was no significant difference in the remaining indicators. In the FEV(1)%pred ≥60% group, there was no significant difference between 2 years after treatment and 1 year after treatment in the above indicators except the amount of inhaled budesonide (all P>0.05). In the FEV(1)%pred <60% group, FEV(1) and the FEV(1)%pred were significantly lower than the FEV(1)%pred ≥60% group before treatment, 1 year after treatment and 2 years after treatment [FEV(1):(1.21±0.41) vs (2.26±0.80)L, (1.84±0.73) vs (2.30±0.78)L, (1.70±0.66) vs (2.38±0.76)L; FEV(1)%pred:46.2 (38.5, 53.7)% vs 80.8(66.5, 93.6)%, 60.1 (48.2, 71.6)% vs 87.4 (68.5, 96.5)%, 58.5 (48.6, 74.8)% vs 86.6 (73.0, 97.3)%] (all P<0.05). In the FEV(1)%pred <60% group, FEV(1) and FEV(1)%pred 1 year after treatment and 2 years after treatment were all increased compared with before treatment (all P<0.05). In the FEV(1)%pred ≥60% group, there was no statistical difference in FEV(1) at each time point before and after treatment (all P>0.05), but the FEV(1)%pred at 2 years after treatment was higher than before treatment (P<0.05). There were no significant differences in adverse events between the two groups (all P>0.05). Conclusion: BT can significantly improve the lung function, reduce the times of acute attack and the dosage of glucocorticoids in severe asthma patients with FEV(1)% pred<60%, which is safe and effective.

Reduced lysosomal clearance of autophagosomes promotes survival and colonization of Helicobacter pylori.

Evasion of autophagy is key for intracellular survival of bacteria in host cells, but its involvement in persistent infection by Helicobacter pylori, a bacterium identified to invade gastric epithelial cells, remains obscure. The aim of this study was to functionally characterize the role of autophagy in H. pylori infection. Autophagy was assayed in H. pylori-infected human gastric epithelium and the functional role of autophagy was determined via genetic or pharmacological ablation of autophagy in mouse and cell line models of H. pylori infection. Here, we showed that H. pylori inhibited lysosomal function and thereby promoted the accumulation of autophagosomes in gastric epithelial cells. Importantly, inhibiting autophagosome formation by pharmacological inhibitors or genetic ablation of BECN1 or ATG5 reduced H. pylori intracellular survival, whereas inhibition of lysosomal functions exerted an opposite effect. Further experiments demonstrated that H. pylori inhibited lysosomal acidification and the retrograde trafficking of mannose-6-phosphate receptors, both of which are known to positively regulate lysosomal function. We conclude that H. pylori subverts autophagy into a pro-survival mechanism through inhibition of lysosomal clearance of autophagosomes. Disruption of autophagosome formation offers a novel strategy to reduce H. pylori colonization in human stomachs. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Intratumoral Polymorphism of Peroxisome Proliferator-Activated Receptor Delta-87 T>C in Colorectal Cancer.

Peroxisome proliferator activated receptor delta (PPARD) is a nuclear receptor transcription factor whose single nucleotide polymorphism (SNP), especially PPARD-87 T>C (rs2016520), may play an important role in expression regulation of PPARD. But its expression patterns as well as contribution in colorectal cancer (CRC) are still controversial. In this study, whether the intratumoral heterogeneity of polymorphism of PPARD-87 T>C (rs2016520) existed and its influence in CRC were investigated. Tumor masses from primary CRC patients were collected during the operation of tumorectomy, specimens at the different sites of the same tumor mass were sampled and stored individually. The SNP of PPARD-87 T>C was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the expression of PPARD in vivo was observed by immunohistochemistry. The correlation of PPARD -87 T>C intratumoral polymorphism and the clinicopathological parameters of patients was analyzed statistically. Tumor samples were collected from 106 CRC patients (70 males and 36 females) with an average age of 61.04±13.67 years. A total number of 808 samples (7.60±1.60 per patient) were mainly harvested at peripheral superficial (n=376), central superficial (n=163), invasive front (n=112) and mesenteric cancer foci (n=42) of tumor tissues as well as cancerous adjacent mucosa (n=104). PCR-RFLP analysis showed that T/T (n=460, 56.9%) and T/C (n=334, 41.3%) were the main genotypes of -87 T>C among these samples. Furthermore, intratumoral genotype of -87 T>C was homogeneous in 90 patients and heterogeneous in other 16 patients. The intratumoral heterogeneity was related to patients' age (P=0.016), tumor location (P=0.011) and the grade of differentiation (P=0.022). For patients with intratumoral heterogeneity, immunochemistry showed the expressions of PPARD were not influenced by T/T or T/C genotypes. Intratumoral heterogeneity of PPARD-87 T>C wildly existed in CRC, and associated with patients' age, tumor location and differentiation. However, the immunochemistry assay revealed that there's no significant link between heterogeneity and expression of PPARD.

