The new generation cyclooxygenase (COX-2) inhibitor could reduce the gastrointestinal side effect of NSAID drugs, but eventually increase the cardiovascular risk, because its selective inhibition of COX-2 induces the imbalance between PGI2 and TXA2 and the reduction of vasodilatory NO. Under pathological conditions, active oxygen species (O2-*2, etc) were used to induce endo- thelial dysfunction, activate NF-κB to induce expressions of pro-inflammatory cytokines IL-1β and TNF-α, increase ET-1, TXA2 with vasoconstrictor effect, reduce PGI2 and NO with vasodilatory effect, generate further oxidative damage together with NO, and reduce the bioavailability of NO. NO-NSAIDs and NO-Coxibs drugs raised the level of NO by introducing NO-donor (ONO2). NSAIDs drugs enhanced the anti-inflammatory activity of COX-2 and reduced gastrointestinal side effects by inhibiting selectively COX-2. If antioxidant structures with active ingredients of traditional Chinese medicines were introduced to improve the antioxidant activity of NSAIDs, they could scavenge the active oxygen species to protect the normal function of vascular endothelia and enhance the bioavailability of NO, which is conducive to enhance the cardiovascular safety of cyclooxygenase (COX-2) inhibitor.
Anti-Inflammatory Agents ; therapeutic use ; Biomarkers, Pharmacological ; Cardiovascular Diseases ; drug therapy ; enzymology ; immunology ; Cyclooxygenase 2 ; immunology ; Cyclooxygenase 2 Inhibitors ; adverse effects ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; NF-kappa B ; immunology ; Reactive Oxygen Species ; immunology ; Tumor Necrosis Factor-alpha ; immunology

Female ; Humans ; Integrative Medicine ; Polycystic Ovary Syndrome ; therapy

Objective To explore the clinical value of guide-wire shaping in subclavian vein catheter-ization.Methods Totally 400 patients requiring right subclavian vein catheterization were equally divided into two groups according to the clinic date: intervention group ( with guide-wire shaping , n =200 ) and control group (without guide-wire shaping, n=200).The catheterization was carried out by the same doctor .The rates of ectopic wire were compared between the two groups .Results The overall success rate of catheteriza-tion was 98.25%(393/400) [98.5% (197/200) in intervention group and 98.0% (196/200) in control group, P=0.500].The incidence of catheter displacement was 1.02%(2/197) in intervention group, which was significantly lower than that [7.14% (14/196)] in control group (P=0.002).Conclusion As a sim-ple procedure , guide-wire shaping can effectively prevent catheter displacement during catheterization .

Objective To observe the effect of autophagy on paclitaxel-induced CaSki cell death through the regulation of the expression of autophagy gene Beclin1, and to explore the interaction and relationship between autophagy and apoptosis. Methods Eukaryotic expression vector pcDNA3.1-Beclin1 and RNA interference vector pSUPER-Beclin1 were transfected into human cervical cancer CaSki cells in vitro and screened for stable expression cell lines. The formation of autophagic vacuoles was observed with an electronic microscope. The expression of Beclin1 and LC3 was measured by Western blot. After being treated with paclitaxel, the change of cell proliferation was assessed by MTT assay, the percentage of apoptotic cells and autophagic cells were analyzed by flow cytometry. Results A lot of autophagic vacuoles were observed in pcDNA3.1-Beclin1 cells by electronic microscopy. Beclin1 and LC3 protein expression was up-regulated in CaSki cells transfected with pcDNA3.1-Beclin1, and was inhibited in cells transfected with pSUPER-Beclin1. MTT assay revealed the survival rate of CaSki cells was significantly decreased after being transfected with pcDNA3.1-Beclin1. After being treated with paclitaxel, the percentages of apoptotic cells and autophagic cells were both increased in pcDNA3.1-Beclin1 group compared with that of the blank control group especially the increase of apoptosis was particularly evident. Conclusion Autophagy and apoptosis have different roles in the process of paclitaxel-induced cervical cancer CaSki cell line death. Overexpression of Beclin1 in CaSki cells may enhance the apoptosis induced by paclitaxel.

Objective To evaluate the value of real-time three-dimensional echocardiography(RT-3DE)in diagnosing congenital tricuspid valve anomaly.Methods Eighteen patients with congenital tricuspid valve anomaly were studied by RT-3DE,the spatial framework and neighboring structures of the tricuspid valve were analyzed and compared with result of the operation.Results The anomaly of tricuspid,chorda tendineae,the papillary muscle and their connection with neighboring structures could be displayed clearly from different directions.The diagnose accordance rate of RT-3DE was 83%.Conclusions RT-3DE may provide more information on congenital tricuspid valve anomaly than 2DE.

