Chronic obstructive pulmonary disease and asthma are complex inflammatory diseases with airway obstruction as the main characteristics, and have become common respiratory diseases that seriously affect human health. Compared with the clinical use of PDE3 or PDE4 inhibitors alone, dual PDE3/4 inhibitors have synergistic anti-inflammatory and bronchodilator effects, and have attracted widespread attention in recent years. This article reviews the representative research results of dual PDE3/4 inhibitors currently in the preclinical and clinical research stages, summarizing their latest progress and their potential for the treatment of chronic obstructive pulmonary disease and asthma.

Four-week-old male Sprague-Dawley rats were rendered diabetic by intraperitoneal injection of streptozotocin (STZ) after feeding high-fat-diet for 8 weeks,and divided into diabetes group and tumor necrosis factorrelated apoptosis ligand(TRAIL) group.Normal rats severed as a control group.Treatment with TRAIL lasted for 3 months.Total cholesterol,triglycerides,low-density lipoprotein-cholesterol,blood glucose,and insulin levels were decreased in TRAIL group,as compared with diabetes group.Area of atherosclerotic lesion in TRAIL group [(23.8 ± 5.7) ％] was significantly smaller than that in diabetes group [(47.6 ± 7.8) ％].It suggested that TRAIL may reduce the area of atherosclerotic lesion in diabetic rats.

Forty-two patients with type 2 diabetes mellitus (DM) were refered to 3 groups:type 2 DM without diabetic nephropathy (DN),type 2 DM with DN in the initial stage and type 2 DM with DN in the clinical stage.Ten healthy subjects were served as control group.Plasma adrenomedullin (ADM),urinary?_1- microglobulin (MG) and?_2-MG were detected.The results showed that the level of plasma ADM rose gradually with the development of DN and was positively correlated with markers of tubulointerstiial injury such as urinary?_1- MG and?_2-MG (both P

Objective:To determine berberine and palmatine in Phellodendron chinense Schneid.and its granules.Methods: The reversed-phase ion pair high performance liquid chromatography(RP-HPLC) was used and the validation of the method was tested.The chromatography condition was with Lichrospher C18 column(4.6 mm?250 mm,5 ?m), mobile phase was ACN∶25 mmol/L NaH 2PO 4∶25 mmol/L SDS(2∶1∶1),flow speed was 1.0 ml/min,detection wavelength was 345 nm,and temperature of column was 25℃,Phellodendron chinense Schneid.and its granules were extracted with methanol solution of hydrochloric acid.Results: The theoretical plate number of berberine and palmatine were 14 906 and 14 847,the resolution were 2.33 and 2.86,the tailing factor were 1.09 and 1.06,respectively; all the parameters were suitable for determination.The calibration curves were linear in the range of 40-500 ng,Y=698 278X-3 846,r=1.000(berberine) and 20-250 ng, Y= 536 632X- 7 738, r=0.999 9,r=0.999 4(palmatine).The intra-day and inter-day precision(RSD) at low,middle and high injection amount was all less than 2.5%(berberine) and 1.5%(palmatine).The stability(RSD) was 0.66%(berberine) and 0.70% (palmatine) in 48 h.The recurrence(RSD,n=5) was 0.11%(berberine) and 0.12%(palmatine).The limits of detection was 2.0 ng(berberine) and 1.0 ng(palmatine).The recoveries were 100.4% (RSD=0.12%,n=3) for berberine and 99.80%(RSD=0.22%,n=3) for palmatine.The contents of berberine and palmatine in 3 batch of Phellodendron chinense Schneid.and 5 batch of its granules were determined.Conclusion: Our method can be used for determination of berberine and palmatine in Phellodendron chinense Schneid.and its granules, which is simple and reliable.