Increased oestradiol in hepatitis E virus-infected pregnant women promotes viral replication.

Hepatitis E virus (HEV) infection causes subclinical diseases, leading to high mortality (>25%) in pregnant women. HEV replication is aggressively escalated in pregnant women, especially in the third trimester of pregnancy. Oestrogen plays an important role in pregnancy. However, the pathogenesis of HEV in pregnant women or immunosuppressive pregnant women (such as HIV-infected or organ-transplanted pregnant women) remains unclear. We investigated the role of oestradiol in HEV infection in a cell culture system. HEV-infected pregnant women had significantly higher oestradiol levels compared with uninfected individuals. HEV infection was significantly increased in cells treated with analogues of oestradiol, diethylstilbestrol (DES) or 17ß-oestradiol in a dose-dependent way. However, tamoxifen, an antagonist oestrogen, inhibited HEV replication. HEV infection inhibits oestrogen receptor (ER-α) expression. Immunofluorescence and co-immunoprecipitation assays indicated that ER-α interacted with the helicase of HEV ORF1 indirectly. More importantly, HEV infection was exacerbated in immunosuppressive cells treated with an inhibitor of PI3K-AKT-mTOR signal pathway (LY296004) and supplemented with pregnant women serum with high oestradiol simultaneously. These results strongly suggest that pregnant women with high oestradiol and/or immunosuppression will be vulnerable to HEV infection.

Cathelicidin-encoding Lactococcus lactis promotes mucosal repair in murine experimental colitis.

BACKGROUND AND AIM: The preventive effect of intrarectal administration of mouse cathelicidin (mCRAMP) and oral administration of mCRAMP-encoding Lactococcus lactis (N4I) has been shown in murine experimental colitis. It is pivotal to understand the ability of N4I whether it can promote mucosal repair in existing colitis. METHODS: Mice with dextran sulfate sodium-induced ulcerative colitis (UC) were treated orally with L. lactis or its transformed strain with or without nisin induction. The body weight, clinical symptoms, and histological changes of colonic tissues were determined. Sulfasalazine was used as a reference drug. Young adult mouse colon cells were used to further elucidate the direct action and possible mechanisms of mCRAMP to promote colonic wound repair. RESULTS: Results showed that N4I could improve the clinical symptoms, maintain crypt integrity and preserve mucus-secreting layer in colitis animals. The preparation also could prevent cell death and promote cell proliferation. In contrast, effective dose of sulfasalazine only alleviated clinical symptoms but not the mucosal damage and repair in the colon. In vitro study further showed that mCRAMP could directly promote wound repair by accelerating cell migration but not cell proliferation through the GPCR/MAPK pathway. CONCLUSIONS: mCRAMP-encoding L. lactis could be a potential therapeutic preparation better than the traditional anti-inflammatory agent in the treatment of UC.

[Adult peripheral primary neuroectodermal tumor: a case report and literature review].

