Objective o investigate the prophylactic and therapeutic effects of montelukast,a cysteinyl leukotriene receptor-1 (CysLT1R) antagonist,on the delayed neuropsychological sequelae (DNS) in rat model of carbon monoxide (CO) poisoning and to explore the possible underlying mechanism.Methods A total of 90 rats were acclimated for one week prior to screening rat by Morris water maze test.Ten rats were randomly assigned to control group (Con group),and the remaining 80 rats were subjected to modified method of intraperitoneal injection of CO gas to establish animal model of acute CO poisoning,Thereafter,the survival rats randomized into CO poisoning group (Mod group),low-dose montelukast group (ML group),medium-dose montelukast group (MM group),high-dose montelukast group (MH group) (n =10 each).Montelukast was accordingly administered via intragastric tube at different intervals (30 min,4 h and 12 h) after CO poisoning,and then montelukast was administered every 12 hours for 7 consecutive days.The rats of control group and Mod group received equal volume of normal saline instead at given intervals.Twenty-one days after CO exposure,the average escape latency was measured by Morris water maze test to screen DNS rats followed by H-E staining to observe the pathological changes of cortex and hippocampal CA1 region and TUNEL was used to assess the apoptosis of neurons in cortex and hippocampal CA1 region after rats sacrificed.Results All CO-exposed rats exhibited cognition function lowered,and the escape latency (seconds) in Mod group (43.3 ± 15.5),ML group (31.5 ± 13.2) and MH groups (30.1 ± 12.2) was significantly prolonged compared with Con group (12.1 ± 3.0) (P ＜ 0.05),whereas the difference between MM group (15.0 ± 6.6) and Con group was statistically insignificant (P ＞ 0.05).Compared with Mod group,the escape latency in montelukast treatment groups was shortened,whereas the significant difference in escape latency only found between Mod group and MM group (P ＜ 0.05).Except for Con group,DNS was evident in CO-exposed groups,and the numbers of DNS rats in Mod,ML,MM and MH groups were 8,5,1,4,respectively,which made statistically significant differences to Con group (P ＜ 0.05) except MM group.The DNS incidence in MM group was lower than that in Mod group (P ＜ 0.05).Mod group exhibited severe histopathological injury to the brain,with evident apoptosis of neural cells,whereas in the groups with montelukast treatment,histopathological damage to the brain was mitigated and the number of apoptotic neuronal cells was diminished noticeably in MM group.Conclusion Montelukast can ameliorate the cognitive function of rats,decrease the incidence of DNS and reduce the apoptosis of neural cells as well as attenuate neuronal cell injury,thus exerting neuroprotection against DNS in rats with CO poisoning.

Objective To study the risk factors of MRI for the prediction of collapse in patients with avascular necrosis of the femoral head.Methods Twenty-two patients (39 hips) diagnosed avascular necrosis of femoral head by MR were enrolled in our study.The following MR appearances were evaluated:bone marrow edema,joint fluids,signal intensity and location of the lesion.The volume and surface area of the necrosis zone were calculated.The time of follow-up was 18-84 months (median,25 months).Logistic regression analysis was used to predict the risk factors by SPSS 13.0.The maximum value of Youden index was selected as the critical point to predict the collapse of femoral head and to define the sensitivity,specificity and accuracy.Results In the 39 hips with femoral head necrosis,21 hips had collapse.Bilateral collapse occurred in 5 cases.In 25 hips with the necrosis surface larger than 25％,collapse occurred in 21 (84％); In 8 hips with the volume of femoral head necrosis larger than 30％,collapse occurred in all cases; 1n 33 hips with the necrosis locating at the superolateral quadrant,collapse occurred in 21 (63.6％); In 22 hips with necrotic areas showing heterogeneous signal intensity,collapse occurred in 18(81.8％) ;In 25 hips with large amount of joint effusion,collapse occurred in 16 (64％) ;in 18 hips with bone marrow edema,collapse occurred in 13 (65％).Joint fluid,heterogeneous signal intensity and lesions in the superolateral quadrant,volume ratio,and area ratio were the high risk factors,while bone marrow edema was a relatively low risk factor.The area under ROC curves for area ratio of NASA was greater than that for volume ratio (0.987 vs 0.902).When the critical value for area ratio was 26.7％,the true positive rate was 95.2％,true negative rate was 94.4％,and Youden's index was 0.896.Conclusions The collapse of necrosis of femoral head may result from many factors.The femoral head was easy to collapse when it had large enough area of necrosis and mixed signal intensity,a large amount of joint effusion,bone marrow edema,and superolateral quadrant location.The critical value for area ratio to predict the collapse of femoral head was about 26.7％.The area ratio is more accurate than volume ratio in predicting the collapse of necrosis of femoral head.

