Objective To investigate the effects of acetylated HMGB1 on cognitive function in rats with sepsis associated encephalopathy (SAE) and the effect of HMGB1 inhibitor.Methods Forty-eight males mice were randomly assigned to three groups (n=16): sham group (group S),cecal ligation puncture group (group C),cecal ligation puncture+sodium butyrate group (group B).Cecal ligation puncture was applied to establish the SAE model,and group S received sham operation.Rats in groups S and C were injected with normal saline 5 ml/kg 30 min and 4 h after CLP,respectively.The rats in group B were intraperitoneally injected with sodium butyrate 500 mg/kg 0.5 h and 4 h after CLP,respectively.All animals were performed Morris water maze test on 4th day after operation,and the exploring time of space exploration experiments were assessed on 7th day after CLP surgery.IL-6,BDNF,HMGB1 and acetylated HMGB1 expression in hippocampus of all rats were determined by Western Blot.Results Compared with group S,the latency of rats in group C was longer and the exploring time was shorter (P<0.05).Compared with group C,the latency of rats in group B was shorter and the exploring time was longer (P<0.05).Compared with group S,the expression of IL-6,HMGB1 and acetylated HMGB1 in group C increased (P<0.05) and the level of BDNF decreased (P<0.05).Compared with group C,the expression of IL-6,HMGB1 and acetylated HMGB1 in group B decreased (P<0.05) and the level of BDNF increased (P<0.05).Conclusion HMGB1 inhibitor sodium butyrate can inhibit the expression of acetylated HMGB1 in the hippocampus of SAE rats,and reduce the cognitive impairment induced by sepsis.

Objective To investigate the role of hippocampal cyclophilin D (CypD) in sepsis-associated encephalopathy in rats.Methods A total of 36 adult male Sprague-Dawley rats,aged 3-4 months,weighing 300-400 g,were randomly divided into 3 groups (n =12 each) using a random number table:sham operation group (Sham group),sepsis group (S group),and sepsis + CypD inhibitor cyclosporin A group (CsA group).Sepsis was induced by cecal ligation and puncture (CLP).Cyclosporin A 6 mg/kg was injected intraperitoneally at 30 min before CLP in group CsA.All the animals underwent Morris water maze test on 4th day after CLP.The animals were sacrificed after the test,and the hippocampus was isolated for determination of the expression of cytochrome c (Cyt c),CypD,caspase-3,brain-derived neurotrophic factor (BDNF),phosphorylated protein kinase A (p-PKA),and phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB).Results Compared with group Sham,the escape latency was significantly prolonged,the space exploration time was shortened,the expression of Cyt c,CypD,caspase-3,p-PKA and p-CREB was up-regulated,and the expression of BDNF was down-regulated in S and CsA groups (P＜0.05).Compared with group S,the escape latency was significantly shortened,the space exploration time was prolonged,the expression of Cyt c,CypD,caspase-3,p-PKA and p-CREB was down-regulated,and the expression of BDNF was up-regulated in group CsA (P＜0.05).Conclusion Hippocampal CypD may be involved in the pathophysiological mechanism of sepsis-associated encephalopathy,and the downstream mechanism is probably related to promotion of activation of PKA/CREB signaling pathway in rats.

Objective To explore the predictive capability of different methods for difficult la-ryngoscopy and analyze its optimal cutoff value.Methods Three hundred consecutive patients (aged 18-65 years,weighing 42-88 kg,ASA physical status Ⅰ or Ⅱ)scheduled to undergo general anesthe-sia and surgery were invited to participate.Difficult airway assessments were performed by thyromen-tal height (TMH),thyromental distance (TMD),sternomental distance (SMD),modified Mallam-pati test (MMT)and ratio of height and TMD (RHTMD)before anesthetic induction.Cormack-Le-hane (C-L)grade of laryngoscopy view was assessed after induction.Sensitivity,specificity,positive predictive value (PPV),negative predictive value (NPV)and accuracy of these tests were calculated. Receiver operator characteristic (ROC)curve of TMH was performed to determine the optimal cutoff value of TMH.Results There were 22 patients diagnosed as difficult airway.Sensitivity,specificity, PPV,NPV and accuracy of TMH were higher than those of TMD,SMD and MMT tests.Sensitivity of RHTMD was lower than that of TMH test,and specificity,PPV,NPV and accuracy of RHTMD were similar to that of TMH.The optimal cutoff value of TMH was 4.9 cm through ROC curve. Conclusion The optimal cutoff value of TMH detecting difficult laryngoscopy was 4.9 cm.Similar to RHTMD,TMH appears to be more effective for prediction of difficult laryngoscopy than TMD, SMD and MMT.

