Objective To study the real-time gait behavioral changes in rat models of experimental diabetic peripheral neuropathy.Methods Twenty-five SPF Sprague-Dawley rats were randomly divided into experimental group ( 6 males and 7 females) and control group (6 males and 6 females).Diabetes was induced in rats by intraperitoneal injection of streptozotocin ( STZ ) in a dose of 45 mg/kg.The gait behavior in all rats was tested at 12 weeks after diabetes modelling.Results Compared with the control group, the rats with diabetic peripheral neuropathy showed statistically significant different walk cycle extension, walk speed, average print intensity, balance and coordination.The abnormal gait behavior of the rat models was mainly reflected in the increased average and each foot walk cycle extension ( P<0.01 ) , average intensity (P<0.05), absolute average body rotation (P<0.01),and shortened both homologous coupling and homolateral coupling( P <0.05 ) .Conclusions Experimental rat models of diabetic peripheral neuropathy can exhibit obvious changes of gait behavior, and may provide a reference for related clinical and basic research.

Objective To determine the effects of curcumin microemulsion on proliferation and apoptosis of the human leukemia cell line K562 cells.Methods The curcumin microemulsion was prepared with the routine procedure.MTT assay was used to determine cell proliferation in cultured K562 cells,flow cytometry analysis was applied to examine cell apoptosis,and WT1 mRNA was determined with RT-PCR.The results about curcumin microemulsion were compared with these on curcumin.Results The prepared curcumin microemulsion was a stable clear solution with diameter of 10-100 nm.Curcumin microemulsion inhibited K562 cell proliferation by 24％,46％,68％with a 24 h incubation at dose of 2.5 μg/ml,5.0 μg/ml,and 10.0 μg/ml respectively,whereas curcumin reduced the proliferation by 6％,14％,25％at equal concentrations.WT1 mRNA level of curcumin microemulsion group(0.190±0.036)was reduced stronger than that of curcusin group(0.456±0.047).Conclusions Microemulsion is a great carrier for curcumin.Curcumin microemulsion is more effective in inhibiting proliferation,pro-apoptosis,and reducing WT1 gene expression than curcumin.A strong basis of medical value for the use of curcumin microemulsion to treat tumors is provided.

Objective To investigate the effects of bevacizunab on the antioxidative function of human retinal pigment epithelium (RPE),in order to explore the possible mechanism of macular atrophy induced by the application of anti-vascular epithelial growth factor (VEGF) agents in age-related macular degeneration.Methods Human RPE cells were incubated in DMEM/F12 medium containing 0.25 g · L-1 bevacizumab and divided into 5 groups according to incubation period:0 hour(control),12 hours,24 hours,48 hours and 72 hours,and then the oxidative stress was induced by adding H2O2.Cell viability was measured by the CCK8 assay.MitoSox Red was used to determine mitochondrial reactive oxygen species (mtROS) production.Mitochondrial membrane potential was measured using the JC-1 assay.The expression levels of NOX4 and HO-1 were detected by RT-PCR and Western blot,respectively.Results CCK8 assay determination showed that the above treatment had no significant effect on cell viability,the cell viability of 0 hours,12 hours,24 hours,48 hours and 72 hours were (100.2 ±3.3)％,(99.2 ±2.7)％,(102.5 ±6.4)％,(103.9 ±3.7)％,(103.6 ±3.3)％,the difference was not statistically significant (P ＞ 0.05).Compared with the control group,the levels of mtROS increased at 12 hours,24 hours,48 hours and 72 hours,the difference was statistically significant (P ＜ 0.05).Mitochondrial membrane potential at 12 hours,24 hours,48 hours,72 hours were lower than the control group,the difference was significant,48 hours reached the lowest,72 hours significantly increased,but still lower than the control group.RT-PCR and western blot results demonstrated that the expression of NOX4 mRNA and protein increased at 12 hours,24 hours,48 hours and 72 hours,and reached the highest at 24 hours,then decreased significantly,but still higher than the control group,the difference was statistically significant (P ＜0.01).Compared with the control group,the expression of HO-1 mRNA decreased at 24 hours,48 hours and 72 hours,while the expression of HO-1 protein decreased at 48 hours and 72 hours,the difference was statistically significant (P ＜ 0.05).Conclusion The clinical concentration of bevacizumab can reduce the anti-oxidative function of RPE cells,which may be one of the causes of progressive macular atrophy after long-term anti-VEGF therapy.