Objective To investigate the effect of high volume hemofiltration (HVHF) on expression of miRNA-146 in peripheral blood mononuclear cells in posttraumatic sepsis patients and its therapeutic mechanism.Methods Twenty-five cases of posttraumatic sepsis were included as HVHF group.Another 25 age-and gender-matched traumatic sepsis patients with similar APACHE-Ⅱ who received no HVHF treatment for some reasons were used as controls.Therapeutic measurements were the same of the two groups except for HVHF.At 0-,6-,12-,24-and 48-hour time points,the peripheral blood mononuclear cells were isolated from patients of both groups to detect level of miRNA-146.Peripheral blood mononuclear cells isolated at 24 hours were incubated with lipopolysaccharide (LPS) in vitro.At hours 4,8,12,24 and 48 after incubation,level of miRNA-146 in mononuclear cells was determined and levels of TNF-α,IL-6,and IL-10 in the substrate was detected by ELISA.Results (1) Level of miRNA-146 in HVHF group was decreased significantly over time as compared with that in sepsis group;(2) Before incubation and at 4-and 8-hour after incubation,miRNA-146 level was lowered significantly in HVHF group as compared with that in sepsis group.After LPS stimulation,mononuclear cell also presented a stronger inflammatory response in HVHF group than in sepsis group.Conclusions HVHF provides a definite effect on immune function recovery and a significant improvement in prognosis.Moreover,HVHF may attenuate the impact of miRNA-146 on mononuclear cell inflammatory factor release and enhance the cell ability to respond to external stimuli again via down-regulating miRNA-146,as may be one of the therapeutic mechanisms of HVHF for posttraumatic sepsis.

Objective To investigate the prevalence of HBV infection and the risk of hepatitis B virus (HBV) reactivation in patients with inflammatory arthritis receiving tumour hecrosis factor alpha (TNFα) inhibitors.Methods The liver function,serology of HBV and viral loads (HBV DNA) were tested before using TNFα inhibitors,at 3 months and 6 months.Patients with chronic hepatitis B (CHB) infection (HBV DNA ＞ 1 × 103copies/ml) were eliminated.Results A total of 162 patients were investigated including 156 patients who finished the study.Eleven (7.05％) patients were HBsAg-positive.Two patients with HBV DNA ＞ 1 × 103copies/ml were eliminated before starting anti-TNFα therapy.Among HBsAgpositive patients,HBV reactivation was documented in only one of the 11 patients.This patient with rheumatoid arthritis developed elevation of glutamic-pyruvic transaminase (ALT) and HBV DNA copies three months after infliximab therapy.Therefore lamivudine was given for three months,which translated into the fall of ALT and HBV DNA copies back to normal level.After follow-up for six months,the virology and serology remained stable.In contrast,none of the other 155 patients had demonstrated evidence of HBV infection or HBV reactivation.Conclusion The kinetics of HBV viral loads should be carefully monitored in patients with inflammatory arthritis and HBsAg-positive during anti-TNFα therapy.HBV reactivation should be treated with antiviral medicine through out the period of anti-TNFα therapy.

Objective To investigate the selection of operative method and peri operative managements for osteoporotic femoral intertrochanteric fracture in elderly patients aged over 75 years.Methods A total of 132 consecutive patients aged 75-91 years with osteoporotic intertrochanteric fractures from July 2009 to July 2012 were retrospectively analyzed.47 patients were treated with dynamic hip screw (DHS group),44 patients with proximal femoral nail anti-rotation (PFNA group) and 41 patients with Gamma Ⅲ nail (Gamma Ⅲ group).The peri-operative managements,operation circumstance,the time for fracture union,postoperative complications and the degree of functional recovery were analyzed and compared between the 3 groups.Results The mean surgical time was shorter in Gamma Ⅲ nail and PFNA groups than in DHS group [(68.7±9.1) min,(80.5±11.3) min vs (112.2±18.4) min,both P＜0.01].The mean blood loss was less in the Gamma Ⅲ nail and PFNA groups than in DHS group[(156.9±18.5) ml,(183.4±21.3) ml vs (296.2±29.6) ml,both P＜0.01].The mean time for fracture healing was shorter in Gamma [Ⅲ nail and PFNA groups than inDHSgroup [(12.6±2.4) weeks,(13.1±2.4) weeks vs (15.3±3.2) weeks,both P＜ 0.05],and it has no obvious difference between Gamma Ⅲ nail and PFNA groups (P＞0.05).There were significant differences in postoperative complications between Gamma Ⅲ nail,PFNA groups and DHS group (2 cases,3 cases vv 11 cases,P＜0.05,respectively).The mean Harris hip score had no significantly difference among DHS,Gamma Ⅲ nail and PFNA groups (87.4±11.6,90.2±13.0 vs 88.9±12.3,both P＞0.05).Conclusions The 3 operative methods for stable intertrochanteric fracture are feasible and effective in elderly patients,but for unstable intertrochanteric fractures,the treatment with Gamma Ⅲ nail and PFNA has advantages.

