Objective To study whether the protective effects of fenofibrate on insulin resistance in mice of nonal-coholic fatty liver disease(NAFLD) are related to endoplasmic reticulum stress (ERS). Methods Male C57BL/6 mice were fed with high-calorie and high-cholesterol diet ( HCD) to induce a model of NAFLD, then one of those two groups from HCD was treated with fenofibrate 40 mg/( kg · d ) for 2 weeks ( HCF ) . Glucose tolerance test (GTT) and insulin tolerance test (ITT) were used to analyze the improvement on insulin resistance. The serum levels of triglyceride ( TG) , total cholesterol ( TC) , high density lipoprotein-cholesterol ( HDL-C) , low density lip-oprotein-cholesterol ( LDL-C) , alanine aminotransferase ( ALT) and aspartic transaminase ( AST) were detected. The pathological changes of livers were detected with HE and Oil Red O staining, the mRNA and protein expression of peroxisome proliferator-activated receptorα( PPARα) , glucose regulated protein 78 ( GRP78 ) and transcription factors GADD153 ( CHOP) were detected with real-time quantification PCR and Western blot analysis respectively. Results Compared with the SCD mice, the HCD mice showed significant insulin resistance, higher serum levels of TG, TC and LDL-C (P<0. 01, P<0. 05), lower serum level of HDL-C (P<0. 01), micro-and macrovesicular steatosis, ballooned hepatocytes and infiltration of inflammatory cells were observed in the liver, the expressions of PPARα and GRP78 at mRNA and protein levels were decreased (P<0. 05), however, the expressions of CHOP at mRNA and protein levels were increased ( P<0 . 05 ) . Fenofibrate intervention significantly improved insulin resist-ance and decreased the serum level of TG ( P<0. 05 ) . Fenofibrate also alleviated hepatic steatosis and inflammato-ry infiltration, and increased the mRNA and protein expressions of PPARα and GRP78, decreased the mRNA and protein expression of CHOP ( P<0 . 05 ) . Conclusion Fenofibrate significantly improves insulin resistance and de-creases the serum level of TG in NAFLD mice, which may be related to activating PPARα and relieving ERS.

Objective To analyze the immunogenomic characteristics of antibody repertoire in re-sponse to influenza vaccine in order to provide a theoretical basis for further development of antibody. Meth-ods Based on a time-series immunoglobulin heavy chain ( IGH) repertoire sequencing dataset, we analyzed the immunogenomic characteristics of antibody repertoire in response to trivalent influenza vaccine ( TIV ) from three aspects which included the features in complementarity-determining region 3 ( CDR3 ) , antibody mutation and VDJ usage. Results The frequency of antibody mutation increased significantly upon vaccina-tion. Analysis of the CDR3 region indicated that polar and aromatic amino acids had a higher preference. The length of CDR3 region in naive B cells followed a normal distribution, while specific CDR3 sequences with 15 to 18 amino acids in length occupied a dominant position after vaccination. In addition, the VDJ us-age altered obviously and IGHV3-7-derived antibody had a significant response to the vaccine. Response in-tensity reached the peak on day 7 and gradually weakened over time. Conclusion Antibody repertoire evolves dynamically to express specific antibody upon vaccination and the characteristics of immune responses at sequence level could be used to evaluate their effectiveness.

Background As myopia is a common ocular condition which has been reported as the risk factor of primary open angle glaucoma,it is of great importance to evaluate the optic disc morphology in myopic eyes.Objective This study was to evaluate the agreement of optic disc measurements between Cirrus high-density optical coherence tomography (HD-OCT) and Heidelberg retina tomograph (HRT) in myopic eyes;and to investigate the relationships between axial length (AL) and differences of optic disc parameters measured with the two devices.Methods One hundred and fifty myopic subjects were included in this prospective cross-sectional study.One eye from each subject was randomly selected for optic disc imaging by Cirrus HD-OCT and HRT2 in Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong from September to December in 2010 under the approval of Ethic Committee of this hospital and informed consent of each patient was received.Each subject received complete ophthalmic examinations including intraocular pressure (IOP) measurement,visual acuity,refraction,slit lamp,dilated fundus examination and perimetry.The subjects were divided into low (≤-3.00 D,35 eyes),moderate (-3.00 D＜SE＜-6.00 D,60 eyes) and high myopia (SE ≥-6.00 D,55 eyes) groups according to the refractive status.Measurement of axial length was performed with IOL master.Optic disc parameters including disc area,rim area,cup volume,vertical cup-to-disc ratio (VCDR) and average cup-to-disc area ratio (ACDR) were measured by Cirrus HD-OCT and HRT2,respectively.The OCT measurements were corrected for ocular magnification using the Littman's formula,and the results were compared between the instruments.The measurement agreement was evaluated using Bland-Altman plots.Pearson correlation analysis was used to evaluate the associations between AL and the measurement differences of the two instruments.Results The mean axial length and refraction were (25.62±1.10) mm and (-5.22±2.34) D,respectively.The corrected optic disc parameters were significantly larger than those without adjustment by using Cirrus HD-OCT (all at P＜ 0.001).In the high myopic group,the disc area measured by Cirrus HD-OCT was significantly larger than that by HRT2 (P＜0.001).In the moderate myopic group,the rim area measured by HRT2 was significantly larger than that by the Cirrus HD-OCT (P =0.040).The measurements of ACDR,VCDR and cup volume by Cirrus HD-OCT were all larger than those by HRT2 in the three myopic groups (all at P＜0.001).The 95％ limits of agreement (LoA) of disc area and rim area with the two devices were-0.64 to 0.74 and-0.74 mm to 0.62 mm2,respectively.The differences of disc area,rim area and cup volume measurements from the two devices were significantly and positively associated with axial length (r=0.158,0.148,0.156,all at P＜0.05).No significant correlation was detected between AL and the differences of ACDR and VCDR (r =0.012,0.093,both at P ＞ 0.05).Conclusions Optic disc parameters measured by Cirrus HD-OCT are affected by optical magnification in myopic eyes.Poor agreement is found across all of the disc measurements with Cirrus HD-OCT and HRT2.The two devices should not be used interchangeably for measurements of optic disc.Moreover,the differences between measurements of the two devices are significantly associated with AL.

