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JW Zhang,1 WW Liu,1 Timothy A McCaffrey,2 XQ He,1 WY Liang,1 XH Chen,1 XR Feng,1 Sidney W Fu,2 ML Liu1 1Department of Geriatrics, Peking University First Hospital, Beijing, China; 2Department of Medicine, George Washington University Medical Center, Washington, DC, USA Objectives: Previous studies have illustrated the link between high on-aspirin platelet reactivity (HAPR) with increasing thrombotic risks. The aim of our study was to investigate relative risk factors of HAPR in elderly patients with coronary artery disease.Methods: Elderly, hospitalized coronary artery disease patients on regular aspirin treatment were enrolled from January 2014 to September 2016. Medical records of each patient were collected, including demographic information, cardiovascular risk factors, concomitant drugs and routine biological parameters. Arachidonic acid (AA, 0.5 mg/mL) and adenosine diphosphate (ADP, 5 µmol/L) induced platelet aggregation were measured via light transmission assay (LTA) to evaluate antiplatelet responses, referred as LTA–AA and LTA–ADP.Results: A total of 275 elderly patients were included, with mean age of 77.2±8.1 years, and males accounted for 81.8%. HAPR was defined as LTA–AA in the upper quartile of the enrolled population. HAPR patients tended to have lower renal function (P=0.052). Higher serum uric acid (SUA) level, as well as lower platelet count, hemoglobin and hematocrit were observed in HAPR patients, with a higher proportion of diuretics use (P

Wei Xiang, Jingwei Zhang, Meilin Liu, Fang Liu, Xueru Feng, Yuchuan Wang Department of Geriatrics, Peking University First Hospital, Beijing, People’s Republic of China Objective: Non-valvular atrial fibrillation (NVAF) is one common arrhythmia in the elderly. However, use of antithrombotic therapy in this population is not well known in the People’s Republic of China. This study aimed at investigating antithrombotic therapy status in elderly patients with NVAF in our hospital.Methods: A cross-sectional study of consecutive geriatric patients aged ≥60 years with NVAF who discharged from our hospital between January 2012 and December 2013 were collected. CHA2DS2-VASc score (cardiac failure or dysfunction, hypertension, age ≥75 [doubled], diabetes, stroke or transient ischemic attack [doubled], vascular disease, age 65–74, and sex category [female]) was used to analyze antithrombotic indication.Results: We consecutively collected data of 1,000 discharged elderly patients (≥60 years) with NVAF (mean age 75.3±8.0 years, 75 years or older 54.7%, female 42.7%). The proportion of paroxysmal atrial fibrillation and non-paroxysmal atrial fibrillation (persistent or permanent) patients were 39.4% and 60.6%, respectively. Among 1,000 patients, 29.1% received oral anticoagulant therapy (OAT), including warfarin (27.8%) and novel oral anticoagulants (1.3%), 39.5% of patients received antiplatelet therapy, and 31.4% received neither therapy. Based on CHA2DS2-VASc score for stroke risk stratification, 68.9% patients with score ≥1 and 70.2% patients with score ≥2 received antithrombotic therapy, while the rates of OAT were 29.1% and 29.5%, respectively. Among patients with high stroke risk, those with paroxysmal atrial fibrillation were less likely to receive OAT compared with the patients with non-paroxysmal atrial fibrillation (19.5% vs 35.7%, P

Objective: To study biological variation (BV) and analytical performance specifications (APS) of 15 erythrocyte and related parameters. Methods: Sixty healthy participants from Beijing Hospital were prospectively recruited for the study, from July to December, 2023, including 30 males [aged (41.3±11.9) years] and 30 females [aged (40.3±12.4) years]. The study was designed based on the Biological Variation Data Critical Appraisal Checklist and the characteristics of erythrocyte detection. Whole blood samples were collected 10 times at 2-week intervals during 20 weeks. All samples were tested in duplicate using Mindray BC-7500 hematology analyzer and its accompanying reagents. Within-subject biological variation ( CV I ) and between-subject biological variation ( CV G ) were estimated by the nested ANOVA method. The BV data in this study were compared with the BV data of the European Database of Biological Variation. APS, reference change value (RCV) and index of individuality (II) were calculated. Results: The CV I for 15 parameters ranged from 0.49% to 86.46%, and the CV I data for red cell distribution width (RDW)- CV , RDW- SD , reticulocyte (RET) percentage, RET count, reticulocyte hemoglobin content (RHE), medium fluorescence reticulocyte (MFR) and high fluorescence reticulocyte (HFR) were significantly higher in females than in males (all P <0.05). The CV G ranged from 1.27% to 100.79%, and the CV G data for HFR were significantly different between genders ( P <0.05). The CV I data for red blood cell (RBC), hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC) and RHE in this study were lower than those recommended by the European database. The derived indicators of most parameters were influenced by gender. The II values for all parameters were<1.4, where the II values of MCHC and HFR were between 0.6 and 1.4; the II values for the remaining 13 parameters were<0.6. Conclusions: A BV study protocol for erythrocyte parameters is designed. When the reference intervals differ between genders, BV data should be calculated separately and the lower BV data are recommended for calculating APS; the RCV should be set separately for each gender.

Background: The average daily gain (ADG) of preweaning calves significantly influences their adult productivity and reproductive performance. Gastrointestinal microbes are known to exert an impact on host phenotypes, including ADG. The aim of this study was to investigate the mechanisms by which gastrointestinal microbiome regulate ADG in preweaning calves and to further validate them by isolating ADG-associated rumen microbes in vitro., Results: Sixteen Holstein heifer calves were selected from a cohort with 106 calves and divided into higher ADG (HADG; n = 8) and lower ADG (LADG; n = 8) groups. On the day of weaning, samples of rumen contents, hindgut contents, and plasma were collected for rumen metagenomics, rumen metabolomics, hindgut metagenomics, hindgut metabolomics, and plasma metabolomics analyses. Subsequently, rumen contents of preweaning Holstein heifer calves from the same dairy farm were collected to isolate ADG-associated rumen microbes. The results showed that the rumen microbes, including Pyramidobacter sp. C12-8, Pyramidobacter sp. CG50-2, Pyramidobacter porci, unclassified&#95;g&#95;Pyramidobacter, Pyramidobacter piscolens, and Acidaminococcus fermentans, were enriched in the rumen of HADG calves (LDA > 2, P < 0.05). Enrichment of these microbes in HADG calves' rumen promoted carbohydrate degradation and volatile fatty acid production, increasing proportion of butyrate in the rumen and ultimately contributing to higher preweaning ADG in calves (P < 0.05). The presence of active carbohydrate degradation in the rumen was further suggested by the negative correlation of the rumen microbes P. piscolens, P. sp. C12-8 and unclassified&#95;g&#95;Pyramidobacter with the rumen metabolites D-fructose (R <  - 0.50, P < 0.05). Widespread positive correlations were observed between rumen microbes (such as P. piscolens, P. porci, and A. fermentans) and beneficial plasma metabolites (such as 1-pyrroline-5-carboxylic acid and 4-fluoro-L-phenylalanine), which were subsequently positively associated with the growth rate of HADG calves (R > 0.50, P < 0.05). We succeeded in isolating a strain of A. fermentans from the rumen contents of preweaning calves and named it Acidaminococcus fermentans P41. The in vitro cultivation revealed its capability to produce butyrate. In vitro fermentation experiments demonstrated that the addition of A. fermentans P41 significantly increased the proportion of butyrate in the rumen fluid (P < 0.05). These results further validated our findings. The relative abundance of Bifidobacterium pseudolongum in the hindgut of HADG calves was negatively correlated with hindgut 4-hydroxyglucobrassicin levels, which were positively correlated with plasma 4-hydroxyglucobrassicin levels, and plasma 4-hydroxyglucobrassicin levels were positively correlated with ADG (P < 0.05)., Conclusions: This study's findings unveil that rumen and hindgut microbes play distinctive roles in regulating the preweaning ADG of Holstein heifer calves. Additionally, the successful isolation of A. fermentans P41 not only validated our findings but also provided a valuable strain resource for modulating rumen microbes in preweaning calves. Video Abstract., (© 2024. The Author(s).)

Nanobubbles (NBs), given their unique properties, could theoretically be paired with rhamnolipids (RL) to tackle polycyclic aromatic hydrocarbon contamination in groundwater. This approach may overcome the limitations of traditional surfactants, such as high toxicity and low efficiency. In this study, the remediation efficiency of RL, with or without NBs, was assessed through soil column experiments (soil contaminated with phenanthrene). Through the analysis of the two-site non-equilibrium diffusion model, there was a synergistic effect between NBs and RL. The introduction of NBs led to a reduction of up to 24.3 % in the total removal time of phenanthrene. The direct reason for this was that with NBs, the retardation factor of RL was reduced by 1.9 % to 15.4 %, which accelerated the solute replacement of RL. The reasons for this synergy were multifaceted. Detailed analysis reveals that NBs improve RL's colloidal stability, increase its absolute zeta potential, and reduce its soil adsorption capacity by 13.3 %-19.9 %. Furthermore, NBs and their interaction with RL substantially diminish the surface tension, contact angle, and dynamic viscosity of the leaching solution. These changes in surface thermodynamic and rheological properties significantly enhance the migration efficiency of the eluent. The research outcomes facilitate a thorough comprehension of NBs' attributes and their relevant applications, and propose an eco-friendly method to improve the efficiency of surfactant remediation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Major depressive disorder (MDD) poses a significant social and economic burden worldwide. Identifying exposures, risk factors, and biological mechanisms that are causally connected to MDD can help build a scientific basis for disease prevention and development of novel therapeutic approaches., Methods: In this systematic review, we assessed the evidence for causal relationships between putative causal risk factors and MDD from Mendelian randomization (MR) studies, following PRISMA. We assessed methodological quality based on key elements of the MR design: use of a full instrumental variable analysis and validation of the three key MR assumptions., Results: We included methodological details and results from 52 articles. A causal link between lifestyle, metabolic, inflammatory biomarkers, particular pathological states and MDD is supported by MR investigations, although results for each category varied substantially., Conclusions: While this review shows how MR can offer useful information for examining prospective treatment targets and better understanding the pathophysiology of MDD, some methodological flaws in the existing literature limit reliability of results and probably underlie their heterogeneity. We highlight perspectives and recommendations for future works on MR in psychiatry., (© 2023. The Author(s).)