OBJECTIVETo study the correlation of polymorphisms of CYP1A1 MSPI and glutathiones S-transferase (GST-M1) independently and in combination with the risk of lung cancer.

METHODSA case control study which included 91 cases of lung cancer and 138 controls collected from the First Affiliated Hospital of Sun Yat-sen University of Medical Sciences, Guangzhou Tumor Hospital and The Red Cross Hospital of Guangzhou or conmunity area. All subjects were investigated with a uniform questionnaire. Blood samples were collected from all cases and controls for detecting CYP1A1 MSPI and GST-M1 polymorphisms which were analyzed by PCR and RFLP.

RESULTSIt showed that there was no significant difference in frequencies of this genotypes of CYP1A1 MSPI between the two groups. The frequency of GST-M1 null (0/0) genotype was higher in the case group than in the control group, with an OR of 1.38 (95% CI 0.81 - 2.38), but there was no statistical significance. However, combination of several genotypes was strongly associated with lung cancer. There was a synergistic interaction between the m2m2 genotype of CYP1A1 MSPI and GST-M1 (0/0) genotype, with an OR of 2.47 (95% CI 1.03 - 5.90).

CONCLUSIONThe combination of two genetic polymorphisms significantly increases the risk of lung cancer.

Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Cytochrome P-450 CYP1A1 ; genetics ; Female ; Genotype ; Glutathione Transferase ; genetics ; Humans ; Lung Neoplasms ; etiology ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Risk ; Smoking ; adverse effects

Functional magnetic resonance imaging (fMRI) was used to study the activated brain areas of human during simple and complex digital calculation, and to investigate the role of cortical and subcortical structures involved in the mental calculation. Sixteen right-handed healthy volunteers performed mental calculation of simple and complex addition/subtraction respectively, while the fMRI data were recorded by a Seimens 1.5 T MR machine. Block-design was used in the tasks. Two calculation tasks and one base-line tasks were performed for the block-design. Simple calculation task was single-digit addition and subtraction, while the complex was multi-digit addition and subtraction. The base-line task was to tell whether the two numbers were the same in every trial. Statistical parametric mapping (SPM99) was employed to process data and localize functional areas. We compared the average activation intensity of each activated brain regions in the same calculation task and the activation intensity of the same regions in both tasks respectively. Both the cortex and the subcortical structures including basal ganglia and thalamus were activated during simple and complex mental calculations. Similar brain regions in subjects including frontal lobe, parietal lobe, occipital lobe, cingulate gyrus, thalamus and cerebellum were engaged in simple and complex addition/subtraction. In the same task, activation intensity of all activated brain areas differed insignificantly. Compared with the complex task, the right parietal lobe was not activated in the simple one. The subcortical structures such as the caudate nucleus and the left marginal division of the striatum (MrD) were activated in both two calculation tasks. The cortical regions involved in both simple and complex addition/subtraction were similar. In conclusion, both the cortex and the subcortical structures were activated during the mental calculation. The cortex including the frontal cortex, parietal cortex, and cingulate gyrus were activated during mental calculation, while the subcortical structures such as the caudate nucleus, the globus pallidum and the left marginal division of the striatum also played a critical role in the neural networks of the calculation at the same time. Right parietal lobe (supramarginal gyrus) was engaged only in the complex task, which suggested that this region might be involved in the visuospatial memory and processing.
Brain ; physiology ; Brain Mapping ; Humans ; Magnetic Resonance Imaging ; Parietal Lobe ; physiology ; Thinking ; physiology

OBJECTIVEIt is important to use noninvasive methods to differentiate liver fibrosis and liver cirrhosis. A prospective study was conducted to evaluate the validity of ultrasonography (US) in evaluating the severity of liver fibrosis in patients with chronic viral hepatitis in reference to the pathologic diagnosis of their liver biopsy specimens.

METHODSThe liver fibrosis status of 324 chronic viral hepatitis patients was evaluated by both needle biopsy and US. Histologically their liver fibrosis was graded as S0-S4, and the inflammatory reaction in the liver was graded as G1-G4. The US examination included qualitative description of the liver surface and liver parenchyma, and the quantitative parameters were vascular diameters, blood flow volume and spleen size.

RESULTSUS qualitative description of the liver surface and liver parenchyma was correlated to the severity of fibrosis and the degree of the inflammation seen in the liver biopsies. An analysis of US quantitative parameters showed that a cut-off value of 12.1 cm for the length of spleen had a sensitivity of 60.0%, and specificity of 75.3% in detecting early liver fibrosis. For other quantitative parameters, the cut-off values were 8mm for the diameter of the splenic vein, 30.5 cm/sec for maximal blood flow velocity in the portal vein and 12 mm in diameter of the main portal vein. The diagnostic sensitivities for these parameters were 60.0%, 78.6% and 76.7%; the diagnostic specificities were 78.1%, 66.9% and 44.6% respectively.

