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Purpose: To evaluate the relationship of serum vascular endothelial growth factor (VEGF) levels and ocular manifestations in Chinese patients with POEMS syndrome., Methods: This is a prospective study. Forty-one treatment-naive patients were enrolled from April 2014 to November 2014. Among the 41 patients, 40 had complete ocular examination, spectral domain optical coherence tomography scan, and serum VEGF measurement before treatment and every 3-month interval after lenalidomide and dexamethasone treatment., Results: Twenty-seven (67.5%) patients had optic disk edema (ODE) at baseline. Retinal manifestations included retinal hemorrhage, subretinal fluid, macular edema, and cotton wool spot. The difference in mean serum VEGF concentrations between patients with and without ODE was significant (P = 0.017). Among patients with ODE, there was a significant positive correlation between mean serum VEGF levels and the binocular mean retinal nerve fiber layer thickness (P = 0.008), as well as mean peripapillary retinal thickness (P = 0.020) before treatment. After 3 months to 17 months treatment, mean serum VEGF concentrations decreased significantly (P < 0.001). Mean retinal nerve fiber layer thickness and mean peripapillary retinal thickness decreased significantly (P < 0.001). The remission rate of ODE was 87.5%, and complete remission rate was 58.3%., Conclusion: The ODE is a common manifestation in POEMS syndrome, and raised VEGF might explain the development and mechanism. Systemic treatment could lead to decrease in serum VEGF levels accompanied by regression of ODE.

Early-life stress is a potent risk factor for development of psychiatric conditions such as depression. The underlying mechanisms remain poorly understood. Here, we used the early-life social isolation (ESI) model of early-life stress in rats to characterize development of depressive-like behavior, the role of microglia, levels of histone methylation, as well as expression of glutamate receptor subunits in the hippocampus. We found that depressive-like behavior was induced after ESI as determined by sucrose preference and forced swimming tests. Increased expression of microglial activation marker, Iba1, was observed in the hippocampus of the ESI group, while expression of the microglial CD200 receptor, which promotes microglial quiescence, significantly decreased. In addition, increased levels of proinflammatory cytokines, interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were observed in the hippocampus of the ESI group. Moreover, ESI increased levels of neuronal H3K9me2 (a repressive marker of transcription) and its associated "writer" enzymes, G9a and G9a-like protein, in the hippocampus. ESI also decreased expression of hippocampal NMDA receptor subunits, NR1, and AMPA receptor subunits, GluR1 and GluR2, which are involved in synaptic plasticity, but it did not affect expression of PSD95 and NR2B. Interestingly, treatment with minocycline to block microglial activation induced by ESI inhibited increases in hippocampal microglia and prevented ESI-induced depressive-like behavior as well as increases in IL-1β, IL-6, and TNF-α. Notably, minocycline also triggered downregulation of H3K9me2 expression and restored expression of NR1, GluR1, and GluR2. These results suggest that ESI induces depressive-like behavior, which may be mediated by microglial signaling.

Background: Hypothermia reduces immediate paralysis during surgical repair of aortic aneurysms. However, it is unknown what the impact of hypothermia is on delayed paralysis, a serious complication of this type of surgery., Methods: Sprague-Dawley rats were subjected to occlusion of the descending aorta at different duration under normothermia (38.0±0.5) or hypothermia (33.0±0.5°). Neurologic function was assessed. Motor neuron number, glial activation, and cytokine expression in the spinal cord were examined. Minocycline was administered perioperatively by intraperitoneal injection in the rats subjected to the aorta occlusion., Results: In contrast to normothermia conditions at which immediate paralysis occurred when the duration of aorta occlusion exceeded 11.5min, hypothermia did not induce immediate paralysis if the duration of aorta occlusion was less than 41min. However, delayed paralysis was developed when the duration of aorta occlusion exceeded 18min, and reached peak level when the duration of aorta occlusion was 40min at hypothermia condition. The number of motoneurons was significantly decreased (P<0.05) at 30h postoperation. In addition, microglia was activated, and interleukin-1β and interleukin-6 levels were upregulated, both of which were co-localized in microglia at 24h postoperation in the hypothermia group. Minocycline treatment attenuated the incidence and degree of paralysis but did not decrease the mortality., Conclusions: Hypothermia, a neuroprotective strategy in cardiothoracic surgery, increased the incidence of delayed paralysis through activation of spinal microglia and cytokines. Blocking the activated microglia may be a potential intervention to prevent the incidence of delayed paralysis., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The precursor of brain derived neurotrophic factor (proBDNF), the unprocessed BDNF gene product, binds to its receptors and exerts the opposing biologic functions of mature BDNF. proBDNF is expressed in the peripheral tissues but the functions of peripheral proBDNF remain elusive. Here we showed that proBDNF and its predominant receptor, p75 pan-neurotrophin receptor were upregulated in the nerve fibers and inflammatory cells in the local tissue in inflammatory pain. Neutralization of proBDNF by polyclonal antibody attenuated pain in different models of inflammatory pain. Unilateral intra-plantar supplementation of proBDNF by injecting exogenous proBDNF or ectopic overexpression resulted in pain hypersensitivity and induced spinal phosphorylated extracellular signal-regulated kinase activation. Exogenous proBDNF injection induced the infiltration of inflammatory cells and the activation of proinflammatory cytokines, suggesting that inflammatory reaction contributed to the pro-algesic effect of proBDNF. Finally, we generated monoclonal anti-proBDNF antibody that could biologically block proBDNF. Administration of monoclonal Ab-proBDNF attenuated various types of inflammatory pain and surgical pain. Thus, peripheral proBDNF is a potential pain mediator and anti-proBDNF pretreatment may alleviate the development of inflammatory pain.

Background: In highly complex social settings, an animal's motivational drive to pursue an object depends not only on the intrinsic properties of the object, but also on whether the decision-making animal perceives an object as being the most desirable among others. Mimetic desire refers to a subject's preference for objects already possessed by another subject. To date, there are no appropriate animal models for studying whether mimetic desire is at play in guiding the decision-making process. Furthermore, the neuropharmacological bases of decision-making processes are not well understood. In this study, we used an animal model (rat) to investigate a novel food-foraging paradigm for decision-making, with or without a mimetic desire paradigm., Results: Faced with the choice of foraging in a competitive environment, rats preferred foraging for the desirable object, indicating the rats' ability for decision-making. Notably, treatment with the non-competitive N-methyl-D-aspartate receptor antagonist MK-801, but not with the dopamine D1 or D2 receptor antagonists, SCH23390 and haloperidol, respectively, suppressed the food foraging preference when there was a competing resident rat in the cage. None of these three antagonists affected the food-foraging preference for palatable food. Moreover, MK-801 and SCH23390, but not haloperidol, were able to abolish the desirable environment effect on standard food-foraging activities in complex social settings., Conclusions: These results highlight the concept that mimetic desire exerts a powerful influence on food-foraging decision-making in rats and, further, illustrate the various roles of the glutamatergic and dopaminergic systems in mediating these processes.

Rationale: Pain-related anxiety and depression are well known to be comorbid with chronic pain and adversely affect patient quality of life. Recent studies have shown that anxiety-like behaviors also develop with acute surgical pain, but the effects of general anesthetics on acute pain-related anxiety are unknown., Objective: The present study aimed to compare the effects of different general anesthetics on anxiety-like behaviors that follow formalin-induced acute pain in a rat model., Methods: Formalin-induced acute inflammatory pain was established by intraplantar injection of 1% formalin without anesthesia or with anesthesia using the clinical anesthetics sevoflurane, propofol, or pentobarbital sodium. Anxiety-like behaviors were studied using the open-field test and elevated plus maze. Phosphorylated extracellular signal-regulated kinase (p-ERK) 1/2 expression in the anterior cingulate cortex (ACC) and spinal cord was examined using immunohistochemistry., Results: Anxiety-like behaviors were observed at 24 and 72 h post-formalin injection. Concomitantly, p-ERK 1/2 expression was upregulated in the ACC at 1 and 24 h post-formalin injection. While all three general anesthetics effectively blocked nociceptive responses and activation of ERK in the rat ACC following formalin injection during anesthesia, only sevoflurane inhibited ERK activation in the spinal cord and ACC at 24 h post-injection., Conclusions: This study suggests that sevoflurane, but not intravenous anesthetics, inhibits pain-related anxiety, along with ERK activation in the ACC, probably through inhibition of spinal nociceptive transmission. Intraoperative application of inhaled anesthetics may be a better choice to reduce postoperative anxiety.

Background: Neuropathic pain evoked by nerve injury is frequently accompanied by deterioration of emotional behaviors, but the underlying signaling mechanisms remain elusive. Glutamate (Glu) is the major mediator of excitatory synaptic transmission throughout the brain, and abnormal activity of the glutamatergic system has been implicated in the pathophysiology of pain and associated emotional comorbidities. In this study we used the partial sciatic nerve ligation (PSNL) model of neuropathic pain in rats to characterize the development of anxiety-like behavior, the expression of glutamatergic receptors, and the phosphorylation of extracellular signal-regulated kinase (ERK) in the hippocampus, the region that encodes memories related to emotions., Results: We found that the mechanical withdrawal threshold was significantly reduced and an anxiety-like behavior was increased as determined via open field tests and elevated plus-maze tests at 28 days after injury. No significant differences were found in the ratio of sucrose preference and immobility time detected by sucrose preference tests and forced swimming tests respectively, possibly due to the timing factor. The expression of N-methyl-D-aspartate (NMDA) receptor subtypes NR1 and NR2B, but not NR2A, GluR1, or GluR2 (the main subtype of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA] receptor) in the hippocampus of injured rats was significantly reduced. Moreover, PSNL resulted in decreased phosphorylation of ERK1/2 in the hippocampus. Intriguingly, treatment with D-serine (a co-agonist of NMDA receptor, 1 g/kg intraperitoneally) reduced the anxiety-like behavior but not the mechanical hypersensitivity induced by PSNL., Conclusions: PSNL can induce significant anxiety-like but not depression-like behavior, and trigger down-regulation of NMDA but not AMPA receptors in the hippocampus at 28 days after injury.

Making accurate and timely diagnosis is often challenging when patients with a systemic disease first present with ocular manifestations. The possibility that vasculitis associated with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) can be misdiagnosed as cysticercosis has not been discussed in the literatures.

Depression is a common psychiatric disorder associated with chronic stress. Insulin-like growth factor 2 (IGF2) is a growth factor that serves important roles in the brain during development and at adulthood. Here, the role of IGF2 expression in the hippocampus was investigated in a rat model of depression. A chronic restraint stress (CRS) model of depression was established in rats, exhibiting depression-like behavior as assessed with the sucrose preference test (SPT) and forced swimming test (FST), and with evaluation of the corticosterone levels. Hippocampal IGF2 levels were significantly lower in rats suffering CRS than in controls, as were levels of pERK1/2 and GluR1. Lentivirus-mediated hippocampal IGF2 overexpression alleviated depressive behavior in restrained rats, elevated the levels of pERK1/2 and GluR1 proteins, but it did not affect the expression of pGSK3β, GluR2, NMDAR1, and NMDAR2A. These results suggest the chronic restraint stress induces depressive behavior, which may be mediated by ERK-dependent IGF2 signaling, pointing to an antidepressant role for this molecular pathway.

Opioid addiction is a major social, economic, and medical problem worldwide. Long-term adverse consequences of chronic opiate exposure not only involve the individuals themselves but also their offspring. Adolescent maternal morphine exposure results in behavior and morphologic changes in the brain of their adult offspring. However, few studies investigate the effect of adult opiate exposure on their offspring. Furthermore, the underlying molecular signals regulating the intergenerational effects of morphine exposure are still elusive. We report here that morphine exposure of adult male and female rats resulted in anxiety-like behavior and dendritic retraction in the dentate gyrus (DG) region of the hippocampus in their adult offspring. The behavior and morphologic changes were concomitant with the downregulation of insulin-like growth factor (IGF)-2 signaling in the granular zone of DG. Overexpression of hippocampal IGF-2 by bilateral intra-DG injection of lentivirus encoding the IGF-2 gene prevented anxiety-like behaviors in the offspring. Furthermore, exposure to an enriched environment during adolescence corrected the reduction of hippocampal IGF-2 expression, normalized anxiety-like behavior and reversed dendritic retraction in the adult offspring. Thus, parental morphine exposure can lead to the downregulation of hippocampal IGF-2, which contributed to the anxiety and hippocampal dendritic retraction in their offspring. An adolescent-enriched environment experience prevented the behavior and morphologic changes in their offspring through hippocampal IGF-2 signaling. IGF-2 and an enriched environment may be a potential intervention to prevention of anxiety and brain atrophy in the offspring of parental opioid exposure.

Background: Remifentanil, an ultra-short-acting opioid, is widely used for pain control during surgery. However, regular dose (RD) remifentanil exacerbates postoperative pain in a dose-dependent manner. Recent studies suggest that high-dose (HD) remifentanil offers sustained analgesia in experimental studies. We thus hypothesized that intraoperative administration of high-dose remifentanil may attenuate postoperative pain., Methods: In this prospective, randomized, double blind, controlled clinical study, sixty patients undergoing thyroidectomy (18-60 years-of-age) received an intraoperative infusion of 0.2 (RD group) or 1.2 μg kg(-1) min(-1) (HD group) remifentanil during thyroidectomy. A visual analogue scale (VAS) was used to measure pain intensity. Mechanical pain threshold on the forearm was assessed using von Frey filaments before surgery (baseline), 2 h postoperatively and 18-24 h postoperatively. The primary outcome was to compare the difference of VAS score at different time points after operation and morphine consumption 24 h postoperatively between RD and HD groups. The second outcome was to compare the difference of mechanical pain thresholds in the forearm postoperatively between RD and the HD groups., Results: VAS scores were lower 30 min postoperatively in the HD group (1.29 ± 1.67, 95% CI 0.64-1.94) compared with the RD group (2.21 ± 1.67, 95% CI 1.57-2.84) (t = 3.427, p = 0.0043, RD group vs. HD group). Postoperative morphine consumption was much lower in the HD group compared with the RD group (1.27 ± 1.88 mg vs. 0.35 ± 1.25 mg, p = 0.033). In both groups, mechanical pain threshold was decreased 18-24 h postoperatively (2.93 ± 0.209 Ln(g) vs. 3.454 ± 2.072 Ln(g), p = 0.032 in RD group; 2.910 ± 0.196 Ln(g) vs. 3.621 ± 0.198 Ln(g), p = 0.006 in HD group, 18-24 h postoperatively vs baseline)., Conclusions: Intraoperative administration of high-dose remifentanil decreased VAS scores and morphine consumption postoperatively. Thus, modulation of intraoperative opiates may be a simple and effective method of postoperative pain management., Trial Registration: This trial is registered in ClinicalTrials.gov, with the Name: Effect of Higher Doses of Remifentanil on Postoperative Pain in Patients Undergoing Thyroidectomy, and ID number: NCT01761149.

Previous studies have indicated involvement of the mitogen-activated protein kinase (MAPK) pathway in heterosexual interactions among rats. Very few studies, however, have focused its role in isosexual social interactions. We studied the male rat's isosexual social interactional behavior using (i) the three-chambered social interaction box and (ii) phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2) to localize the brain regions that are activated during isosexual behavior. When faced with the social target side of the box versus the inanimate side, all rats preferred the social target side. Within 10min, isosexual social interactions induced a rapid increase in pERK1/2 expression in the brain, especially the main olfactory epithelial (MOE)-related brain regions. After ZnSO4-induced olfactory deprivation, rats showed no preference for either the social target or inanimate side, with a concomitant decrease in pERK1/2 expression in MOE-related brain regions. Additionally, to determine the role of pERK1/2 in isosexual social interactional behavior, rats were injected intraperitoneally with SL327 (30mg/kg, a MAPK kinase inhibitor). Although SL327 dramatically down-regulated expression of brain pERK1/2, experimental animals also spent significantly more time in the social target side. These results indicate that (i) A brief interacting with a male partner induced rapidly phosphorylated ERK1/2 in the rat's brain. (ii) Destroy the function of MOE abolished the rats' isosexual social interactional behavior. (iii) Suppressed the phosphorylated ERK1/2 in the rats' brain disrupt their normal social behaviour., (© 2013 Elsevier B.V. All rights reserved.)

Purpose: To compare coronary plaque burden, composition, distribution and the degree of coronary artery stenosis in invasive coronary angiography (ICA) diagnosed coronary artery disease (CAD) patients with or without metabolic syndrome (MetS)., Methods: From January 2008 to June 2011, consecutive patients underwent both coronary computed tomography angiography (CCTA) and ICA within three months were enrolled. Patients with history of previous percutaneous coronary interventions (PCI) and coronary artery bypass grafting (CABG) were excluded. Plaque characteristics and maximal luminal diameter stenosis were analyzed on a 16-segment basis as suggested by the American Heart Association classification., Results: The study population consisted of 872 patients [age (60.2 ± 10.0) years, 72.70% males] including 377 patients with MetS and 495 patients without MetS. The median coronary artery calcium score (CACS) was higher in MetS patients than in non-MetS patients [102 (10, 410) vs. 58 (0, 274) , P < 0.01]. Percentage of patients with no coronary artery calcium was significantly lower in MetS group than in non-MetS group [19.63% (74/377) vs. 30.71% (152/495) , P < 0.01], while percentage of patients with severe coronary calcium (CACS ≥ 1000) were significantly higher in MetS than non-MetS group [8.22% (31/377) vs. 4.65% (23/495) , P = 0.03]. The proportion of patients with 1-vessel disease was lower [23.61% (89/377) vs. 36.77% (182/495), P < 0.01], 2-vessel [29.71% (112/377) vs. 22.83% (113/495), P < 0.05] and 3-vessel disease [35.54% (134/377) vs. 24.44% (121/495) , P < 0.01] were higher in MetS group than in non-MetS group. Calcified plaque of LM and the middle and distal coronary artery were significantly higher in MetS group than in non-MetS group (all P < 0.05) ., Conclusions: CAD patients with MetS are associated with severer coronary artery calcium deposition and higher percentage of calcified plaque in the middle and distal coronary arteries and severer obstructive coronary vessels.

Cyclooxygenase (COX)-2 inhibitors are widely used for postoperative pain control in clinical practice. However, it is unknown whether spinal sensitization is involved in the analgesic effects of COX-2 inhibitors on surgical pain. Extracellular signal-regulated kinase (ERK) in the spinal cord is implicated in various types of pain, including surgical pain. The present study investigated the role of spinal ERK signaling in the analgesic effect of the COX-2 inhibitor parecoxib on surgical pain. Surgical pain was produced in rats by surgical incision of the hind paw. Phosphorylated (p)-ERK1/2 expression was determined by immunohistochemistry. Pain hypersensitivity was evaluated by measuring the paw withdrawal threshold using the von Frey test. The selective COX-2 inhibitor parecoxib was delivered 20 min before or 20 min after the incision by intraperitoneal injection. Pretreatment with parecoxib markedly attenuated the pain hypersensitivity induced by incision. However, post-treatment with parecoxib produced minimal analgesic effects. Parecoxib inhibited the increase in spinal p-ERK expression following surgical incision. The present study thus suggests that the COX-2 inhibitor parecoxib exerts its analgesic effect on surgical pain through the inhibition of neuronal ERK activation in the spinal cord. COX-2 inhibitor delivery prior to surgery has more potent analgesic effects, suggesting the advantage of preventive analgesia for post-operative pain control.

Extracellular signal‑regulated kinase (ERK) 1/2 in the spinal cord has been implicated in the development of neuropathic pain and inflammatory pain. However, a limited number of studies have investigated the role of spinal ERK in incisional pain. The present study aimed to determine the role of ERK in the spinal cord in incisional pain. Incisional pain was established in rats by a unilateral hind paw incision. ERK1/2 expression was analyzed by immunohistochemistry. Hypersensitivity to pain was evaluated by measuring the paw withdrawal threshold using the von Frey test. The mitogen‑activated protein kinase kinase (MEK) inhibitor, U0126, was administered 20 min prior to or 10 min following the incision by intrathecal or intraperitoneal injection. Phosphorylated ERK1/2 in the ipsilateral L4‑5 spinal superficial dorsal horn was activated 1 min following the incision, reached its peak level at 5 min and then returned to the basal level 20 min following the incision. Pretreatment, but not post‑treatment with U0126 markedly attenuated the pain hypersensitivity induced by the incision. Therefore, the present study indicates that the transient activation of spinal ERK1/2 contributes to the initiation of pain hypersensitivity following surgical incision.

In visceral pain, anxiety and pain occur simultaneously, but the etiogenesis of this effect is not yet well-described. The anterior cingulate cortex (ACC) is known to be associated with the affective response to noxious stimuli. The aim of the current study is to define the role of ACC extracellular signal-regulated (ERK)-1 and-2 (ERK1/2) activity in the development of pain-related anxiety/depression and the nocifensive response in acetic acid (AA)-elicited visceral pain. The model of visceral pain was created by intraperitoneal (ip) injection of AA to female Kunming mice. We found that AA injection resulted in a dynamic, bilateral ERK1/2 activation pattern in the ACC. Inhibition of ERK1/2 activation 2 hr after AA injection by subcutaneous (sc) injection of the mitogen-activating extracellular kinase (MEK) inhibitor, SL327, had no effect on the nocifensive responses, but did attenuate anxiety-like behavior, as determined by elevated plus-maze and open-field testing results. These data suggest that AA-induced visceral pain activates expression of ACC ERK1/2, which regulates visceral pain-related anxiety, but not the nocifensive response.

In a previous study, we showed that a deep thoracic incision induces the segmental upregulation of interleukin-1β (IL-1β) in the spinal cord. However, whether the cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) are also activated in response to surgical incision remains to be determined. The present study aimed to investigate the expression pattern of TNF-α and IL-6 in the spinal cord following a deep thoracic incision. After surgical incision, the mRNA levels of TNF-α and IL-6 in the thoracic spinal cord were transiently upregulated as determined by real-time polymerase chain reaction (PCR) assay. However, the activation of IL-6 was detected at 1 h postoperatively, which was earlier compared to that of TNF-α, observed at 6 h postoperatively. The activated TNF-α was mainly localized in the neurons, but not in microglia or astrocytes as determined by immunohistochemistry and confocal microscopy. However, the increased IL-6-immunoreactivity was mainly expressed in blood vessels. The differential upregulation of TNF-α and IL-6 induced by incision suggests that the proinflammatory cytokines may play different roles in the development of surgical pain.

Food foraging behavior involves food removing, hoarding, and competitive preying upon other animals. It is also associated with high cognitive functions such as investing effort into decision making, but no established laboratory model is available to detect the behaviors. In the present study, we have developed a novel laboratory rodent model to detect competitive, non-competitive, and no-hurdle foraging conditions that can mimic the corresponding environment in nature. We found that normal rats consistently foraged the food from a food container to the field and spread food into piles in the open field. There was no difference between male and female rats in the amount of foraged food in the competitive, non-competitive, and no-hurdle food foraging tests. The amount of foraged food was consistent each day for five consecutive days with a slight increase in following days. There was no significant difference in the amount of food foraged in the presence or absence of bedding materials. A dramatic decrease of foraged food was found in the rats after administration of haloperidol (dopamine D2 receptor antagonist) in the competitive, non-competitive, and no-hurdle food foraging tests. Treatment with MK-801 (non-competitive N-methy-D-aspartate receptor antagonist) reduced the foraged food in the competitive food foraging test, but did not affect the foraged food in the non-competitive and no-hurdle food foraging tests. Our study provides a simple but consistent analogue of natural food foraging behavior. Our study also suggests that dopaminergic and glutaminergic systems are differentially involved in the food foraging behaviors., (Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.)

Aims: Endothelial cell injury induced by inflammatory factors plays a critical role in the pathogenesis of numerous vascular diseases. MicroRNAs are well known to be implicated in cell proliferation and apoptosis in inflammatory responses; however, it remains to be determined whether microRNAs are associated with tumour necrosis factor (TNF)-α-mediated endothelial cell injury. The aim of the present study was to investigate the role of microRNAs in TNF-α-induced endothelial cell apoptosis., Methods and Results: Microarrays were used to analyse the global expression of microRNAs in TNF-α-stimulated human primary endothelial cells. Expression profiles of the microRNAs were verified using qRT-PCR. After TNF-α treatment, 12 miRNAs were dramatically up-regulated and nine were down-regulated. LNA-anti-miR-23a and pre-miR-23a were found to modulate one of the markedly down-regulated miRNAs, miR-23a, which could in turn increase or attenuate TNF-α-induced endothelial cell apoptosis. Bioinformatics analysis suggested that caspase-7 and serine/threonine kinase 4 are potential targets of miR-23a. LNA-anti-miR-23a enhanced but pre-miR-23a inhibited the activation of caspase-7, serine/threonine kinase 4, and its related signalling caspase-3 after TNF-α treatment; however, neither pre-miR-23a nor LNA-anti-miR-23a had an effect on TNF-α-induced Bcl-2 activation., Conclusion: Our results suggest that miR-23a may be involved in TNF-α-induced endothelial cell apoptosis through regulation of the caspase-7 and serine/threonine kinase 4-caspase-3 pathways.

Objectives: The incidence of fentanyl-induced cough (FIC) during induction of general anesthesia varies around 40% and is undesirable. It increases intracranial, intraocular, and intra-abdominal pressures. This prospective, randomized, double-blind, placebo-controlled study evaluated the effect of dexmedetomidine (DEX) pretreatment on the incidence and severity of FIC., Methods: Altogether 300 patients undergoing elective surgical procedures were randomly allocated into three groups (I, II, III; n = 100) and administered intravenously, over 10 min, 10 mL isotonic saline, DEX 0.5 μg/kg in 10 mL isotonic saline, or DEX 1 μg/kg in 10 mL isotonic saline, respectively. All groups subsequently received a fentanyl (4.0 μg/kg) intravenous push. The incidence and severity of cough were recorded for 1 min after fentanyl administration., Results: The incidence of FIC was 61%, 40%, and 18% in groups I, II, and III, respectively (P < 0.05 for treatment groups II and III versus control group I). There was no significant difference in the severity or onset time of cough, or hemodynamic variables, among the three groups., Conclusions: . Intravenous DEX (0.5 μg/kg or 1 μg/kg) immediately before the administration of intravenous fentanyl (4.0 μg/kg) significantly reduced the incidence of FIC.

Objective: To provide novel spectral domain optical coherence tomography (SD OCT) findings of Vogt-Koyanagi-Harada (VKH) disease as well as new insights into the pathogenesis of this disease., Methods: Detailed SD OCT and fluorescein angiography (FA) findings of 18 consecutive VKH patients (11 women and 7 men) from December 2007 to April 2009 who were in acute uveitic stage at presentation were reviewed. All the patients had been followed up for at least 6 months with reevaluation(s) of SD OCT performed in 10 patients., Results: Intraretinal cysts were found to be located in various layers of the outer retina. In addition to the photoreceptor layer, they could also be found between the outer plexiform layer and the outer nuclear layer, or spanning the external limiting membrane. On FA, intraretinal cysts could be hypofluorescent, normofluorescent, or hyperfluorescent. Some intraretinal cysts had a characteristic FA pattern, in which a small round hypofluorescent area was surrounded by a ring of hyperfluorescence (donut-shaped dye pooling). Subretinal fibrinoid deposit appeared in acute uveitic stage in two severe VKH patients and seemed to develop from subretinal exudates and evolved into typical subretinal fibrosis. Gradual transfiguration/migration and progressive proliferation/pigmentation of the subretinal fibrinoid deposit/subretinal fibrosis was observed in one patient., Conclusions: Intraretinal cysts could form in various layers of the outer retina and may result from extension of choroidal inflammation. Subretinal fibrosis may develop from subretinal exudates in VKH patients and may cause substantial visual impairment.

Objective: To evaluate the fundus manifestation and treatment of Takayasu's arteritis., Methods: Retrospective case series was taken to study the clinical data of 15 patients (30 eyes) diagnosed with Takayasu's arteritis at Peking Union Medical College Hospital from 1992 to 2010. Examinations included visual acuity, slit-lamp, fundus, fundus fluorescein angiography (FFA), large vascular ultrasound, digital subtraction angiography (DSA), erythrocyte sedimentation rate (ESR) and reactive protein C (CRP). All patients were given systemic corticosteroids, immunosuppressive agents and anticoagulants. Three patients (4 eyes) received retinal photocoagulation, and 1 patient (1 eye) received vitrectomy combined with silicone oil tamponade., Results: Fifteen cases aged 13 - 49 years [mean (33.6 ± 11.1) years] were enrolled, including 2 male and 13 female patients. Two patients recognized by initial presentation of impaired vision prior to the diagnosis of Takayasu's arteritis. Visual acuity: light perception -0.05, 6 eyes; 0.1 - 0.5, 4 eyes; 0.6 - 1.0, 5 eyes; and above 1.0, 15 eyes. The fundus examination revealed chronic ischemic retinopathy in 16 eyes characterized by microaneurysms, cotton-wool spots and peripapillary arteriovenous anastomosis, and complicated by vitreous hemorrhage, retinal detachment and proliferative retinopathy at the late stage. There was hypertensive retinopathy in 14 eyes with features of narrow retinal artery, arteriovenous crossing signs and retinal hemorrhage. FFA showed prolonged arm-to-retina circulation time and retinal circulation time, microaneurysms and neovasculature. Six cases were classified as brachiocephalic arteritis, and 9 patients belonged to extensive arteritis. ESR increased in 9 patients and CRP elevated in 5 patients. Capillary non-perfusion areas in 4 eyes subsided after retinal photocoagulation, and retina reattached in 1 eye after vitrectomy with visual acuity improved from light perception to count finger., Conclusions: Fundus manifestation of Takayasu's arteritis is usually characterized by chronic ischemic retinopathy and hypertensive retinopathy, and complications such as vitreous hemorrhage, retinal detachment and proliferative retinopathy occur at advanced stage. The first symptom in some patients can be impaired vision. The prognosis could be improved if ophthalmologists know fundus characteristics of Takayasu's arteritis and give timely and correct diagnosis and treatment.

Objective: To evaluate the correlation between retinal artery atherosclerosis and renal dysfunction and compare their risk factors in an urban population of Beijing., Methods: The non-diabetic adults > 40 years old undergoing annual physical examinations during June 2010 and February 2011 at one medical center were evaluated. Pearson correlation coefficient was calculated between retinal artery atherosclerosis and renal dysfunction. The analyses of multivariate Logistic regression were performed to compare the risk factors of these two diseases., Results: Among 10 191 subjects included, retinal artery atherosclerosis was diagnosed in 1287 (12.6%) and renal dysfunction in 434 (4.3%). And 1.0% of subjects had both two diseases versus 12.2% with retinal artery atherosclerosis alone and 3.3% with renal dysfunction alone. Correlation coefficient was low between two diseases (r = 0.21; P < 0.01). According to the analyses of multivariate Logistic regression, the strongest predictors of retinal artery atherosclerosis were obesity (OR = 2.5, 95%CI 2.0 - 3.2) and hypertension (OR = 2.2, 95%CI 2.0 - 2.6) while advanced age (OR = 3.1, 95%CI 2.8 - 3.5 per 10 year increment) was the strongest factor for renal dysfunction., Conclusion: The low-level correlation and different risk factor profiles between retinal artery atherosclerosis and renal dysfunction indicate different pathogenic mechanisms of two diseases and suggest different preventive strategies.

Reinforcing effects of addictive drugs can be evaluated with the conditioned place preference (CPP) test which involves both the action of drugs and environmental cues. However, the encoded neural circuits and underlying signaling mechanism are not fully understood. In this study, we have used morphine-CPP model in the rat and characterized the role of N-methyl-D: -aspartate (NMDA) receptor and the phosphorylation of extracellular signal-regulated kinase (ERK) in the central nuclei of amygdala (CeA) in the expression of morphine-induced CPP. We have found that morphine repeated pairing treatment causes a significant preference for compartment paired with morphine after 1 day or 7 days post-training, which is associated with increased ERK1/2 phosphorylation (p-ERK1/2, a measure of ERK activity) in the CeA. More than 80% of the positive p-ERK1/2 neurons express NMDA receptor subunit NR1 by double immunofluorescence studies. The infusion of either MEK inhibitor U0126 or NMDA receptor antagonist MK-801 in the CeA not only suppresses the activation of ERK1/2 in the CeA but also abolishes the expression of CPP. These results suggest that the activation of the NMDA receptor-ERK signaling pathway in the CeA is required for the expression of morphine-induced place preference in the rat.

Objective: To evaluate the value of dual-source computed tomography (DSCT) in quantitatively measuring pulmonary arteries and major aortopulmonary collateral vessels in comparison with conventional angiographic (CA) on preoperative patients with pulmonary artery atresia and ventricular septal defect (PAA-VSD)., Materials and Methods: Twenty PAA-VSD patients who had complete imaging data of DSCT, CA and echocardiography (ECHO) studies were retrospectively analyzed. Using final clinical diagnosis as the standard, results of DSCT, CA and ECHO on the detection of cardiac malformations, measurement of diameters of pulmonary artery and collateral vessel, as well as the values of McGoon ratio, pulmonary arterial index (PAI) and total neopulmonary arterial index (TNPAI) were derived and compared., Results: In 20 patients, 51 of 54 (94.4%) cardiac malformations were visualized by DSCT, whereas 42 (77.8%) by ECHO (p = 0.027). Fourteen cases with aortopulmonary collateral vessels were all (100%) detected by DSCT, whereas 5 cases (35.7%) by ECHO (p = 0.001), and 13 cases (92.9%) by CA (p = 0.995). Sixteen cases with confluence of native pulmonary arteries were diagnosed by DSCT, whereas 10 cases by CA (p = 0.024). Measurement of the diameters of pulmonary arteries, collateral vessels, and descending aorta at the level of diaphragm were correlated well between DSCT and CA (r = 0.95-0.99). McGoon ratio (DSCT=1.18 ± 0.60, CA = 1.23 ± 0.64), PAI (DSCT=130.96 ± 99.38 mm²/m², CA = 140.91 ± 107.87 mm²/m²) and TNPAI (DSCT=160.31 ± 125.62 mm²/m², CA = 169.14 ± 122.81 mm²/m²) were calculated respectively, without significant differences between DSCT and CA by paired t-tests (all p > 0.05)., Conclusion: DSCT was efficient for evaluating and measuring native pulmonary artery and aortopulmonary collateral vessels prior to surgical procedures in PAA-VSD patients. Combined with echocardiography, DSCT showed potential to replace CA for evaluating pulmonary artery atresia noninvasively., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: To analyze the diagnostic feature, treatment and prognosis of patients with Cantrell syndrome., Methods: Clinical manifestation, diagnosis, operation and follow-up data of 5 patients with Cantrell syndrome were summarized in this retrospective analysis., Results: The age of the 5 patients was 7 days-76 years, definite diagnosis was made in 3 cases and 2 cases presented feature of incomplete Cantrell syndrome. Three patients with full Cantrell syndrome were correctly diagnosed before operation and confirmed by operation. One patient with incomplete Cantrell syndrome (two-vessel stenosis) received bypass surgery. Another asymptomatic patient with incomplete Cantrell syndrome (apical diverticulum of the left ventricle) does not need operation and is under observation. During follow-up, 1 patient died at 60 months after operation and the remaining 4 patients are alive and well., Conclusions: With the development of modern imaging technology, it becomes easy to make correct diagnose Cantrell syndrome before operation. Prognosis is fine post timely operation and related intervention.

Objective: To analyze the tomographic features of branching vascular networks and polypoidal lesions in patients with polypoidal choroidal vasculopathy (PCV) by spectral domain optical coherence tomography (SD-OCT)., Methods: It was a retrospective case series study. Retrospective review of 63 eyes of 54 patients with PCV identified with indocyanine green angiography (ICGA). Tomographic features of branching vascular networks and polypoidal lesions on SD OCT, ICGA and fluorescein angiography were analyzed., Results: Both branching vascular network and polypoidal lesions were found in 45 eyes on ICGA, branching vascular network only was found in 8 eyes and polypoidal lesions only in 10 eyes. Retinal pigment epithelial detachment (RPED) was found in all 53 eyes with branching vascular networks on SDOCT. Thirty-eight eyes had areas of moderate reflectivity of branching vascular network between the fluctuating retinal pigment epithelium and Bruch membrane. Fifteen eyes had moderate reflectivity of branching vascular network and/or hemorrhage between high doom-like RPED and incomplete Bruch membrane. Solitary polypoidal lesions in 28 patients showed local moderate reflectivity between the RPE and Bruch membrane on SDOCT. Other aggregate polypoidal lesions in 27 patients showed moderate reflectivity between high doom-like RPED and incomplete Bruch membrane., Conclusion: The vascular abnormalities of PCV identified with ICGA were visualized on SD-OCT images as areas of moderate reflectivity between RPE and Bruch membrane.

Objective: To determine the prevalence and risk factors of atherosclerotic lesions in retinal arteries of an urban population undergoing routine physical examinations., Methods: Demographic and clinical information of subjects participating in annual routine physical examinations at Peking Union Medical Center from January to October of 2010 were collected and summarized. Univariate and multivariate Logistic regression analyses were conducted to evaluate the demographic and clinical factors associated with retinal arterial atherosclerosis., Results: Among a total of 17 886 non-diabetic adults evaluated during the study period, retinal arterial atherosclerosis was diagnosed in 1721 (9.6%). There were predominantly grade 1 (88%) and grade 2 (11%) lesions. Prevalence of retinal arterial atherosclerosis increased with age. And traditional risk factors for cardiovascular diseases included overweight or obesity, hypertension, dyslipidemia and elevated fasting serum glucose. In a multivariate Logistic regression model, advanced age, male gender, obesity or overweight, hypertension and dyslipidemia were independently associated with a higher risk of retinal arterial atherosclerosis. Hypertension was prevalent in subjects above 40 years old while overweight or obesity had a high prevalence in all age groups., Conclusion: Retinal arterial atherosclerosis is common in this urban population. And aging, overweight/obesity and hypertension are the dominant risk factors. Routine physical examination is valuable for both the prevention and an early diagnosis of this disease.

Objective: To assess the relationship between central visual acuity and retinal volume of macular fovea in patients with Stargardt disease by spectral-domain optical coherence tomography (SD OCT)., Methods: It was a retrospective case series study. Twenty eyes of 10 patients with Stargardt disease were investigated by three-dimensional spectral-domain optical coherence tomography. SD OCT images were obtained and retrospectively analyzed. The retinal volumes of macular fovea were measured by SD OCT, whose diameters were set as 3 mm and 1 mm separately (volume 3 and volume 1). The retinal thickness of macular fovea (macular thickness) and the width of IS/OS conjunction loss of macular fovea (IS/OS loss) were also measured by SD OCT. We correlated the logMAR BCVA with IS/OS loss, macular thickness, volume 3 and volume 1 by linear regression analysis., Results: LogMAR BCVA was from 0.3 to 1.22. IS/OS loss was from 847 µm to 5306 µm. Macular thickness was from 20 µm to 126 µm. Volume 3 and volume 1 was from 1.06 to 1.76 mm(3) and 0.06 to 0.13 mm(3). LogMAR BCVA correlated with the IS/OS loss (r = 0.695, P < 0.05), macular thickness (r = -0.601, P < 0.05), and volume 3(r = -0.725, P < 0.05). LogMAR BCVA did not correlate with volume 1(r = -0.364, P > 0.05)., Conclusions: SD OCT could demonstrate the retinal structure of Stargardt disease clearly. The retinal volume of macular fovea accessed by SD OCT correlated with the visual acuity of Stargardt disease.

Objective: To evaluate the findings of spectral domain optical coherence tomography (SD-OCT) in patients with idiopathic macular hole (IMH)., Methods: It was a retrospective case series study. Pre- and post-operative data from patients with IMH during 14 months were analyzed retrospectively. The main outcome data included logarithm of the minimal angle of resolution (logMAR) and SD-OCT findings, including the size of the IMH and the disruption of the boundary line between inner segments (IS) and outer segments (OS) of the photoreceptors. The data were analyzed using the statistical software SPSS14.0. The correlation among various data was analyzed by Bivariate correlation. The pre-and post-operative data were compared by paired-samples t-tests., Results: Thirty two eyes of 32 patients were studied. The mean logMAR was 1.16 ± 0.46 (ranged from 0.40 to 2.00), the mean diameter of macular hole was (859.7 ± 292.0) µm (ranged from 332 to 1568 µm). The mean diameter of IS/OS disruption was (1965.1 ± 584.1) µm (ranged from 867 to 3444 µm). In eyes after surgery, the mean logMAR was 0.89 ± 0.46 (ranged from 0.30 to 2.00), the mean diameter of the IS/OS disruption was (1350.4 ± 642.6) µm (ranged from 153 to 2546 µm), both were decreased significantly as compare with the preoperative data (t = 3.384, 6.360; P < 0.05). Preoperative diameter of macular hole (r = 0.583) and IS/OS disruption (r = 0.416) were correlated significantly with postoperative logMAR (P < 0.05)., Conclusions: Preoperative diameter of macular hole and IS/OS disruption play the main role in vision prognosis. The IS/OS disruption is decreased significantly after the operation.

Objective: To investigate the clinical manifestations of patients with pulmonary artery hypertension (PAH) associated with hereditary hemorrhagic telangiectasia (HHT)., Methods: This retrospective analysis summarized the clinical features of 6 patients with PAH associated with HHT hospitalized at department of cardiology in Cardiovascular Institute and Fuwai Hospital between January 2006 and May 2009., Results: The mean age of the 6 patients (3 male) was 34 years (8 - 67 years). Recurrent epistaxis were present in all patients, there were 4 patients with severe PAH and 2 patients with moderate PAH. All of the six patients with PAH associated with HHT were misdiagnosed at the first hospital visit. Clinical symptoms were significantly improved in 4 patients and remained unchanged in 2 patients combined hepatic venous malformation post medical therapy., Conclusions: Misdiagnosis for patients with PAH associated with HHT is a common phenomenon in daily clinical practice. Patients could benefit from the corresponding medical therapy after the establishment of the correct diagnosis.

Objective: To study the correlation of visual acuity and photoreceptor in eyes with persistent cystoid macular edema associated with branch retinal vein occlusion (BRVO)., Methods: It was a retrospective case series study.Medical records of 41 patients (41 eyes) with persistent cystoid macular edema secondary to BRVO diagnosed in Department of Ophthalmology, Peking Union Medical College Hospital from January 2008 to January 2010 were studied retrospectively. On the images obtained by spectral-domain OCT, the thickness of foveal neurosensory retina and photoreceptor layer that was beneath the foveal cystoid spaces, and the transverse length and height of foveal cystoid spaces were measured. The status of the junction between inner and outer segments of the photoreceptors (IS-OS) in the fovea was also assessed. The correlations between the parameters above and visual acuity were analyzed., Results: The average foveal neurosensory thickness was (484.71 ± 131.86) µm, the photoreceptor layer thickness was (92.04 ± 45.53) µm and the size of foveal cavity was 772.59 µm × 362.17 µm. By the Spearman's rank correlation analysis, among the parameters above, only photoreceptor layer thickness showed correlation with logMAR visual acuity (r = -0.373, P = 0.016), while other parameters showed no correlation with logMAR visual acuity. Cases were classified as three groups according to the status of IS-OS layer: continuous group (8 cases), discontinuous group (19 cases) and interrupted group (14 cases). LogMAR visual acuity in these eyes with an interrupted IS-OS line in the fovea was significantly worse than that in eyes with a continuous or discontinuous IS-OS line (P = 0.030 and 0.003, respectively). There was no statistical difference between continuous and discontinuous group (P = 0.750)., Conclusions: In patients with persistent cystoid macular edema associated with BRVO, the thickness of the foveal photoreceptor layer are positively associated with visual acuity, and the eyes without IS-OS layer have worse visual acuity than eyes with IS-OS layer.

Differentiation of human embryonic stem cells (hESCs) into hematopoietic lineages using various methods has been reported. However, the phenotype that precisely defines the hematopoietic progenitor compartment with clonogenic activities has yet to be determined. Here, we measured and characterized progenitor function of subfractions of cells prospectively isolated from human embryoid bodies (hEBs) during hematopoietic differentiation basing on surface markers CD45, CD34, CD43, and CD38. We report that hematopoietic progenitors predominantly resided in the CD45(+) subset. CD43(+) cells lacking CD45 expression were largely devoid of progenitor activity. However, progenitor activity and multipotentiality was more enriched in CD45(+) cells co-expressing CD43. CD45(+) subset co-expressing CD34 but lacking CD38 expression (CD45(+)CD34(+)CD38(-)) were further enriched for CFU capacity compared to the CD45(+)CD34(+)CD38(+) subset. Our study demonstrates a role of CD43 in enriching hematopoietic progenitors derived from hEBs and reveals a hierarchical organization of hESC-derived hematopoietic progenitor compartments defined by phenotypic markers.

Objective: To determine the optimal contrast injection protocol for 64-MDCT coronary angiography., Materials and Methods: One hundred and fifty consecutive patients scheduled to undergo retrospectively electrocardiographically gated 64-MDCT. Each 30 patients were assigned to use a different contrast protocol: group 1: uniphasic protocol (contrast injection without saline flush); group 2: biphasic protocol (contrast injection with saline flush); group 3A, 3B and 3C: triphasic protocol (contrast media+different saline diluted contrast media+saline flush). Image quality scores and artifacts were compared and evaluated on both transaxial and three-dimensional coronary artery images among each contrast protocol., Results: Among the triphasic protocol groups, group 3A (30%:70% contrast media-saline mixture was used in second phase) used the least contrast media and had the least frequency of streak artifacts, but there were no significant differences in coronary artery attenuation, image quality, visualization right and left heart structures. Among the uniphasic protocol group (group 1), biphasic protocol group (group 2) and triphasic protocol subgroup (group 3A), there were no significant differences in image quality scores of coronary artery (P=0.18); uniphasic protocol group had the highest frequency of streak artifacts (20 cases) (P<0.05) and had the most amount contrast media (67.0+/-5.3 ml); biphasic protocol group had the least amount of contrast media (59.9+/-4.9 ml) (P<0.05) and had the highest attenuation of left main coronary artery and right coronary artery (P<0.01), but had the least amount of clear visualization right heart structure (6 cases); triphasic protocol group (group 3A) had the most amount of clear visualization right heart structures (29 cases) were the most among the three groups (P<0.05)., Conclusion: Biphasic protocol are superior to the traditional uniphasic protocols for using the least total contrast media, having the least Streak artifacts and without image quality degradation. However, it is also important to visualize the right atrium and ventricle, so triphasic protocol (30%:70% contrast media-saline mixture was used in second phase) should be used for 64-MDCT coronary CT angiography., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