Objective To investigate the effect of growth differentiation factor 11 ( GDF11 ) on aorta in apolipoprotein E-Null( ApoE-/-) mice and its possible mechanisms. Methods Four-week-old healthy male ApoE-/-mice were fed with high-fat diet for 1 week and were then divided into 4 groups:vehicle group(n=10), GDF11 group (n=10),adeno-associated virus-green fluorescent protein group(AAV-GFP group, n=10), and AAV-GDF11 group ( n=10 ) . The mice received intraperitoneal injection with phosphate buffered saline, GDF11 protein, a single injection of purified AAV-GDF11 or AAV-GFP through the tail vein, respectively. After 4 weeks, serum GDF11/8 level and endothelium-dependent vasodilatation were detected. After 12 weeks, serum GDF11/8, interleukin-6 (IL-6), tumor necrosis factor-α( TNF-α), total cholesterol ( TC), triglycerides ( TG), oxidized low density lipoprotein(ox-LDL), and free fatty acids(FFA)levels were measured, the plaque areas in aortic enface and cross sections were measured by oil red O or HE staining, the macrophages/T lymphocytes infiltration in plaques were detected with immunohistochemistry, and the mRNA expressions of IL-6, TNF-α, and IL-10 were determined by real-time PCR. Results Compared with vehicle or AAV-GFP groups, GDF11 and AAV-GDF11 groups presented improved endothelium-dependent vasodilatation, decreased levels of blood inflammatory factors, blood lipid, reduced plaque on face area sections[Vehicle group : GDF11 group:(31. 23 ± 3. 12)% vs (17. 18 ± 2. 17) %;AAV-GFP group : AAV-GDF11 group:(38.01±4.43)% vs(14.54±2.86)%,P<0.05]andcrosssections[Vehiclegroup :GDF11 group:(19. 87 ± 2. 11)% vs (10. 32 ± 1. 47)%;AAV-GFP group : AAV-GDF11 group:(23. 02 ± 2. 76)%vs (9.06±1.63)%, P<0. 05]. There were less macrophages and T lymphocytes infiltration in plaques and lower mRNA expressions of inflammatory factors at aortic wall. Conclusion GDF11 reduces the area of atherosclerotic lesion in ApoE-/-mice, which may be involved in endothelial protection, such as to reduce inflammatory reaction, and to change cellular composition in plaques.

Objective: To explore the effect of irisin on atherosclerosis with possible mechanisms in diabetes mellitus (DM) mice. Methods: A total of 30 ApoE-/- mice were randomly divided into 2 groups: Control group, the mice received citrate buffer solution for modeling control,n=10. DM group, the mice received streptozotocin injection for DM modeling,n=20; the DM group was further divided into 2 subgroups as DM control (DM-C) group, the mice received normal saline injection for 12 weeks and DM + irisin group, the diabetic mice received irisin injection for 12 weeks.n=10 in each subgroup. With 4 weeks of irisin intervention, the endothelium-dependent vasodilatation was detected. With 12 weeks of intervention, the blood levels of tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and oxidized low-density lipoprotein (ox-LDL) were examined by ELISA, the plaque areas in aortic en face and cross sections were measured by Oil red O or HE staining, the macrophages/T lymphocytes inifltration in plaques were detected with immunohistochemistry, and the mRNA expressions of IL-6, IL-10, TNF-α were determined by RT-PCR. Results: Compared with DM-C group, DM + irisin group presented improved endothelium-dependent vasodilatation, decreased levels of blood inlfammatory factors, reduced plaque on face area sections (22.57 ± 2.17) % vs (35.09 ± 2.38) % and cross sections (19.36 ± 1.85) % vs (25.53 ± 7.87) %,P < 0.05, less macrophages (30.5 ± 2.79) % vs (41.34 ± 9.13) % T and lymphocytes infiltration (28.11 ± 4.24) % vs (35.79 ± 9.11) % in plaques and lower mRNA expressions of inflammatory factors(IL-6: 1.76 ± 0.50 vs 3.78 ± 1.15; TNF-α: 1.05 ± 0.30 vs 2.11 ± 0.48; ICAM-1: 1.96 ± 0.69 vs 2.71 ± 0.72; VCAM-1: 0.87 ± 0.21vs 1.45±0.25; MCP-1: 1.34 ± 0.34 vs 1.77 ± 0.55) at aortic wall, P<0.05.Conclusion: Irisin may improve atherosclerosis condition in ApoE-/- DM mice, the endothelial protection and antiinflammatoryreaction were the important mechanisms. Irisin has the potential for preventing/treating atherosclerosis.

