Objective To know the inhibitory effects of 5aza-CdR in combination with HDAC inhibitors on RD-ES cells in culture.Methods This study was to investigate that the HDAC inhibitors (MS-275,Trichostatin-A and depsipeptide)and 5azaCdR inhibition effect on RD-ES cells by MTT.High sensitivity DNA kit was used to detect DNA inhibition rate.RT-PCR method was used to detect the expression of ECAD and TSLC1 for 5aza-CdR joint Depsi on RD-ES cells.Results IC50 of 5aza-CdR for RD-ES cell was 40 ng/ml,for 48 h 50 % DNA inhibition rate,the concentration was approximately 50 ng/ml.IC50 of HDAC inhibitors (MS-275,trichostatin-A,Depsi) for RD-ES cell was 400 ng/ml,2.5 ng/ml and 0.6 ng/ml respectively.The inhibition rate of 5aza-CdR jointed HDAC inhibitors was significantly higher compared with the single used groups (P

In this paper, the effects of the blend of nanoparticles and microneedle matrix materials on the mechanical properties of dissolving microneedles were studied mainly, so as to construct microneedles with excellent mechanical properties. Different kinds of nanoparticles (calcium carbonate, hydroxyapatite, silica), particle sizes (20, 60, 100 nm) and the proportion of prescription (2%, 6%, 10%) were blended with the matrix material [polyvinyl pyrrolidone (PVP), poly(1-vinylpyrrolidone-co-vinyl acetate)(PVP/VA)] to form dissolving microneedles. The effects of nanoparticles on the elastic modulus and hardness of the microneedles were investigated using a nanoindenter. The results showed that the elastic modulus and hardness of PVP microneedles were significantly improved by nano-calcium carbonate (P < 0.001), and the elastic modulus and hardness of PVP/VA microneedles were significantly improved by nano-hydroxyapatite (P < 0.001). When the particle size of hydroxyapatite was 20 nm, the elastic modulus of PVP/VA microneedles was (10.6 ± 1.0) GPa, and the hardness was (0.47 ± 0.06) GPa. As the size of the nanoparticles increases, the mechanical performance of the microneedles decreases. When the mass proportion of nano-hydroxyapatite increased from 2% to 6%, the elastic modulus and hardness of the microneedles were significantly improved (P < 0.001), but the effect of continue increasing the proportion of nanoparticles on the microneedles was not significant. The nano-enhanced PVP/VA dissolving microneedles has no irritant effect on intact skin and has a slight irritation to damaged skin, but they disappear completely after 72 h. Animal experiments have been approved by the Laboratory Animal Welfare and Ethics Committee of Zhejiang University of Technology. Therefore, the nano-enhanced dissolving microneedles has good biological safety. To sum up, it is necessary to select the appropriate kind of nanoparticle, particle size, and prescription ratio when microneedles constructing with a given matrix material, so as to effectively improve its mechanical performance.

The mucous barrier is a major physiological obstacle that the mucosal drug delivery system needs to deal with. In response to this physiological barrier, many achievements have been made in research of mucosal adhesion and mucus penetration. This review puts emphasis on the progress of the research on new mucosal adhesion strategies such as cationization, sulfhydrylization, maleimide functionalization, lectinization and catechol conjugation; polyethylene glycol (PEG), polyvinyl alcohol (PVA), poly (2-alkyl-2-oxazoline) (POZ), zwitterionic polymers and other mucus-inert materials, strategies to enhance mucus penetration ability such as enzyme functionalization, reducing agent pretreatment and so on. The problems of each strategy are also analyzed and discussed, which can provide some references for clinical transformation.

