Background Doxycycline is a broad spectrum antibiotic,and it is frequently used in the treatment of ocular surface diseases.Objective The purpose of the present study was to investigate the effect of doxycycline on the inhibition of cell proliferation in bovine corneal myofibroblasts in vitro and assess its contribution to ocular surface repairing mechanism.Methods Six fresh bovine corneas were collected.The corneal stromal layer was isolated by two-step method of 1.0 g/L and 2.0 g/L collegenase-1.Isolated cells were plated at mantaryay culture flask in 10％ FBS of RPMI-1640.Vimentin and alpha-smooth muscle actin (α-SMA) organization were evaluated by immunocytochemistry,and the cells with influoresccence staining for vimentin and α-SMA were identified as the corneal myofibroblasts.Doxycycline at the concentrations of 10,20,40,60,80 mg/L was added to the medium,respectively,in different concentrations of doxycycline groups.Dexamethasone (120 mg/L)was used in the same way in the positive control group,and no drug was used in the negative control group.Cell proliferation was evaluated by MTT and the cell cycle was analyzed by BD FACScan flow cytometer assay 24 hours and 48 hours after addition of any drug.Results The cells grew well and showed the positive response for vimentin and α-SMA.MTT assay showed that the A570values of bovine corneal myofibroblasts were gradually declined with the increase of the concentration of doxycycline and lapse of active time,showing statistically significant difference (Fconcentration =1233.778,P＜0.001 ; Ftime =227.564,P ＜ 0.001).And the difference between the two factors was also statistically significant (Ftime*concentration =51.656,P＜0.001).Flow cytometry cell cycle analysis showed that 24 hours after 10,20,40,60,80 mg/L doxycycline treated,the perentage of of corneal myofibroblast cell in G0-G1 phase was 82.85％,84.36％,85.18％,87.12 ％ and 89.31％,showing significant increase in comparison with 63.89％ of the negative control group (all P＜0.05),and that of 40 mg/L doxycycline group was near the positive control group.Forty-eight hours after 10,20,40,60,80 mg/L doxycycline treated,the perentage of of corneal myofibroblast cell in G0-G1 phase was 82.78％,86.15％,88.23％,89.57％,93.00％,with significant increase in comparison with 70.17％ of the negative control group (all P ＜ 0.01),and that of 40 mg/L doxycycline group was near the positive control group.Conclusions The growth of the bovine corneal myofibroblasts is inhibited by doxycycline in time-and dosedependent manner in the range from 10 mg/L to 80 mg/L,and 40 mg/L of doxycycline has an obviously inhibitory action as 120 mg/L dexamethasone.

Currently, chemotherapy is one of the main therapy for cancer. But the traditional antitumor drugs are systemic distribution in vivo, they are difficult to achieve an effective drug concentration in the tumor tissue and don't have the ability to distinguish normal cells and tumor cells by themselves, that cause systemic toxicity easily and can not meet the clinical needs. With the research on mesoporous silica nanoparticles (MSNs) deepening, more and more attention in the drug delivery system have been payed to in recent years, because of its unique physicochemical structure characteristics, it has the effect on specific targets, directly inhibits the tumor cell growth, reduces the side effects to normal cells, tissues and organs and can be long-term medication, etc. It is expected to be excellent carriers of antitumor drugs. MSNs application in the field of cancer treatment has now become a hot research field of medicine. In this paper, the latest research about MSNs in antitumor drugs targeting delivery system from 2008 to 2015 is summarized, including the application of MSNs separately in antitumor drug targeting, passive targeting, active targeting, physical or chemical conditions response targeting and other compound targeting drug delivery system. We expect it to provide a reference to the toxicity reducing and efficacy enhancing and further development of chemical medicine, natural medicine and monomeric compound of chinese herbal medicine.
Animals ; Antineoplastic Agents ; chemistry ; pharmacology ; Drug Delivery Systems ; methods ; trends ; Humans ; Nanoparticles ; chemistry ; Neoplasms ; drug therapy ; Silicon Dioxide ; chemistry

OBJECTIVETo investigate the effects of taurine on myocardial mitochondria and their enzyme activities in rats with severe burn.