Objective To investigate the effects of growth differentiation factor 11 ( GDF11 ) on β-cell function in db/db mice and its possible mechanism. Methods Twenty eight-week-old male db/db mice were randomizedtoi.p. administration of GDF11(0.3mg·kg-1·day-1)or equivalent PBS(n=10)for 6 weeks.10age-matched male db/m were used as normal control, received equivalent PBS injection for 6 weeks. Blood glucose levels, body weights and food intake were monitored weekly. IPGTT and glucose-stimulated insulin secretion ( GSIS) were analyzed. After 6 weeks of intervention, serum HbA1C , TG, TC, and FFA were measured respectively. The concentrations of hormones in serum and pancreas were evaluated. The mRNA expression of Pdx-1, MafA, Nkx6. 1, and insulin2 were determined by RT-PCR. The expression of phosphorylated Smd2 (P-Smad2), Smad2 in islet were examined by western blot. Results Compared with NC group, GDF11 administration decreased FBG, HbA1C , modified lipid profiles. GDF11 improved glucose tolerance and augmented GSIS. Moreover, GDF11 increased serum insulin and pancreatic insulin content, while decreased serum glucagon concentration. The expression of Pdx-1, MafA, Nkx6. 1, and Insulin2 were significantly increased in GDF11 group. GDF11 elevated the expression of P-Smad2 in islets. Conclusion s GDF11 may preserve β-cell function and facilitate the secretion and production of insulin. Diminishing the metabolic abnormalities, alleviating the secretion of glucagon, as well as maintaining the key transcript factor activation may contribute to the amelioration of β-cell function after GDF11 administration. Smad2 pathway may be related to the protective effects of GDF11.

ObjectiveTo observe the effect of megace (MA) on the survival condition of cancer patients in chemotherapy (CT) periods.Methods92 patients with cancer were divided into the MA group (treated with MA+CT) and control group (treated only with CT). The changing of the appetite, normal food amount, weight, gastrointestinal reaction and whole body conditions of two groups were evaluated.ResultsIn the MA group, 52.2% patients had appetite improvement, 47.8% had more food amount, 45.7% gained more weight, 50% had no obvious gastrointestinal reaction such as vomiting and nausea, and 50% had improve the survival condition according to the Karnofsky performance status (KPS) scores (increment >10). In the control group, only 6.5% had appetite improvement, 4.3% had more food amount, 13% gained more weight, 28.3% had no vomiting and nausea, and 15.2% had improved the survival condition. There was a significant difference between two groups (P<0.01).ConclusionMegace is able to reduce nausea and vomiting caused by CT, improve appetite, increase patients weight, protect bone marrow from the inhibition of CT, improve the life quality of cancer patients, and has no evident side-effects.

Molecular methods and fluoroscopic techniques suggest that rich microbial diversity exist in the marine environment, but less than 1% of these microbes can be cultured in the laboratory conditions, and that the cultivable dominant species were even less. This limitation has long been a barrier to the development of environmental microbiology and the utilization of marine resources. In the past decade, novel methods for culture and detection of these uncultured marine microbes have successfully applied to obtain several conventionally-uncultured microbes including those from extreme environments. Those progresses have inspired researchers greatly. Developments in the research of marine microbial resources are an important basis for the study of the micro-world and deserve increasing scientific attention.

Humanumbilicalveinendothelialcells(HUVECs)weretreatedwith3nmol/Lliraglutidefor10, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, and 270 minutes at the concentrations of 5. 5 or 30 mmol/L glucose. Western blot analysis was used to detected protein expression and phosphorylation of insulin receptor substrates-1 ( IRS-1 ) and endothelial nitric oxide synthase ( eNOS ) . The results showed that the baseline level of phosphorylated-eNOS/eNOS was lower in high glucose group than that in normal group(0. 239 ± 0. 016 vs 0. 400 ± 0. 02,P<0. 05). Liraglutide time-dependently increased phosphorylated-eNOS/eNOS and phosphorylated-IRS-1/IRS-1 levels at 5. 5 or 30 mmol/L glucose.