Genome wide analysis of narcolepsy in China implicates novel immune loci and reveals changes in association prior to versus after the 2009 H1N1 influenza pandemic.

Previous studies in narcolepsy, an autoimmune disorder affecting hypocretin (orexin) neurons and recently associated with H1N1 influenza, have demonstrated significant associations with five loci. Using a well-characterized Chinese cohort, we refined known associations in TRA@ and P2RY11-DNMT1 and identified new associations in the TCR beta (TRB@; rs9648789 max P = 3.7 × 10(-9) OR 0.77), ZNF365 (rs10995245 max P = 1.2 × 10(-11) OR 1.23), and IL10RB-IFNAR1 loci (rs2252931 max P = 2.2 × 10(-9) OR 0.75). Variants in the Human Leukocyte Antigen (HLA)- DQ region were associated with age of onset (rs7744020 P = 7.9×10(-9) beta -1.9 years) and varied significantly among cases with onset after the 2009 H1N1 influenza pandemic compared to previous years (rs9271117 P = 7.8 × 10(-10) OR 0.57). These reflected an association of DQB1*03:01 with earlier onset and decreased DQB1*06:02 homozygosity following 2009. Our results illustrate how genetic association can change in the presence of new environmental challenges and suggest that the monitoring of genetic architecture over time may help reveal the appearance of novel triggers for autoimmune diseases.

[Intervention effect of dimercaptopropansulfonate sodium on central toxic induced by bromoxynil in vivo].

OBJECTIVE: to investigate the changes of γ-aminobutyric acid (GABA) and glutamate (Glu) in the cerebral cortex following acute bromoxynil intoxication in mice and the protective effect of sodium dimercaptopropane sulfonate (Na-DMPS). METHODS: 30 ICR mice were randomly divided into blank control group (10), exposure group (10) and Na-DMPS protection group (10). The levels of GABA and Glu in the cerebral cortex were measured by RP-HPLC. The glutamine (Gln) level and the glutamine synthetase (GS), glutamate decarboxylation enzyme (GAD), γ-aminobutyric acid transaminase (GABA-T) activity in the cerebral cortex were determined by UV colorimetric. RESULTS: compared with the control group [GABA: (3.41 ± 0.12) micromol/g, Glu (14.00 ± 0.16) micromol/g, Gln (1.25 ± 0.19) micromol/g, GAD (13.50 ± 0.25) micromol × g(-1) × h(-1), GABA-T (25.51 ± 0.21) micromol × g(-1) × h(-1), GS(142.19 ± 1.31) U/mg pro], the level of GABA [(3.14 ± 0.14) micromol/g] was decreased (P < 0.05), whereas the level of Glu [(17.54 ± 0.40) micromol/g] and Gln [(3.35 ± 0.27) micromol/g] were increased (P < 0.05), the activity of GAD [(11.93 ± 0.15 micromol × g(-1) × h(-1)], GABA-T [(24.15 ± 0.22) micromol × g(-1) × h(-1)], GS [(140.75 ± 1.01) U/mg pro] was decreased (P < 0.05) in acute intoxication group; Compared with the acute intoxication group, the level of GABA [(3.52 ± 0.30) micromol/g] was increased (P < 0.05), whereas the level of Glu [(14.20 ± 0.32) micromol/g] and Gln [(1.32 ± 0.17) micromol/g] were decreased (P < 0.05), the activity of GAD [(13.01 ± 0.45 micromol × g(-1) × h(-1)], GABA-T [(25.19 ± 0.26) micromol × g(-1) × h(-1), GS [(142.35 ± 1.20) U/mg pro] was increased (P < 0.05); In contrast, the levels of GABA, Glu, Gln and the activity of GAD, GABA-T, and GS in Na-DMPS protection group were not significantly different in comparison with control group (P > 0.05). CONCLUSION: the central toxic effects of mice with acute bromoxynil intoxication may be related to the changes of GABA and Glu content in the cerebral cortex;Na-DMPS can protect mice from bromoxynil-induced central toxic effects and GABA and Glu abnormal change in the cerebral cortex.

[A non-invasive equation in diagnosis of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia].

OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP) are the two largest subsets of idiopathic interstitial pneumonia (IIP). They have a sharply differences in therapy and survival, however, the identification of them is difficult. In general, NSIP has a much better responsiveness to therapy and good survival. On the other hand, in IPF, was demonstrated to be associated with poorer survival and responsiveness to therapy. To diagnosis of IPF and NSIP need histopathologic classification which however, requires surgical lung biopsy. Therefore, we try to set up an equation using those data from non-invasive methods to identify IPF and NSIP. METHODS: A retrospective review of 32 patients with IPF (n = 14) and NSIP (n = 18) was carried out. General clinical data, pulmonary function, chest radiographic, and bronchoalveolar lavage fluid were recorded. The statistical methods of logistic regression and multiple linear regression are used to establish the equation. The method of curve fitting is used to find the critical value of the equation to the differential diagnosis between the IPF and NSIP. RESULTS: (1) Compare to NSIP, patients of IPF are older, more males than females, having a bigger proportion of smokers. (2) Compared with NSIP patients, IPF patients have higher CT score of "grid shadow", "cellular shadow" and lower CT score of "ground-glass shadow". (3) Bronchoalveolar lavage (BAL) lymphocytosis was more frequently observed in NSIP than IPF. (4) We get an equation: y = 0.9 + 0.123 x 1 - 0.045 x 2 + 0.009 x 3 + 0.033 x 4 and it can improve the differential diagnosis between the IPF and NSIP in this group of patients. CONCLUSION: Clinical, high resolution computerized tomography and BAL are useful non-invasive tools in diagnosis IPF and NSIP. The equation:y = 0.9 + 0.123 x 1 - 0.045 x 2 + 0.009 x 3 + 0.033 x 4 can help us to distinguish the IPF and NSIP.