Humans ; Protein Kinase Inhibitors ; therapeutic use ; Protein-Tyrosine Kinases ; antagonists & inhibitors

Objective To explore the relationship between quality of life and sub-health state of Guangdong urban dwellers.Methods A total of 2 200 urban dwellers were investigated using SF-36 and Sub-Heahh Measurement Scale Version 1.0(SHMS V1.0).Results As for the scores in PCS,MCS,psychosocial symptom,cognitive function,social adaptability,those of man urban dwellers (respectively (78.89± 15.25),(73.15 ± 15.26),(63.73± 18.82),(62.13± 19.34),(68.04± 17.90)) were higher than those of woman dwellers (respectively(76.98± 14.20),(71.76± 14.72),(60.53± 18.28),(57.00± 17.89),(65.73± 17.07)).The difference was statistically significant (P＜0.05).Bivariate correlation analysis showed that the PCS and MCS of quality of life were positively related with all dimensions of sub-health (P＜0.001).Canonical correlation analysis indicated that vitality,social adaptability,psychosocial symptom and positive emotion were the main factors of sub-health status,and MCS was of quality of life.Conclusion Sub-health state of Guangdong urban dwellers is positively related with quality of life,and the more serious sub-health state is,the worse quality of life is.Therefore,intervention of subhealth and quality of life should be targeted to be strengthened according to the investigation.

Objective To investigate the necessity and tolerance of operation for hip fracture in patients aged 75 years and over. Methods The general tolerance including the self-care ability, comorbidities and postoperative complications was retrospectively analyzed in 70 elderly patients with hip fracture. Then the relationship between operation and survival status was estimated. Results The average tolerance score was significantly higher in 46 patients who accepted the operation than in 24 patients who didn't C(76. 1±12. 2) vs. (65. 5±13. 9), P<0. 01]. The median survival period was significantly higher in operation group than in non-operation group ( 97 mouths vs. 48 mouths, P< 0. 05). Kaplan Meier analysis showed that the survival status was better in operation group than in non-operation group. Conclusions For elderly patients over 75 years old with hip fracture, comprehensive evaluations of surgical tolerance before operation are very important for assessing the perioperative risk and feasibility of surgery. The operative treatment is a reasonable choice, as long as the operation is well tolerated by the patients.

Objective To evaluate the effects of recombinant human bone morphogenetic-2-polylactide sustained release nanospheres (rhBMP-2-PLA-Ns) on cultured rabbit osteoblasts in vitro. Methods Rabbit osteoblasts were cultured in vitro, and rhBMP-2-PLA-Ns was added into the medium of the third generation of rabbit osteoblasts. The expression of the proliferating cell nuclear antigen (PCNA) was examined by immunofluoreacence staining, and the formation of tuberculums observed with alizarin red staining. Western blot was used to detect the effects of rhBMP-2-PLA-Ns on the expression of vascular endothelial growth factor (VEGF), which was compared with that in rhBMP-2 group and blank group. Results There was no significant difference in the number of osteoblasts with positive PCNA expression among three groups five days later. Ten days later, the number of osteoblasts with positive PCNA expression in rhBMP-2-PLA-Ns group was significantly higher than that in rhBMP-2 group and blank group, which indicated that rhBMP-2-PLA-Ns could enhance the expression of PCNA. Compared with rhBMP-2 group and blank group, rhBMP-2-PLA-Ns could significantly enhance the formation of tuberculums, with statistical difference (P<0.05). The expression of VEGF was detected in all three groups, and the level of the VEGF expression in rhBMP-2-PLA-Ns group was significantly higher than that in the other 2 groups (P<0.05). Conclusion The biological activity of rhBMP-2-PLA-Ns is superior than that of rhBMP2, and rhBMP-2-PLA-Ns can promote the proliferation, mineralization of osteoblasts and the secretion of VEGF, which has a better prospect in facilitating traumatic bone healing.

