ObjectiveTo investigate the association between cumulative atherogenic index of plasma （cumAIP） and the risk of new-onset nonalcoholic fatty liver disease （NAFLD） in young and middle-aged individuals. MethodsA prospective cohort study was conducted among the young and middle-aged individuals （aged 18 to <60 years） in the Kailuan study cohort who underwent physical examination in Kailuan General Hospital and its 10 affiliated hospitals in June 2006 to October 2010， and after screening based on the inclusion and exclusion criteria， 33 987 individuals were included in the observation cohort. The individuals were divided into Q1， Q2， Q3， and Q4 groups based on the quantiles of cumAIP. The Kaplan-Meier method was used to calculate the cumulative incidence rate of new-onset NAFLD in the four groups， while the log-rank test was used for comparison between groups. A multivariate Cox regression analysis was used to obtain the hazard ratio （HR） and 95% confidence interval （CI） of the risk of new-onset NAFLD in the four groups. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups； the chi-square test was used for comparison of categorical variables between groups. ResultsThe mean follow-up was 10.89±2.54 years， and there were 6 011 cases of new-onset NAFLD， including 995 cases in the Q1 group， 1 366 in the Q2 group， 1661 in the Q3 group， and 1 989 in the Q4 group， with an incidence density of 11.37， 16.02， 19.97， and 24.91 per thousand person-years. The log-rank test showed that there was a significant difference in cumulative incidence rate between the four groups （P<0.001）. With the presence or absence of NAFLD as the dependent variable and the quantiles of different exposure levels to cumAIP as the independent variable， the multivariate Cox regression model analysis showed that compared with the Q1 group， the Q2， Q3， and Q4 groups had an HR of 1.30 （95%CI： 1.20 — 1.41）， 1.52 （95%CI： 1.41 — 1.65）， and 1.79 （95%CI： 1.64 — 1.95）， respectively， for new-onset NAFLD， with a P_trend value of <0.001. With the presence or absence of new-onset NAFLD as the dependent variable and the cumulative exposure to AIP for 0， 2， 4， and 6 years as the independent variable， the Cox regression analysis showed that compared with cumulative exposure to AIP for 0 years， cumulative exposure to AIP for 2， 4， and 6 years had an HR of 1.24 （95%CI： 1.15 — 1.35）， 1.51 （95%CI： 1.40 — 1.64）， and 1.70 （95%CI： 1.56 — 1.84）， respectively， with a P_trend value of <0.001. A sensitivity analysis was performed after exclusion of the individuals with new-onset NAFLD within 2 years， the individuals who experienced atherosclerotic cardiovascular disease events during follow-up， and the individuals taking antihypertensive， hypoglycemic， and lipid-lowering drugs， and the results were similar to those of the main analysis. Considering the competitive relationship between all-cause death and outcome events， a competing risk analysis of death was performed， which showed that the results of risk analysis were similar to those of the main analysis. ConclusionA high level of cumAIP exposure can increase the risk of new-onset NAFLD in young and middle-aged individuals.

