Objective To investigate the relationship between inflammatory bowel disease (IBD) activity and choroidal thickness,and evaluate the utility of a choroidal thickness measurement in assessing IBD activity.Methods A total of 100 eyes of 50 patients of IBD with different disease activity,including 23 patients of ulcerative colitis,27 patients of Crohn's disease (CD).Ninety-six eyes of 48 healthy volunteers were recruited as control group.Choroidal thickness was measured using enhanced depth imaging(EDI)optical coherence tomography.Results Compared with the subfoveal choroidal thickness (294.37 ± 35.04) μm in healthy volunteers,the subfoveal choroidal thickness (349.28 ± 76.57) μm in UC patients with severe disease activity,the subfoveal choroidal thickness (326.71 ± 59.71) μm and (354.24 ± 66.34) μm,respectively,in CD patients with moderate and severe disease activity were found to be increased significantly (all P ＜ 0.05).Conclusion Choroidal thickness should be considered as a potential marker to assess the disease activity in patients with IBD,especially in patients with CD.

Objective To investigate the clinical value of bone metabolism biochemical marker N-MID,TP1NP and beta-CTx combined with whole body bone scintigraphy in early diagnosis of bone metastasis of tumor.Methods The concentration of the 3 markers were measured by the electrochemical luminescence analysis method in 30 cases of healthy control group and 210 cases of patients with malignant tumor,which were divided into non bone metastasis group(45 cases) and bone metastasis group(165 cases).The bone metastasis group were divided into 4 grades(0-grade Ⅲ) by Soloway classification according to whole body bone imaging.Results The levels of serum N-MID,TP1NP and beta-CTx in 165 malignant tumor patients with bone metastasis were significantly higher than in 45 malignant tumor patients with bone metastasis and in 30 healthy control group,the difference was statistically significant(P<0.05).With the increase of the number of metastatic lesions in the bone metastasis group,the serum levels of N-MID,TP1NP,and beta-CTx were increased gradually,and they were positively correlated with the progression of the disease.According to the analysis of ROC curve,the cut-off value,sensitivity and specificity in the diagnosis of tumor bone metastasis were 17.59 ng/mL,70.3％,88.9％ for serum N-MID,43.04 ng/mL,78.2％,95.6％ for TP1NP,and 0.48 ng/mL,73.9％,93.3％ for beta-CTx.Under the ROC curve(AUC) was 0.831 for serum N-MID,0.890 for TP1NP,and 0.869 for beta-CTx.The sensitivity and specificity of three bone metabolic markers in the diagnosis of bone metastasis of malignant tumor were significantly higher.Conclusion Bone metabolism biochemical markers:Serum N-MID,TP1NP and beta-CTx for diagnosis of bone metastasis of malignant tumor are sensitive,accurate and simple,which can significantly improve the efficiency of diagnosis of bone metastasis,and can be combined with whole-body bone scintigraphy in early diagnosis of bone metastasis with malignant tumor.

OBJECTIVEGlucocorticoid (GC) has occupied a central role in the treatment of acute lymphoblastic leukemia due to its ability to induce apoptosis in neoplastic lymphoid cells. Glucocorticoid resistance is present among 20% initial acute lymphoblastic leukemia, even 80% refractory acute lymphoblastic leukemia. Glucocorticoid resistance has been an important determinant of clinical outcome. Glucocorticoid depends on glucocorticoid receptor (GR) to induce apoptosis. Glucocorticoid receptor, a number of nuclear hormone receptor superfamily, is mediated by many signal transduction systems. The mitogen-activated protein kinases (MAPK) superfamily of serine/threonine kinases has emerged as an important component of cellular signal transduction. Four MAP kinase families, ERK, p38 MAP kinase, JNK, and ERK5, have been well characterized. p38 MAPK usually plays a role in regulating apoptosis, cell cycle arrest and cytokines production, et al. In steroid resistance patients, IL-2 combined with IL-4 can decrease glucocorticoid receptor ligand-binding affinity via p38MAPK. In human alveolar epithelial A549 cells, dexamethasone could inhibit the activation of p38MAPK. It is unclear that the effect of p38MAPK on glucocorticoid receptor function induced by dexamethasone in CEM cells. This study aimed to investigate effect of p38 mitogen-activated protein kinase on glucocorticoid receptor function induced by dexamethasone in CEM cells.