Objective This study was undertaken to evaluate the ecological association between terrestrial natural radionuclide,indoor radon concentration,natural radioactivity and leukemia incidence among children under 18 years of age.Methods Data were gathered from the disease surveillance program and literature reading while software SPSS 13.0 was used to calculate the Spearman's correlation.Results The incidence rates of childhood(0-18 year)leukemia showed significant differences in different places with the highest as 3.13/105in Jiangmen area and the lowest as 0.42/105 in Maoming area.The incidence in Jiangmen was 7.45 times higher than that in Maoming.There was a rank correlation between the incidence of childhood leukemia and the mean concentrations of natural radio-nuclides in soll(226Ra and 232Th),with a Positive correlation observed for overall leukemia(rs=0.70,P=0.011;rs=0.66,P=0.02 for226 Raand 232Th respectively)and acute lymphoblastic leukemia(ALL)(rs=0.66,P=0.019;rs=0.64,P=0.025 for 226 Ra and 232Th respectively).Associations between the incidence of childhood leukemia and the indoor γ radiation dose rate,the total annual average effective dose equivalent from natural background radiation were also analyzed(both rs=0.59,P=0.042).Conclusion The natural radioactivity was likely to be a causative factor for childhood leukemia in Guangdong.

OBJECTIVETo investigate the effect of subanaesthetic dose of ketamine on mechanical stimulus on brain regions.

METHODSTotally 13 healthy male volunteers were enrolled in this study, in whom 0 and 100 ng/ml ketamine were administrated by target controlled infusion system in pilot study. After von Frey filaments (vFFs) 300 g were used as mechanical stimuli, Visual Analogue Scale scores were evaluated. Functional magnetic resonance imaging (fMRI)was taken 1 week after pilot study at the following sequences: structure imaging + functional imaging (stimulus sequence with 300 g vFFs, ketamine sequence); stimulus sequence = 6×(20s on + 20s off), with target concentration of ketamine at 0,100 ng/ml.fMRI result was processed by SPM2 and Metlab 7.01 software package.

RESULTSPosterior cerebellum lobe and corpus callosum were inhibited at 100 ng/ml under vFFs stimulus, whereas cingulate gyrus, middle frontal gyrus, inferior parietal lobule, occipital lobe, and posterior cerebellum lobe were activated at 100 ng/ml under vFFs stimulus.

CONCLUSIONSKetamine 100 ng/ml exerts its effect on pain related brain regions. It can both activate and inhibit these brain regions, with the activating effect being the primary effect.

Adult ; Analgesics ; administration & dosage ; pharmacology ; Brain ; drug effects ; physiopathology ; Humans ; Ketamine ; administration & dosage ; pharmacology ; Magnetic Resonance Imaging ; Male ; Pain ; physiopathology ; Pilot Projects

OBJECTIVETo investigate the effect of chloride channel blocker--niflumic acid (NFA) on the pathological process of hypoxia hypercapnia-induced pulmonary vasoconstriction in rats.

METHODSWe used the model of hypoxia hypercapnia-induced pulmonary vasoconstriction rats, and divided the second, third branch pulmonary artery rings randomly into four groups (n = 8): control group (N group), hypoxia hypercapnia group (H group), DMSO incubation group (HD group), niflumic acid group (NFA group). Under acute hypoxia hypercapnia conditions, we observed the effects of the three stages of hypoxia hypercapnia-induced pulmonary vasoconstriction (HHPV) incubated by NFA in the second, third brach pulmonary artery rings. At the same time, the values of rings' tension changings were recorded via the method of hypoxia hypercapnia conditions reactivity. And investigated the effect of NFA to HHPV.

RESULTS(1) Under the hypoxia hypercapnia condition, we observed a biphasic pulmonary artery contractile (the phase I rapid contraction and vasodilation; the phase II sustained contraction) response in both the second and the third branch pulmonary artery rings compared with the control group (P < 0.05 , P < 0.01); (2) The second and third pulmonary artery rings incubated by NFA which phase II persistent vasoconstriction were significantly attenuated compared with the H group (P < 0.05 , P < 0.01).