Objective To investigate the anti-inflammatory activity of the main active ingredients in the dried stem bark of Daphne giraldii Nitsche.Methods Severialchemical compounds like vladinol D, pinoresinol, daphneticin, daphnoretin, daphnetin, giraloid A and giraldoid B were isolated from the stem barks. The CCK-8 experiemnts were analyzed for the cytotoxicity study. The cells were divided into the control group, the model group and the treatment group according to random number table method. The control group and the model group were added with 50μl culture medium. Moreover, treatment group was added with different concentrations (50.00, 25.00, 12.50, 6.25, 3.12μg/ml) of the solutions of giraloid A, giraldoid B and daphneticin. Then, RAW264.7 cells were treated with 50μl LPS (4μg/ml) for 24 h in the model group and treatment group. Griess reagent was used to determine the amount of NO release, and the secretion of TNF-α was detected by ELISA kit.Results Cytotoxicity test indicated that giraldoid A (50.00μg/ml), giraldoid B (50.00μg/ml) and daphneticin (50.00μg/ml) showed noobvious cytotoxicity. Giraldoid B (12.50, 25.00, 50.00μg/ml) could inhibit the production of NO (271.86% ± 20.92%, 256.48% ± 20.92%, 199.31% ± 15.16%vs.358.62% ± 28.64%) and  TNF-α (647.87% ±115.79%, 618.42% ± 87.52%, 588.33% ± 87.94%vs. 1035.06% ± 58.29%) in RAW264.7 induced by LPS compared with the model group. Giraldoid A (25, 50μg/ml) could inhibit the production of NO (234.99% ± 34.28%, 167.36% ± 25.76% vs.358.62%±28.64%) and TNF-α (691.76% ± 60.37%, 534.01% ± 41.60% vs. 1035.06% ± 58.29%) in RAW264.7 induced by LPS compared with the model group. Daphneticin (12.5, 25, 50μg/ml) could inhibit the production of NO (283.89% ± 36.69%, 243.08% ± 48.19%, 225.92% ± 33.67% vs.358.62% ± 28.64%) and TNF-α (713.77% ± 121.96%, 670.62% ± 18.70% vs. 1035.06% ± 58.29%) in RAW264.7 induced by LPS compared with the model group.Conclusions Giraldoid A, giraldoid B and daphneticin exhi bited anti-inflammatory effect through inhibiting the release of NO and the production of TNF-α in RAW264.7 induced by LPS.

Objective To investigate the risk factors of worsening renal function (WRF) in patients with chronic heart failure ( CHF) and WRF influence on prognosis. Methods A case-control study were undertaken to analyze independent risk factor statistically related to incidence of WRF, and to assess the influence of WRF on prognosis. Results The independent predictors of WRF were creatinine level at admission (OR 2.248,95% CI 1.088-4.647, P = 0.029) and NYHA class on admission ( OR 2.485, 95% CI 1.3854. 459, P = 0.002). The mortality of patient with WRF was obviously higher than that of control group during hospitalization( OR 3. 824,95% CI 2. 452-5. 637 ,P ＜0.015). Conclusions WRF is a common complication among patients hospitalized for CHF, and is obviously associated with mortality during hospitalization. Higher creatinine level and weak heart function are independent risk factors for incidence of WRF of patients with CHF.

Objective To explore the effect of hospital-community-based collaborative management on elderly out-patients with chronic heart failure (CHF).Methods A total of 228 out-patients with CHF were randomly assigned to the community-based health management group (n =106 ) and the hospitalcommunity-based collaborative health management group (n =122).In community-based health management group,the patients only received community-based health management,while in hospital-community-based collaborative health management group the patients accepted comprehensive health management.One year later,medication compliance,readmission rate,mortality,average length of hospitalization,medical costs and Minnesota living with heart failure questionnaire (LiHFe) were compared between the two groups.Results No statistically significant differences in clinical data were found between the two groups at baseline.After one year,medication compliance was significantly improved in hospital-community-based collaborative health management group when compared to community-based health management group ( x2 =8.97,P ＜ 0.05 ).Readmission rate,averagelengthof hospitalizationandmedicalcostsof hospital-community-based collaborative health management group were lower than community-based health management group (x2 =9.91 ; t =3.78,3.61 ; all P ＜ 0.05 ).One year ago,the items of LiHFe including physical dimension,emotion,symptom and social dimension and total score showed no significant between the two group (t =0.42,0.81,0.66,0.44,0.41 ; all P ＞ 0.05 ).While one year later,all the scores of hospital-communitybased collaborative health management group were significantly declined( t =6.37,11.81,6.16,9.64,9.13;P ＜ 0.05 ).Mortality showed no significant difference between the two groups ( x2 =0.247,P ＞ 0.05 ).Conclusion Hospital-community-based collaborative management for health care may be a practical and valuable strategy for decreasing readmission rate and medical burden and improving quality of life of elderly patients with CHF.