Background: Intracranial atherosclerotic stenosis is a major cause of ischemic stroke, accounting for 30% of ischemic strokes in Asian populations., Purpose: To investigate the relationship between the degree of arterial stenosis and enhancement grade of intracranial atherosclerotic disease (ICAD), the plaque characteristics in different remodeling patterns, and its potential impact., Material and Methods: A total of 210 patients diagnosed with ICAD were enrolled in this retrospective study. Patients were divided into the middle cerebral artery (MCA) group (101 cases), posterior cerebral artery (PCA) group (14 cases), basilar artery (BA) group (71 cases), and intracranial segment of vertebral artery (VA) group (90 cases) according to the difference of diseased vessels. Data on presence or absence of ischemic infarction, intracranial vascular position of lesions, plaque characteristics, ICAD enhancement grade, remodeling index, and degree of arterial stenosis were collected for analysis., Results: The incidence of ischemic infarction in enhancement grade 2 was significantly higher than that in enhancement grade 1 in MCA group ( P  = 0.019). Enhancement grade 2 of ICAD was an independent risk factor for the development of ischemic infarction (odds ratio = 4.60; 95% confidence interval: 1.91-11.03; P  = 0.001). There was no significant statistical difference in infarct rate between different remodeling modalities ( P >0.05)., Conclusion: Enhancement grade of ICAD is significantly associated with the degree of stenosis and the occurrence of ischemic stroke, which varies in different intracranial vessels. The pattern of vascular remodeling varies among different intracranial vessels, and the pattern of vascular remodeling has a significant impact on plaque characteristics.

Objective: To investigate the etiology of intracranial artery stenosis and the distribution characteristics of intracranial artery atherosclerotic stenosis using high-resolution magnetic resonance imaging (HR-MRI)., Methods: A total of 262 patients with intracranial artery stenosis that underwent HR-MRI from November 2019 to December 2020 were retrospectively enrolled. The etiology of intracranial anterior and posterior circulation artery stenosis was analyzed, and the relationship between the location of plaques and the distribution characteristics of plaques and the occurrence of ischemic stroke was summarized., Results: A total of 276 plaques were identified with HR-MRI. There were 101 cases (36.59%) in the middle cerebral artery (MCA), 14 cases (5.07%) in the posterior cerebral artery (PCA), 90 cases (32.62%) in vertebral artery (VA), and 71 cases (25.72%) in the basilar artery (BA). The infarct rate of ventral and superior wall MCA plaques was higher than that of dorsal and inferior wall (63.33% vs 31.25% P = 0.021) (100.00% vs 50% P = 0.022). MCA with plaques throughout the course had the greatest degree of stenosis (P < 0.001). Sphenoid segment (M1) of MCA was most susceptible (85 cases, 84.16%), MCA plaques were most common in the proximal M1 segment (35 cases, 34.65%), and most BA plaques were found in the distal segment (28 cases, 39.44%). PCA plaques were most frequently involved in traffic anterior segment (P1) (7 cases, 50.00%)., Conclusion: HR-MRI could provide accurate imaging reference for clinical evaluation of intracranial arterial stenosis and formulation of treatment plans. The intracranial arterial plates mostly appeared in the middle cerebral artery and vertebral artery. Middle cerebral arteries with atherosclerotic plaques are more likely to narrow., (© 2022. Fondazione Società Italiana di Neurologia.)

Idiopathic pulmonary fibrosis (IPF) is a type of pulmonary disease that progresses acutely or slowly into irreversible pulmonary diseases, resulting in the end severe damages to patients' lung functions, as well as deaths. At present, the pathogenesis of pulmonary fibrosis is still not clear and there is no effective therapeutic measure available to control the progression of the disease. Research findings indicate that stem cells, being the origin of all cells of organisms, participate in the development of individuals at various stages and play an important role in repairing pulmonary tissue damage. Stem cells are attracting growing attention in the field of regenerative medicine, providing new ideas for treating IPF with transplanted stem cells. Herein, in order to better explore the potential applications of stem cell transplantation in treating IPF, we attempt to summarize preliminary studies of stem cell-mediated pulmonary remodeling after IPF, as well as cutting-edge clinical trials in stem cell-based IPF therapy., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Aim of the Study: To explore the high-resolution magnetic resonance imaging (HR-MRI) characteristics of central nervous system (CNS) vasculitis and to explore the value of HR-MRI in the treatment effect and prognosis evaluation of CNS vasculitis., Material and Methods: During the follow-up of 24 patients diagnosed as CNS vasculitis by the Second Hospital of Hebei Medical University, 3.0T HR-MRI was used for imaging examination and HR-MRI characteristics were analysed., Results: The affected vessel wall of 24 patients showed diffuse uniform centripetal thickening. The HR-MRI examination showed varying degrees of lumen stenosis, including 5 cases (20.8%) involving a single arterial segment, and 19 cases (79.2%) involving multiple arterial segments. And most cases (92.9%) showed grade 2 enhancement of the involved vessel wall. Except for one case involving the basilar artery at the same time, the remaining 23 cases involved only the anterior circulation vessels. We analysed and compared the affected vessels between the relapsed group and the non-relapsed group, and found that the average number of involved vascular segments was 6.5 ±3.4 (3-11) in the relapsed group and 3.5 ±2.1 (1-8) in the non-relapsed group, with a significant difference between the two groups (p = 0.039)., Conclusions: The CNS vasculitis was more likely to involve the anterior circulation vessels. The number of affected vascular segments in the relapsed group of CNS vasculitis was higher than in the non-relapsed group, suggesting that the more vascular segments involved, the more prone to recurrence.

Purpose: High-resolution magnetic resonance imaging (HR-MRI) has high spatial resolution and can simultaneously perform wall and lumen imaging. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can evaluate the integrity of the blood-brain barrier. In this paper, the result of 3.0T HR-MRI and 3.0T DCE-MRI has been evaluated to explore the application value of unilateral middle cerebral artery inflammatory stenosis and changes in vascular permeability parameters of stroke events., Methods: Thirty-six cases of neurological suspicion of central nervous system vasculitis of our hospital were selected from 20 January 2018 to 1 January 2019, who were diagnosed as unilateral middle cerebral artery M1 stenosis/occlusion by 3D TOF MRA. 3.0T HR-MRI and 3.0T DCE-MRI has been applied., Results: Among the 36 patients who met the inclusion criteria, 23 patients with central nervous system vasculitis were diagnosed. The 23 patients with HR-MRI showed diffuse thickening and enhanced stenosis. The K trans value of 10/23 patients with acute-subacute cerebral infarction and 3/23 patients in chronic phase were significantly higher than that of the mirror side, and the K trans value of these patients remeasured in the same region of interest is lower than before after 6 months treatment. The K trans value in the target area of 10 patients without cerebrovascular events was not statistically significant compared with the mirror side. The K trans value of patients with acute-subacute cerebral infarction was significantly higher than that without cerebrovascular events (0.098 ± 0.038 vs. 0.007 ± 0.001, p = .000), and there was no significant difference between K trans in the chronic infarction group and the other two groups (0.098 ± 0.038 vs. 0.044 ± 0.012, p = .058; 0.044 ± 0.012 vs. 0.007 ± 0.001, p = .057)., Conclusion: HR-MRI is an accurate direct imaging method and has a high value for the etiological diagnosis of central nervous system vasculitis. DCE-MRI could be an effective way to evaluate and monitor blood-brain barrier to prevent clinical ischemic stroke., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Micromotion can accelerate fracture healing, with critical parameters being range of motion, frequency of motion, duration of motion, as well as initial timing of the motion. However, these parameters of micromotion have not been optimized. It is because in previous studies large animals were used. The displacement among fracture fragments caused by animal activity brings a considerable systemic error to experimental data. Also, the sample size is limited by time and cost. Thus, the rat with femur fracture can be a good animal model in investigating this problem as its advantages on high consistency of experimental results, short convalescence, and low maintenance cost. The challenge in using a small animal model in the micromotion study include 1) highly specific stiffness of the fixator; 2) lightweight fixator to bring less interference to animal's activity; 3) high accuracy on measurement method. This study aims to solve this problem by integrating 1) an aluminum fixator with a solid construction; 2) a modularized experimental device with dismountable parts; 3) a non-contact measurement model based on video identification technology. Our preliminary validation results confirmed the reliability and reproducibility of the external fixation device used in the investigation on the effect of applied micromotion on bone healing.

Background: Oxidative stress-induced cardiomyocytes apoptosis is a key pathological process in ischemic heart disease. Glutathione reductase (GR) reduces glutathione disulfide to glutathione (GSH) to alleviate oxidative stress. Ginsenoside Rb1 (GRb1) prevents the apoptosis of cardiomyocytes; however, the role of GR in this process is unclear. Therefore, the effects of GRb1 on GR were investigated in this study., Methods: The antiapoptotic effects of GRb1 were evaluated in H9C2 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, annexin V/propidium iodide staining, and Western blotting. The antioxidative effects were measured by a reactive oxygen species assay, and GSH levels and GR activity were examined in the presence and absence of the GR inhibitor 1,3-bis-(2-chloroethyl)-1-nitrosourea. Molecular docking and molecular dynamics simulations were used to investigate the binding of GRb1 to GR. The direct influence of GRb1 on GR was confirmed by recombinant human GR protein., Results: GRb1 pretreatment caused dose-dependent inhibition of tert-butyl hydroperoxide-induced cell apoptosis, at a level comparable to that of the positive control N-acetyl-L-cysteine. The binding energy between GRb1 and GR was positive (-6.426 kcal/mol), and the binding was stable. GRb1 significantly reduced reactive oxygen species production and increased GSH level and GR activity without altering GR protein expression in H9C2 cells. Moreover, GRb1 enhanced the recombinant human GR protein activity in vitro , with a half-maximal effective concentration of ≈2.317 μM. Conversely, 1,3-bis-(2-chloroethyl)-1-nitrosourea co-treatment significantly abolished the GRb1's apoptotic and antioxidative effects of GRb1 in H9C2 cells., Conclusion: GRb1 is a potential natural GR agonist that protects against oxidative stress-induced apoptosis of H9C2 cells., (© 2019 The Korean Society of Ginseng, Published by Elsevier Korea LLC.)

BACKGROUND Aspirin hyporesponsiveness increases the risk of ischemic events. Therefore, it is important to investigate the factors influencing aspirin hyporesponsiveness. MATERIAL AND METHODS Patients aged 60 years or older who did not take aspirin before enrollment were included, with aspirin 100 mg/day administered after enrollment. The arachidonic acid-induced platelet aggregation rate (Ara) was measured by light transmission assay to evaluate aspirin responsiveness. Patients with Ara in the upper quartile after taking aspirin were assigned to the aspirin hyporesponsive group (Ara-Q4). RESULTS A total of 292 elderly patients were included. The median value of Ara after taking aspirin was 5.87% (interquartile range 3.86-10.04%). Compared with the aspirin non-hyporesponsive group (Ara-Q1-3, Ara ≤10.04%, n=220), the level of uric acid (UA) (341.30 µmol/L vs. 299.10 µmol/L, p=0.027) and the ratios of ß-blockers (9.72% vs. 2.27%, p=0.015) and diuretics (6.94% vs. 1.36%, p=0.036) were higher in the aspirin hyporesponsive group (Ara-Q4, Ara >10.04%, n=72). After multivariate adjustment, the results demonstrated baseline Ara (odds ratio [OR]: 1.030, 95% confidence interval [CI]: 1.004-1.056, p=0.021), UA level (OR: 1.003, 95% CI: 1.000-1.006, p=0.038), and ß-blockers use (OR: 5.487, 95% CI: 1.515-19.870, p=0.010) were independently and positively associated with aspirin hyporesponsiveness. CONCLUSIONS This study found that baseline Ara, UA level, and ß-blockers use were independently and positively associated with aspirin hyporesponsiveness in elderly Chinese patients, which needs to be validated in large-scale studies.

Objective: To delineate the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of patients with cervical spondylotic radiculopathy by diffusion tensor imaging and fiber bundle tracing., Methods: Thirty patients with cervical spondylotic radiculopathy and 24 healthy volunteers were assessed using the International Standards for Neurological Classification of Spinal Cord Injury scale. All subjects underwent conventional sagittal T1- and T2-weighted imaging and horizontal 3-dimensional T2 driven equilibrium radiofrequency reset pulse and diffusion tensor imaging scan. The ADC and FA values were measured in the cervical nerve at most stenotic segment and heterolateral nonstenotic segment of patients., Results: Fiber tractography revealed thinned and sparse nerve roots and disruption of the fiber bundles in patients with cervical spondylotic radiculopathy. The FA values of C5-C8 in healthy volunteers or heterolateral nonstenotic nerve of patients with cervical spondylotic radiculopathy were significantly greater than those of the stenotic cervical segments of patients with cervical spondylotic radiculopathy (both P < 0.01). Furthermore, the ADC values of C5-C8 in healthy volunteers or heterolateral nonstenotic nerve of patients with cervical spondylotic radiculopathy were significantly lower than those of the stenotic cervical segments of cervical spondylotic radiculopathy patients (both P < 0.01)., Conclusions: Fiber tractography is capable of delineating microstructural changes of cervical nerve roots and cervical spondylotic radiculopathy exhibits significant changes in FA and ADC values., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Two new lignans named neourticol A (1) and neourticol B (2), together with seven known compounds (3-9), were isolated from Urticae Fissae Herba, a folk medicine for rheumatism arthritis in China. The active evaluation results showed that 1 and 2 possessed the potent anti-complement and anti-inflammatory activities.

Objective: To investigate the influence of the TOLL-like receptor 4 (TLR4)-mediated p38MAPK signaling pathway on chronic intermittent hypoxic (CIH)-induced oxidative stress and inflammatory cytokines in rats., Materials and Methods: A total of 120 healthy male Sprague Dawley (SD) rats, aged between 8-10 weeks, were randomly divided into 9 groups (normoxia control group, CIH 2 weeks group, CIH 4 weeks group, CIH 6 weeks group, CIH 8 weeks group, CIH 6 weeks + p38MAPK receptor inhibit group, CIH 6 weeks + Tempol group, CIH 8 weeks + p38MAPK receptor inhibitor group and CIH 8 weeks + Tempol group). The expression of TLR4 and p38MAPK in the adipose tissue was evaluated, as well as the level of serum oxidative stress markers (SOD, TRx-1, MDA) and inflammatory cytokines (adiponectin, TNF-α, hsCRP and IL-6). RT-PCR and Western-blot were conducted to detect the expression of TLR4 and p38MAPK mRNA., Results: With increased hypoxia, the levels of SOD and adiponectin in the serum of the CIH group decreased significantly, and the levels of TNF-α, hsCRP, IL-8 and IL-6 in serum increased significantly. After the intervention of antioxidant Tempol and p38MAPK inhibitor SB203580, SOD increased significantly but with significant MDA reduction. The levels of TNF-α, hsCRP, IL-8 and IL-6 in serum significantly decreased. The results of RT-PCR and Western-Blot indicated that the P-p38 and TLR4 proteins related to the MAPK pathway were expressed in rat adipose tissue. With the hypoxia intensity, expression of P-p38 decreased after initially increasing. The expression of TLR4 showed a continuously growing trend. After Tempol treatment, the expression of p38MAPK protein decreased, and the expression of TLR4 did not change significantly, indicating the inhibiting effect of Tempol on p38MAPK, without a significant inhibiting effect on TLR4., Conclusions: The TLR4-mediated p38MAPK signaling pathway was active in adipose tissue and the expression of the corresponding molecules increased as the duration of intermittent hypoxia increased. The expression of TLR4 and p38MAPK components regulated the level of oxidative stress and inflammatory cytokines; the application of p38MAPK inhibitors and antioxidant free radical scavengers improved the levels of oxidative stress and inflammatory cytokines.

In order to study the flux characteristics of CH 4 , CO 2 and N 2 O in different ditches and their influencing factors, three types of ditches (an agricultural ditch, agricultural-living compound ditch, and living ditch) were monitored once a month from March 2014 to February 2015 using static floating chambers in the Chengdu Plain. The results showed that:① Affected by human activities, CO 2 , CH 4 , and N 2 O fluxes were high in ditches and ranged from -2.26-1504.40 mg·(m 2 ·h) -1 , 0.69-40.00 mg·(m 2 ·h) -1 , and -2.27-70.35 μg·(m 2 ·h) -1 ,respectively. All are higher in summer compared to autumn and spring, and are lowest in winter. ② The flux of CO 2 in agricultural-living compound ditches was significantly higher than that in agricultural ditches and living ditches ( P <0.05), and the fluxes of CH 4 and N 2 O in living ditches were significantly higher than those in agricultural ditches and agricultural-living compound ditches ( P <0.05). ③ Water temperature and rainfall were the main environmental factors affecting CO 2 , CH 4 , and N 2 O fluxes, and DO (dissolved oxygen) and TN (total nitrogen) were the main environmental factors affecting CO 2 and N 2 O fluxes. NH 4 + -N (ammonium nitrogen) and DO were the main water quality parameters affecting the CH 4 flux.

This study examined the application of 64-slice spiral double-low computed tomography (CT) to evaluate the degree of coronary artery stenosis. We examined 45 patients with coronary heart disease by 64-slice spiral double-low CT and coronary angiography (CAG) to determine CT accuracy in evaluating coronary artery stenosis. Imaging analysis from 64-slice spiral double-low CT identified 199 segments with coronary stenosis from 45 patients, including 46 segments with mild stenosis, 38 with moderate stenosis and 115 with severe stenosis or artery occlusion. CT analysis agreed with CAG on the identification of the degree of stenosis in 122 segments, with an overall accuracy of 61.3%. The accuracy for serious stenosis or occlusion was the highest at 69.6%. We also found a strong correlation between coronary plaque compositions and the degree of stenosis. Correspondence analysis showed that the presence of soft plaques closely correlated with severe stenosis, whereas mixed plaques closely correlated with moderate stenosis. Overall, 64-slice spiral double-low CT imaging can effectively assess the degree of coronary artery stenosis in patients with coronary heart disease and accurately detect plaque composition. Thus, 64-slice spiral double-low CT imaging can predict the risk of coronary heart disease and the degree of coronary artery stenosis, which is helpful for early diagnosis and treatment of coronary heart disease.

Aspirin is widely used in the prevention of cardiovascular diseases, but the antiplatelet responses vary from one patient to another. To validate aspirin response related transcripts and illustrate their roles in predicting cardiovascular events, we have quantified the relative expression of 14 transcripts previously identified as related to high on-aspirin platelet reactivity (HAPR) in 223 patients with coronary artery disease (CAD) on regular aspirin treatment. All patients were followed up regularly for cardiovascular events (CVE). The mean age of our enrolled population was 75.80±8.57years. HAPR patients showed no significant differences in terms of co-morbidities and combined drugs. Besides, the relative expression of HLA-DQA1 was significantly lower in low on-aspirin platelet reactivity (LAPR) patients, when compared with HAPR and high normal (HN) group (p=0.028). What's more, the number of arteries involved, HAPR status and the relative expression of CLU, CMTM5 and SPARC were independent risk factors for CVE during follow up (p<0.05). In addition, overexpression of CMTM5 attenuated endothelial cells (ECs) migration and proliferation, with significantly decreased phosphorylated-Akt levels, while its inhibition promoted these processes in vitro (p<0.05).Our study provides evidence that circulating transcripts might be potential biomarkers in predicting cardiovascular events. CMTM5 might exert anti-atherosclerotic effects via suppressing migration and proliferation in the vessel wall. Nevertheless, larger-scale and long-term studies are still needed., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To assess the consequences of switching aspirin dosage from 100 mg/d to 40 mg/d on cardiovascular benefit, bleeding risk and platelet aggregation in very elderly patients., Methods: Arachidonic acid induced platelet aggregation(AA-Ag) was measured in 537 patients aged 80 or older treated with aspirin (100 mg/d). In the study, 100 patients with low on-treatment platelet aggregation and at high risk of bleeding and low risk of cardiovascular events, were switched to aspirin (40 mg/d) and their platelet aggregation was measured again 7 days later.Their bleeding and upper gastrointestinal symptoms were also recorded in following 3 months., Results: The study observed a heterogeneous distributed aspirin 100 mg/d AA-Ag (range: 0.42% to 28.78%)in the 537 very elderly patients.Aspirin 100 mg/d AA-Ag before the switch in aspirin 40 mg/d group was 5.00%±2.32% and the rate of the patients with low on-treatment platelet aggregation was 71.00%. The rates of melena or occult blood positive, other minimal bleeding,upper gastrointestinal symptoms and a history of gastrointestinal bleeding in 40 mg/d group were higher than those in 100 mg/d group. On a regimen of aspirin 40 mg/d, AA-Ag increased to 11.21%±4.95%(range: 2.12% to 28.84%) with 95.00%of the patients with AA-Ag<20% and the rate of the patients with low on-treatment platelet aggregation was 15.00%. Multiple variable analysis revealed that aspirin 40 mg/d AA-Ag was significantly influenced by aspirin 100 mg/d AA-Ag, BMI and platelet counts. The rate of gastrointestinal bleeding decreased from 12.00% to 5.00%,and upper gastrointestinal symptoms decreased from 59.00% to 21.00% after the switch in 40 mg/d group., Conclusion: Switching aspirin dosage from 100 mg/d to 40 mg/d reduces the bleeding events and improves upper gastrointestinal symptoms, thus inhibiting platelet aggregation effectively in very elderly patients.

Background and Aims: Recent studies have suggested that serum uric acid (SUA) induces oxidative stress and inflammation, which are involved in the mechanism of cardiac hypertrophy. In patients with atrial fibrillation (AF), comorbidity of left ventricular hypertrophy (LVH) exacerbates cardiac function. In this study, we investigated the association between SUA and cardiac hypertrophy in AF patients., Methods and Results: Initially, 1296 consecutive elderly patients (age >60) with nonvalvular AF were retrospectively selected from the inpatient clinic between January 2012 and April 2015. Demographic, clinical, and echocardiographic characteristics were carefully recorded. The final study population was 577 patients. The mean SUA level was significantly higher in patients with LVH than those without LVH. Compared with the non-LVH group, the LVH group was older, had a higher percentage of female patients, and had lower hemoglobin levels and estimated glomerular filtration rates. Patients in the LVH group also had a higher rate of coronary heart disease and fewer had history of radiofrequency ablation compared with the non-LVH group. In the hyperuricemia group, B-type natriuretic peptide levels, left atrial diameter, left ventricular mass index, and percentage of NYHA (New York Heart Association) class III/IV were significantly higher than the SUA normal group. Multivariate logistic regression analysis indicated the independent risk factors for LVH in elderly AF patients included SUA, age, male sex, the presence of coronary heart disease, and diuretic therapy. Subgroup analysis identified SUA as a significant risk factor associated with LVH in men., Conclusions: SUA was independently associated with LVH in elderly male patients with nonvalvular AF., (Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

The new hybrid flocculant polyaluminum chloride-poly (dimethyl diallyl ammonium chloride) (PAC-PDMDAAC) was used to treat disperse violet and reactive brilliant red dye wastewater. The experimental results indicated that the decolorization effect of hybrid PAC-PDMDAAC was better than that of PAC and composite PAC-PDMDAAC. The decolorization rates of disperse violet and reactive brilliant red dye wastewater were 99% and 86.8% respectively when the dosages of hybrid flocculant were 400 and 450 mg·L-1. When the pH of disperse violet wastewater was 7～12, the hybrid flocculant had the best decolorization effect. When the pH of reactive brilliant red wastewater was 7～9, the hybrid flocculant had the best decolorization effect. Each of the two dyes and their flocs were characterized with FTIR. Results showed that the hybrid flocculant had a complex reaction with the dye wastewater, and the main decolorization mechanism was charge neutralization and adsorption bridging capacity. The UV scanning results indicated an adsorption peaks shift and an absorbance decreases, which further explained the main mechanism above. At the same time, it also indicated the ether linkage and —NH2 of disperse violet were destroyed and replaced by hybrid flocculant, and the -SO3 , Cl- of reactive brilliant red were also replaced. The study will provide a new method in decolorization effiency and decolorization mechanism for the new inorganic-organic hybrid polymer flocculant. And it has significant practical meaning and application value.

Objective: To elucidate the correlation between the single nucleotide polymorphism of CKLF-like MARVEL transmembrane member 5 (CMTM5) gene rs723840 and the occurrence of high on aspirin platelet reactivity (HAPR)., Methods: The present study is a case-control study. A total of 210 hospitalized patients in Peking University First Hospital were enrolled. Aspirin response was assessed by 0.5 g/L arachidonic acid (AA)-induced platelet aggregation ratio (PR), and ≥ 3/4 quartile of PR of the population was defined as HAPR. Accordingly all the enrolled 210 coronary artery diseases (CAD) patients were divided into HAPR group and No-HAPR group. The genotypes were determined by polymerase chain reaction (PCR) and sequencing analysis for rs723840 of CMTM5 gene., Results: The genotype frequencies in rs723840 C>T of CMTM5 gene conformed well to the Hardy-Weinberg equilibrium in both HAPR group and No-HAPR group. Between the two groups, the genotypes frequencies in HAPR and No-HAPR groups were 48.4%, 51.6%, 0.0% and 73.7%, 22.9%, 0.034%, respectively (P=0.004). The C, T allele frequencies were significantly different in the two groups (P=0.031,OR=0.501, 95% CI: 0.264-0.947)., Conclusion: Our study finds a significant correlation between CMTM5 gene rs723840 polymorphism and high on aspirin platelet reactivity.

Objective: To elucidate the correlation between urinary 11-dehydro-thromboxane B2 (11dhTxB2) and clinical efficacy of aspirin treatment in patients with type 2 diabete and coronary artery disease (CAD)., Methods: In this prospective cohort study, 169 aged patients with type 2 diabete accompanying CAD in Peking University First Hospital were enrolled. The level of urinary 11dhTxB2 was detected using enzyme-linked immuno-sorbent assay. Low aspirin response or high on aspirin platelet reactivity (HAPR) was defined as urinary 11dhTxB2>1 500 ng/g. All the included patients were divided into two groups based on the results, HAPR group and No-HAPR group., Results: Baseline urinary 11dhTxB2 of the patients with type 2 diabete accompanying CAD was (3 687±3 052) ng/g, while the urinary 11dhTxB2 was (1 954±859) ng/g in patients after 100 mg/d aspirin treatment (P<0.001). Prevalence of HAPR in patients with type 2 diabete accompanying CAD were 32.5%. Within a mean follow-up time of 12 months, the outcomes occurred more frequently in HAPR group than in No-HAPR group (P<0.05)., Conclusion: Urinary 11dhTxB2 can be recognized as an effective indicator in evaluating aspirin clinical efficacy of patients with type 2 diabete accompanying CAD.

Background and Aims: Hyperuricemia is an important risk factor for atherosclerosis, yet the potential mechanisms are not well understood. Migration and adhesion of leukocytes to endothelial cells play key roles in initiation and development of atherosclerosis. We investigated monocyte-endothelial cell interactions and potential signaling pathways under uric acid (UA)-stimulated conditions., Methods and Results: Primary human umbilical vein endothelial cells (HUVECs) were cultured and exposed to different concentrations of UA for various periods. Experimental hyperuricemia rat models were established. Expression of chemoattractant protein-1 (MCP-1), interleukin 8 (IL-8), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were evaluated. Monocyte-endothelial cell interactions were elucidated by chemotaxis and adhesion assays, and nuclear factor-kappa B (NF-κB) pathway was studied using fluorescent microscopy and electrophoretic mobility shift assay. Results showed that high concentration of UA stimulated generation of chemokines and adhesion molecules in ex vivo and in vivo experiments. Migration and adhesion of human monocytic leukemia cell line THP-1 cells to HUVECs were promoted and activated NF-κB was significantly increased. UA-induced responses were ameliorated by organic anion transporter inhibitor probenecid and NF-κB inhibitor BAY11-7082. It was also observed that human endothelial cells expressed urate transporter-1, which was not regulated by UA., Conclusion: High concentration of UA exerts unfavorable effects directly on vascular endothelium via the NF-κB signaling pathway, the process of which requires intracellular uptake of UA., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Clostridium difficile carriage has been considered as a potential source for the deadly infection, but its role in cancer patients is still unclear. We aimed to identify the clinical and immunological factors that are related to C. difficile carriage in Chinese cancer patients., Methods: A total of 400 stool samples were collected from cancer patients who received chemotherapy in three hospitals of eastern China. Bacterial genomic DNA was extracted and two toxin genes (tcdA and tcdB) were detected. PCR ribotyping was performed using capillary gel electrophoresis. Concentrations of prostaglandin E2 (PGE2), transforming growth factor beta (TGF-β) and interleukin-10 (IL-10) were measured using enzyme-linked immunosorbent assay (ELISA) kits., Results: Eighty-two (20.5%) samples were confirmed to be C. difficile-positive and positive for tpi, tcdA, and tcdB genes. The C. difficile-positive rates in patients with diarrhea and no diarrhea were 35% and 19.7%, respectively (p = 0.09). Patients who were younger than 50 years old and were hospitalized for at least 10 days had a C. difficile-positive rate as high as 35%. In contrast, patients who were older than 50 years old and were hospitalized for less than 10 days had a C. difficile-positive rate of only 12.7% (p = 0.0009). No association was found between C. difficile carriage and chemotherapy regimen, antibiotic drug use, or immunosuppressive mediators, such as prostaglandin E2 (PGE2), transforming growth factor beta (TGF-β), or interleukin-10 (IL-10). Twelve ribotypes of C. difficile were identified, but none of them belonged to ribotype 027., Conclusions: We conclude that younger patients and those with longer hospitalization stays may be more prone to C. difficile carriage. Studies of larger populations are warranted to clarify the exact role of C. difficile carriage in hospitalized cancer patients in China.

Ethnopharmacological Relevance: The decoction of American Ginseng and Corydalis Tuber has been widely used for treatment of cardiovascular diseases due to their anti-ischemic and anti-arrhythmic effects. The aim of this study is to evaluate the anti-apoptotic effect of Shenyuan, which is composed of the bioactive components extracted from the mixture of American Ginseng and Corydalis Tuber, and to explore potential mechanisms involved in the regulation of apoptosis., Materials and Methods: A porcine model of acute myocardial infarction (AMI) was established by ligation of the left anterior descending coronary artery. Thirty-eight pigs were randomized into six groups: Group S, sham (n=6); Group C, AMI controls (n=8); Group L, AMI+low-dose Shenyuan (240 mg/kg·d, n=6); Group M, AMI+moderate-dose Shenyuan (320 mg/kg·d, n=6); Group H, AMI+high-dose Shenyuan (400 mg/kg·d, n=6); Group B, AMI+Metoprolol Tartrate (1 mg/kg·d, n=6). The treatment of Shenyuan or Metoprolol started one week before AMI and continued for another two weeks after AMI., Results: Treatment with all doses of Shenyuan as well as Metoprolol produced a significant decrease of apoptotic index (P < 0.05), which was confirmed by TUNEL staining method. This anti-apoptotic effect was accompanied by less release of cardiac enzymes and limit of infarct size. In Group H, levels of MDA, 8-iso-prostaglandin F2α, GRP78/bip, calregulin, CHOP/GADD153, Bax, caspase-3, cleaved caspase-3 and activity of caspase-3 were reduced, while GSH, SOD, Bcl-2 and the Bcl-2/Bax ratio were significantly increased (P < 0.05). In groups M and L, some results did not show statistical difference. There was no statistical difference in cardiac function between treatment groups and Group C., Conclusion: Shenyuan treatment significantly inhibited ERS and oxidative stress, balanced the Bcl-2/Bax ratio, suppressed activation of caspase-3, and finally exerted an anti-apoptotic effect in pigs with a large anterior wall AMI. This was accompanied by less release of cardiac enzymes and limit of infarct size. Shenyuan treatment inhibited apoptosis and may have a therapeutic role in improving the natural process of AMI., (© 2013 Published by Elsevier Ireland Ltd.)

Objective: To deepen the understanding about Heyde's syndrome by investigating the clinical characteristics and prognosis of the patients with aortic valve stenosis complicating with gastrointestinal bleeding., Methods: Patients with aortic valve stenosis and gastrointestinal bleeding coincidently admitted to our hospital from 2001 to 2011 were retrieved and analyzed., Results: In all the 443 157 in-patients, 474 patients were diagnosed with aortic valve stenosis (0.11%, 474/443 157) and 14 patients (9 males and 5 females, aged 53-87 years old) with gastrointestinal bleeding coincidently(2.95%, 14/474). Among the 14 patients, 3 were moderate aortic valve stenosis, 11 severe aortic valve stenosis. The aortic valve peak flow velocity was 324-709 (480.54 ± 188.25) cm/s and the mean aortic valve pressure gradient was 21.04-91.56 (56.93 ± 29.90) mm Hg(1 mm Hg = 0.133 kPa).Heavy gastrointestinal bleeding was manifested in all the 14 patients with 1 of haematemesis and 13 of hematochezia.Hemoglobin (Hb) and red blood cell (RBC) count were significantly lower than the normal range [(69 ± 28) g/L and (2.71 ± 2.04)×10(12)/L, P < 0.05]. Their mean corpuscular volume(MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet(PLT) count, prothrombin time (PT) and international normalized ratio (INR) were in normal range [(90.21 ± 2.94) fl, (29.39 ± 1.99) pg, (327.57 ± 14.82) g/L, (185.13 ± 22.55)×10(9)/L, (11.4 ± 1.04) s and 1.22 ± 0.44, respectively]. Among all the 14 patients, 13 were over 65 years old and they all accepted gastrointestinal imaging (13/14).Vascular malformation of intestine was found in 6 patients with 4 lesions located in descending colon and 2 located in sigmoid colon.Hemorrhage foci were found in 2 patients with one of colon cancer, and another of duodenal ulcer, while no definite hemorrhage foci were found in the other 11 patients. A total of 6 patients with severe aortic valve stenosis underwent aortic valve replacement (AVR) successfully (6/11) and no recurrent gastrointestinal bleeding was ever found. Conservative treatment was performed in the other 5 patients with severe aortic valve stenosis (5/11) and resulted in sudden death in 2 patients (2/5)., Conclusions: Prompt echocardiography and gastrointestinal endoscopy should be performed in the elderly patients with obscure gastrointestinal bleeding to facilitate the early diagnosis and treatment of Heyde's syndrome. AVR is a fundamental procedure to improve the prognosis of Heyde's syndrome.

Aim: To investigate the expression profile of microRNAs in inoperable advanced non-small cell lung cancer (NSCLC) patients receiving chemotherapy and the potential relevance of microRNAs to clinicopathological characteristics and prognosis., Methods: Serum samples were taken from 260 inoperable advanced NSCLC patients and 260 healthy individuals. All the patients received cisplatin-based chemotherapy, including NP/NC regimens, GP/GC regimens, and TP/TC regimens. The serum levels of microRNAs (miR-125b, miR-10b, miR-34a and miR-155) were determined by quantitative real-time PCR., Results: Serum levels of the 4 microRNAs examined in NSCLC patients were significantly increased as compared with healthy individuals. The levels of miR-125b and miR-155 were changed in a similar pattern: the patients with stage IV disease had the highest one, while the patients with stage III A and stage III B disease showed similar increased levels. The levels of miR-10b and miR-34a in the patients with different stages were increased to similar extent. The level of miR-125b in poorly differentiated cancer was significantly higher than those in well and moderately differentiated cancers, while the levels of miR-10b, miR-34a, and miR-155 did not significantly differ with cancer differentiation. Among the 4 microRNAs examined, only miR-125b was significantly associated with therapeutic response, exhibiting higher expression levels in non-responsive patients. Furthermore, the high level of miR-125b was significantly correlated with poor patient survival. A multivariate Cox regression analysis showed that the expression level of miR-125b was an independent prognostic marker in NSCLC patients., Conclusion: Our results suggest that miR-125b is a potential diagnostic or prognostic biomarker for NSCLC. This finding has important implications for development of targeted therapeutics to overcome chemotherapeutic resistance in NSCLC.

Objective: To explore clinical and laboratory factors associated aspirin response, and the association between gastrointestinal bleeding and aspirin response in aged patients., Methods: A total of 136 patients aged 60 and over [mean age (74.9 ± 7.0) years] with ischemic heart disease and at high risk for ischemic heart disease were included. Arachidonic acid induced platelet aggregation (AA-Ag) was measured before and at 7(th) day after taking aspirin (100 mg/d). Patients were followed for 6 months and incidence of gastrointestinal bleeding was obtained., Results: Post-treatment AA-Ag was significantly reduced compared to baseline (13.29% ± 5.52% vs. 73.20% ± 7.32%, P < 0.05). A heterogeneous distributed post-treatment AA-Ag was observed (range 0.42% to 30.50%). Post-treatment AA-Ag was positively correlated with baseline AA-Ag (r = 0.493, P < 0.01). The level of post-treatment AA-Ag was significantly higher in the fourth quartile group at baseline than in the others quartile groups at baseline. Patients aged 80 years and over had significantly lower post-treatment AA-Ag (10.25% ± 4.68%) compared with patients of 60 - 69 years (13.96% ± 5.20%) and of 70 - 79 years (13.73% ± 5.48%, all P < 0.01). The incidence of patients in the lowest quartile of post-treatment AA-Ag was significantly higher in patients ≥ 80 years (38.24%) than in patients of 60 - 69 years (11.1%) and of 70 - 79 years (24.0%). Multiple variable analysis revealed post-treatment AA-Ag was significantly influenced by baseline AA-Ag, ≥ 80 years old, diabetes mellitus and acute coronary syndrome. We observed 4 (2.9%) mild gastrointestinal bleeding during follow up. Post-treatment AA-Ag was in the lowest quartile in 3 patients with mild gastrointestinal bleeding., Conclusions: Increased baseline platelet reactivity as well as diabetes mellitus and acute coronary syndrome are associated with low aspirin response in the aged patients. Aspirin response is significantly higher in very old patients.

A combination of nucleos(t)ides and hepatitis B immunoglobulin (HBIg) has been found to be effective for the prevention of hepatitis B viral (HBV) reinfection after liver transplantation (LT), but its administration is costly, and not always available. We report the case of a male, 33-year-old cirrhotic patient who has tested positive for serum HBsAg, and HBeAg, with 9.04 × 10(7) copies/mL of HBV DNA. He suffered from acute liver failure and was near death before undergoing emergency LT. No HBIg was available at the time, so only lamivudine was used. He routinely received immunosuppression medication. Serum HBV DNA and HBsAg still showed positive post-LT, and the graft re-infected. Hepatitis B flared three months later. Adefovir dipivoxil was added to the treatment, but in the 24(th) mo of treatment, the patient developed lamivudine resistance and a worsening of the hepatitis occurred shortly thereafter. The treatment combination was then changed to a double dosage of entecavir and the disease was gradually resolved. After 60-mo of post-LT nucleos(t)ide analogue therapy, anti-HBs seroconverted, and the antiviral was stopped. By the end of a 12-mo follow-up, the patient had achieved sustained recovery. In conclusion, the case seems to point to evidence that more potent and less resistant analogues like entecavir might fully replace HBIg as an HBV prophylaxis and treatment regimen.

Heat shock proteins (HSPs) are potent protectors of cellular integrity against environmental stresses, including toxic microbial products. To investigate the mechanism of HSP-70 cell protection against bacterial lipopolysaccharide (LPS), we established a stable HSP-70 gene-transfected RAW 264.7 murine macrophage model of LPS-induced cell death. Bacterial LPS increases the activity of sphingosine kinase 1 (SK1), which catalyzes formation of sphingosine-1-phosphate (S1P). S1P functions as a critical signal for initiation and maintenance of diverse aspects of immune cell activation and function. When mouse macrophages were incubated with Escherichia coli LPS (1 microg/ml) and sphingosine kinase inhibitor (SKI, 5 microM), 90% of cells died. Neither LPS nor SKI alone at these doses damaged the cells. The LPS/SKI-induced cell death was partially reversed by overexpression of HSP-70 in gene-transfected macrophages. The specificity of HSP-70 in this reversal was demonstrated by transfection of HSP-70-specific siRNA. Down-regulation of HSP-70 expression after transfection of siRNA specific for HSP-70 was associated with increased LPS/SKI-induced cell damage. Overexpression of human or murine HSP-70 (HSPA1A and Hspa1a, respectively) increased both cellular SK1 mRNA and protein levels. Cellular heat shock also increased SK1 protein. These studies confirm the importance of SK1 as a protective moiety in LPS-induced cell injury and demonstrate that HSP-70-mediated protection from cells treated with LPS/SKI is accompanied by upregulating expression of SK1. HSP-70-mediated increases in SK1 and consequent increased levels of S1P may also play a role in protection of cells from other processes that lead to programmed cell death., (Published by Elsevier Inc.)

Objective: To evaluate the predictive value of Holter ECG recordings for patients with moderate-severe obstructive sleep apnea and hypopnea syndrome (OSAHS)., Methods: Holter recordings was performed in 76 patients who were diagnosed OSAHS by polysomnography (PSG) within one month from Jan. 2008 to July 2009 in our hospital. Twenty-eight patients were identified as mild OSAHS (AHI < or = 20) and forty-eight patients were moderate-to-severe OSAHS (AHI > 20). The indexes of heart rate variability (HRV), total scores of thirteen sleep apnea risk indexes of Holter recordings and BMI were analyzed by bivariate Logistic regression analysis., Results: Clinical features (eg. Gender, age, complicated with hypertension, coronary heart disease, diabetes mellitus, hyperglycemia, and taken beta-blocker), total scores, the sum of thirteen sleep apnea risk scores collected by Holter recordings (5.64 + or - 2.33 vs. 6.42 + or - 2.22, respectively, P > 0.05) were similar between patients with mild OSAHS and moderate-to-severity OSAHS. VLF/Total Power > 70%, the difference of daytime/nighttime LF Power < -70 and BMI were independent predictors of moderate-to-severe OSAHS with OR 3.98 (1.087 - 14.596), 3.69 (1.106 - 12.285) and 1.28 (1.062 - 1.544), respectively (all P < 0.05)., Conclusions: VLF/Total Power and the difference of daytime/nighttime LF Power and BMI could be used as screening parameters to recognize patients with moderate-to-severe OSAHS.

This article, introduces setting up of reflectance confocal microscope which is divided into four parts: optical system, scanning system, detecting system and software controlling system. This reflectance confocal microscope realizes in vivo epidermis tissue imaging in mouse skin as well as disease diagnosis related cell parameters measurement.

Objective: To analyze the relationship between plasma level of cortistatin(CST) and coronary heart disease(CHD) and the factors that influence the level of CST., Methods: Plasma levels of CST were measured using ELISA method. The clinical data and the levels of CST of 40 healthy subjects and 39 CHD patients before and 1 d after percutaneous coronary intervention (PCI) were compared. And the factors that influenced the CST level were analyzed., Results: The CST levels of CHD group before or 1 d after PCI were significantly higher than those of the control group (1.97+/-1.12 and 2.01+/-0.77 vs 1.21+/-0.27, P<0.01);The procedure of PCI didn't influence the CST levels(1.97+/-1.12 vs 2.01+/-0.77, P>0.05);There was no correlation between CST levels and fasting blood glucose(FBG), high sensitivity C-reactive protein (hsCRP), left ventricular ejection fraction(LVEF), severity of lesions of coronary arteries or history of hypertension; The levels of triglyceride(TG) and total cholesterol(TCHOL) negatively correlated with CST levels(beta=-2.594, P<0.05;and beta=-0.650, P<0.01), but history of diabetes mellitus(DM) or myocardial infarction(MI) positively correlated with CST levels(beta=4.149 and 6.430, P<0.05).The CST level of subgroup of CHD with DM or MI was higher than that of CHD without DM or MI, but the difference was not significant(2.07+/-10.7 vs 1.85+/-1.20; 2.20+/-1.53 vs 1.79+/-0.66, P<0.05)., Conclusion: Patients with CHD have higher plasma levels of CST. CST may play an important role in the procedure of CHD.