Objective: To analyze the clinical features, diagnosis and differential diagnosis of peripheral primary neuroectodermal tumor(pPNET). Methods: The clinical data and diagnosis of a patient with rapid progressive pPNET in Shandong Provincial Hospital affiliated to Shandong University in January 2016 was reported and the related literatures were reviewed.The literature reviews were carried out respectively in CNKI, Wanfang and PubMed by July 2016 with "primitive neurotodermal tumour" and "PNET" being the search term from March 1994 to July 2016, including 13 articles. Results: A 41 year-old male patient was admitted to the hospital because of shortness of breath and occasional chest tightness, accompanied by general asthenia of about 15 d. Positron emission and transmission-CT of total trunk showed a mass in the right femoral osteoperiosteal mass, and multiple nodules in the left lung, lumps and nodules in the right lung, and right pleural thickening and effusion. Thoracoscopy was performed and pathology study confirmed the diagnosis of peripheral primary neuroectodermal tumor. The patient was given 2 courses of chemotherapy, but had rapid progressive worsening and died 1 month after PNET diagnosis. A total of 13 literatures of PNET were retrieved, all of which were case reports, and a total of 15 cases were reported.There were 9 male and 7 female patients, with a median age of 26 years.The symptoms had no specificity and most of them were solid masses in chest images, with or without pleural effusion. Eight cases were diagnosed by imaging guided percutaneous biopsy, 7 by operation and pathology, and 1 by medical thoracoscopy. Four cases underwent chemotherapy, and the survival time was less than 6 months. Twelve cases got surgical resection: 2 with surgical treatment, 7 with postoperative chemotherapy, 2 with postoperative radiotherapy and chemotherapy, 1 with postoperative chemotherapy and autologous bone marrow transplantation treatment, among which 11 patients completed follow-up. During follow-up, 3 cases died, and the survival time was 10 months, 3 years and 7 years, respectively. Conclusions: PNET is rare.Due to the lack of specificity of clinical manifestations, clinical diagnosis depends on biopsy. Early diagnosis and surgical resection are especially important for prognosis and quality of life.

Drug use and its associated factors among money boys in Hunan Province, China.

OBJECTIVES: To describe drug use, types of drugs and related factors among money boys in Hunan Province, China. STUDY DESIGN: A cross-sectional study was conducted between July 2012 and January 2013. METHODS: Based on respondent-driven sampling, researchers located seven 'seeds' via a gay-dating website: http://www.ixxqy.org. After three waves of recruitment, 234 money boys were enrolled. They were asked to complete a 23-item questionnaire regarding demographic characteristics, drug use, a history of human immunodeficiency virus infection and family environment. Descriptive statistics and logistic regression analysis were conducted using Statistical Package for the Social Sciences Version 20.0. RESULTS: In total, 205 valid questionnaires were collected. Based on the data collected, 80 (39.0%) money boys had used drugs within the last 3 months. Rush popper (36.6%) and methamphetamine (12.7%) were used most commonly, and other drugs used were ecstasy (7.8%), ketamine (5.9%), marijuana (2.4%), morphine (1.5%), heroin (1.0%) and cocaine (0.5%). Factors included in the logistic regression were length of service (odds ratio [OR] 0.395, 95% confidence interval [CI] 0.175-0.896), being an only child (OR 2.272, 95% CI 1.108-4.659), relationship between parents (OR 0.428, 95% CI 0.213-0.858) and social network (OR 2.387, 95% CI 1.144-4.970). A shorter length of service and a good relationship between parents were protective factors against drug use, while being an only child and having a wide social network were risk factors. CONCLUSION: Drug use is common among money boys. This study found that length of service, being an only child, relationship between parents and social network are associated with drug use.

[Rapidly progressive pulmonary malignant perivascular epithelioid cell tumor: a case report and literature review].