CONCLUSIONEarly cirrhosis can be detected by US, and the sonographic results were well paralleled with their pathologic diagnoses made by liver biopsies. Individual US parameter has limited sensitivity and specificity in diagnosing early cirrhosis. In clinical practice a combination of 2-3 parameters could be used to detect or exclude severe liver fibrosis.

Adult ; Female ; Hepatitis B, Chronic ; complications ; diagnostic imaging ; Hepatitis C, Chronic ; complications ; diagnostic imaging ; Humans ; Liver Cirrhosis ; diagnostic imaging ; virology ; Male ; Prospective Studies ; Ultrasonography

Objective To evaluate the role of C-X-C motif chemokine 13 (CXCL13) in sepsis-associated encephalopathy in mice.Methods A total of 64 healthy male C57BL/6J mice,aged 3-4 months,weighing 20-25 g,were divided into 4 groups (n=16 each) using a random number table method:sham operation group (Sham group),sepsis group (S group),CXCL13 siRNA group (si-CXCL13 group) and negative control siRNA group (si-control group).5-bromo-2-deoxyuridine (BrdU) 50 mg/kg was intraperitoneally injected twice a day for 3 consecutive days in the four groups,and then lipopolysaccharide 500 μg/kg was intraperitoneally injected to establish the sepsis model in S,si-CXCL13 and si-control groups.CXCL13 siRNA 5 μl and siRNA 5 μl were injected into the left lateral cerebral ventricle in si-CXCL13 and si-control groups,respectively,at 3 days before establishing the model.Morris water maze test was performed at 5 days after establishing the model.The escape latency,time spent in the target quadrant,and the number of crossing the platform were recorded.Mice were sacrificed after the end of test,brains were removed and hippocampi were isolated for examination of the pathological changes of the dentate gyrus (with a light microscope) and for determination of the expression of CXCL13,C-X-C motif chemokine receptor 5 (CXCR5) and brain-derived neurotrophic factor (BDNF),and the number of BrdU and BrdU/NeuroD positive cells (by immunofluorescence).Results Compared with sham group,the escape latency was significantly prolonged,the time spent in the target quadrant was shortened,and the number of crossing the platform was reduced on 2nd-4th days,the number of BrdU positive cells in the dentate gyrus was increased,and the number of BrdU/NeuroD positive cells in the dentate gyrus was decreased in S,siCXCL13 and si-control groups,and the expression of CXCL13 and CXCR5 was up-regulated,and the expression of BDNF was down-regulated in LPS and si-control groups (P＜0.05).Compared with S group,the escape latency was significantly shortened,the time spent in the target quadrant was prolonged,and the number of crossing the platform was increased on 2nd-4th days,the number of BrdU positive cells in the dentate gyrus was decreased,the number of BrdU/NeuroD positive cells in the dentate gyrus was increased,and the expression of CXCL13 and CXCR5 was down-regulated,and the expression of BDNF was up-regulated in si-CXCL13 group (P＜0.05),and no significant change was found in the parameters mentioned above in si-control group (P＞0.05).Conclusion CXCL13 is involved in sepsis-associated encephalopathy through regulating hippocampal neurogenesis,and the mechanism may be related to down-regulating the expression of hippocampal BDNF in mice.

Objective To investigate the changes of serum C-X-C motif ligand 13 (CXCL13) concentration in senior patients undergoing total hip replacement and its role in post-operative dys-function(POCD).Methods Eighty consecutive senior patients aged 65-80 years with BMI 18.4-27.3 kg/m2,ASA physical status Ⅱ or Ⅲ,were recruited and scheduled to undergo hip joint replacement operation.Neuropsychological test was performed 1-5 d after operation and patients were divided into POCD group and non-POCD group.Serum C reactive protein (CPR),procalcitonin (PCT),IL-6, TNF-α,CXCL13 concentration were detected 1 d before and 1,2,3,4,5 d after operation. Results A total of 21 (26%)patients developed POCD 1-5 d after operation (recruited in POCD group),and the other 59 patients were recruited in non-POCD group.Compared with the time point of 1 d before operation,serum CRP,PCT,IL-6,TNF-αand CXCL13 concentration were higher 1-5 d after operation in all patients (P<0.05).The concentrationsof these factors were higher in patients from POCD group than in those from non-POCD group 1-5 d after operation (P < 0.05). Conclusion The CXCL13 concentration insenior patients undergoing total hip replacement who devel-oped POCD were higher than in those who did not developed POCD.Whether it is correlated with POCD remains further study.