CONCLUSIONThe blocker of the chloride channels attenuates the second and third branch pulmonary artery rings constriction in rat, especially the phase II persistent vasoconstriction, so then have an antagonistic effect on HHPV.

Animals ; Chloride Channels ; antagonists & inhibitors ; Hypercapnia ; physiopathology ; Hypoxia ; physiopathology ; Niflumic Acid ; pharmacology ; Pulmonary Artery ; physiopathology ; Pulmonary Circulation ; Rats ; Vasoconstriction ; drug effects

OBJECTIVETo investigate the role of Xuebijing injection(XBJI, traditional Chinese medicine), in inhibiting TLR4--NF-kappaB--IL-1beta pathway of myocardial hypoxia/reoxygenation in rats.

METHODSThirty six male SD rats (280 +/- 30) g were randomly divided into six groups (n = 6): normal group (N group), balanced perfusion group (BP group), model group (M group), low dose XBJI group (XBJI(L) group), middle dose XBJI group (XBJI(M) group), high dose XBJI group (XBJI(H) group). By Langendorff isolated heart perfusion device to establish the model of myocardial hypoxia/reoxygenation in rats. ELISA was used to detect the concentration of interleukin-1beta (IL-1beta); Western blot was used to detect the expression of nuclear factor kappa B p65 (NF-kappaB p65) protein and toll like receptor 4 (TLR4) protein; and RT-PCR to determine the expression of NF-kappaB p65 mRNA and TLR4 mRNA;To observe microstructure changes of hypoxia/reoxygenation myocardial by light microscopy.

RESULTSCompared with M group, the IL-1beta concentration, NF-kappaB p65 and TLR4 protein,NF-kappaB p65 and TLR4 mRNA of XBJIL group, XBJI(M) group, XBJI(H) group expression decreased in varying degrees,and decreased most obviously all in XBJI(M) group (P < 0.05, P < 0.01); Myocardical structural damage was serious in M group, and improved after treatment XBJI, the most obvious was the XBJI(M).

CONCLUSIONDifferent dose of XBJI can inhibit TLR4--NF-kappaB--IL-1beta signal transduction pathway and reduce several inflammatory reaction after myocardial hypoxia/reoxygenation injury, the 4 ml/100 ml of XBJI is the best.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Heart ; drug effects ; Inflammation ; Interleukin-1beta ; metabolism ; Male ; Myocardium ; pathology ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; Signal Transduction ; Toll-Like Receptor 4 ; metabolism ; Transcription Factor RelA ; metabolism

OBJECTIVETo investigate the role of p38 MAPK on ischemic postconditioning (IPO) attenuating pneumocyte apoptosis after lung ischemia/reperfusion injury (LIRI).

METHODSForty adult male SD rats were randomly divided into 5 groups based upon the intervention (n = 8): control group (C), LIR group (I/R), LIR + IPO group (IPO), IPO + solution control group (D), IPO + SB203580 group (SB). Left lung tissue was isolated after the 2 hours of reperfusion, the ratio of wet lung weight to dry lung weight (W/D), and total lung water content (TLW) were measured. The histological structure of the left lung was observed under light and electron transmission microscopes, and scored by alveolar damage index of quantitative assessment (IQA). Apoptosis index (AI) of lung tissue was determined by terminal deoxynuleotidyl transferase mediated dUTP nick end and labeling (TUNEL) method. The mRNA expression and protein levels of and Bax were measured by RT-PCR and quantitative immunohistochemistry (IHC).

RESULTSCompared with C group, W/D, TLW, IQA, AI and the expression of Bax of I/R were significantly increased, the expression of Bcl-2 and Bcl-2/Bax were significantly decreased (P < 0.05, P < 0.01), and was obviously morphological abnormality in lung tissue. Compared with I/R group, all the indexes of IPO except for the expression of Bcl-2 and Bcl-2/ Bax were obviously reduced, the expression of Bcl-2 and Bcl-2/Bax were increased (P < 0.05, P < 0.01). All the indexes between D and IPO were little or not significant( P > 0.05). The expression of Bcl-2 and Bcl-2/Bax of SB were significantly increased and other indexes were reduced than those of IPO (P < 0.05, P < 0.01).

CONCLUSIONIPO may attenuate pneumocyte apoptosis in LIRI by inactivation of p38 MAPK, up-regulating expression of Bcl-2/Bax ratio.

Alveolar Epithelial Cells ; cytology ; Animals ; Apoptosis ; Disease Models, Animal ; Ischemic Postconditioning ; Lung ; blood supply ; enzymology ; pathology ; Male ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; enzymology ; pathology ; prevention & control ; bcl-2-Associated X Protein ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism