Objective To study the effects of found in inflammatory zone 1(FIZZ1) on the migration of cul- tured mouse vascular smooth muscle cell(VSMC) and the potential mechanism.Methods Using Boyden chamber, immunofluorescence and Western blot,the migratory effects,F-actin content and Akt/Akt1 expression were deter- mined in VSMC after stimulation by FIZZ1.Results FIZZ1 markedly increases the migratory ratio,F-actin con- tent and the Akt1 expression of VSMC.Ly294002,a PI3K inhibitor,attenuated migratory ratio,F-actin content and the Akt1 expression of VSMC promoted by FIZZ1 in a dose-dependent manner (10-30 ?mol/L).Conclusion Our data demonstrated FIZZ1 by activating PI3K/Akt1 pathway induced the expression of F-actin of VSMC,and promoted the migration of VSMC.

Objective To analyze the differences of the clinical and neuropathological features among the common Charcot-Marie-Tooth disease (CMT) subtypes.Methods There were 81 CMT patients confirmed by genetic testing from 2005 to 2015 in Department of Neurology,Peking University First Hospital,including 31 cases of CMT1A (38.3％),19 cases of CMTX1 (23.5％),16 cases of CMT2A2 (19.8％) and 15 cases of 9 rare types of CMT (1.2％-4.9％).We compared the onset age,duration,muscles weakness of legs,frequency of pes cavus,and main pathological changes of the sural nerve biopsy in 48 cases of the common CMT subtypes.Results The mean age of the onset was (12.00 ± 6.77) years in CMT1A patients,(11.81 ±4.65) years in CMTX1 patients and (5.00 ±2.68) years in CMT2A2 patients (Brown-Forsythe test,P =0.001).The duration was (12.00 ± 6.75) years in CMT1A patients,(8.50 ± 4.75) years in CMTX1 patients and (5.00 ± 2.73) years in CMT2A2 patients (Brown-Forsythe test,P =0.001).The muscle force of the dorsi flexors was Ⅳ (0,Ⅴ) in CMT1A patients,Ⅲ + (0,Ⅳ) in CMTX1 patients and 0 (0,Ⅳ) in CMT2A2 patients (H =11.359,P =0.020).The pes cavus appeared in 15/23 cases of CMT1A,10/16 cases of CMTX1 and 1/9 cases of CMT2A2 (Fisher test,P=0.017).The leukoencephalopathy appeared only in 3 cases of CMTX1 and the visual loss appeared only in 3 cases of CMT2A2.The onion-bulb formations of myelinated fibers appeared in 23/23 cases of CMT1 A,5/16 cases of CMTX1 and 2/9 cases of CMT2A2(Fisher test,P =0.000).The axonal regeneration appeared in 16/23 cases of CMT1A,16/16 cases of CMTX1 and 9/9 cases of CMT2A2 (x2 =7.666,P =0.016).There were significant differences among the three common CMT subtypes in the above parameters.Conclusions CMT1A,CMT2A2 and CMTX1 are the most common subtypes of CMT in the present study.For the clinical diagnosis,more attention should be paid to the onset of the disease,duration,muscles weakness,pes cavus,cerebral symptoms and visual loss.The present frequency of onion-bulb and the axonal regeneration of myelinated fibers help the different pathological diagnosis among them.

OBJECTIVETo study the effects of dry red wine in the different stages of experimental atherosclerosis (AS) at the cell, molecular and gene regulation levels in order to provide scientific basis for using dry red wine in the prevention of atherosclerosis.

METHODSBlood vessel wall pathological changes, activity of NF-kB and the expressions of monocyte chemotactic protein-1 (MCP-1) and protein kinase C (PKC alpha) were observed in dietary induced atherosclerosis rabbit model by morphology study, electrophoretic mobility shift assay (EMSA), and in situ hybridyzation, and the effects of dry red wine intervention were examined.