Objective To evaluate the feasibility and safety of embedding the totally implantable venous access port (TIVAP) via the access of right brachiocephalic vein (BCV).Methods The clinical data of 493 patients,who underwent the placement of TIVAP by using right BCV route during the period from March 2013 to December 2015,were retrospectively analyzed.The patients included 137 males and 356 females,with a mean age of (47.3±13.2) years old (ranging from 29 to 78 years old).The puncture success rate and TIVAP indwelling procedure-related complications were analyzed.Results The technical success rate was 100％,the success rate of initial puncturing was 99％ (488/493).The mean operation time was (22.5± 8.3) minutes (range of 18-35 minutes).Mis-puncturing of artery happened in 3 patients (0.61％,3/493);and no severe complications such as hemothorax or pneumothorax occurred.After implantation,the patients carried TIVAP for 124-986 days,with a mean of (271.1±53.8) days.The incidence of complications was 2.25％ (11/488),including hemorrhage at port site (n=2),catheter-related infection (n=l),partial thrombosis (n=2),and formation of fibrous protein sheath (n=6).No serious complications such as displacement or rupture of catheter,or catheter pinch-off syndrome (POS),etc.were observed.Conclusion The implantation of TIVAP by using right BCV route has high puncturing success rate,the technique is safe and reliable,and it can provide another option of catheter access for the clinical performance of TIVAP implantation.

BACKGROUND:Titanium and titanium aloy are used mostly in artificial joints, fracture fixation, and oral transplantation, while there are complex cases of insufficient bone mass in these areas. The deepened research of stem cels offers a solution for bone injury to promote new bone formation. The biocompatibility of titanium and stem cels and optimization of titanium surface modification have aroused people's attention. OBJECTIVE:To investigate whether the biocompatibility of titanium and human adipose-derived mesenchymal stem cels can be improved by type I colagen modification of titanium sheets. METHODS:The experiment was divided into two groups. Modification group: titanium sheet was modified with type I colagen; control group: titanium sheet was not modified with type I colagen. Human adipose-derived mesenchymal stem cels at passage 6 were implanted into titanium sheet in two groups. Then we calculated the number of adherent cels in two groups at 1, 2 and 4 hours after implantation, and compared the celladhesion rate. MTT assay was used to observe the proliferation of cels on titanium sheet at 2, 4, 6 and 8 days after implantation. DNA and protein content of cels were detected at 3, 6, 9 days after implantation. The growth of human adipose-derived mesenchymal stem cels seeded upon the titanium sheets was observed under scanning electron microscope at 6 days. RESULTS AND CONCLUSION:When the cels were cultured for 1 hour and 2 hours, the number of adherent cels in the modification group was higher than in the control group (P < 0.05). The absorbance of cels in two groups was increased as the culture time, as detected by MTT assay. The modification group had a significantly higher absorbance value than the control group at 4, 6, 8 days (P < 0.05). DNA and protein contents of the cels in the modification group were higher than that in control group at 6 and 9 days (P < 0.05). At 6 days, the number of adherent cels and secretion of adherent stromal cellmatrix in the modification group were significantly better than that in control group, observed by scanning electron microscopy. Type I colagen modified titanium sheets have good surface activity and biocompatibility, and can promote the proliferation of human adipose-derived mesenchymal stem cels.

BACKGROUND/AIMS: This study was performed to determine whether adding coenzyme Q10 (CoQ(10)) to metformin (MET) has a beneficial effect as a treatment for sirolimus (SRL)-induced diabetes mellitus (DM). METHODS: DM was induced in rats by daily treatment with SRL (0.3 mg/kg, subcutaneous) for 28 days, and animals were treated with CoQ(10) (20 mg/kg, oral) and MET (250 mg/kg, oral) alone or in combination for the latter 14 days of SRL treatment. The effects of CoQ(10) and MET on SRL-induced DM were assessed with the intraperitoneal glucose tolerance test (IPGTT) and by determining plasma insulin concentration and the homeostatic model assessment of insulin resistance (HOMA-R) index. We also evaluated the effect of CoQ(10) on pancreatic islet size, apoptosis, oxidative stress, and mitochondria morphology. RESULTS: IPGTT revealed overt DM in SRL-treated rats. The addition of CoQ(10) to MET further improved hyperglycemia, decreased HOMA-R index, and increased plasma insulin concentration compared with the SRL group than MET alone therapy. While SRL treatment induced smaller islets with decreased insulin staining intensity, the combination of CoQ(10) and MET significantly improved insulin staining intensity, which was accompanied by a reduction in oxidative stress and apoptosis. In addition, co-treatment of CoQ(10) and MET significantly increased the levels of antiperoxidative enzymes in the pancreas islet cells compared with MET. At the subcellular level, addition of CoQ(10) to MET improved the average mitochondrial area and insulin granule number. CONCLUSIONS Addition of CoQ(10) to MET has a beneficial effect on SRL-induced DM compared to MET alone.