METHODSOne hundred and twenty healthy adult Wistar rats were subjected to 30% TBSA full-thickness burn. They were randomly divided into burn group (B, with intraperitoneal injection of isotonic saline), treatment group (T, with intraperitoneal injection of taurine, 200 mg/kg),with 60 rats in each group . Ten rats with sham scald were used as control (S group). The myocardial tissue samples in B and T groups were harvested at 1, 3, 6, 12, 24 and 48 postburn hours (PBH) for determination of activity respectively of succinate dehydrogenase (SDH), cytochrome oxidase (CCO), the superoxide dismutase (SOD), Ca2+ -ATPase in mitochondria, and contents of cytochrome c (Cyt c), cytochrome aa3 (Cyt aa3), malondialdehyde (MDA), and Ca2+ in mitochondria and cytoplasm . The myocardial tissue samples of controls were harvested at 1 PBH for determination of above indices.

RESULTSThe activity of CCO in B group was decreased at 1 PBH , especially at 6 ,12 PBH. The activity of SDH in B group was decreased to lowest level at 6 PBH, and its value was lower than that of S group at each time point. The activity of CCO or SDH in T group was not obviously decreased, and the activity of CCO at 3, 6, 12 PBH showed significant difference compared with B group (P < 0.05). The contents of Cyt aa3 and Cyt c in B group at 3, 6, 12, 24 PBH were obviously decreased, which were significantly lower than those in T group (P < 0.05). The activity of SOD in B group at 3, 6, 12 PBH was obviously decreased, the activity of Ca2+ -ATPase at 3, 6, 12 and 24 PBH was decreased to different extent, which was significantly lower than those in T group (P < 0.05). The MDA contents in B and T groups were higher than that in S group at 3-48 PBH ,and it was highest in B group (P < 0.05). The Ca2+ content of mitochondria in B group at 1 PBH was increased (13.7 +/- 1.5), and it was (24.8 +/- 2.6), (29.7 +/- 3.1), (16.3 +/- 1.9) and (13.5 +/- 1.7) at 3, 6, 12, 24 PBH respectively,and they were all higher than that of S group (10.7 +/- 1.6, P < 0.05). The Ca2 contents of cytoplasm in group B at 3 - 24 PBH were also higher than that in S group (P < 0.05). The Ca2+ content of mitochondria in T group at 3, 6, 12, 24 PBH was (16.8 +/- 2.8), (18.7 +/- 1.9), (10.5 +/- 1.8) and (13.3 +/- 1.7)respectively, which were lower than that in B group at every time point.

CONCLUSIONTaurine have protective effect on mitochondria and their enzyme activities in myocardium in rats with severe burn, and it may be attributable to improving the ability of eradicating oxygen free radicals and alleviating Ca2+ overload in the mitochondria.

Animals ; Burns ; drug therapy ; enzymology ; metabolism ; Calcium ; metabolism ; Calcium-Transporting ATPases ; metabolism ; Cytochromes c ; metabolism ; Electron Transport Complex IV ; metabolism ; Female ; Male ; Mitochondria, Heart ; enzymology ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Succinate Dehydrogenase ; metabolism ; Superoxide Dismutase ; metabolism ; Taurine ; therapeutic use

Objective To investigate the cognition impairment in depression patients with its event-related potential P300 and MR diffusion tensor imaging (DTI) and explore the mechanism of depression combined with cognition impairment Methods We conducted a study of 60 people: 30 patients with depression and 30 healthy controls group-matched by age, educational level andsocioeconomic status. The latency period and amplitude of P3, and the data of fractional anisotropy (FA) were measured by P300 examination and DTI, respectively, in the bilateral white matter of interested region. Correlation analysis of these 3 factors was performed in the 2 groups. At the same time, the scores of Wisconsin card sorting test (WCST) were detected. Results The WCST scores of each sub-item,and the P3 latency and amplitude between the control group and depression group had statistically significant differences (P<0.05). FA value in the white matter of the both frontal lobe, the anterior cingulate gyms, the supramarginal gyrus, splenium of the corpus callosum in the patients was significantly lower than that in the controls (P<0.05). P3 latency and percentage of persistent errors in depression patients were positively correlated (r= 0.677, P=0.009). P3 amplitude and both percentage of persistent errors and percentage of not being able to maintain a complete classification were negatively correlated, respectively (r=0.765,P=0.001; r=-0.654, P=0.012). FA values and both percentage of persistent errors and percentage of not being able to maintain a complete classification were negatively correlated in patients with depression in the bilateral frontal white matter, respectively (left: r=-0.544,P=0.003; r=0.489, P=0.023; right: r=0.665, P=0.002; r=0.448,P=0.027). Conclusions Neuropsychology and event-related potential P300 reflected the cognition impairment in patients with depression; the latency period and amplitude of P3 could be a reference index of evaluating the cognitive function. The outcome of DTI can reveal the possible abnormality of neurofibra in the white matter region, which may be one of its neuropathology in depression patients with cognition impairment.