Objective: To analyze the pathogenesis, clinical features, diagnosis and differential diagnosis of primary perivascular epithelioid cell tumor(PEComa). Methods: The clinical features, auxiliary examinations and diagnosis of a case with rapidly progressive pulmonary malignant PEComa were reported and the related literatures were reviewed.The literature review was carried out respectively in Wanfang Data, CNKI and PubMed from Jan. 1975 to Jul. 2015 with "pulmonary malignant perivascular epithelioid cell tumor" and "PEComa" being the search terms. Results: A 50 year-old female patient was admitted to the hospital on September 4, 2014 because of cough and dyspnea for 60 days, hemoptysis for 40 days and fever for 7 days.Chest CT scan showed diffuse small nodules with infiltrative border and multiple pure and mixed ground-glass opacity. Transbronchial lung biopsy (TBLB) was performed and the pathological study confirmed the diagnosis of primary pulmonary malignant PEComa. The patient declined further specific therapy, but followed by rapidly progressive respiratory failure, and died two weeks after the diagnosis. A total of 8 literatures were retrieved from Wanfang Data, CNKI and PubMed and all of them were case reports.There were 3 male and 5 female patients, aging from 50 to 79 years.Radiographically, the previously reported cases presented as round and well-circumscribed masses with or without multiple nodules in both lungs. The symptoms had no specificity. Conclusions: Pulmonary malignant PEComa is a rare disease.It is easily misdiagnosed because of non-specific clinical and imaging manifestations.The final diagnosis depends on pathological biopsy.TBLB is an effective diagnostic method.

Ivacaftor improves appearance of sinus disease on computerised tomography in cystic fibrosis patients with G551D mutation.

BACKGROUND: Most patients with Cystic fibrosis (CF) have chronic sinus disease which may require multiple sinus surgeries and antibiotic courses. Ivacaftor can improve lung function, lower sweat chloride levels and improve weight by targeting the primary defect, a faulty gene and its protein product, cystic fibrosis transmembrane conductance regulator (CFTR) in patients with the G551D mutation. Its role in improving sinus disease has not been evaluated. OBJECTIVE: The objective of this study was to evaluate efficacy of ivacaftor in improving CF related sinus disease. DESIGN: Observational study. PARTICIPANTS: Twelve patients with cystic fibrosis and a G551D-CFTR mutation. METHODS: Twelve patients with a G551D-CFTR mutation were monitored for at least one year before and after starting ivacaftor. OUTCOME MEASURES: Sinus disease progression was monitored by comparing computed tomography (CT) of sinuses before and at one year on therapy. Hospital admissions, pulmonary exacerbations, weight, BMI and lung function were also compared. RESULTS: Median age was 17 years (range 10-44). Weight, BMI, FEV1 significantly increased and sweat chloride significantly decreased by six months on ivacaftor therapy. CT of the sinuses in all patients improved. Seven patients had severe sinus disease, improved to moderate in three and mild in remaining four. Four patients had moderate disease which improved to mild in all. One patient had normal sinus CT before and after the therapy. CONCLUSIONS: Patients with CF and G551D mutation, within 6 months of starting ivacaftor had significant improvements in weight, BMI and mean % FEV1. Significant lessening of underlying sinus disease measured by CT scan was noted, suggesting a disease modifying effect.

Effects of fixed pattern noise on single molecule localization microscopy.

The newly developed scientific complementary metal oxide semiconductor (sCMOS) cameras are capable of realizing fast single molecule localization microscopy without sacrificing field-of-view, benefiting from their readout speed which is significantly higher than that of conventional charge-coupled device (CCD) cameras. However, the poor image uniformity (suffered from fixed pattern noise, FPN) is a major obstruction for widespread use of sCMOS cameras in single molecule localization microscopy. Here we present a quantitative investigation on the effects of FPN on single molecule localization microscopy via localization precision and localization bias. We found that FPN leads to almost no effect on localization precision, but introduces a certain amount of localization bias. However, for a commercial Hamamatsu Flash 4.0 sCMOS camera, such localization bias is usually <2 nm and thus can be neglected for most localization microscopy experiments. This study addresses the FPN concern which worries researchers, and thus will promote the application of sCMOS cameras in single molecule localization microscopy.

[Association of sleep duration and physical exercise with dyslipidemia in older adults aged 80 years and over in China].