Melittin exhibits high antibacterial potency against drug-resistant bacteria. However, the clinical utility of melittin is limited by its serious hemolytic activity. Thus, the need for developing novel melittin analogues with high antimicrobial activity and low hemolytic activity has grown. We designed, synthesized, and evaluated 20 novel melittin analogues with varying hydrophobic, polar or positively charged amino acids. The results showed that 8 compounds had antimicrobial activity (MIC: 1-4 μg·mL^-1) against gram-positive pathogens equal to or better than that of melittin, and 16 compounds had low hemolytic activity (HC₅₀ ≥ 11.9 μg·mL^-1). Compounds 13 (MIC: 2-4 μg·mL^-1) and 15 (MIC: 1-2 μg·mL^-1) showed equal or better antimicrobial activity against both susceptible and resistant strains of Staphylococcus aureus and Enterococcus faecium compared to melittin (MIC: 4 μg·mL^-1). Compound 13 (HC₅₀: 24.0 ± 4.3 μg·mL^-1) displayed noticeably decreased hemolytic activity compared to melittin (HC₅₀: 5.3 ± 0.4 μg·mL^-1). This work established a base for further study on the structure-activity relationships and structure-toxicity relationships of melittin.

OBJECTIVETo investigate the effects of atorvastatin on C-reactive protein (CRP) induced Toll-Like receptor 4 (TLR4)expression on CD14+ monocyte, and the production of proinflammatory cytokines tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), matrix metalloproteinases-9 (MMP-9), and to study the anti-inflammatory mechanisms of statins.

METHODSThe monocytes were isolated from blood of healthy volunteers by the Ficoll density gradient and stimulated by CRP with different doses (5, 25, 50, 100 microg/ml) and different exposure time (6, 12, 24, 48 h). Cells were also incubated with atorvastatin of different doses (1.0, 2.5, 5.0, 7.5, 10.0 micromol/L) in the presence of CRP 50 microg/ml. The protein expression of TLR4 was measured by flow cytometry, mRNA expression of TLR4 and of myeloid differentiation protein (MD2)was detected by quantitative PCR. TNFalpha, IL-6, MMP-9 concentrations in supernatants of cultured medium were measured by ELISA.

RESULTS(1) Compared with the un-stimulated control group, enhanced TLR4 protein expression was already detected at a concentration of 5 microg/ml of CRP and increased in a dose-dependent manner (32.22 +/- 2.80)%, (49.94 +/- 5.58)%, (74.82 +/- 3.24)% and (90.82 +/-2.88)% at 5, 25, 50 and 100 microg/ml CRP. (2) TLR4 protein expression on 50 microg/ml CRP stimulated cells also increased in a time-dependent manner (29.80 +/- 2.70)%, (47.44 +/- 4.41)%, (81.71 +/- 2.92)% and (50.57 +/- 3.34)% after 6 h, 12 h, 24 h, 48 h. (3) When monocytes were incubated with CRP 50 microg/ml and atorvastatin (1.0, 2.5, 5.0, 7.5, 10.0 micromol/L), protein expression [(68.17 +/- 1.71)%, (52.43 +/- 1.38)%, (27.72 +/- 4.55)%, (17.46 +/- 3.20)%, (9.99 +/- 2.81)%] and mRNA expression (82.72%, 67.34%, 48.16%, 30.88%, 13.85%) of TLR4 as well as mRNA expression of MD2 (81.78%, 71.04%, 47.85%, 27.06%, 18.30%) were reduced in a dose-dependent manner. (4) Level of TNFalpha, IL-6 and MMP-9 in supernatants was significantly reduced by atorvastatin (2.5 micromol/L) compared with control group (P < 0.01). When monocyte incubated with CRP 50 microg/ml and atorvastatin 10.0 micromol/L, the level of TNFalpha, IL-6, MMP-9 decreased to (25.8 +/- 2.5) microg/ml, (128.2 +/- 14.7) pg/ml, (65.2 +/- 12.3) ng/ml, respectively.

CONCLUSIONCRP increased the protein expression of TLR4 on CD14+ monocyte in a dose-dependent and time-dependent manner. Atorvastatin can inhibit the signal transduction of TLR4 and reduce proinflammatory cytokines release induced by CRP on CD14 monocyte, and this might be one of the anti-inflammatory mechanisms of atorvastatin.

Anti-Inflammatory Agents ; pharmacology ; Atorvastatin Calcium ; C-Reactive Protein ; metabolism ; Cells, Cultured ; Heptanoic Acids ; pharmacology ; Humans ; Lipopolysaccharide Receptors ; Monocytes ; drug effects ; metabolism ; Pyrroles ; pharmacology ; Toll-Like Receptor 4 ; metabolism