In spite of the fact that brain derived neurotrophic factor (BDNF) has been reported to be implicated in the development of visceral pain, it remains to be determined whether the role of BDNF in pain is gender dependent. The present study investigated the effect of BDNF on visceral pain in different gender rats. A model for visceral pain was established by intraperitoneal (i.p.) injection of acetic acid (AA) into Sprague-Dawley rats: males, females and females with an ovariectomy (OVX). The pain behavior index was assessed by counting the number of abdominal contractions for 60min after i.p. injection of AA. Anti-BDNF antibody, or BDNF, was administered 1h before the AA injection to examine the role of BDNF in visceral pain. After the AA injection, the number of abdominal contraction was dramatically increased in all rats but females showed more severe pain behavior than males. The higher sensitivity to AA-induced nocifensive response was attenuated by OVX. Pretreatment with anti-BDNF antibody significantly exacerbated the nocifensive response in males but attenuated it in females. While exogenous BDNF administration did not alter AA injection-induced nocifensive response in females, BDNF pretreatment attenuated the nocifensive response in males but exacerbated it in females with OVX. The present study suggests there is a gender dichotomy in visceral pain induced by AA injection. In addition, the modulation of visceral pain by BDNF is also sex dependent, i.e., BDNF facilitates the visceral pain in female rats but displays an opposite effect in male rats. Our results may have important implications in the management of clinical pain., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: To describe features of vitreomacular traction syndrome (VMT) on three-dimensional (3D) spectral-domain optical coherence tomography (SD OCT)., Methods: Eighteen eyes of 18 patients with VMT were diagnosed by SD OCT. SD OCT images were obtained and retrospectively analyzed. These VMT cases were defined as focal type or broad type by the region of the vitreous attachment to the macula. The relationship between the logMAR best corrected visual acuity (BCVA) and the retinal thickness of macular fovea was evaluated by linear regression analysis., Results: SD OCT provided detailed 3D images of VMT and revealed information about the extent of vitreomacular traction. Focal VMT was seen in 14 eyes. Broad VMT was seen in four eyes. Eight cases had concurrent epiretinal membrane in the areas surrounding the fovea. Two cases had concurrent full thickness macular hole and two cases had concurrent lamellar macular hole. LogMAR BCVA correlated with the retinal thickness of macular fovea (r = 0.616, P = 0.007, linear regression analysis)., Conclusions: SD OCT allows good visualization of the architectural morphology of the vitreous and retina in vitreomacular traction syndrome. It is useful and irreplaceable for the diagnosis and follow-up of VMT.

The role of affective dimension in the postoperative pain is still poorly understood. The present study investigated the development of anxiety-like behavior and amygdala sensitization in incisional pain. Using hind-paw incision model in rats, we showed that surgical incision induced the anxiety-like behavior as determined by elevated plus-maze and open-field tests. Intraperitoneal (IP) morphine administration reversed mechanical allodynia and anxiety-like behavior in a dose-dependent manner. Gabapentin also partially reduced incision-evoked mechanical allodynia and anxiety-like behavior in a dose-dependent manner. After incision, the expression of phosphorylated cAMP response elements (CRE-) binding protein (p-CREB) was transiently upregulated in the central and basolateral nuclei in the bilateral amygdala. The upregulation of p-CREB was inhibited by morphine and gabapentin. The present study suggested that surgical incision could induce anxiety and amygdala sensitization that can be inhibited by morphine and gabapentin. Thus treatment of surgery-induced affective disturbances by morphine and gabapentin may be a potential important adjunct therapy in the postoperative pain management.

Objective: To analyze the incidence and cause of complications during and after interventional therapy for congenital heart disease (CHD)., Methods: From April 1986 to April 2009, 388 out of 6029 patients with CHD developed complications during and post interventional therapy, another 5 patients died post procedure, clinical data from these 393 patients were retrospectively analyzed. The patients with severe functional insufficiency requiring intervention or surgery during and after interventional therapy were classified as severe complications., Results: The overall complication rate was 6.44% [7.69% post atrial septal defect occlusion, 4.20% post patent ductus arteriosus (PDA) occlusion, 1.31% post percutaneous balloon pulmonary valvuloplasty, 14.94% post ventricular septal defect occlusion, 3.13% post percutaneous closure of aortopulmonary collaterals, 30.95% post catheter embolotherapy of pulmonary arteriovenous malformations, 12.50% post transcatheter closure of coronary artery fistulae, 20.00% post transcatheter closure of ruptured sinus of Valsava aneurysm, 66.67% post percutaneous balloon aortic valvuloplasty]. The severe complication rate was 0.65%(39/6029). The procedure-related mortality rate was 0.08% (5/6029), 0.26% (2/761) post percutaneous balloon pulmonary valvuloplasty, 0.05% (1/2070) post PDA occlusion, 9.10% (1/11) post balloon atrial septostomy, 33.33% (1/3) post percutaneous balloon aortic valvuloplasty. Emergency Cardiovascular surgery rate was 0.22% (13/6029). Selective surgery was required in 0.13% (8/6029) of patients post procedure. Two patients (0.03%) received permanent pacemaker implantation., Conclusions: The severe complications and mortality rate of interventional therapy for CHD are relative low. Post procedure follow-up is needed fro monitoring possible procedure-related complications.

Eukaryotic cells sense extracellular glucose concentrations via diverse mechanisms to regulate the expression of genes involved in metabolic control. One such example is the tight correlation between the expression of thioredoxin-interacting protein (Txnip) and extracellular glucose levels. In this report, we show that the transcription of the Txnip gene is induced by adenosine-containing molecules, of which an intact adenosine moiety is necessary and sufficient. Txnip promoter contains a carbohydrate response element, which mediates the induction of Txnip expression by these molecules in a glucose-dependent manner. Max-like protein X and MondoA are transcription factors previously shown to stimulate glucose-dependent Txnip expression and are shown here to convey stimulatory signals from extracellular adenosine-containing molecules to the Txnip promoter. The regulatory role of these molecules may be exerted via amplifying glucose signaling. Hence, this revelation may pave the way for interventions aimed toward metabolic disorders resulting from abnormal glucose homeostasis.

Objective: To analyze the clinical presentations, and explore the diagnosis, and differential diagnosis of combined hamartomas of the retina and retinal pigment epithelium (CHRRPE)., Methods: A retrospective review of five patients with suspected CHRRPE presented to Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, from Nov 2001 to July 2008. The clinical presentations, fundus characteristics, fundus fluorescein angiography (FFA), optic coherence tomography (OCT), as well as B ultrasound scan examinations were analyzed., Results: The five patients were all male, ranging in age from 6 to 18 years (mean 12 years). The lesion was unilateral; there were not any associated diseases. Presenting symptoms included painless decrease in vision, metamorphopsia, and discovery of strabismus. Initial visual acuity ranged from 20/333 to 20/50. Locations of the lesion included on optic disk and adjacent retina, and in the macular area. Clinical characteristics were slight elevation on optic disk or in retina, different degree of hyperpigmentation, retinal vascular tortuosity, as well as epiretinal membrane formation. In arterial phase of FFA, there was hypofluorescence of choroid background, retinal vascular was tortuous and telangiectatic, and there was leakage from vessels within the lesion in venous phase and late phase. OCT showed obscuration of the normal retinal layers, elevated lesion with high reflectivity of the inner retina, and hyporeflective shadowing of the underlying tissue. B ultrasound scan showed slightly elevated solid mass involving the disc or adjacent retina in some patients., Conclusions: CHRRPE may be confused with other masses of the retina and choroid. Diagnosis of CHRRPE mainly depends on fundus manifestations, FFA and OCT. B ultrasound scan is useful for differential diagnosis.