Objective To study the influences of fenofibrate on oxidative stress and endoplasmic reticulum stress in livers of hyperlipidemic rats. Methods Male SD rats were fed with high-fat diet for 12 weeks to induce a model of hyperlipidemia, then divided into control group, high-fat diet group with another four-week high-fat diet and fenofibrate group, in which rats were treated with fenofibrate [100 mg / (kg·d)] for 4 weeks. Then improvement of insulin resistance was detected in rats with GTT and ITT experiment. The serum levels of glucose (GLU), fasting insulin (FINS),triglyceride (TG) and total cholesterol (TC) were detected. The pathological changes of livers were detected with Oil Red O staining. The oxidative stress indices such as T-SOD, Mn-SOD, GSH and T-AOC were detected with liver homogenate. The expression of GRP78 was detected with real-time quantification RT-PCR and Western blot analysis respectively. Results Compared with rats with high-fat-diet, rats after fenofibrate treatment showed obviously improved insulin resistance, lower serum level of TG, TC and FINS (P < 0.05), decreased number and size of lipid droplets in liver tissue sections. T-SOD level in liver homogenate was significantly increased (P < 0.05), while GSH and T-AOC levels increased but had no obvious differences when compared with control group (P > 0.05). The expression of GRP78 at mRNA and protein levels were increased significantly after fenofibrate treatment (P < 0.05). Conclusions Fenofibrate has significant effects on improving insulin resistance and lipid regulation, which might be related to decreased oxidative stress and subsequent endoplasmic reticulum stress.

Aim To investigate endoplasmic reticulum stress ( ERS)-mediated high-fat diet and palmitic acid-induced insulin resistance ( IR) in skeletal muscle and interventional effects of fenofibrate both in vivo and in vitro tests. Methods Female SD rats were randomly subjected to a standard control diet ( SCD) or high-fat diet ( HFD) for 20 weeks, then the HFD group was di-vided into high-fat-diet group and high-fat-diet group treated with fenofibrate ( HFD +FF, 30 mg · kg-1 · d-1 ) for another 8 weeks. The changes of IR and ex-pression of peroxisome proliferator-activated receptor α( PPARα) , glucose regulated protein 78 ( GRP78 ) and transcription factors GADD153 ( CHOP ) were as-sessed respectively. C2C12 myotubes were divided into normal control group ( NC ) , model group ( palmitic acid, PA) , postive control drug group ( tunicamycin, TM) and treatment group ( fenofibric acid, FA+PA) , the expressions of GRP78 and CHOP were assessed re-spectively. Insulin-stimulated phosphorylation of Akt was also analyzed to detect changes of insulin sensitivi-ty in C2 C12 . Results The high-fat diet induced obvi-ous IR and upregulated ERS markers GRP78 and CHOP in skeletal muscle of rats, and these responses were attenuated by treatment with fenofibrate. Incuba-tion of myotubes with palmitic acid or tunicamycin sig-nificantly increased expression of ERS markers GRP78 and CHOP. Meanwhile, insulin-stimulated phosphoryl-ation of Akt was inhibited obviously. Pre-incubation with FA markedly inverted PA-induced ERS and insu-lin-stimulated phosphorylation of Akt. Conclusion Fenofibrate ( fenofibric acid) has obvious effects of IR on skeletal muscle tissues and cells, which may be re-lated with reduced expression of GRP78 and CHOP in ERS.

Objective To investigate the clinical significance of homocysteine(Hcy) and glycated hemoglobin (HbA1c) in patients with diabetic retinopathy.Methods From March 2013 to February 2015,a total of 168 patients with diabetes from Beijing Jishuitern Hospital were divided into diabetic retinopathy group (76 cases,32 male,44 female,average age 62.97 ± 12.46) and non-diabetic retinopathy group (92 cases,46male,46 female,average age 58.14 ± 13.71),and 65 cases of healthy subjects (46male,46 female,average age 60.24 ± 10.85) were enrolled as normal control group as well.Hcy and HbA1c were detected in all groups.Multiple independent samples nonparametric tests were used to compare the difference between groups.The concentrations of Hcy and HbA1c between DR group and NDR group were analysised by ROC curve analysis.Result The Hcy levels in normal control group,NDR group and DR group were 7.00 (4.55-10.50) μmol/L,12.45 (10.30-15.10) μmol/L,20.10 (16.63-25.68) μmol/L respectively.The HbA1c levels in normal control group,NDR group and DR group were 5.30 (5.00-5.70) ％,6.80 (5.83-8.03) ％,7.25 (6.50-8.60) ％ respectively.There was no significant difference in Hay and HbA1c levels between groups (P ＜ 0.01);Compared with non-diabetic retinopathy group,levels of Hcy,HbA1c in diabetic retinopathy group were obviously higher;The optimal diagnostic cut-off values of Hcy was 14.35 μmol/L,at this cut-off value,the sensitivity was 96.05％,specificity was 68.48％;The optimal diagnostic cut-off values of HbA1c was 6.05％,at this cut-off value,the sensitivity was 98.68％,specificity was31.25％.Conclusion Patients with Diabetic retinopathy might have hyperhomocystinemia,and detection of Hcy may contribute to the early diagnosis of diabetic retinopathy.