Objective: To explore the impact of sleep duration, physical exercise, and their interactions on the risk of dyslipidemia in older adults aged ≥80 (the oldest old) in China. Methods: The study subjects were the oldest old from four rounds of Healthy Aging and Biomarkers Cohort Study (2008-2009, 2011-2012, 2014 and 2017-2018). The information about their demographic characteristics, lifestyles, physical examination results and others were collected, and fasting venous blood samples were collected from them for blood lipid testing. Competing risk model was used to analyze the causal associations of sleep duration and physical exercise with the risk for dyslipidemia. Restricted cubic spline (RCS) function was used to explore the dose-response relationship between sleep duration and the risk for dyslipidemia. Additive and multiplicative interaction model were used to explore the interaction of sleep duration and physical exercise on the risk for dyslipidemia. Results: The average age of 1 809 subjects was (93.1±7.7) years, 65.1% of them were women. The average sleep duration of the subjects was (8.0±2.5) hours/day, 28.1% of them had sleep duration for less than 7 hours/day, and 27.2% had sleep for duration more than 9 hours/day at baseline survey. During the 9-year cumulative follow-up of 6 150.6 person years (follow-up of average 3.4 years for one person), there were 304 new cases of dyslipidemia, with an incidence density of 4 942.6/100 000 person years. The results of competitive risk model analysis showed that compared with those who slept for 7-9 hours/day, the risk for dyslipidemia in oldest old with sleep duration >9 hours/day increased by 22% (HR=1.22, 95%CI: 1.07-1.39). Compared with the oldest old having no physical exercise, the risk for dyslipidemia in the oldest old having physical exercise decreased by 33% (HR=0.67, 95%CI: 0.57-0.78). The RCS function showed a linear positive dose-response relationship between sleep duration and the risk for hyperlipidemia. The interaction analysis showed that physical exercise and sleep duration had an antagonistic effect on the risk for hyperlipidemia. Conclusion: Physical exercise could reduce the adverse effects of prolonged sleep on blood lipids in the oldest old.

On protein abundance distributions in complex mixtures.

Mass spectrometry, an analytical technique that measures the mass-to-charge ratio of ionized atoms or molecules, dates back more than 100 years, and has both qualitative and quantitative uses for determining chemical and structural information. Quantitative proteomic mass spectrometry on biological samples focuses on identifying the proteins present in the samples, and establishing the relative abundances of those proteins. Such protein inventories create the opportunity to discover novel biomarkers and disease targets. We have previously introduced a normalized, label-free method for quantification of protein abundances under a shotgun proteomics platform (Griffin et al., 2010). The introduction of this method for quantifying and comparing protein levels leads naturally to the issue of modeling protein abundances in individual samples. We here report that protein abundance levels from two recent proteomics experiments conducted by the authors can be adequately represented by Sichel distributions. Mathematically, Sichel distributions are mixtures of Poisson distributions with a rather complex mixing distribution, and have been previously and successfully applied to linguistics and species abundance data. The Sichel model can provide a direct measure of the heterogeneity of protein abundances, and can reveal protein abundance differences that simpler models fail to show.

Novel techniques of preparing TEM samples for characterization of irradiation damage.

Focus ion beam preparation of transmission electron microscopy (TEM) samples has become increasingly popular due to the relative ease of extraction of TEM foils from specific locations within a larger sample. However the sputtering damage induced by Ga ion bombardment in focus ion beam means that traditional electropolishing may be a preferable method. First, we describe a special electropolishing method for the preparation of irregular TEM samples from ex-service nuclear reactor components, spring-shaped spacers. This method has also been used to prepare samples from a nonirradiated component for a TEM in situ heavy ion irradiation study. Because the specimen size is small (0.7 × 0.7 × 3 mm), a sandwich installation is adopted to obtain high quality polishing. Second, we describe some modifications to a conventional TEM cross-section sample preparation method that employs Ni electroplating. There are limitations to this method when preparing cross-section samples from either (1) metals which are difficult to activate for electroplating, or (2) a heavy ion irradiated foil with a very shallow damage layer close to the surface, which may be affected by the electroplating process. As a consequence, a novel technique for preparing cross-section samples was developed and is described.