Objective: To assess the efficacy in patients undergoing pars plana vitrectomy for the treatment of idiopathic macular hole (IMH)., Methods: Retrospective observational case series. Retrospective analysis of vitrectomy for IMH patients treated between January 2001 and January 2008 was performed. The statistical software SPSS10.0 were used to analyze the data such as surgical technique, closure rate, BCVA, hole size and stage etc. The variables in normal distribution were compared by independent sample t-tests, the qualitative data were compared by R x C table, and the ordered data were compared by nonparametric tests., Results: Fifty eight eyes of 57 patients underwent vitrectomy with gas (10% C(3)F(8)) injection. Primary closure was achieved in 44 eyes (75.9%) with an average hole size of 0.20 mm(2) (0.01 - 0.85 mm(2)), whereas the size in the remaining 14 eyes was 0.69 mm(2) (0.08 - 3.16 mm(2)). The closure rate of the 36 eyes treated with ILM peeling was 80.6% (29/36), and decreased visual acuity was not observed in 72.2% of them (26/36). The closure rate of the 22 eyes without ILM peeling was 68.2% (15/22), and decreased visual acuity was not observed in 59.1% of them (13/22). There was a significant difference in the size and the change of BCVA between the closed cases and the unclosed cases, and no other factors had significant effect on the BCVA., Conclusions: Vitrectomy was evaluated as an useful treatment for IMH. ILM peeling in vitrectomy could not improve the closure rate and the visual outcomes. Preoperative hole size may be a sensitive predictor for postoperative closure.

Many biological activities naturally oscillate. Here, we show that the NAD(+)/NADH ratios (redox status) fluctuate during mammalian cell cycle, with the S-phase redox status being the least oxidative. The S-phase NAD(+)/NADH redox status gates histone expression and S-phase progression, and may provide a genome protection mechanism during S-phase DNA replication as implicated in yeast. Accordingly, perturbing the cellular redox inhibits histone expression and leads to S-phase arrest. We propose that the S-phase NAD(+)/NADH redox status constitutes a redox signaling, which along with the cyclin E/cdk2 signaling regulates histone expression and S-phase progression.

Objective: To study the incidence and risk factors of intraocular pressure (IOP) elevation in patients who underwent vitreoretinal surgery., Methods: Data for 422 patients (446 eyes) who underwent vitreoretinal surgery from June 2005 to June 2007 were retrospectively analyzed. IOP was measured before surgery and on day 1, 2, 3, 7-14 after surgery with Goldmann applanation tonometer. Ocular hypertension was defined as IOP 25 mmHg or more. All factors were analyzed for association with Ocular hypertension., Results: 232 of the 422 patients were female. 190 were male. The IOP was elevated significantly in 185 eyes (41%) after surgery within 2 weeks. Among them the IOP occurred mostly in day 1 (152 eyes, 82%). The rate of IOP elevation with intraocular tamponade of C3F8 or silicone oil was 53% or 55%, the difference being not statistically significant (P>0.05). The incidence of high IOP in C3F8 injection group and silicone oil injection group were statistically higher than simple pars plana vitrectomy group (P<0.01). The risk factors of ocular hypertension include C3F8 injection (chi2=37.82, P<0.01), silicone oil injection (chi2=27.84, P<0.01), lentectomy (chi2=8.98, P<0.01), scatter endolaser (chi2=7.41, P<0.01), diabetes (chi2=12.12, P<0.01) and increasing patient age (chi2=7.07, P<0.01)., Conclusion: IOP elevation was a common complication of vitreoretinal surgery. The risk factors of ocular hypertension include C3F8 injection, silicone oil injection, lentectomy, scatter endolaser, diabetes and increasing patient age.

Objective: To study the clinical features of silicone oil dependent eyes., Method: Retrospective observational case series. Twenty four silicone oil dependent eyes collected from the Peking Union Medical College from Jan.2000 to Dec.2006 were studied. The pathogeny, surgical process and prognosis were analyzed., Results: There were 5.9% silicone oil dependent eyes in eyes underwent vitrectomy and silicone oil tamponade. Silicone oil tamponade was performed again in 17 eyes because of severe proliferative vitreoretinopathy (PVR) or repeated vitreous hemorrhage after silicone oil removal and C3F8 tamponade. Silicone oil replacement was performed in 3 eyes because of severe PVR. Continually low intraocular pressure occurred after silicone oil removal in 4 eyes with 360 degree peripheral retinotomy. Thirteen of 24 patients had visual acuities of finger counting to 0.1, 9 had hand movement, one had light perception and one had no light perception., Conclusions: The incidence of silicone oil dependent eye is approximately 5.9%. This is often seen in the patients with severe or repeated PVR, or 360 degree peripheral retinotomy. The visual prognosis is poor in most cases.

S-phase transcription of the histone 2B (H2B) gene is dependent on Octamer-binding factor 1 (Oct-1) and Oct-1 Co-Activator in S-phase (OCA-S), a protein complex comprising glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase (p38/GAPDH and p36/LDH) along with other components. H2B transcription in vitro is modulated by NAD(H). This potentially links the cellular redox status to histone expression. Here, we show that H2B transcription requires a proper NAD(+)/NADH redox status in vitro and in vivo. Therefore, perturbing a properly balanced redox impairs H2B transcription. A redox-modulated direct p38/GAPDH-Oct-1 interaction nucleates the occupancy of the H2B promoter by the OCA-S complex, in which p36/LDH plays a critical role in the hierarchical organization of the complex. As for p38/GAPDH, p36/LDH is essential for the OCA-S function in vivo, and OCA-S-associated p36/LDH possesses an LDH enzyme activity that impacts H2B transcription. These studies suggest that the cellular redox status (metabolic states) can directly feedback to gene switching in higher eukaryotes as is commonly observed in prokaryotes.

Background: The involvement of central nervous system (CNS) interleukin-1 beta (IL-1 beta) in the pathogenesis of acute cardiac injury is still an unexplored issue. The present study was aimed to investigate whether cardiac injury could induce the activation of IL-1 beta in the spinal cord., Methods and Results: Cardiac injury model in rats was established by intra-myocardial injection of formalin through the diaphragm. Western blot showed that IL-1 beta was upregulated in the upper thoracic spinal cord following cardiac injury. The upregulated IL-1 beta was distributed in the dorsal and ventral horns in the thoracic spinal cord as determined by immunohistochemistry. In situ hybridization demonstrated that IL-1 beta mRNA localized in the neurons was elevated in response to cardiac injury. The DNA binding activities of two IL-1 beta transcription factors, activator protein (AP)-1 and nuclear factor kappa B (NF-kappaB), were enhanced after cardiac injury. In correlated with the upregulation of the spinal IL-1 beta, the circulating IL-1 beta level was also increased following cardiac injury., Conclusions: Acute cardiac injury could activate the spinal IL-1 beta signaling, which, in turn, may contribute to disease progression in the acute phase of cardiac injury in clinical practice.

Background: The pathogenic role of brain derived neurotrophic factor (BDNF) in the incisional pain is poorly understood. The present study explores the role of the BDNF in the incision-induced pain hypersensitivity., Methods: A longitudinal incision was made in one plantar hind paw of isoflurane-anesthetized rats. Dorsal root ganglias (DRG) and spinal cords were removed at various postoperative times (1-72 h). Expression pattern of BDNF was determined by immunohistochemistry and double-labeling immunofluorescence. Lidocaine-induced blockade of sciatic nerve function was used to determine the importance of afferent nerve activity on BDNF expression in the DRG and spinal cord after incision. BDNF antibody was administered intrathecally (IT) or intraperitoneal (IP) to modulate the spinal BDNF or peripheral BDNF after incision., Results: After hind-paw incision, the BDNF was upregulated in the ipsilateral lumbar DRG and spinal cord whereas thoracic BDNF remained unchanged in response to incision. The upregulated BDNF was mainly expressed in the large-sized neurons in DRG and the neurons and the primary nerve terminals in the spinal cord. Sciatic nerve blockade prevented the increase of BDNF in the DRG and spinal cord. IT injection of BDNF antibody greatly inhibited the mechanical allodynia induced by incision whereas IP administration had only marginal effect., Conclusion: The present study showed that incision induced the segmental upregulation of BDNF in the DRG and spinal cord through somatic afferent nerve transmission, and the upregulated BDNF contributed to the pain hypersensitivity induced by surgical incision.