Objective To investigate the role of triggering receptor expressed on myeloid cells 1 (TREM1)in rats with neuropathic pain and its possible mechanism.Methods Forty-eight male a-dult Sprague-Dawley rats,weighing 220-300 g,were successfully placed intrathecal catheters,and then randomly divided into 4 groups (n=1 2 ):sham operation group (group S),neuropathic pain group (group CCI),TREM1 shRNA group (group RNAi)and negative lentivirus group (group Vi-rus).The neuropathic pain was induced by chronic sciatic nerve compression injury (CCI).In group RNAi,30 μl pGLVU6/RFP/Puro-shRNA (1×109IU/ml)was injected intrathecally 1 week before modeling.Group Virus was injected with 30 μl negative lentivirus,whereas group CCI and group S with equal amount of normal saline.MWT and TWL were measured 1 day before (baseline)and 1,3, 7,14 day after modeling.When behavioral test finished,the expression levels of TREM1,TLR4, MyD88,IκBαand p-NF-κB p65 in spinal cord were determined by Western blot.Whereas the mRNA expression levels of IL-1β,TNF-αand IL-6 in spinal cord were measured by RT-PCR.Results Com-pared with group S,the expression levels of TREM1 in groups CCI and Virus significantly increased (P<0.05).While compared with group CCI,the TREM1 expression of group RNAi in spinal cord significantly decreased (P<0.05).Compared with group S,MWT and TWL of groups CCI,Virus and RNAi after modeling and the expression of IκBαsignificantly decreased (P<0.05),whereas the expression of TLR4,MyD88,p-NF-κB p65 increased significantly (P<0.05),as well as the expres-sion of IL-1β,TNFαand IL-6 mRNA (P<0.05).Compared with group CCI,the MWT and TWL of group RNAi after modeling and the expression of IκBαremarkably increased (P<0.05),whereas the expression of TLR4,MyD88 and p-NF-κB p65 in the spinal cord remarkably decreased (P<0.05), as well as the expression of IL-1β,TNF-αand IL-6 mRNA (P<0.05).Conclusion TREM1 knock-down can alleviate neuropathic pain,the underlying mechanism might be the inhibition of TLR4/MyD88/NF-κB signaling pathway.

Objective To evaluate the accuracy of different biomarkers for early diagnosis of acute kidney injury ( AKI ) in the patients undergoing cardiovascular surgery under cardiopulmonary bypass ( CPB) . Methods A total of 200 patients, aged 22-86 yr, weighing 46-87 kg, scheduled for elective cardiovascular surgery under CPB, were enrolled in this study. The concentration of serum creatinine was determined at 1 day before operation and 1-7 days after operation. At 1 day before operation and 0, 2, 6 and 12 h after operation, the concentrations of urine neutrophil gelatinase-associated lipocalin (NGAL), cystatin C ( Cys C) , tissue inhibitor of matrix metalloproteinase type 2 ( TIMP-2) and insulin-like growth factor binding protein-7 ( IGFBP-7) were determined. The TIMP-2 and IGFBP-7 product ( TI) was calcu-lated. AKI was diagnosed after surgery according to Kidney Disease Improving Global Outcomes criteria. The receiver operating characteristic curve was plotted, and the area under receiver operating characteristic curve ( AUC) was calculated. Results The incidence of AKI was 20. 5％. The AUC of AKI diagnosed by the concentration of urine NGAL was 0. 689, 0. 709, 0. 713 and 0. 803 at 0, 2, 6 and 12 h after opera-tion, respectively ( P<0. 05) . The AUC of AKI diagnosed by the concentration of urine Cys C was 0. 639, 0. 762, 0. 774 and 0. 812 at 0, 2, 6 and 12 h after operation, respectively ( P<0. 05) . The AUC of AKIdiagnosed by TI was 0. 687, 0. 721, 0. 740 and 0. 779 at 0, 2, 6 and 12 h after operation, respectively ( P<0. 05) . The AUC of AKI diagnosed by combined three indices the parallel test was 0. 694, 0. 773 and 0. 794 at 0, 2 and 6 h after operation, respectively ( P<0. 05) . The AUC of AKI diagnosed by the serial test was 0. 610, 0. 631 and 0. 667 at 0, 2 and 6 h after operation, respectively. Conclusion Urine NGAL or Cys C concentrations or TI single detection and parallel test have a certain accuracy for early diag-nosis of AKI in the patients undergoing cardiovascular surgery under CPB.