This article was aimed to study the action of antigout effects of compoundWeifu. Through the acute gouty arthritis models of rabbits and rats induced by micro-crystal sodium urate (MSU). The histopathological changes of synovial tissues among rabbits were observed. And the contents of TNF-α, IL-1β, IL-6 in rabbit serum were determined. The swelling degree of the rats’ feet and the content of prostaglandin E2 (PGE2) from the inflammatory exudate foot induced by MSU were also determined. The antigout effects of compoundWeifu were observed. The results showed that the grade of the vascular congestion, swelling and inflammatory cell infiltration in synovial tissues in the high-dose and medium-dose CompoundWeifu group had significantly improved (P <0.05). And the levels of TNF-α, IL-1β, IL-6 in serum were significantly decreased (P< 0.05, orP < 0.01). It can obviously reduce the swelling degree induced by MSU, and the level of PGE2 in the inflammatory exudate foot (P< 0.05, orP < 0.01). It was concluded that CompoundWeifu had obvious antigout effects in the study.

Over the last decade, chronic critically ill (CCI) has emerged as an epidemic in intensive care unit (ICU) survivors worldwide. Advances in ICU technology and implementation of care bundles has significantly decreased early deaths of critically ill patients, and have allowed them to survive previously lethal multiple organ failure (MOF). However, more and more survivors leave persistent low grade organ dysfunctions, depend on continues organ support, need to stay in ICU, and become CCI patients. These patients experience a persistent immune dysregulation with persistent inflammation, immunosuppression, and catabolic syndrome. Therefore, malnutrition is an important feature of patients with CCI, and nutritional support is a crucial part of their treatment. The main strategies of nutritional support are as follows: providing sufficient calories and proteins with appropriate anabolic agents to promote anabolic metabolism, using immunomodulators to improve immune suppression and inflammatory responses, and supplementing micronutrients to enhance metabolic support. In this review, the nutritional assessment, calorie assessment, protein assessment and other nutrient supplementation (such as β blocker, testosterone and oxandrolone, immunonutrition, vitamins) of CCI patients were reviewed, so as to provide reference for the treatment of CCI.

Objective To evaluate the effect of hydrogen (H2) inhalation on brain injury in septic mice.Methods One hundred and eighty male ICR mice,aged 6-8 weeks,weighing 20-25 g,were randomly divided into 4 groups (n =45 each) using a random number table:sham operation group (SH group),H2 group,sepsis group (S group) and sepsis + H2 group (S + H2 group).Sepsis was produced by cecal ligation and puncture (CLP) in chloral hydrate-anesthetized mice.H2 and S + H2 groups inhaled 2％ H2 for 1 h starting from 1 and 6 h after CLP.At 7,12 and 24 h after CLP,6 mice in each group were sacrificed and brains were removed for determination of Evans Blue (EB) and water contents in brain tissues.Another 6 mice in each group were chosen at 7,12 and 24 h after CLP,blood samples were obtained,the mice were then sacrificed and brains were removed to measure the concentrations of tumor necrosis factor-α (TNF-α),high mobility group protein B1 (HMGB1) and interleukin-10 (IL-10) in serum and brain tissues by ELISA.Three mice in each group were sacrificed at 24 h after LPS and brains were removed for microscopic examination of pathological changes in hippocampal CA1 region.Six mice in each group were sacrificed at 24 h after LPS and brains were removed for determination of the expression of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in brain tissues by Western blot.Results Compared with SH group,the contents of EB and water in brain tissues were significantly increased,and the levels of TNF-α,HMGB1 and IL-10 in serum and brain tissues were increased at 7,12 and 24 h after CLP,and the expression of Nrf2 and HO-1 in brain tissues was up-regulated at 24 h after CLP in S and CLP + H2 groups,and no significant difference was found in the index above in H2 group.Compared with S group,the contents of EB and water in brain tissues were significantly decreased,the levels of TNF-α and HMGB1 in serum and brain tissues were decreased and the level of IL-10 in serum and brain tissues was increased at 7,12 and 24 h after CLP,and the expression of Nrf2 and HO-1 in brain tissues was up-regulated at 24 h after CLP and the pathological changes were attenuated in group CLP + H2.Conclusion H2 inhalation can attenuate brain injury in septic mice and the mechanism is related to activation of Nrf2/ARE signaling pathway and inhibition of inflammatory responses.