Conjugated linoleic acids alleviate the immunosuppression of peripheral blood T lymphocytes in broiler chickens exposed to cyclosporin A.

The immunoregulatory actions of conjugated linoleic acids (CLA) of relevance immunosuppression were investigated. To test the hypothesis that CLA ameliorate immunosuppression, we developed the immunosuppressive model of peripheral blood T lymphocytes in broiler chickens induced by cyclosporin A. Peripheral blood T lymphocytes of broiler chickens were cultured with media containing various concentrations (25, 50, 100, and 200 µmol/L) of c9, t11-CLA and t10, c12-CLA to investigate the effects of CLA isomers on peripheral blood T lymphocyte proliferation, interleukin-2, the activity of phospholipase C, and protein kinase C production. Results suggested that CLA alleviated the immunosuppression of T lymphocytes in broiler chickens exposed to cyclosporin A through increasing of peripheral blood T lymphocyte proliferation and interleukin-2. The 2 CLA isomers enhanced T lymphocyte proliferation at low concentration and inhibited T lymphocyte proliferation at high concentration. In addition, the effect of c9, t11-CLA was better than that of t10, c12-CLA. At the cellular level, the effects of CLA on the alleviation of immunosuppression in T lymphocytes are mainly attributable to increasing the signaling molecules, such as phospholipase C and protein kinase C.

Optimizing single DNA molecules manipulation by AFM.

Recent progress in single DNA manipulation with atomic force microscope has proved its potential in analysing genetic information at the molecular level instead of macro ensemble approach. However, current manipulation of DNA is mainly carried out by manual operations, which is labour-intensive and time-consuming, thus limits the further applications in other fields. In this paper, an optimized DNA manipulation method is successfully established. An image correlation technique is introduced to realize automatic thermal drift compensation. Combined with elaborately designed tip movement control for different manipulation purposes, accurate and efficient DNA manipulations such as dissection, folding and picking are realized. The efficiency has been improved for an order of magnitude compare to manual manipulations, whereas the performance is demonstrated to be the same. This newly developed method has shed light on high-efficiency nanomanipulation of small molecules with complex structures, and thus provides the possibility of deeply understanding the intrinsic properties of single biomolecules.

Conjugated linoleic acids alleviate infectious bursal disease virus-induced immunosuppression in broiler chickens.

The immunoregulatory actions of conjugated linoleic acid (CLA) of relevance to viral disease pathogenesis and immune responses were investigated. To test the hypothesis that CLA ameliorates immunosuppression, we developed a viral challenge model by infecting chickens with infectious bursal disease virus (IBDV). After 14 d of dietary supplementation with either soybean oil or CLA, half of the chickens in each group were challenged with IBDV. We examined the effect of CLA on the development of lesions (i.e., lymphoid depletion and necrosis) and observed the immune responses against IBDV. The IBDV infection depleted lymphocytes in the medullary area and significantly stimulated interferon (IFN)-γ and IL-6 mRNA relative expression of bursa (P < 0.05) compared with the uninfected bursa. Compared with the CLA diet, lymphocytes depletion was more accentuated in chickens fed the control diet, whereas IFN-γ and IL-6 mRNA relative expression were upregulated (P < 0.05). Additionally, histopathological examination of the bursa revealed that the pathological changes tended to be more severe in infected chickens fed the control diet, which also significantly decreased (P < 0.05) on lymphocyte proliferation. Significant interactions were found between infection and diets for lymphocyte proliferation, antibody titers, and IFN-γ mRNA relative expression (P < 0.05). The results of this study indicate that dietary CLA enhanced immune function in chickens, particularly those of the IBDV-immunosuppressive status. Furthermore, at the molecular level, the immunoregulatory functions of CLA on chickens are attributable mainly to the antiinflammatory properties of CLA and are mediated, at least in part, through suppressing IBDV-specific proinflammatory cytokines mRNA relative expression.