Objective By comparing the changes in cerebral blood flow,neuronal morphology in brain tissue,and the levels of serum oxidation and inflammatory factors in models of cerebral hypoperfusion,three experimental rat models were assessed for their suitability as subjects of studies on the mechanisms and therapeutic drugs of cerebrovascular diseases and neurodegenerative diseases.Methods A total of 88 male SD rats were randomly divided into a sham operation group(n=16),classic bilateral common carotid artery occlusion group(classic 2-VO group,n=24),modified 2-VO group(n=24),and intraluminal thread technique group(n=24).Bilateral common carotid artery ligation was performed on the classic 2-VO group,while blood was drawn from the common carotid artery before ligation in the modified 2-VO group(1 mL/100 g).Middle cerebral artery occlusion was performed on the intraluminal thread technique group.In the sham operation groups of the first two models,the common carotid artery was separated but not ligated,while the proximal end of the common carotid artery and the external carotid artery were ligated;in addition,the bolt thread was not inserted in the sham group of the intraluminal thread technique group.Cerebral blood flow,infarct volume,serum inflammatory factor levels,hematoxylin and eosin-stained morphology,and ultrastructure of the hippocampal tissue were assessed at 1,3,and 7 days after the operations.Results Laser speckle interferometry showed a decrease in cerebral blood flow of the modified 2-VO group that was more obvious than that of the other two groups.On day 7,only the modified 2-VO group still had significant differences in cerebral blood flow compared with the sham group,and it remained in a state of hypoperfusion(cerebral blood flow decreased by 30％compared with that before the operation).TTC staining showed that infarcts in the striata of the three groups gradually increased with time after the operation;4 rats(about 26.7％)in the modified 2-VO group and 10 rats(about 66.7％)in the intraluminal thread technique group had infarcts in both the cortex and striatum.ELISA showed that the levels of inflammatory factors,such as TNF-α,IL-1 β,and hs-CRP,in the three groups were increased after the operations,and levels of the pro-oxidation factor ROS were also increased.In contrast,levels of the antioxidant factor SOD decreased.On postoperative day 7,there was no significant difference in the hs-CRP of the classic 2-VO and intraluminal thread technique groups compared with that of the sham group.However,the modified 2-VO group still exhibited significant differences in all the above indicators compared with the sham group.Hematoxylin and eosin staining showed that the modified 2-VO group had more severe damage to the hippocampal CA1 and CA3 regions compared with the other groups.Transmission electron microscopy demonstrated that the modified 2-VO group showed more severe damage to the mitochondrial and endoplasmic reticulum in the hippocampal region compared with the other groups.Conclusions A cerebral hypoperfusion model was successfully established.Compared with the classic 2-VO and intraluminal thread techniques,the modified 2-VO method can induce more complete cerebral hypoperfusion and more severe neural damage within the same time frame,resembling the pathological state of human cerebral hypoperfusion more closely.

The corneal epithelium, an essential refractive interface, plays an integral role in the corneal healing after corneal refractive surgery. All existing corneal refractive surgeries entail a degree of corneal epithelial remodeling; however, excessive epithelial remodeling precipitates adverse outcomes on the refractive correction efficacy of such surgeries. This review summarizes the application of corneal epithelial remodeling in the corneal refractive surgery, and more comprehensively investigates the influencing factors of perioperative epithelial remodeling after corneal refractive surgery, with a view to augmenting the safety, efficacy, predictability, and stability of corneal refractive surgical outcomes.

Objective:To investigate the effect of resveratrol ( Res ) on endoplasmic reticulum stress induced by cerebral ischemia/reperfusion(I/R)injury in rats.Methods:The seventy-two male SD rats were divided randomly into three groups(n=20):sham operation group ( group S ) , I/R group and Res-treatment group ( group R ) .Focal cerebral I/R model was induced by electrocoagulation of left middle cerebral artery and occlusion of bilateral common carotid arteries followed by reperfusion after 30 min.The rats in Res group were treated with Res(50 mg/kg)i.p.7 d before the operation,once a day for 7 d.Neurological deficits were assessed at 24 h post-injury,followed by collecting the brain tissues.Cerebral infarct size was detected by TTC staining,and the water content of brain tissue were measured by wet-dry weight method.The expression of GRP78,p-PERK and CHOP proteins were deter-mined by immunohistochemistry and Western blot analysis.Results:Compared with sham group,the neurological deficit score and the brain water content were significantly increased(P<0.05),cerebral infarct size was enlarged(P<0.05),and the expression of GRP78, p-PERK and CHOP were up-regulated in I/R group(P<0.05).At the corresponding time,compared with I/R group,the neurological deficit score and the brain water content were markedly decreased(P<0.05),cerebral infarct size was smaller(P<0.05),the level of GRP78 was notablely increased(P<0.05),while the expression of p-PERK and CHOP were down-regulated in Res group(P<0.05). Conclusion:Resveratrol plays a protection role in ischemia-reperfusion injury, through inhibiting the endoplasmic reticulum stress in rats.