Objective To observe the changes of serum S100B and MBP in rats with liquid petroleum gas poisoning. Methods Fifty-four healthy adult male SD rats were randomized into normal control group (n=6), 20% LPG poisoning group (n=24) and 50% LPG poisoning group (n=24). Rat models of liquid petroleum gas poisoning were established in the later 2 groups, and controls were given the same volume of air. The rats of each group(n=6) were scored with neurological severity scale (NSS) and the blood serum was collected on the 1st, 2nd, 3nd and 7th d of poisoning, respectively. The levels of S100B and MBP were detected by euzymelinked immunosorbent assay (ELISA).Results As compared with the scores of NSS in the normal control group, those on the 1st d of poisoning in the 20% LPG poisoning group and those on the 1st and 2nd d of poisoning in the 50% LPG poisoning group were significantly higher (P＜0.05). The levels of Sl00B and MBP in 20% and 50% LPG poisoning groups were higher than those in the control group on the 1st and 2nd d of poisoning (P＜0.05); the levels of S100B and MBP in 50% LPG poisoning group were higher than those in 20% LPG poisoning group on the 1st and 2nd d of poisoning (P＜0.05). The levels of S 100B and MBP in 50% LPG poisoning group were higher than those in 20% LPG poisoning group and normal control group on the 3rd of poisoning (P＜0.05). The NSS scores and the levels of S100B and MBP in rats with LPG poisoning enjoyed the highest scores or levels on the 1st d of poisoning and those decreased after that. Conclusion The levels of S100B and MBP of rats with LPG poisoning increase, indicating that gliocytes participate in the mechanism of nervous system injury in rats with liquid petroleum gas poisoning.

Objective To study the effect of borneol on myelin of the central and peripheral nervous systems. Methods The rats were divided randomly into low-dose borneol treatment group (10 mL/kg,n=18) and high-dose borneol treatment group (13 mL/kg, n=18). Controls (n=18) were chosen and treated with 10 mL/kg paroline. Rats were sacrificed 24, 48 and 72 h after the treatment, and the blood, brain and sciatic nerves of these rats were prepared, respectively; the level of serum myelin basic protein (MBP) was detected and the morphological structure of myelin was observed with transmission electron microscope. Results The content of serum MBP in the 2 treatment groups was advanced markedly as compared with that in the control group 24, 48 and 72 h after the treatment (P<0.05);however, no significant difference was noted between the 2 treatment groups (P>0.05). The content of serum MBP was the highest 24 h after the treatment, gradually decreased following the prolongation of time; significant difference was noted between each 2 time points (P<0.05). Transmission electron microscope indicated abnormality in myelin of the central nerves at all time points, showing inordinate shape, rupture between layers and tangle among fibers; the abnormality was the most obvious 24 h after the treatment, gradually abatement following the prolongation of time; decreased myelin in the sciatic nerves was showed only at 24 h after the treatment, while normal at other time points. Conclusion A certain degree of abnormality of myelin of the central and peripheral nervous systems in rats can be caused by borneol.

OBJECTIVETo assess the feasibility of [(18)F]fluoroerythronitroimidazole ((18)F-FETNIM) with integrated positron emission tomography and computed tomography (PET-CT) imaging in detection of hypoxia in non-small-cell lung cancer (NSCLC) patients.

METHODSForty-two patients with newly diagnosed NSCLC underwent (18)F-FETNIM PET-CT before treatment. Nineteen patients rested for approximately 120 minutes before undergoing PET-CT, 23 patients underwent 2 sequential PET-CT scans at 60 minutes and 120 minutes after intravenous injection (18)F-FETNIM. (18)F-FETNIM uptake was quantified by calculating the maximum standardized uptake value in the tumor (SUVmax-T) and contralateral normal lung tissue (SUVmax-N). Regions of interest (ROIs) were drawn in the tumor and contralateral position and the radioactivity ratio of tumor to normal (T/N) was calculated.

RESULTSSUVmax-T (2.43 +/- 1.34) was significantly higher than SUVmax-N (0.87 +/- 0.46, P < 0.001) at 120 min. SUVmax-T (2.80 +/- 1.09) and SUVmax-N (1.16 +/- 0.56) at 60 min were significantly higher than SUVmax-T (2.61 +/- 1.10) and SUVmax-N (P < 0.01) at 120 min. T/N (2.56 +/- 0.71) at 60 min was higher than that at 120 min (2.48 +/- 0.60), but the difference between them was not significant (P = 0.324).

CONCLUSIONOur results indicate that (18)F-FETNIM PET-CT may be a useful tool for evaluating hypoxia and may be a means to target specifically tumor cells resistant to conventional treatment before and during ongoing therapy in NSCLC.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; diagnostic imaging ; pathology ; Cell Hypoxia ; Female ; Humans ; Lung Neoplasms ; diagnostic imaging ; pathology ; Male ; Middle Aged ; Nitroimidazoles ; Positron-Emission Tomography ; methods ; Tomography, X-Ray Computed

OBJECTIVETo evaluate the safety and efficacy of umbilical cord-derived mesenchymal stem cells (MSCs) infusion in patients with steroid-resistant severe acute graft-versus-host disease (aGVHD).

METHODSA total of 19 patients with steroid-resistant severe aGVHD received MSCs infusion treatment. The treatment response, transplantation-related mortality, events associated with infusion and relapse rate were analyzed.

RESULTSTwo patients with grade II, 5 patients with grade III and 12 patients with grade IV aGVHD received a total of 58 infusions of MSCs. The mean total dose of MSCs was 2.13 (range 0.60 - 7.20)×10(6) cells per kg bodyweight. Seven patients received one infusion, 2 patients received two infusions, and 10 patients received three or more infusions. Eleven patients had a complete response and 4 had a partial response and 4 had no response. No patients had side-effects during or immediately after infusions, and no MSCs related tumorigenesis was detected to date. Eleven patients survived and 8 died, 4 for aGVHD, 1 for infection and 2 for aGVHD with concomitant infection and 1 for underlying leukemia relapse. The cell viability of freshly prepared MSCs is 93% (92% - 95%) by trypan blue staining. The cell viability of programmatically frozen and thawed MSCs is 72% (70% - 74%).

CONCLUSIONInfusion of umbilical cord-derived MSCs expanded in vitro is an effective therapy for patients with steroid-resistant severe aGVHD without negative impact on relapse. Freshly prepared MSCs are superior to frozen and thawed cells in terms of cell viability.

Adolescent ; Adult ; Cord Blood Stem Cell Transplantation ; Female ; Graft vs Host Disease ; etiology ; surgery ; Humans ; Male ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; Middle Aged ; Steroids ; pharmacology ; Survival Rate ; Umbilical Cord ; cytology ; Young Adult

Objective To study the HIV incidence and risk factors among sero-negative spouses of HIV patients in Dehong prefecture of Yunnan province. Methods A cohort of sero-negative spouses of the HIV patients had been developed and followed up since November, 2005.HIV new infections and related behaviors had been investigated every six months. Results By the end of June, 2008, 790 sero-negative spouses of HIV patients had been recruited, of whom 702 were followed-up for at least one time. During the total 1202.35 person-years, 31 new HIV infections were identified, with an overall incidence of 2.58/100 preson-years. The HIV incidence rates were 2.22/100person-years in 2006, 2.95/100 person-years in 2007 and 2.74/100 person-years in 2008. Data from the Cox proportional hazard regression model indicated that those who resided in Yingjiang county [hazard ratio (HR) =4.37, 95% CI: 1.48-12.90, P=0.008] , ever using drugs (HR=3.49, 95% CI:1.09-11.18, P=0.035) , or having an HIV-infected spouse who never exposed to antiretroviraltreatment (HR=3.60, 95% CI: 1.41-9.16, P=0.007) were at higher risk for HIV infection.Conclusion Sero-negative spouses of HIV patients in Dehong prefecture of Yunnan province had a relatively high incidence of HIV new infection during 2006-2008. More efforts should put on those people living in these areas, having a history of drug use or having an HIV-infected spouse who had never been exposed to antiretroviral treatment.