Objective To evaluate clinical features,insulin sensitivity and β-cell function of pregnant women with different glucose tolerance status,so as to identify the possible risk factors for adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM).Methods We retrospectively analyzed the clinical data of 360 pregnant women with positive results of 50 g glucose challenge test who received antenatal care and admitted for delivery in the period from January 2009 to June 2012 in Peking Union Medical College Hospital.According to the result of 100 g oral glucose tolerance test (OGTT),the 360 women were divided into GDM group (n =83),impaired glucose tolerance (IGT) group (n =75),and normal glucose tolerance (NGT) group (n =202).The blood glucose level in all those women was controlled in normal range for gestational period.We compared the general clinical data,biochemical indexes,insulin resistance index,insulin sensitivity index,function index of islet β-cell,first-and second-phase insulin secretion,insulin secretion-sensitivity index as well as the pregnancy outcomes of the 3 groups,analyzing the possible risk factors for adverse pregnancy outcomes in women with GDM.Results Compared with the NGT group,the pregnant women in GDM group were older [(33.1 ± 3.7) years vs.(31.7 ± 3.4) years,P =0.008],had higher systolic blood pressure [(115.8 ± 9.7) mmHg vs.(111.4 ± 13.5) mmHg (1 mmHg =0.133 kPa),P =0.031] and diastolic blood pressure in first trimester [(75.4 ±9.0) mmHg vs.(71.8 ±8.8) mmHg,P =0.010],higher positive rate of family history of diabetes in first-degree relatives (37.3％ vs.22.3％,P =0.012),positive rate of insulin therapy (10.8％ vs.0％,P =0.001),serum triglyceride level [(2.8 ±0.9) mmol/L vs.(2.3 ±0.9) mmol/L,P =0.001],free fatty acid level [(486.7 ± 137.6) μmol/L vs.(438.1 ± 140.7) μmol/L,P =0.033],and C-reactive protein level [(5.7 ± 4.3) mg/L vs.(3.6 ± 3.0) mg/L,P =0.001].The GDM group had a larger pre-pregnancy body mass index [(22.6 ± 2.9) kg/m2] than that in IGT group [(21.3 ± 2.7) kg/m2] (P =0.049) and NGT group [(21.2 ±2.8) kg/m2] (P =0.003).In the order from NGT to IGT to GDM group,the hemoglobin A1c [(5.2 ± 0.3) ％ vs.(5.3 ± 0.3) ％ vs.(5.4 ± 0.3) ％,P =0.001,P =0.007],the areas under curve of glucose [(20.4±2.0) mmol · h/L vs.(22.9 ± 1.5) mmol · h/L vs.(26.9 ±2.1) mmol · h/L,both P=0.001] and the areas under curve of insulin [(1.7 ±0.9) × 103 pmol · h/L vs.(2.1 ± 1.1) × 103 pmol · h/L vs.(2.7±1.3) ×103 pmol · h/L,P=0.001,P=0.007] increased gradually,while insulin sensitivity index (88.1 ± 52.1 vs.80.0 ± 30.6 vs.50.0 ± 24.1,P =0.001,P =0.014) and insulin secretion-sensitivity index (134 507.0 ± 43 291.0 vs.102 542.0 ± 15 291.0 vs.77 582.0 ± 20 764.0,both P =0.001) decreased gradually.The insulin resistance index in the GDM group (3.3 ± 2.2) was significantly higher than that in IGT (2.2 ± 1.0) and NGT groups (3.0 ± 1.1) (both P =0.001).The function of β-cell,first-and second-phase insulin secretion were not significantly different among the 3 groups.Compared with the NGT group,pregnant women with GDM had shorter gestational age [(38.8 ± 1.1) weeks vs.(39.4 ± 1.1) weeks,P=0.004] and higher incidence of adverse pregnancy outcomes (44.6％ vs.21.8％,P =0.001).Seven risk factors predicting adverse pregnancy outcomes in women with GDM were identified,including pre-pregnancy body mass index (P=0.017),0-,1-,and 2-hour blood glucose in 100 g OGTT (P=0.036,P=0.009,P=0.004),3-hour insulin (P =0.014),and hemoglobin A1 c (P =0.002) and C-reactive protein (P =0.005) in second trimester,among which 1-hour blood glucose displayed the highest coefficient (OR =2.767).Conclusions Pregnant women with GDM have elevated blood pressure,dyslipidemia and increased inflammatory cytokine C-reactive protein.Women with GDM and IGT both show insulin resistance and β-cell dysfunction,and these impairments are more severe in women with GDM.Higher pre-pregnancy body mass index and blood glucose levels during pregnancy are associated with adverse pregnancy outcomes in women with GDM.