Objective: To study the effects of chemokine-like factor 1(CKLF1)-plasmid transfer on cardiac function in a rat acute myocardial infarction (AMI) model., Methods: Thirty male SD rats were randomly devided into 3 groups. One hundred micrograms of CKLF1-plasmid, empty plasmid or saline were injected intramuscularly with in vivo electroporation, respectively. Rats were subjected to left coronary artery ligation on the 6th day after gene transfer. Ultrasonic cardiography and hemodynamics were conducted and evaluated on the 22nd day after gene transfer. Then, the animals were sacrificed for determination of percentage of myocardial infarcion., Results: The left ventricular ejection fraction in CKLF1 group (67.02% +/- 12.24%) was significantly higher than that in the saline group (43.64% +/- 7.82%) and empty plasmid group (47.56% +/- 4.10%), P<0.05. Fractional shortening of left ventricle in CKLF1 group (33.83% +/- 10.15%) was higher than that in saline group (18.49% +/- 3.96%) and empty plasmid group (20.85% +/- 2.24%), P<0.05. The maximal velocity of left ventricular pressure ascensus was higher in CKLF1 group [(5 720.01 +/- 826.32) mmHg/s, 1 mmHg=0.133 kPa] than in saline group [(3 955.69 +/- 685.91) mmHg/s] and in empty plasmid group [(4 412.03 +/- 500.74) mmHg/s)], P<0.05. And the maximal velosity of left ventricular pressure descensus was higher in CKLF1 group [(4 636.23 +/- 407.17) mmHg/s] than in saline group [(2 984.82 +/- 615.24) mmHg/s] and in empty plasmid group [(2 963.87 +/- 419.36) mmHg/s], P<0.05. While the percentage of myocardial infarction in CKLF1 group (29.63% +/- 3.93%) was smaller than that in saline group (38.01% +/- 5.48%) and in empty plasmid group (37.50% +/- 6.33%), P<0.05., Conclusion: CKLF1 gene transfer can limit the mass of myocardial infarction and improve post-infarction cardiac function.

Objective: To evaluate the value of gray-scale ultrasound, contrast-enhanced ultrasound and multislice spiral CT in early and differential imaging diagnosis of small hepatocellular carcinoma (SHCC)., Methods: This study included 35 patients with space-occupying lesions in the liver identified by routine ultrasound examination. The hemodynamics of the patients was recorded during the arterial, portal and lag phases using contrast-enhanced ultrasound. The enhancement features of the 3 phases were observed using multislice spiral CT. All the cases were confirmed by pathological examinations., Results: For SHCC diagnosis, gray-scale ultrasound, contrast-enhanced ultrasound and multislice spiral CT showed a sensitivity of 77.8%, 94.4%, and 100%, specificity of 88.2%, 100%, and 94.1%, positive predictive value of 87.5%, 100%, and 94.7%, negative predictive values 78.9%, 94.4%, and 100%, concordance rate of 82.9%, 97.1%, and 97.1% and Younden index of 0.66, 0.94, and 0.94, respectively., Conclusions: Contrast-enhanced ultrasound and multislice spiral CT have significantly greater diagnostic efficacy than gray-scale ultrasound in early and differential diagnosis of SHCC. But in some atypical cases, gray-scale ultrasound, contrast-enhanced ultrasound and multislice CT have to be combined to establish a diagnosis.

Background and Aim: Several models for significant fibrosis or cirrhosis have been introduced for hepatitis C, but are seldom for hepatitis B. The present study retrospectively evaluates the relationship between ultrasonography, blood tests, and fibrosis stage, and constructs a model for predicting compensated cirrhosis., Methods: A total of 653 patients with chronic hepatitis B who underwent liver biopsies, ultrasonographic scanning, and routine blood tests were retrospectively analyzed. The patients were divided into the model set and validation set. Blood tests and ultrasonographic indexes were analyzed statistically. An ultrasonographic scoring system consisting of liver parenchyma, gallbladder, hepatic vessel, and splenomegaly was introduced., Results: There were significant differences between cirrhosis and other fibrosis stages in ultrasonographic indexes of liver parenchyma, gallbladder, hepatic vessel, and splenomegaly. Ultrasonographic scores were significantly different between F4 and other fibrosis, and significantly correlated with fibrosis stage. Apart from alanine aminotransferase and alkaline phosphatase, blood tests and patients' age were correlated with fibrosis, and were significantly different between patients with and without cirrhosis. The model for cirrhosis indexes consisting of ultrasonographic score, patient's age, and variables, including platelet, albumin, and bilirubin predicted cirrhosis with area under receiver-operator curve of 0.907 in the model set and 0.849 in the validation set. Using proper cut-off values, nearly 81% patients could be accurately assessed for the absence or presence of cirrhosis., Conclusion: The model consisting of ultrasonographic score, patients' age, blood variables of platelet, albumin, and bilirubin can identify hepatitis B cirrhosis with a high degree of accuracy. The application of this model would greatly reduce the number of biopsies.

Objective: To investigate the factors influencing the success rate and stability of transient elastography(FibroScan)for assessment of liver fibrosis., Methods: Liver stiffness was assessed using transient elastography in totally 637 subjects including healthy subjects, asymptomatic hepatitis B virus (HBV) carriers, patients with chronic hepatitis B and patients with HBV-related cirrhosis. Of these subjects, 302 received 2 examinations and totalling 939 examinations were performed. In each case, one operator performed 2 consecutive series of 10 validated measurements, or 2 operators performed a series of 10 validated measurements. The factors including gender, age, body mass index (BMI) and the state of diseases were analyzed for their association with the success of the examination. Intraclass correlation coefficient (ICC) was used to evaluate the reproducibility of the operation., Results: Failure of the measurement occurred in 14 cases (2.2%), which was not associated with the age of the subjects and the state of diseases. The success rate of measurement decreased as the BMI increased (t=3.112, P=0.002), and was lower in female subjects (t=-2.193, P=0.029). The intra- and inter-operator stability of liver stiffness measurement was satisfactory, with ICC of 0.970 and 0.847, respectively. But for healthy subjects and asymptomatic HBV carriers, the stability was lower, with ICC of 0.736 and 0.639, respectively. Liver stiffness in patients with liver cirrhosis was positively correlated to complications and Child-Turcotte-Pugh (CTP) score., Conclusion: Liver stiffness measurement has high stability with FibroScan, and high BMI could lower success rate of the measurement. Liver stiffness as measured by FibroScan allows prediction of the liver function and presence of complications in patients with liver cirrhosis.

Objective: To investigate the related to relapse of chronic hepatitis B (CHB) after recombinant interferon-alpha (rIFN-alpha) treatment., Methods: This investigation involved 523 pathologically confirmed CHB patients including 403 HBeAg-positive and 120 HBeAg-negative patients, who were treated with 5 MU rIFN-alpha subcutaneously thrice a week for 6-25 months. For each patient, serum alanine aminotransferase (ALT) was measured biochemically, serum HBV DNA level detected with quantitative fluorescent PCR, and HBeAg level with enzyme immuoassay every 1-3 months during therapy and every 3-6 months during the follow-up period., Results: Early response to rIFN-alpha treatment was observed in 302 (57.7%) patients at the end of treatment, among whom 39.4% (119/302) suffered relapse during the follow-up for 39.2-/+21.5 months. Age, HBeAg status before treatment, and follow-up duration were the predictive factors for post-treatment relapse. The mean age of patients with CHB relapse was significantly higher than that of the sustained responders (P<0.001), and the relapse rates in HBeAg-negative group (55.8%, 43/77) were significantly higher than that in HBeAg-positive group (33.8%, 76/225) at the end of follow up (P<0.001). The relapse rate and accumulative relapse rates at each year during the follow-up (for 5 years as the longest) differed significantly (P<0.001, P=0.000), but the accumulative relapse rates differed little between the years after the initial 2 of the follow-up (P=0.670). The relapse was not related to the patient's gender, pretreatment serum ALT, HBV DNA, grade of liver inflammation, stage of liver fibrosis, or duration of treatment. In HBeAg-positive patients, however, the mean HBV DNA was significantly higher in relapse group than in sustained response group (P=0.017)., Conclusion: Age, pretreatment HBeAg status, and follow-up duration are independent predictive factors for post-treatment CHB relapse. In HBeAg positive patients, pretreatment serum HBV DNA is also one of the risk factors for relapse.

Objective: To investigate the relapse of patients with chronic hepatitis B (CHB) undergoing first and repeated recombinant interferon-alpha (rIFN-alpha) therapy during long-term follow up., Method: Five hundred and twenty three patients with chronic hepatitis B including 403 hepatitis B e-antigen (HBeAg) positive patients and 120 HBeAg negative ones were treated with 5MU recombinant interferon-alpha 1b (rIFN-alpha1b) subcutaneously thrice weekly for 6 - 25 (median 10) months. For each patient, serum alanine aminotransferase (ALT) was measured biochemically and serum HBV DNA level was detected by fluorescent-quantitative PCR, HBeAg with enzyme immunoassay every 1 - 3 month during therapy and every 3 - 6 month during the follow up period. Some of the individuals who relapsed during the follow-up period were treated with interferon-alpha repeatedly., Results: Ratios of early response to interferon-alpha were similar in HBeAg positive patients (55.8%, 225/403), and HBeAg negative patients (64.2%, 77/120) at the end of naive treatment (chi(2) = 2.633, P = 0.105). 39.4% (119/302) of early responders relapsed during 39 +/- 22-month follow up, and relapse rates in HBeAg negative group (55.8%, 43/77) were higher than those in HBeAg positive group (33.8%, 76/225) at the end of follow up (chi(2) = 19.335, P = 0.000). Divided the follow-up period into six fragments as 1 - 12 months, 13 - 24 months, 25 - 36 months, 37 - 48 months, 48 - 60 months and > or = 61 months, we found that the differences of relapse incidence were significant (chi(2) = 73.518, df = 5, P = 0.000), and accumulative relapse rates were significant too (chi(2) = 32.167, df = 5, P = 0.000) in all follow-up periods. Constituent ratios of HBeAg in relapsed patients of every follow-up period were similar. 57 relapsed individuals (25 in HBeAg positive group and 32 in HBeAg negative group) were retreated with interferon-alpha, and complete response were achieved in all cases at the end of repeated therapy. The relapse rates in HBeAg positive group (52.0%, 13/25) were higher than in HBeAg negative group (21.9%, 7/32) during the follow-up period after the end of retreatment (chi(2) = 5.592, P = 0.018)., Conclusion: Rates of early response to interferon-alpha therapy were similar in HBeAg positive and HBeAg negative patients at the end of nave treatment, and relapse rates in HBeAg negative group were higher than in HBeAg positive group during long term follow-up. Combined response was achieved in all relapse cases received repeated interferon-alpha therapy at the end of retreatment. The relapse rates in HBeAg positive group were higher than in HBeAg negative group during the follow-up period after repeated therapy.

