Lung cancer presenting with acute myocardial infarction and pulmonary embolism within 1 month.

Acute myocardial infarction and pulmonary embolism can have life-threatening consequences such as congestive heart and respiratory failure, respectively. Cancer patients are at great risk of both acute myocardial infarction and pulmonary embolism complications because the malignancy sparks the patient's blood hypercoagulable state. Nevertheless, the literature currently offers only a few reports on acute myocardial infarction associated with pulmonary embolism, and two of them occurred in the same cancer patient. Here, we present a case of a 60-year-old woman who had been diagnosed with lung cancer. She was admitted to the emergency department twice. She was diagnosed with acute myocardial infarction at her first admission, when she experienced sudden-onset chest pain. Electrocardiography showed ST-segment elevation in leads V1-V3 with inverted T wave and pathological Q wave, suggesting an acute myocardial infarction. Coronary angiography revealed a thrombus in the left anterior descending coronary artery, and thrombus aspiration was performed. After 1 month, she had an attack of pulmonary embolism with syncope upon the second admission. A computed tomographic pulmonary angiography showed branches of right and left pulmonary embolism. Anticoagulation and antiplatelet measures were taken. In this article, we discuss the relationship between cancer and thrombosis with a special focus on the conservative management strategy regarding anticoagulant and antiplatelet therapy in our case.

Chinese Children with Congenital and Acquired Blindness Represent Concrete Concepts in Vertical Space through Tactile Perception.

Many studies have tested perceptual symbols in conceptual processing and found that perceptual symbols contain experiences from multisensory channels. However, whether the disability of one sensory channel affects the processing of the perceptual symbols and then affects conceptual processing is still unknown. This line of research would extend the perceptual symbol theory and have implications for language rehabilitation and mental health for people with disabilities. Therefore, the present study filled in this gap and tested whether Chinese children with congenital and acquired blindness have difficulty in recruiting perceptual symbols in the processing of concrete concepts. Experiment 1 used the word-pair-matching paradigm to test whether blind children used vertical space information in understanding concrete word pairs. Experiment 2 used the word-card-pairing paradigm to test the role of tactile experiences in the processing of concrete concepts for blind children. Results found that blind children automatically activated the spatial information of referents in the processing of concepts through the tactile sensory channel even when the visual sensory channel was disabled. This finding supported the compensatory phenomenon of other sensory channels in conceptual representation. In addition, the difference between elementary school blind children and middle school blind children in judging the spatial position of concrete words also indicated the vital influence of perceptual experiences on perceptual symbols in conceptual representation. Interestingly, there were no significant differences between children with congenital or acquired blindness. This might suggest that the compensatory of other sensory channels did not have a sensitive period. This study not only provided new evidence for the perceptual symbol theory but also found that perceptual symbols could be developed by a compensatory mechanism. This compensatory mechanism can be used to develop a rehabilitation program for improving language learning in blind children. Improved language ability in blind children will also improve their mental health problems caused by difficulties in social interaction (e.g., social anxiety).

Bi-directional cross-language activation in Chinese Sign Language (CSL)-Chinese bimodal bilinguals.

In bilingual word recognition, cross-language activation has been found in unimodal bilinguals (e.g., Chinese-English bilinguals) and bimodal bilinguals (e.g., American Sign language-English bilinguals). However, it remains unclear how signs' phonological parameters, spoken words' orthographic and phonological representation, and language proficiency affect cross-language activation in bimodal bilinguals. To resolve the issues, we recruited deaf Chinese sign language (CSL)-Chinese bimodal bilinguals as participants. We conducted two experiments with the implicit priming paradigm and the semantic relatedness decision task. Experiment 1 first showed cross-language activation from Chinese to CSL, and the CSL words' phonological parameter affected the cross-language activation. Experiment 2 further revealed inverse cross-language activation from CSL to Chinese. The Chinese words' orthographic and phonological representation played a similar role in the cross-language activation. Moreover, a comparison between Experiments 1 and 2 indicated that language proficiency influenced cross-language activation. The findings were further discussed with the Bilingual Interactive Activation Plus (BIA+) model, the deaf BIA+ model, and the Bilingual Language Interaction Network for Comprehension of Speech (BLINCS) model.