[Comparison of the effects of BiPAP ventilation combined with lung recruitment maneuvers and low tidal volume A/C ventilation in patients with acute respiratory distress syndrome].

OBJECTIVE: To compare the effects of BiPAP ventilation combined with lung recruitment maneuvers (LRM) with low tidal volume A/C ventilation in patients with acute respiratory distress syndrome (ARDS). METHODS: A prospective, randomized comparison of BiPAP mechanical ventilation combined with lung recruitment maneuvers (test group) with low tidal volume A/C ventilation (control group) was conducted in 28 patients with ARDS. FiO2/PaO2 ratio, respiratory system compliance (Cs), central venous pressure (CVP), duration of ventilation support were recorded at 0 h, 48 h and 72 h separately. The ventilation associated lung injury and mortality at 28 d were also recorded. RESULTS: The FiO2/PaO2 ratio were (298+/-16) and (309+/-16) cm H2O, Cs were (38.4+/-2.2) and (42.0+/-1.3) ml/cm H2O, CVP were (13.8+/-0.8) and (11.6+/-0.7) cm H2O in the test group at 48 h and 72 h separately. In the control group, FiO2/PaO2 ratio were (212+/-12) and (246+/-17) cm H2O, Cs were (29.5+/-1.3) and (29.0+/-1.0) ml/cm H2O, CVP were 18.6+/-1.1 and (16.8+/-1.0) cm H2O. The results were better in the test group as compared with the control group (t=10.03-29.68, all P<0.01). The duration of ventilation support in the test group was shorter than the control group [(14+/-3) d vs (19+/-3) d, t=4.80, P<0.01]. The mortality in 28 d and ventilation associated lung injury were similar in the two groups. CONCLUSION: The results show that combination of LRM with BiPAP mode ventilation, as compared with the control group, contributes to improved FiO2/PaO2 ratio, pulmonary compliance, stable hemodynamic and shorter duration of ventilation support in patients with ARDS.

[Efficacy of goal-directed therapy in the treatment of septic shock].

OBJECTIVE: To investigate the efficacy and effect on outcome of goal-directed therapy in patients with septic shock compared with conventional therapy. METHODS: Sixteen patients with septic shock were randomly assigned to receive goal-directed therapy, with central venous pressure (CVP) 8-12 mm Hg (1 mm Hg=0.133 kPa), mean arterial pressure (MAP) >or=65 mm Hg, venous oxygen saturation (SvO(2))>0.70 (superior vena cava saturation), and urine output >or=0.5 ml/min as therapeutic goals. Another 17 patients received conventional therapy as controls. The arterial oxygen saturation (SaO(2)), SvO(2), MAP, CVP, heart stroke volume cardiac index (CI), serum lactate, volume of fluid, amount of vasopressors, the numbers of organ injured and patients who needed continuity blood purification (CBP) and/or ventilation were recorded serially for 6-48 hours, and they were compared between the two groups. The mortality of the patients in two groups on 7 days and 14 days were also recorded. RESULTS: There were no significant differences between the groups with respect to base-line characteristics. During the interval from 24 to 48 hours, the patients assigned to goal-directed therapy had a significantly higher in SaO(2), SvO(2), MAP, CVP, CI (P<0.05 or P<0.01), a lower lactate concentration (P<0.01), significantly more fluid during 6-24 hours and less vasopressors (both P<0.01). Seven and 14 days in-hospital mortality were lower in goal-directed therapy group as compared with the control group(P<0.05). CONCLUSION: The efficacy of goal-directed therapy in patients with septic shock is significantly better than conventional therapy in ameliorating outcome of shock and can be easily used in intensive care unit (ICU).

[Nestin activation after rat cerebral ischemia-reperfusion injury and its changes in response to Tongxinluo treatment].

OBJECTIVE: To investigate nestin activation in rat brain subjected to ischemia-reperfusion injury and its changes in response to Tongxinluo treatment. METHODS: Cerebral ischemia was induced by temporary middle cerebral artery occlusion (MCAO) in rats. At 3, 7, 14 and 21 days after MCAO, nestin expression in the ependyma, subventricular zone (SVZ), hippocampal subdentate gyrus zone (HDG) of the rats treated with Tongxinluo were guantified by immunohistochemistry. RESULTS: Compared with the sham operation group, nestin was significantly increased 7, 14 and 21 days after MCAO (P<0.05), and immunofluorescence of BrdU+nestin-positive neurons significantly increased in the SVZ. After treatment with Tongxinluo, the number of BrdU-positive neurons and BrdU+nestin-positive neurons significantly increased as compared with MCAO group (P<0.05). CONCLUSION: Focal cerebral ischemia in the rat results in rapid response and proliferation of neural stem cells in the SVZ and HDG in the ischemic hemisphere, and Tongxinluo may enhance the differentiation and proliferation capacity of the neural stem cells after MCAO.