Objective: To investigate the relationship of virological breakthrough and production of neutralizing anti-interferon antibody (NAb) in chronic hepatitis B patients treated with recombinant interferon-alpha (rIFN-alpha)., Method: Four hundred eighty-five patients with histological proven chronic hepatitis B were treated with 5 MU recombinant interferon-alpha 1b (rIFN-alpha1b) thrice weekly for 6-37 months (median 10). Serum HBV DNA, HBeAg and NAb levels of the patients were detected by fluorescent-quantitative PCR, enzymoimmunoassay and antiviral neutralizing biological assay respectively during the therapy., Results: Virological breakthrough occurred in 66 patients (13.6%), and NAb was found in 98 patients (20.2%) of the total 485 patients. The rate of NAb positivity was higher in patients with viral breakthrough than those without it (68.2%, 45/66, vs 12.6%, 53/419, chi(2)=109.06, P < 0.01), and viral breakthrough occurred more in patients with positive NAb than with negative NAb (45.9%, 45/98, vs 5.4%, 21/387, chi(2)=109.06, P < 0.01). The time of the viral breakthrough occurrence and the time of NAb production had a significant correlation (P < 0.01). The occurrence of viral breakthrough was also influenced by the age of patients (P < 0.05) and HBeAg status (P < 0.01) before they were treated., Conclusion: Viral breakthrough occurred in 13.6% of our 485 chronic hepatitis B patients treated with recombinant interferon-alpha. Their viral breakthrough and production of NAb production had a significant correlation.

Objective: To assess the influence of different doses of CKLF1 plasmid on the dynamics and magnitude of the mobilization of the mobilization bone of marrow stem cells in a rat AMI model., Methods: Different doses of plasmid DNA encoding CKLF1 gene, empty plasmid or saline were injected into male SD rats intramuscularly with in vivo electroporation. Rats were subjected to left coronary artery ligation 6 days after gene transfer. Peripheral blood samples were drawn and CD34+ cells were assayed by FACS calibur flow-cytometer. The changes in absolute number of CD34+ cells were evaluated., Results: Expressions of CKLF1 mRNA and protein were detected in the injection site 7 days after gene transfer. Five days after gene transfer, the CD34+ cells numbers in CKLF1 groups were significantly higher than those in empty plasmid group, especially in CKLF1 100 microg group (16.63x10(6)/L vs 4.98x10(6)/L, P<0.01). On the 5-7 days, the CD34+ cell numbers in CKLF1 groups reached the peak and the peak number was 3.88 times that of baseline in CKLF1 100 microg group (P<0.01). After AMI, the cell numbers of 1 day to 7 days were significantly higher than those of the baseline in empty plasmid group and saline group. In comparison to empty plasmid group, CKLF1 groups were associated with still higher numbers of cells 1 day after AMI (P< 0.05), especially in CKLF1 100 microg group (14.61x10(6)/L vs 7.85x10(6)/L, P<0.01)., Conclusion: CKLF1 gene transfer significantly increases the mobilization of CD34+ stem cells in acute myocardial infarction rats.

Objective: To study the causes of poorer antiviral response to neutralizing anti-interferon-alpha antibodies (NA) in male chronic hepatitis B patients treated with recombinant interferon-alpha (rIFN-alpha)., Methods: Two hundred sixty-nine patients (198 males and 71 females) with histologically proven chronic hepatitis B were treated with 5 MU recombinant interferon-alpha 1b (rIFN-alpha 1b) subcutaneously thrice weekly for 6-37 (median 10.0) months. For each patient, serum HBV DNA levels were detected with fluorescent-quantitative PCR, HBeAg with enzymoimmunoassay, and NA with an antiviral neutralizing biological assay during therapy., Results: NA was found in 70 (35.4%) of the 198 males and in 15 (21.1%) of the 71 females during treatment (x2 = 4.894, P = 0.027). At the end of treatment combined-response was achieved in 21 (24.7%) of the 85 NA-positive patients and in 100 (54.3%) of the 184 NA-negative cases (x2 = 20.642). Stratification analysis by NA showed that combined-response rate was significantly lower in males than in females (18.6%, 13/70 vs. 53.3%, 8/15, x2 = 8.024) among NA-positive patients while it was similar in males and in females (50.8%, 65/128, vs. 62.5%, 35/56, x2 = 2.156) among NA-negative patients. In stratification analysis by gender, it was significantly lower in NA-positive patients than in NA-negative ones (18.6%, 13/70 vs. 53.3%, 8/15, x2 = 8.024) among males but there was no significant difference between combined-response rates among females., Conclusion: The poorer antiviral response to recombinant interferon-alpha in male chronic hepatitis B patients than in female patients is related to the neutralizing anti-interferon antibodies.

Objective: To assess the correlation of routine blood and serum biochemical indices with liver histology, and identify the sensitive non-invasive ones indicative of liver inflammation and fibrosis in patients with chronic hepatitis B., Methods: A total of 252 patients were enrolled in this retrospective analysis. The indices including the patients' age, gender, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, globulin, total bilirubin, prothrombin time (PT) and its activity (PTA), WBC, and platelet count were analyzed statistically., Results: The status of liver inflammation was correlated to patients' routine blood indices (P<0.05). Serum AST, total bilirubin, WBC, and platelet count was related significantly to the degree of liver inflammation, but serum ALT and AST alone did not describe exactly the degree of liver inflammation. The status of liver fibrosis was independent of patients' serum ALT, but correlated to other routine blood indices (P<0.05). The patients' age, serum AST, total bilirubin and platelet count had significant relation to the stage of liver fibrosis, and the age, blood PT, total bilirubin and platelet count were significant relevant indices for early liver cirrhosis, and their sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 31.5%, 94.4%, 60.7%, 83.3% and 80.7%, respectively., Conclusions: Single examination of serum ALT and AST does not help much to predict the status of liver test in patients with chronic hepatitis B. Serum AST, total bilirubin, WBC and platelet count are associated with the degree of liver inflammation. The patients' age, serum total bilirubin, AST and platelet count are relevant indices for liver fibrosis, and patients' age, serum total bilirubin, PT, and platelet count provide valuable assistance in confirmation of early liver cirrhosis with high specificity, but not so for screening purpose.

Objective: To investigate the efficacy of interferon-alpha (IFN-alpha) therapy for HBeAg-negative chronic hepatitis B., Methods: Sixty-five Chinese HBeAg-negative chronic hepatitis B patients were treated with 5 MU recombinant rIFN-alpha 1b subcutaneously thrice weekly for 5 to 24 months, followed by 12 months of treatment-free follow-up; one hundred and eighty-eight Chinese HBeAg-positive patients served as controls. For each patient, serum alanine transaminase (ALT) was measured biochemically and serum HBV DNA level was detected with fluorescent-quantitative PCR, HBeAg with enzymoimmunoassay every 1 to 3 months during therapy and during the follow-up period. HBeAg loss (only for HBeAg-positive cases), HBV DNA undetectable, and ALT normalization: the three together were considered a combined response., Results: Rates of combined response were similar in HBeAg-negative patients (58.5%, 38/65) or HBeAg-positive ones at the end of treatment (weighted chi square test, chi2 = 1.878, P<0.05), but were higher at the end of the follow-up period in the HBeAg-negative cases (75.4%, 49/65) (weighted chi square test, chi2 = 4.796, P<0.05). Furthermore, relapse rates at the end of the follow-up period, were also similar in HBeAg-negative patients (15.8%, 6/38) or HBeAg positive (chi2 = 0.205, P>0.05). Combined response was achieved at a median of 6.0 months (2-16 months) of treatment course in HBeAg-negative patients while at a median of 6.0 months (1-22 months) in HBeAg-positive cases (Z = -0.186, P>0.05, by the Wilcoxon rank sum test). The only factor predictive of combined response, by binary logistic regression analysis, was inflammatory activity in the liver biopsy. Gender, age, baseline ALT level, baseline HBV DNA level, and anti-HBe were not predictive factors., Conclusion: Interferon-alpha therapy induces a similar primary and sustained response in HBeAg-negative and in HBeAg-positive chronic hepatitis B patients.