METHODSCell viability was determined by trypan blue dye exclusion. Apoptosis was evaluated by morphology and flow cytometry. Glucocorticoid receptor protein and p-p38MAPK protein were analyzed by Western Blot.

RESULTSWhen treatment with SB203580 and dexamethasone for 24 h to 72 h, the survival percentage was increased from 62.3%, 35.5% and 11.6% to 82.8%, 54.7% and 48.1%, respectively (P < 0.01). Co-treatment with SB203580 and dexamethasone resulted in the decrease of apoptotic percentage from 26.2% to 7.1% for 36 h (P < 0.01). p38 MAPK activation was apparent at 15 min, peaked at 1 h after dexamethasone treatment, and was sustained for 6 h. The phosphorylation was still observed at 48 h. Treatment with dexamethasone at 5 micromol/L for 12, 24, 36 and 48 h resulted in increase of GR(alpha) protein to 117%, 121%, 122% and 125% respectively. Unbinding to dexamethasone, GR(alpha) is in the cytoplasm. Nuclear-to-cytoplasmic ratio of GR(alpha) is 0.27. Treatment with dexamethasone at the same concentration and time resulted in the nuclear-to-cytoplasmic ratio increase to 0.48, 0.59, 0.95, 2.16 and 4.08 respectively. Combined treatment with SB203580 and dexamethasone resulted in the nuclear-to-cytoplasmic ratio decrease from 4.08 to 0.43 for 48 h (P < 0.05). The total GR(alpha) protein was unaffected.

CONCLUSIONSExpression of GR(alpha) protein is upregulated and translocated into nucleus. p38MAPK enhances GR(alpha) protein translocation into nucleus.

Apoptosis ; drug effects ; Cell Line, Tumor ; Dexamethasone ; pharmacology ; Enzyme Activation ; drug effects ; Enzyme Inhibitors ; pharmacology ; Glucocorticoids ; pharmacology ; Humans ; Imidazoles ; pharmacology ; Mitogen-Activated Protein Kinases ; metabolism ; Phosphorylation ; drug effects ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; pathology ; Protein-Serine-Threonine Kinases ; Pyridines ; pharmacology ; Receptors, Glucocorticoid ; drug effects ; metabolism ; Signal Transduction ; drug effects ; p38 Mitogen-Activated Protein Kinases ; drug effects ; metabolism

OBJECTIVETo evaluate effect of amygdalin on expression of four biomarkers in the animal model of pulmonary fibrosis induced by bleomycin.

METHODSRats were given one dose (5 mg/kg) of bleomycin in bleomycin-treated groups, amygdalin-treated groups and saline in controls by intratracheal instillation exposed surgically. The amygdalin-treated groups rats were treated with intraperitoneal injection of amygdalin (15 mg x kg(-1) x day(-1)). The rats were sacrificed 7, 14 and 28 days after bleomycin administration. Polarized light microscopy and Image-Pro Plus detected I and III collagen expressed in Paraffin-embedded lung sections stained with Sirius red. Surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF MS) with weak cationic proteinchip (CM10) detected differentially expressed proteins in the pooled serum samples of all groups.

RESULTSConsistent fibrotic responses were found in all bleomycin and amygdalin-tread groups. On the 7th, 14th and 28th day after bleomycin or saline instillation, four differentially expressed proteins were detected in the pooled serum of all groups rats, consisting of 4 proteins with mass/charge ratio of 3530.7, 7043.5, 8332.6 and 9068.0, respectively. Compared with control groups, protein peaks intensity ratio with mass/charge ratio of 3530.7 on 7, 28 d and 7043.5, 8332.6 and 9068.0 on 7, 14 and 28 d was > 2 in bleomycin-treated groups. Compared with amygdalin-treated groups, protein peaks intensity with mass/charge ratio of 3530.7 at 7, 14, 28 d had no change almost, but protein peaks intensity ratio with mass/charge ratio of 7043.5 at 7 d, 8332.6 on 28 d and 9068.0 on 14 d was > 2 in bleomycin-tread groups. All the four protein peaks intensity had no change almost at other point.

CONCLUSIONAmygdalin may reduce the bleomycin-induced increase of differentially expressed protein peak intensities in rat serum.

Amygdalin ; pharmacology ; Animals ; Biomarkers ; blood ; Bleomycin ; adverse effects ; Blood Proteins ; metabolism ; Male ; Pulmonary Fibrosis ; blood ; chemically induced ; Rats ; Rats, Wistar

Objective:To evaluate the effect of resveratrol on ferropotosis in cardiomyocytes of mice with diabetic cardiomyopathy.Methods:Thirty healthy adult male C57BL/6 mice, aged 8 weeks, weighing 22-26 g, were divided into 3 groups ( n=10 each) using a random number table method: control group (group C), diabetic cardiomyopathy group (group DCM) and resveratrol group (group RSV). Freshly prepared streptozotocin (STZ) 40 mg·kg -1·d -1 was intraperitoneally injected for 5 consecutive days to develop the model of type 1 diabetes mellitus. After the model was successfully developed, resveratrol 25 mg·kg -1·d -1 was intragastrically given for 12 consecutive weeks in group RSV, while the equal volume of dimethyl sulfoxide was given instead in group C and group DCM. Echocardiography was performed to examine the cardiac structure and function at the end of the 12th week. Then mice were sacrificed, and myocardial tissue specimens were harvested for microscopic examination of the pathological changes of myocardial tissues (by Hematologist-Eosin staining) and mitochondrial morphology of myocardial cells (with a transmission electron microscope) and for determination of the contents of iron, malondialdehyde (MDA) and glutathione (GSH) (by colorimetry) and expression of glutathione peroxidase 4 (GPX4) (by Western blot). Results:Compared with group C, the left ventricular end-diastolic diameter and left ventricular end-systolic diameter were significantly increased, the left ventricular ejection fraction and left ventricular fractional shortening were decreased, the contents of iron and MDA were increased, the content of GSH was decreased, and the expression of GPX4 was down-regulated in group DCM ( P<0.05). Compared with group DCM, the left ventricular end-diastolic diameter and left ventricular end-systolic diameter were significantly decreased, the left ventricular fractional shortening and ejection fraction were increased, the contents of iron and MDA were decreased, the content of GSH was increased, the expression of GPX4 was up-regulated ( P<0.05), and the pathological changes of myocardial tissues and changes in mitochondrial morphology of myocardial cells were significantly attenuated in group RSV. Conclusions:The mechanism by which resveratrol attenuates myocardial injury and further improves cardiac dysfunction is related to inhibition of ferroptosis in cardiomyocytes of mice with diabetic cardiomyopathy.

Central retinal artery occlusion(CRAO)refers to occlusion of the central retinal artery(CRA), which acts as the primary blood supply to the inner neurosensory retina, and leads to an acute loss of vision and permanent visual disability. The natural history of visual prognosis in CRAO is generally poor. Despite a variety of treatment options have been studied, such as ocular massage, anterior chamber paracentesis, hyperbaric oxygen therapy(HBOT)and intra-arterial infusion of tissue plasminogen activator(tPA), but there is currently no evidence-based management strategies for the treatment of CRAO. Furthermore, the efficacy of all available managements is debatable and many have uncertain risks. This review will offer a summary of the currently known treatment options for CRAO and probe into their safety and efficacy on the prognosis of CRAO.

Parkinson's disease is a common neurodegenerative disease in middle-aged and elderly people, in which the pathogenic factors are not yet clear. Genetics, dietary habits, environmental toxins, immunological abnormalities, inflammation and oxidative stress response, apoptosis, and mitochondrial dysfunctions which caused by a variety of physiological and biogenic changes are likely to exacerbate the occurrence of Parkinson's disease. In recent years, studies have shown that the activity of microglia is closely related to Parkinson's disease, and that the active microglia can promote the release of inflammatory factors, while the differentiation of dopamine neurons in the substantial nigra of midbrain area is also closely related to Parkinson's disease. As a histone H3K27me3 demethylase, JMJD3 is involved and affects the activity of microglia, which can regulate the polarization of microglia as well and affect the survival of dopaminergic neurons in the mesencephalon. This provides new methods and strategies for treating Parkinson' s disease. This paper summarizes the structure and function of JMJD3, as well as its role in neuro-inflammation mediated by microglia and its effect on neurons, and explores the functions and related research progress of JMJD3 in Parkinson's disease.

miR-214 plays a major role in the self-renewal of skin tissue. However, whether miR-214 regulates the proliferation and differentiation of human hair follicle stem cells (HFSCs) is unknown. Primary HFSCs were isolated from human scalp skin tissue, cultured, and identified using flow cytometry. An miR-214 mimic and inhibitor were constructed for transfection into HFSCs. The MTS and colony formation assays examined cell proliferation. Immunofluorescence detected the localization and expression levels of TCF4, β-catenin, and differentiation markers. Luciferase reporter and TOP/FOP Flash assays investigated whether miR-214 targeted EZH2 and regulated the Wnt/β-catenin signaling pathway. Western blot determined the expression levels of enhancer of zeste homolog 2 (EZH2), Wnt/β-catenin signaling-related proteins, and HFSC differentiation markers in cells subjected to miR-214 transfection. miR-214 expression was remarkably decreased during the proliferation and differentiation of HFSCs into transit-amplifying (TA) cells. Downregulation of miR-214 promotes the proliferation and differentiation of HFSCs. Overexpression of miR-214 led to decreased expression of EZH2, β-catenin, and TCF-4, whereas downregulation of miR-214 resulted in increased expression of EZH2, β-catenin, and TCF-4 as well as TA differentiation markers. Immunofluorescence assay revealed that inhibiting miR-214 triggered the entry of β-catenin and TCF-4 into the nucleus. The luciferase reporter and TOP/FOP Flash assays demonstrated that miR-214 directly targets EZH2 and affects Wnt/β-catenin signaling. The miR-214/EZH2/β-catenin axis could be considered a candidate target in tissue engineering and regenerative medicine for HFSCs.
Antigens, Differentiation ; Blotting, Western ; Cell Proliferation ; Down-Regulation ; Flow Cytometry ; Fluorescent Antibody Technique ; Hair Follicle* ; Hair* ; Humans* ; In Vitro Techniques* ; Luciferases ; Regenerative Medicine ; Scalp ; Skin ; Stem Cells* ; Tissue Engineering ; Transfection

Objective To evaluate the effects,safety and economic cost of long-term home noninvasive ventilation (NIV) therapy in elderly patients with chronic hypercapnic respiratory failure.Methods A total of 128 elderly patients with chronic hypercapnic respiratory failure were randomly assigned to two groups:the NIV group (n=66) with conventional therapy in addition to long-term home NIV therapy,and the control group (n=62) with conventional therapy alone.Compared were parameters before and after two year follow up,which included dyspnea grade,scale for accessory muscle use,scoring for emotional disorders,mean pulmonary pressure (mPAP) by electrocardiography,arterial blood gas,the times of pulmonary infection and hospitalization rates,the duration of hospitalization invasive ventilation,the duration of in RICU and in hospital stay,tracheal intubation rates and mortality.The medical cost was calculated.Results After two years,the differences in the dyspnea grade,scale for accessory muscle use,anxiety scores,depression scores,mPAP,arterial PaCO2 and PaO2,hospitalization rates,the times of pulmonary infection,the days of hospitalization for exacerbation in the home NIV group [2.2± 0.2,2.4 ± 0.3,4 ± 1,5.3 ± 1.2,(36.6±5.2)mm Hg,(50.2±4.5)mm Hg,(63.5±4.2)mm Hg,(1.3±0.2) times/year,(2.4±0.2) times/year,(15.8 ± 4.4) days/times] were statistically significant compared to the control group [4.1±0.2,4.9±0.5,12±3,11.3±1.6,(45.2±5.2)mm Hg,(67.3±4.5) mm Hg,(48.3±4.3)mm Hg,(5.4±0.4)times/year,(8.9 ±0.3) times/year,(38.5± 6.3) days/times] (all P＜0.01).The duration of invasive ventilation,the days in RICU and in hospital stay,tracheal intubation rates on admission to the hospital were significantly decreased in the home NIV group [(8.2 ± 2.2)days,(9.6±3.1) days,(15.8±4.4) days,(2±0.2) times/two years],as compared with the control group [(15.8±3.4) days,(18.6±4.4)days,(38.5±6.3)days,(8.0±0.8) times/two years].The mortality was decreased significantly in the home NIV group (3.0 ％)compared with the control group (29.0％) (P＜0.05).The medical cost in two years was significant lower in the home NIV group [(6.4 ± 0.5) thousand yuan],compared with the control group (18.4 ±0.6) thousand yuan (P＜0.01).Conclusions Long-term home NIV therapy in patients with chronic hypercapinc respiratory failure is effective,safe and can decrease the mortality and medical cost.

ObjectiveTo investigate its dynamic characteristics and pathological mechanism on magnatic resonance diffusion weighted imaging (DWI) after chemoembolization in rabbit liver VX-2 tumor model.MethodsForty New Zealand rabbits were included in the study and forty-seven rabbit VX-2 tumor models were raised by implanting directly and intrahepatically after abdominal cavity was opened.Forty VX-2 tumor models from them were divided into four groups.DWI was performed periodically and respectively for each group after chemoembolization.All VX-2 tumor samples of each group were studied by pathology.The distinction of VX-2 tumors on DWI was assessed by their apparent diffusion coefficient (ADC) values.The statistical significance between different time groups,different area groups,or different b-value groups was calculated using SPSS 12.0 software.ResultsWhen b-value was 100 s/mm2,ADC values in the area of VX-2 tumor periphery,VX-2 tumor central,or normal liver parenchyma around tumor became gradually low in sixteen hours after chemoembolization,and were the lowest at sixteenth hour,and then they increased gradually from sixteenth hour to fourty-eighth hour after chemoembolization.The distinction of ADC between different time groups was significant,respectively ( F =7.325,P ＜ 0.01 ; F =2.496,P ＜ 0.05 ; F =6.856,P ＜0.01 ).Cellular edema in the area of VX-2 tumor periphery or normal liver parenchyma around tumor increased quickly in sixteen hours after chemoembolization; however,from sixteenth hour to forty-eighth hour,cellular edema in the area of normal liver parenchyma around tumor decreased gradually and that in the area of VX-2 tumor periphery decreased lightly at first and then increased continually.Cellular necrosis in the area of VX-2 tumor periphery after chemoembolization was more significant than that before chemoembolization.The areas of dead cells in VX-2 tumors manifested low signal and high ADC value while the areas of viable cells manifested high signal and low ADC value.ConclusionsDWI is able to detect and discriminate tumor necrotic areas from viable cellular areas before and after chemoembolization.ADC of normal liver parenchyma and VX-2 tumor are influenced by intracellular edema,tissue cellular death,and microcirculation disturbance after chemoembolization.