RESULTSDry red wine significantly suppressed the proliferation of atherosclerosis intima and NF-kappaB activation (4w: 18.5 +/- 0.6 vs 13.7 +/- 0.3; 8w: 26 +/- 0.9 vs 17.8 +/- 0.5; 12w: 39.9 +/- 1.2 vs 27.8 +/- 0.8), and down-regulated the expressions of MCP-1 and PKC alpha.

CONCLUSIONSThe results confirmed that dry red wine could protect AS tissues and prolong its development by suppressing NF-kappaB activation, down-regulating the expressions of MCP-1 and PKC alpha, which may take part in pathogenesis of AS.

Animals ; Arteriosclerosis ; etiology ; pathology ; prevention & control ; Blood Vessels ; metabolism ; pathology ; Chemokine CCL2 ; genetics ; Diet, Atherogenic ; Disease Models, Animal ; Gene Expression ; In Situ Hybridization ; Male ; NF-kappa B ; metabolism ; Protein Kinase C ; genetics ; Rabbits ; Random Allocation ; Wine

Objective To report the clinical and peripheral neuropathological findings in two patients with autosomal recessive Charcot-Marie-Tooth disease 2K(AR-CMT2K).Methods Case one was a nine year-old girl.She had distal weakness of lower limbs for six years, with calf atrophy and contracture of Achilles tendon for three years.Case two was an eight year-old boy.He had distal weakness of lower limbs with contracture of Achilles tendon and calf muscle atrophy for three years, and proximal weakness of low limbs for two years.The motor nerve conduction velocities in median nerves were 48.1 m/s in case one and 47.6 m/s in case two.The compound motor action potential amplitude of median nerves decreased by 46% in case one and 69% in case two.Sural nerve biopsies and gene targeted next-generation sequencing were performed in both patients.Results Density of myelinated fibers was 8 407/mm2 in case one and 7 714/mm2 in case two.The ratio of myelinated fibers with diameter over 8 μm was 2.6% in case one and 0 in case two.Both patients had small regenerating cluster of myelinated fibers.Thin myelinated fibers appeared in case one.In case two, atypical onion bulb formations with focal folded myelin appeared, and electromicroscopy revealed mitochondrial aggregate in axons.Compound heterozygous mutations of ganglioside-induced differentiation associated protein 1 gene were detected in both patients, including c.767A>G(p.H256R) and c.466G>A (p.A156T) in case one and c.767A>G and 845G>A(p.R282H) in case two.Conclusions Contracture of Achilles tendon may appear in early childhood of AR-CMT2K patients.The main pathological changes in sural nerve are loss of large myelinated fibers, mitochondrial aggregate in axons and myelin abnormalities.

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 investigate the change and correlation of carbon monoxide/heme oxygenase and nitrogen monoxide/nitric oxide synthase system in atherosclerosis and the influence of the two systems on atherosclerotic progress.

METHODSThe rabbits received 1% cholesterol diet (chol group, n = 8), or 1% cholesterol diet plus L-arginine (L-arg group, n = 8) or L-NAME (L-NAME group, n = 8) by drinking water, or 1% cholesterol diet plus heme-L-lysinate (Heme group, n = 8) or ZnPP-IX (ZnPP group, n = 8) by injection in abdominal cavity for 10 weeks.

RESULTSCompared with those in control group, aortic NO production and expression of NOS decreased markedly; while CO production (P < 0.01) and HO-1 activity increased obviously in chol group. The aortic plaques area was (40.2 +/- 8.9)% in chol group. Compared with those in chol group, aortic areas [(26.6 +/- 9.2)%] reduced distinctly in heme group, aortic CO production and NOS activity increased obviously (P < 0.01) in L-arg group. However, compared with those in control group, HO-1 expression and CO production decreased markedly (P < 0.01) in heme group, while they were not different from those in chol group. Compared with those in chol group, aortic cNOS activity and NO production increased obviously and aortic plaques area [(28.1 +/- 7.7)%] greatly reduced (P < 0.01) in L-arg group. However, HO-1 expression and CO production of L-arg group decreased distinctly compared with those of control group, but they were similar to those of chol group. The aortic c-myc and c-fos expressions in both heme group and L-arg group reduced markedly compared with those in chol group, while they were similar to those in ZnPP and L-NAME group.

CONCLUSIONThe reciprocal relationship between heme oxygenase/carbon monoxide and nitric oxide synthase/nitrogen monoxide system in atherosclerosis may play the inhibitory role against atherosclerotic lesion.

Animals ; Atherosclerosis ; metabolism ; pathology ; physiopathology ; Carbon Monoxide ; metabolism ; Heme Oxygenase-1 ; metabolism ; Male ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Rabbits

Objective To summarize the clinical features of Chinese patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes ( MELAS).Methods A total of 190 patients with MELAS who presented to Peking University First Hospital between 1997 and 2015 were recruited.Among 190 patients, 175 were identified carrying mitochondrial DNA mutations, and the remaining 15 patients were diagnosed by muscle biopsy.The clinical features, including predisposing factors of stroke-like episodes, the onset symptoms and frequencies of various manifestations were analyzed and reported.Results In our cohort of MELAS patients, the male-to-female ratio was 1.44∶1.The median age of onset was 14 years ( from 7 months to 45 years).The peak onset ages were 8-12 years.The median onset age of the first stroke-like episode was 16 years ( from 1 to 53 years ).There were 66 ( 46.15%) patients who had predisposing factors before the onset, and fatigue and upper respiratory tract infection were the most common predisposing factors of stroke-like episodes in these patients ( 37.88%, 25/66 and 34.85%, 23/66, respectively).Other predisposing factors included emotional agitation, drinking alcohol, trauma, withdrawal of antiepileptic drugs, being frightened, satiation and hunger.Stroke-like episodes appeared in 70.53%(134/190) patients as an onset symptom and developed in all patients with disease progression.The neurological manifestations included seizure ( 89.42%, 169/189 ) , mental retardation or dementia (82.87%, 150/181), headache (74.30%, 133/179), hemianopia or cortical blindness (67.72%, 107/158), exercise intolerance (50.87%, 88/173), hemiplegia or hemianesthesia (47.44%, 74/156), sensorineural deafness (46.20%, 85/184), aphasia (39.47%, 60/152), behaviour disorder (17.71%, 31/175) and ophthalmoplegia ( 9.60%, 17/177 ).The manifestations of extra-nervous systems included hirsutism (67.57%, 100/148), vomiting (65.58%, 101/154), fever (62.07%, 90/145), short stature (45.32%, 63/139), diarrhea or constipation (43.48%, 70/161), low body mass index (26.62%, 37/139), diabetes mellitus (20.79%, 37/178) and kidney disease (3.16%, 6/190).Conclusions The majority of the patients in this study have the disease onset during childhood.There are more male MELAS patients than females.Most common clinical manifestations are seizure, mental retardation or dementia, headache, cortical blindness, hirsutism, vomiting and fever in this patient group.

Abstract: Objective To understand the mental health literacy level of residents in Hainan Province, and to provide evidence for promoting mental health promotion and improving the mental health literacy level of residents. Methods Multi-stage random sampling method was used to investigate The National Mental Health Literacy Questionnaire among 6 895 residents in 12 districts including Changjiang, Chengmai, Dongfang, Ledong, Lingshui, Haikou Longhua District, Haikou Meilan District, Qionghai, Sanya, Tunchang, Wenchang and Wuzhishan. Results　In the survey 6 895 residents in 12 counties, cities, districts of Hainan Province, 365 of them reached the standard of mental health with the standard rate of 5.3%. The mental health knowledge score was (54.00±17.02) with the standard rate of 7.7%; the self-assessment score was (26.11±3.99) with the standard rate of 75.9%; the score of mental health skill was (26.22±7.25) with the standard rate of 44.8%. The mental health literacy level of medical workers was the highest, with the standard rate of 13.5% (112/830), and the mental health literacy level of farmers was the lowest, with the standard rate of 0.8% (13/1 647). The results of unconditional Logistic regression showed that the factors entering the regression model included educational background (OR=2.268), personal monthly income (OR=1.129), gender (OR=1.302), household registration (OR=0.776), and whether they had participated in mental health related courses OR training (OR=0.511). The higher the educational background and personal monthly income, the higher the psychological quality. The mental health of women was higher than that of men, and that of urban was higher than that of rural, and those who had participated in mental health related courses were higher than those who had not. Conclusions The mental health literacy level of Hainan residents is at a low level, and the influencing factors are multifaceted. It is suggested to strengthen the mental health monitoring comprehensively and carry out rich health education service mode for different groups.