Granulocyte colony-stimulating factor reduces the endoplasmic reticulum stress in a rat model of diabetic cardiomyopathy.

Prolonged endoplasmic reticulum (ER) stress contributes to the apoptosis of cardiomyocytes, which leads to the development of diabetic cardiomyopathy. Previously, we reported that the granulocyte colony-stimulating factor (G-CSF) reduces the cardiomyocyte apoptosis in diabetic cardiomyopathy; however, the precise mechanisms associated with this process are not yet fully understood. Therefore, in this study, we investigated whether the mechanism of the anti-apoptotic effect of G-CSF was associated with ER stress in a rat model of diabetic cardiomyopathy. Diabetic cardiomyopathy was induced in rats using a high-fat diet combined with the administration of a low-dose of streptozotocin. Diabetic rats were treated with G-CSF or saline for 5 days. Cardiac function was evaluated using serial echocardiography before and 4 weeks after treatment. The rate of cardiomyocyte apoptosis and the expression levels of proteins related to ER stress, including glucose-regulated protein 78 (GRP78), caspase-9, and caspase-12 were analyzed in the cardiac tissue. G-CSF treatment significantly reduced cardiomyocyte apoptosis in the diabetic myocardium and downregulated the expression levels of these proteins in diabetic rats treated with low-dose streptozotocin when compared to that in rats treated with saline. In addition, G-CSF treatment significantly downregulated the expression levels of proteins related to ER stress, such as GRP78, inositol-requiring enzyme-1α (IRE-1α), and C/EBP homologous protein (CHOP) in H9c2 cells under high glucose (HG) conditions. Moreover, G-CSF treatment significantly improved the diastolic dysfunction in serial echocardiography assessments. In conclusion, the anti-apoptotic effect of G-CSF may be associated with the downregulation of ER stress.

Role of Autophagy in Granulocyte-Colony Stimulating Factor Induced Anti-Apoptotic Effects in Diabetic Cardiomyopathy.

BACKGROUND: We previously, reported that granulocyte-colony stimulating factor (G-CSF) reduces cardiomyocyte apoptosis in diabetic cardiomyopathy. However, the underlying mechanisms are not yet fully understood. Therefore, we investigated whether the mechanisms underlying of the anti-apoptotic effects of G-CSF were associated with autophagy using a rat model of diabetic cardiomyopathy. METHODS: Diabetic cardiomyopathy was induced in rats through a high-fat diet combined with low-dose streptozotocin and the rats were then treated with G-CSF for 5 days. Rat H9c2 cardiac cells were cultured under high glucose conditions as an in vitro model of diabetic cardiomyopathy. The extent of apoptosis and protein levels related to autophagy (Beclin-1, microtubule-binding protein light chain 3 [LC3]-II/LC3-I ratio, and P62) were determined for both models. Autophagy determination was performed using an Autophagy Detection kit. RESULTS: G-CSF significantly reduced cardiomyocyte apoptosis in the diabetic myocardium in vivo and led to an increase in Beclin-1 level and the LC3-II/LC3-I ratio, and decreased P62 level. Similarly, G-CSF suppressed apoptosis, increased Beclin-1 level and LC3-II/LC3-I ratio, and decreased P62 level in high glucose-induced H9c2 cardiac cells in vitro. These effects of G-CSF were abrogated by 3-methyladenine, an autophagy inhibitor. In addition, G-CSF significantly increased autophagic flux in vitro. CONCLUSION: Our results suggest that the anti-apoptotic effect of G-CSF might be significantly associated with the up-regulation of autophagy in diabetic cardiomyopathy.

Modified method for effective primary vascular smooth muscle progenitor cell culture from peripheral blood.

In previous studies, vascular smooth muscle progenitor cells (vSMPCs) isolated from peripheral blood mononuclear cells (PBMCs) were cultured using medium containing platelet-derived growth factor-BB (PDGF-BB) for 4 weeks. However, this method requires long culture periods of up to 4 weeks and yields low cell counts. Therefore, we proposed the modified method to improve the cell yield and purity and to reduce the cell culture period. PBMCs were isolated from human peripheral blood and cultured by the conventional method using medium containing PDGF-BB alone or the modified method using medium containing PDGF-BB, basic fibroblast growth factor (bFGF), and insulin-transferrin-selenium ITS for 4 weeks. The purity of vSMPCs was analyzed for the expression of a- smooth muscle actin (SMA) by flow cytometry and significantly higher in the modified method than conventional methods at the 1st and 2nd weeks. Also, mRNA expression of a-SMA by real-time PCR was significantly higher in the modified method than conventional method at the 2 weeks. The yield of vSMPCs by trypan blue exclusion assay was significantly higher in the modified method than conventional method at the 1st, 2nd and 3rd weeks. The primary culture using the modified method with PDGF-BB, bFGF, and ITS not only improved cell purity and yield, but also shortened the culture period, compared to the conventional culture method for vSMPCs. The modified method will be a time-saving and useful tool in various studies related to vascular pathology.

Granulocyte Colony Stimulating Factor Ameliorates Hepatic Steatosis Associated with Improvement of Autophagy in Diabetic Rats.

Background: We previously reported that the granulocyte colony stimulating factor (G-CSF) ameliorated hepatic steatosis with the enhancement of ß-oxidation-related gene expression. However, the mechanisms underlying this process remain unclear. This study aimed to determine whether the improvement of hepatic steatosis by G-CSF was associated with autophagy in a rat model of diabetes. Methods: Eight rats were fed a standard diet, and 16 rats were fed high-fat diet (HFD) for 5 weeks. All HFD-fed rats were then injected with streptozotocin (STZ). One week later, HFD rats injected with STZ were randomly treated with either G-CSF (200 µg/kg/day; diabetes mellitus (DM)/G-CSF) or saline (DM/saline) for 5 consecutive days. Four weeks later, serum biochemical and histology analyses were conducted. The expression of autophagy-associated proteins was determined by Western blotting. The mRNA expression of ß-oxidation-related genes was determined by quantitative real-time polymerase chain reaction. HepG2 cells were cultured under high glucose (HG) conditions with G-CSF treatment, followed by Oil Red O staining for quantification of lipids. Results: Histological analysis showed lower lipid accumulation in the DM/G-CSF group than in the DM/saline-treated rats. Protein levels of LC3 and beclin-1 were higher, and those of p62 were lower in the DM/G-CSF rats than in the DM/saline-treated rats. The mRNA expression of ß-oxidation-related genes was higher in DM/G-CSF rats than in the DM/saline-treated rats. Quantification of lipid levels in HepG2 cells cultured with HG and G-CSF treatment revealed no significant differences. Conclusions: Our data suggested that G-CSF potentially improves hepatic steatosis and autophagy in the liver of diabetic rats.

Bone marrow mesenchymal stem cell-derived vascular endothelial growth factor attenuates cardiac apoptosis via regulation of cardiac miRNA-23a and miRNA-92a in a rat model of myocardial infarction.

Bone marrow-mesenchymal stem cell (BM-MSC) therapy improves the recovery of cardiac function after myocardial infarction (MI); however, the underlying molecular mechanisms are not completely understood. Recent studies have shown that microRNAs (miRNAs) modulate the pathophysiology of cardiovascular diseases. Here, we investigated the mechanisms underlying the effects of BM-MSC-derived paracrine factors and cardiac miRNAs on myocardial regeneration after MI. In our study, MI was induced by permanent ligation of the left anterior descending (LAD) coronary artery. BM-MSCs transplanted in infarcted rats significantly downregulated the expression of miRNA-23a and miRNA-92a and inhibited apoptosis in the myocardium. An in vitro experiment showed that supernatant from BM-MSCs cultured under hypoxia contained higher levels of vascular endothelial growth factor (VEGF) than that from BM-MSCs under normoxia. In addition, inhibition of miRNA-23a and miRNA-92a reduced cardiac apoptosis. Moreover, the VEGF-containing BM-MSC supernatant inhibited miRNA-23a and miRNA-92a expression and reduced apoptotic signaling in cardiomyocytes under hypoxia. These effects were inhibited when the supernatant was treated with neutralizing antibodies against VEGF. Our results indicate that the paracrine factor, VEGF, derived from transplanted BM-MSCs, regulated the expression of miRNAs such as miRNA-23a and miRNA-92a and exerted anti-apoptotic effects in cardiomyocytes after MI.

The Effects of Granulocyte-Colony Stimulating Factor on Regeneration in Nerve Crush Injuries in Rats.

Granulocyte-colony stimulating factor (G-CSF) is widely known to have a neuroprotective effect, but its effects on function and morphology in mechanical nerve injury are not well understood. The aim of this study was to confirm the time course of the functional changes and morphological effects of G-CSF in a rat model of nerve crush injury. Twelve-eight rats were divided into three group: sham-operated control group, G-CSF-treated group, and saline treated group. 2 weeks after the nerve crush injury, G-CSF was injected for 5 days. After 4 weeks, functional tests such as motor nerve conduction velocity (MNCV), mechanical and cold allodynia tests, and morphological studies were performed. G-CSF-treated rats had significantly improved nerve function including MNCV and mechanical and cold allodynia. In addition, G-CSF-treated rats had significantly higher the density of myelinated fibers than saline-treated rats. In conclusion, we found that 100 µg/kg administration of G-CSF promoted long-term functional recovery in a rat model of nerve crush injury.

Local injection of granulocyte-colony stimulating factor accelerates wound healing in a rat excisional wound model.

A systemic treatment of granulocyte-colony stimulating factor (G-CSF) is known to improve healings of damaged tissues. However, recent studies suggested local actions of G-CSF on the healing processes of damaged tissues. We investigated the treatment effect of locally injected G-CSF and compared to that of systemically injected G-CSF in a rat model. A wound was created on the rat dorsum and treated either by local injection or by systemic injection of G-CSF. Wound healing rate, deposition of collagen, and gene expression were evaluated. G-CSF receptor (G-CSFR) protein was detected by Western blotting. The wound healing rate in the local injection group was significantly higher than that in the systemic injection group at days 9 and 15; it was also significantly higher than that in the control group at days 3, 9, and 15. The expression of G-CSFR protein in wound tissues was higher than in normal skin tissues. The local injection of G-CSF is more effective than systemic injection of G-CSF in promoting wound healing, which may implicate the local action of G-CSF treatment in wound healing processes.

Granulocyte-colony stimulating factor prevents the development of hepatic steatosis in rats.

BACKGROUND AND AIMS: Previously, we reported that granulocyte-colony stimulating factor (G-CSF) improves hepatic steatosis in experimental animals. It may also have preventive effects on the development of hepatic steatosis. Therefore, we investigated the preventive effects of G-CSF by using a high-fat diet (HFD) rat model. MATERIALS AND METHODS: Twelve rats were fed HFD and 6 rats were fed control diet from 10 weeks of age. Once little steatosis was confirmed in the liver (after 10 weeks of feeding the HFD; at 20 weeks of age), HFD rats were randomly divided into two groups and treated with either G-CSF (100 µg kg-1 day-1 for 5 consecutive days every other week; HFD/G-CSF rats) or saline (HFD/saline rats) for 10 weeks at 20 weeks of age. All rats were sacrificed at 30 weeks of age. Histology was examined by hematoxylin and eosin (H-E) and Oil Red O staining, and the expression levels of genes of associated with lipogenesis and ß-oxidation enzymes were determined by qRT-PCR. RESULTS: Histological examinations revealed that HFD/G-CSF rats had significantly lower lipid accumulation in their hepatocytes than did HFD/saline rats (p < 0.05). HFD/G-CSF rats also showed lower expression levels of genes associated with lipogenesis and higher expression levels of genes associated with ß-oxidation than HFD/saline rats (p < 0.05). CONCLUSION: In conclusion, we found that G-CSF prevented development of hepatic steatosis in an HFD rat model. The preventive effect may be associated with the regulation of gene expression involved in hepatic lipogenesis and ß-oxidation.

Transplanted Human Amniotic Epithelial Cells Secrete Paracrine Proangiogenic Cytokines in Rat Model of Myocardial Infarction.

Human amniotic epithelial cells (h-AECs) have been shown to differentiate into cardiomyocyte-like cells in vivo that can regenerate myocardial tissue and improve cardiac function in a rat model of myocardial infarction (MI). In this study, we investigated the paracrine factors released from h-AECs under hypoxic conditions to elucidate the possible mechanisms underlying this previously reported phenomenon of h-AEC-mediated cardiac repair. We used hypoxic cell culture conditions to simulate myocardial infarction in vitro. In comparison to normal conditions, we found that h-AECs secreted higher levels of several cytokines, including angiogenin (ANG), epidermal growth factor (EGF), interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1. To determine whether transplanted h-AECs express these proangiogenic cytokines in vivo, we ligated the coronary artery of rats to cause MI and injected either h-AECs or saline into the infarcted area. We found that the infarct and border zones of rat myocardium treated with h-AECs had higher expression levels of the human-origin cytokines ANG, EGF, IL-6, and MCP-1 compared to the tissues of saline-treated rats. In conclusion, h-AECs secreted proangiogenic cytokines in a rat model of MI, which may suggest that the paracrine effect by h-AECs could regenerate myocardial tissue and improve cardiac function.

Anti-obesity effects of granulocyte-colony stimulating factor in Otsuka-Long-Evans-Tokushima fatty rats.

Granulocyte-colony stimulating factor (G-CSF) has molecular structures and intracellular signaling pathways that are similar to those of leptin and ciliary neurotropic factor (CNTF). It also has immune-modulatory properties. Given that leptin and CNTF play important roles in energy homeostasis and that obesity is an inflammatory condition in adipose tissue, we hypothesized that G-CSF could also play a role in energy homeostasis. We treated 12 38-week-old male Otsuka-Long-Evans-Tokushima fatty rats (OLETF, diabetic) and 12 age-matched male Long-Evans-Tokushima rats (LETO, healthy) with 200 µg/day G-CSF or saline for 5 consecutive days. Body weight reduction was greater in G-CSF-treated OLETF (G-CSF/OLETF) than saline-treated OLETF (saline/OLETF) following 8 weeks of treatment (-6.9±1.6% vs. -3.1±2.2%, p<0.05). G-CSF treatment had no effect on body weight in LETO or on food intake in either OLETF or LETO. Body fat in G-CSF/OLETF was more reduced than in saline/OLETF (-32.2±3.1% vs. -20.8±6.2%, p<0.05). Energy expenditure was higher in G-CSF/OLETF from 4 weeks after the treatments than in saline/OLETF. Serum levels of cholesterol, triglyceride, interleukin-6 and tumor necrosis factor-α were lower in G-CSF/OLETF than in saline/OLETF. Uncoupling protein-1 (UCP-1) expression in brown adipose tissue (BAT) was higher in G-CSF/OLETF than in saline/OLETF, but was unaffected in LETO. Immunofluorescence staining and PCR results revealed that G-CSF receptors were expressed in BAT. In vitro experiments using brown adipocyte primary culture revealed that G-CSF enhanced UCP-1 expression from mature brown adipocytes via p38 mitogen-activated protein kinase pathway. In conclusion, G-CSF treatment reduced body weight and increased energy expenditure in a diabetic model, and enhanced UCP-1 expression and decreased inflammatory cytokine levels may be associated with the effects of G-CSF treatment.

[Effectiveness comparison of proximal femoral nail antirotation and dynamic hip screw for intertrochanteric fractures in the elderly patients].

OBJECTIVE: To compare the effectiveness of the proximal femoral nail antirotation (PFNA) and dynamic hip screw (DHS) in the treatment of elderly patients with intertrochanteric fractures. METHODS: Between May 2007 and May 2010, 63 elderly patients with intertrochanteric fractures were treated, and fractures were fixed with PFNA in 31 patients (PFNA group) and with DHS in 32 patients (DHS group). There was no significant difference in gender, age, injury cause, disease duration, and fracture type between 2 groups (P > 0.05). RESULTS: All incisions healed by first intention. The incision length, operation time, and blood loss in PFNA group were significantly less than those in DHS group (P < 0.05). The average follow-up time was 13.6 months in PFNA group and was 13.8 months in DHS group. The fracture healing time was (11.80 +/- 1.32) weeks in PFNA group and was (12.21 +/- 1.26) weeks in DHS group, showing no significant difference (t=1.23, P=0.29). The complication rate was 0 in PFNA group and was 12.5% (4/32) in DHS group, showing no significant difference (P=0.06). After 1 year, Harris hip score of PFNA group (86.55 +/- 10.32) was higher than that of DHS group (80.36 +/- 11.18) (t=2.28, P=0.03). CONCLUSION: There are two surgical methods to treat intertrochanteric fractures in the elderly patient: PFNA and DHS, and each has advantages; for unstable intertrochanteric fractures, PFNA treatment is the first choice.

[Comparison study on effectiveness between arthroscopy assisted percutaneous internal fixation and open reduction and internal fixation for Schatzker types II and III tibial plateau fractures].

OBJECTIVE: To compare the effectiveness of arthroscopy assisted percutaneous internal fixation and open reduction and internal fixation for Schatzker types II and III tibial plateau fractures. METHODS: Between August 2006 and April 2010, 58 patients with tibial plateau fractures of Schatzker types II and III were treated with arthroscopy assisted percutaneous internal fixation (arthroscopy group, n = 38), and with open reduction and internal fixation (control group, n = 20). There was no significant difference in gender, age, disease duration, fracture type, and complication between 2 groups (P > 0.05). The operation time, incision length, fracture healing time, and complications were compared between 2 groups. Knee function score and the range of motion were measured according to American Hospital for Special Surgery (HSS) score standard. RESULTS: All patients achieved primary incision healing. The arthroscopy group had smaller incision length and longer operation time than the control group, showing significant differences (P < 0.05). The patients of 2 groups were followed up 12 to 14 months. At 6 months, the HSS score and the range of motion of the arthroscopy group were significantly greater than those of the control group (P < 0.05). The X-ray films showed bony union in 2 groups. The fracture healing time of the arthroscopy group was shorter than that of the control group, but no significant difference was found (t = 2.14, P = 0.41). Morning stiffness occurred in 2 cases (5.3%) of the arthroscopy group, joint pain in 6 cases (30.0%) of the control group (3 cases had joint stiffness) at 1 week, which were cured after symptomatic treatment. There was significant difference in the incidence of complications between 2 groups (chi2 = 6.743, P = 0.016). CONCLUSION: The arthroscopy assisted percutaneous internal fixation is better than open reduction and internal fixation in the treatment of tibial plateau fractures of Schatzker types II and III, because it has smaller incision length and shorter fracture healing time.