Objective To evaluate the diagnostic value of the level of plasma D-dimer,high-density lipoprotein (HDL),carcino embryonic antigen (CEA) and carbohydrate antigen 724 (CA724) in gastric cancer.Methods The plasma and clinicopathological data of 103 gastric cancer patients and 111 normal controls were collected.The levels of D-dimer,HDL,CEA and CA724 were detected.SPSS 13.0 statistical software was applied to analysis the sensitivity and specificity of each examination method and to find out the appropriate combination.Results The levels of D-dimer,CEA and CA724 in patients with gastric carcinoma were 0.87 (2.69) μg/ml,2.66 (4.38) ng/ml,5.10 (7.79) U/ml,respectively,they were distinctly higher than those in normal controls [0.22 (0.21) μg/ml,1.28 (1.60) ng/ml,1.81 (1.60) U/ml,all P =0.000].HDL level was significantly lower in patients than that in normal controls [0.86 (0.35) mmol/L vs 1.29 (0.44) mmol/L,P=0.000].The area ofROC curve of D-dimer,HDL,CEA,CA724 were 0.799,0.859,0.739,0.743,respectively.The cut-off of D-dimer was 0.46 μ.g/ml,the sensitivity was 68.0 ％,the specificity was 86.5 ％.The cut-off of HDL was 0.995 mmol/L,the sensitivity was 73.8 ％,the specificity was 84.7 ％.The cut-off of CEA was 3.585 ng/ml,the sensitivity was 44.7 ％,the specificity was 92.0 ％.The cut-off of CA724 was 3.765 U/ml,the sensitivity was 57.3 ％,the specificity was 89.2 ％.The sensitivity of D-dimer+HDL+CA724 was 83.5 ％,the specificity was 89.2 ％.The sensitivity and specificity of D-dimer+HDL+CEA+CA724 were 84.5 ％ and 89.2 ％,respectively.Conclusions The D-dimer+HDL+CEA+CA724 may provide the evidence for diagnosis of gastric cancer.Combined detection has higher sensitivity and specificity.

Objective To understand the awareness degree and the dietary intake of acrylamide (AA) in food among preventive medicine professional undergraduate students in a university of Xianyang city .Methods 28 kinds of fried and baked food frequently eaten by undergraduates were selected as the respondents .The food-frequency method was adopted to perform the questionnaire in-vestigation on 248 undergraduates sampled from grade 1-5 of preventive medicine professional undergraduate students by the clus-ter sampling .Results More than 38 .71% of the investigated students had never known about the acrylamide ,32 .26% of the inves-tigated students had heard but did not know what it was ,11 .26% students knew about its hazard .The AA dietary intake was about 31 .57 μg/d per person ,and there was no statistical difference in the AA dietary intake between different sexes and grades .Conclu-sion The awareness degree of AA among investigated preventive medicine professional undergraduates is relatively low .Therefore it is necessary to strengthen the publicity and education of the AA-related food safety knowledge .

In order to enhance the position accuracy of ablation catheter in heart electrophysiology operation, signals of respiration and heartbeat must be removed for subsequent data processing. Based on locating principle of electrical field with low frequency, synchronous detector with MC1496 has been developed in this study. In the present research, several methods are utilized to optimize the circuit performance, such as coupling and stopping direct current, low-pass filtering, as well as limiting ripple voltage etc. Through simulation results, it showed that the demodulation performance of the circuit was fine. Through simulation platform of thorax electric field and animal experiment, the circuit feasibility were further proved good for extracting signals of respiration and heartbeat.
Atrial Fibrillation ; surgery ; Catheter Ablation ; methods ; Computer Simulation ; Electromagnetic Fields ; Heart ; anatomy & histology ; physiology ; Humans ; Models, Biological ; Signal Processing, Computer-Assisted ; Thorax

OBJECTIVETo study the effect of GABA transporter (GAT-1) on the analgesic action of oxysophoridine (OSR) in the central nervous system of mice.

METHODHot plate test was used to observe and analyze the effect of gamma aminobutyric acid and the inhibitor of GAT-1 (NO-711) on the analgesic action of oxysophoridine. Real time RT-PCR was used to investigate the influence of OSR on the expression of GAT-1 mRNA induced by formalin in spinal cord and brain of mice.

RESULTBoth GABA (2.0 mg x kg(-1), icv) and NO-711(0.125 mg x kg(-1), icv) enhanced the analgesic action of OSR (32.0 mg x kg(-1), iv) in the hot plate test, and the latencies was markedly increased (P < 0.05, P < 0.01). OSR (500.0 mg x kg(-1), iv) significantly inhibited the expression of GAT-1 mRNA induced by formalin (P < 0.05).

