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 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 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.

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 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.

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 investigate the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in the protective effects of hydrogen against cerebral dysfunction in a mouse model of sepsis.Methods Male ICR mice were randomly divided into sham operation group,hydrogen control group,sepsis group and hydrogen treatment group,with 20 in each group.Sepsis model was reproduced by cecal ligation and puncture (CLP).2％ hydrogen inhalation was given for 1 hour at 1 hour and 6 hours after operation in hydrogen treatment group.The brain tissues were obtained at 24 hours after operation.The histopathologic changes and neuron apoptosis in the hippocampus were observed under the microscope.The expressions of nucleus and total Nrf2 in hippocampus were detected by Western Blot.The activities of superoxide dismutase (SOD),catalase (CAT),malondialdehyde (MDA) and 8-iso-prostaglandin F2α (8-iso-PGF2α)in hippocampus were also detected.The changes of learning and memory abilities were observed by Morris water maze test at day 4 to 9 after operation.Results Compared with the sham operation and hydrogen control groups,in the sepsis group,the number of normal pyramidal neurons in the hippocampal CA1 region was markedly reduced,the apoptotic index was marked increased,the expressions of nucleus and total Nrf2 were partly increased,the activities of SOD and CAT in the hippocampus were significantly decreased,and the levels of MDA and 8-iso-PGF2α were markedly increased,the escape latency at day 4 to 8 after operation was significantly extended,and there was no difference in swimming speed,the percentage of time in the target quadrant and the times of the platform crossing were significantly decreased on probe day.Compared with the sepsis group,in the hydrogen treatment group,the number of normal pyramidal neurons in the hippocampal CA1 region was markedly increased (67.33 ± 6.89 vs.42.33 ± 6.02,P＜0.01),the apoptotic index was dramatically reduced [(30.00 ± 4.77)％ vs.(80.50 ± 6.99)％,P＜0.01],the expressions of nucleus and total Nrf2 were significantly increased [nucleus Nrf2 (A value):5.07 ± 0.35 vs.3.04 ± 0.34,total Nrf2 (A value):4.24 ± 0.58 vs.2.91 ± 0.37,both P＜0.01],the activities of SOD and CAT in the hippocampus were significantly increased [SOD (U/mg):120.96 ± 13.44 vs.81.16 ± 12.28,CAT (U/mg):9.11 ± 1.28 vs.5.64 ± 1.88,both P＜0.01],and the levels of MDA and 8-iso-PGF2α were markedly reduced [MDA (nmol/mg):16.12 ± 1.49 vs.27.64 ± 1.87,8-iso-PGF2α (pg/mg):183.43 ± 13.07 vs.864.07 ± 49.92,both P＜0.01],the escape latency at day 5 to 8 after operation was significantly shortened,and there was no difference in swimming speed,the percentage of time in the target quadrant [(37.06 ± 1.16)％ vs.(24.42 ± 1.82)％,P＜0.01] and the times of the platform crossing (7.13 ± 0.98 vs.4.88 ± 0.99,P＜0.01) were significantly increased on probe day.There was no statistical difference in above indexes between sham operation group and hydrogen control group.Conclusion Hydrogen inhalation can ameliorate pathological injury in brain and impairment of learning and memory abilities of septic mice,which may be associated with the up-regulation of Nrf2,the increase of antioxidant enzymes activities and the decrease of oxidative products.

Objective To investigate the awareness,willingness,motivation,and influencing factors of outpatients for participating drug clinical trials,and provide references for decision-making of drug clinical trials.Methods An amnonymous survey was conducted in the departments of internal medicine,surgery,gynecology,and obstetrics of a randomly selected tertiary referral center,and the results were statistically analyzed.Results A total of 1 067 available questionnaires were received.The total awareness rate of clinical trials was 31.02％,which was closely correlated with age and the degree of education.40.86％ of respondents were willing to participate in drug clinical trials.And 55.28％ of them chose yes because of the willingness to contribute to the development of medical science.People having cognition on clinical trials had more willingness to participate in drug(OR:1.361,95 ％ CI:1.042-1.777).59.14％ of the respondents refused to participate in drug clinical trials,68.62％ of whom refusing to participate mainly worried about the safety of drugs.57.37％ of the respondents comfirmed that they might change their idea if experts were involved.41.33％ were willing to accept training about clinical trials.Conclusion Investigators'overall cognition on clinical trials is closely correlated with the willingness to participate in drug clinical trials.There should propagandize drug clinical trials to make sure the improvement of drug clinical trial progress.