OBJECTIVETo determine the role and related mechanisms of heme oxygenase-1/carbon monoxide (HO-1/CO) on VSMCs proliferation induced by insulin-like growth factor-I (IGF-I).

METHODSVSMCs isolated from rabbit aorta were cultured in vitro and proliferation was induced by IGF-I. Hemin (a substrate and inducer of HO-1) or zinc protoporphyrin-IX (Znpp-IX, an inhibitor of HO-1) was added to stimulate or inhibit the expression of HO-1. The mRNA and protein expressions of HO-1 were detected by RT-PCR and Western blot analysis. CO released into the culture media was quantitated by measuring carbon monoxide hemoglobin (COHb), VSMCs proliferation and cell cycle were determined by (3)H-TdR incorporation assay and flow cytometry, respectively.

RESULTSThe HO-1 mRNA and protein expressions in VSMCs and the amount of COHb in the culture media were significantly increased and the IGF-I-induced (3)H-TdR incorporations of VSMCs significantly reduced by hemin in a dose-dependent manner (P < 0.01). Furthermore, VSMCs in the G(0)/G(1) phase were increased and in the S and G(2)/M phase decreased by hemin (P < 0.01). Opposite results were observed in VSMCs treated with Znpp-IX.

CONCLUSIONSEndogenous HO-1 and CO are important mediators for inhibiting IGF-I induced VSMCs proliferation by reducing VSMCs DNA synthesis and decelerating cell cycle progression.

Animals ; Carbon Monoxide ; metabolism ; Cell Proliferation ; Cells, Cultured ; Heme Oxygenase-1 ; metabolism ; Insulin-Like Growth Factor I ; pharmacology ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; cytology ; metabolism ; RNA, Messenger ; genetics ; Rabbits

OBJECTIVETo investigate the correlation between serum resistin level, cardiovascular risk factors and severity of coronary disease in acute coronary syndrome (ACS).

METHODSAfter evaluated by clinical history, electrocardiography, exercise tolerance tests, laboratory tests, and coronary angiography, 220 consecutive patients with suspected chest pain were divided into normal control group, stable angina pectoris (SAP) group, and ACS group, respectively. Baseline clinical characteristics, including height, weight, waist circumference, hip circumference, white blood cell count, high-sensitive C-reactive protein (hsCRP), total cholesterol, triglyceride, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, were compared among three groups. ELISA was used to detect serum resistin levels. Pearson's correlation coefficient analysis was used to assess association between resistin and other traditional cardiovascular risk factors. Multinomial logistic regression analyses were used to define the relationship between serum resistin level and SAP or ACS.

RESULTSSerum resistin level in ACS group (1.18+/-0.48 microg/L) was significantly higher than that in normal control and SAP groups (0.49+/-0.40 and 0.66+/-0.40 microg/L; P<0.01). Only in ACS group, increased serum resistin level was significantly correlated with hsCRP (r=0.262, P=0.004) and white blood cell count (r=0.347, P=0.001). Furthermore, serum resistin levels showed a stepwise increase with the number increase of > 50% stenosed coronary vessels. Multinomial logistic regression test demonstrated that serum resistin was a strong risk factor for ACS (OR=29.132, 95 % CI: 10.939-77.581, P<0.001).

CONCLUSIONThese findings suggested the potential role of resistin in atherosclerosis and especially its involvement in ACS.

Acute Coronary Syndrome ; blood ; pathology ; physiopathology ; Aged ; Biomarkers ; blood ; Case-Control Studies ; Coronary Disease ; blood ; pathology ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Resistin ; blood ; Risk Factors