CONCLUSIONGAT-1 was involved in the analgesia effect of OSR and the down-regulation of GAT-1 mRNA enhanced the analgesic effect.

Alkaloids ; pharmacology ; Analgesics ; pharmacology ; Animals ; Brain ; drug effects ; metabolism ; Down-Regulation ; drug effects ; Female ; GABA Plasma Membrane Transport Proteins ; genetics ; metabolism ; Gene Expression Regulation ; drug effects ; Male ; Mice ; RNA, Messenger ; analysis ; Spinal Cord ; drug effects ; metabolism

Human NUDT16 (hNUDT16) is a decapping enzyme initially identified as the human homolog to the Xenopus laevis X29. As a metalloenzyme, hNUDT16 relies on divalent cations for its cap-hydrolysis activity to remove m⁷GDP and m²²⁷GDP from RNAs. Metal also determines substrate specificity of the enzyme. So far, only U8 small nucleolar RNA (snoRNA) has been identified as the substrate of hNUDT16 in the presence of Mg²(+). Here we demonstrate that besides U8, hNUDT16 can also actively cleave the m⁷GDP cap from mRNAs in the presence of Mg²(+) or Mn²(+). We further show that hNUDT16 does not preferentially recognize U8 or mRNA substrates by our cross-inhibition and quantitative decapping assays. In addition, our mutagenesis analysis identifies several key residues involved in hydrolysis and confirms the key role of the REXXEE motif in catalysis. Finally an investigation into the subcellular localization of hNUDT16 revealed its abundance in both cytoplasm and nucleus. These findings extend the substrate spectrum of hNUDT16 beyond snoRNAs to also include mRNA, demonstrating the pleiotropic decapping activity of hNUDT16.
Amino Acid Motifs ; Biocatalysis ; Cell Nucleus ; enzymology ; Consensus Sequence ; Cytoplasm ; enzymology ; metabolism ; Guanosine Diphosphate ; metabolism ; Histidine ; metabolism ; Humans ; Hydrolysis ; Luciferases ; genetics ; Magnesium ; metabolism ; Manganese ; metabolism ; Mutagenesis ; Mutation ; Pyrophosphatases ; antagonists & inhibitors ; chemistry ; genetics ; metabolism ; RNA Caps ; chemistry ; metabolism ; pharmacology ; RNA, Small Nucleolar ; chemistry ; metabolism ; pharmacology

Influenza virus contains three integral membrane proteins: haemagglutinin, neuraminidase, and matrix protein (M1 and M2). Among them, M2 protein functions as an ion channel, important for virus uncoating in endosomes of virus-infected cells and essential for virus replication. In an effort to explore potential new functions of M2 in the virus life cycle, we used yeast two-hybrid system to search for M2-associated cellular proteins. One of the positive clones was identified as human Hsp40/Hdj1, a DnaJ/Hsp40 family protein. Here, we report that both BM2 (M2 of influenza B virus) and A/M2 (M2 of influenza A virus) interacted with Hsp40 in vitro and in vivo. The region of M2-Hsp40 interaction has been mapped to the CTD1 domain of Hsp40. Hsp40 has been reported to be a regulator of PKR signaling pathway by interacting with p58(IPK) that is a cellular inhibitor of PKR. PKR is a crucial component of the host defense response against virus infection. We therefore attempted to understand the relationship among M2, Hsp40 and p58(IPK) by further experimentation. The results demonstrated that both A/M2 and BM2 are able to bind to p58(IPK) in vitro and in vivo and enhance PKR autophosphorylation probably via forming a stable complex with Hsp40 and P58(IPK), and consequently induce cell death. These results suggest that influenza virus M2 protein is involved in p58(IPK) mediated PKR regulation during influenza virus infection, therefore affecting infected-cell life cycle and virus replication.
HSP40 Heat-Shock Proteins ; genetics ; metabolism ; Humans ; Orthomyxoviridae ; genetics ; metabolism ; Phosphorylation ; Protein Binding ; genetics ; Signal Transduction ; genetics ; Two-Hybrid System Techniques ; Viral Matrix Proteins ; metabolism ; Virus Replication ; genetics ; Virus Uncoating ; eIF-2 Kinase ; metabolism