Objective:To investigate the door-to-balloon (D2B) time and its influencing factors for Percutaneous Coronary Intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI).Methods:180 cases of patients with STEMI in our hospital from January 2014 to April 2016 were selected.PCI therapy were operated on all patients after their consent.The pre-hospital delay time and D2B time of the patients were recorded.The related information of the patients,including demographic data,clinical factors,background of the disease and psychological factors,were investigated by the questionnaire survey.The patients were divided into short D2B group (D2B time≤ 126 min,n=96) and long D2B group (D2B time＞126 min,n=84).Univariate and multivariate logistic regression methods were used to analyze the influencing factors of D2B time.Results:The median D2B time of all the patients was 126 min,and only 26.7％ of patients' D2B time controlled within 90 min.Univariate analysis showed that differences of sudden attack,pay attention to symptoms,someone was present when attack,symptoms progress was fast,in hospital during holiday,no symptom in CCU,outpatient treatment,transfered by emergency medical service system (EMSS),time in CCU (6 am-10 pm),angina before infarction and pre-hospital delay time between the two groups were statistically significant (P＜0.05).Multivariate logistic regression analysis showed that in hospital during holiday,outpatient service,no symptom in CCU,pay attention to symptoms,use of transfered by EMSS,time in CCU (6am-10pm) are the factors affecting the time of D2B (OR=2.62,2.04,1.59,0.52,0.28,0.61 P＜0.05).Conclusion:The D2B time of most patients with STEMI can not reach the guidelines.The factors of patients,doctors,accepting mechanism of hospital are all related with D2B time.

To investigate the influence factors and effects of metal or dissolving microneedles on the formation and healing of skin microchannels, the pencil-shaped or conical stainless steel microneedles with different lengths, tip to tip space and base area, and the pencil-shaped dissolving microneedles with different tip to tip space were used. The microneedles were applied to the skin of epilatory mice and rats, and the effects of various microneedle parameters, application parameters, and animals on the microchannels were explored by the transepidermal water loss (TEWL) and methylene blue staining. Visually observe the skin local irritation caused by the microneedles. The animal experiments were approved by the Animal Experiments Welfare and Ethical Committee of Zhejiang University of Technology. The application time of the microneedle should be maintained at 30 s or more. When the insertion forces were 2, 4, 8 N, and the TEWL initial values of the formed microchannels were 12.9, 33.0, 40.4 g·m^-2·h^-1, respectively. When the length of metal microneedle were 400, 600, 800 μm, and the TEWL initial values of the formed microchannels were 37.1, 40.4, 49.5 g·m^-2·h^-1, respectively. When the tip to tip space of metal microneedle were 400, 600, 800 μm, and the TEWL initial values of the formed microchannels were 33.2, 40.4, 55.8 g·m^-2·h^-1, respectively. When the base area of metal microneedle were 0.16, 0.35, 0.62 cm², and the TEWL initial values of the formed microchannels were 35.1, 40.4, 67.1 g·m^-2·h^-1, respectively. The effects of conical and pencil-shaped microneedles are similar. When the tip to tip space of pencil shaped dissolving microneedle were 400, 600, 800 μm, and the TEWL initial values of the formed microchannels were 49.8, 60.5, 70.5 g·m^-2·h^-1, respectively. The TEWL baseline values of animal skins of different genders and series are different, but the tendency of microchannels formation and closure is similar. Visual inspection revealed that the slight erythema caused by the microneedles subsided within 24 h. Microneedles of different parameters have different effects on microchannels. The microchannels closed within 24 or 48 h, and the skin local irritation caused by microneedle was mild.

Objective To explore the influence of continuous veno-venous hemofiltration (CVVH) therapy on cardiac index (CD, global end-diastolic volume index (GEDI) and extravascular lung water index (ELWI) monitored by Pulse-indicated continuous cardiac output (PiCCO). Methods The 12 critically ill patients with acute renal failure were selected consecutively from department of intensive care unit (ICU) in Beijing Hospital. The patients who received CVVH therapy were monitored by PiCCO plus device. The hemodynamic measurements were performed during the process and interruption of CVVH. Pared t-test was used to analyze the values of CI, GEDI and ELWI. Results A total of 48 groups of data from 12 patients were analyzed. There were no significant differences in CI [(4.75±0.93) L ? min(-1) · m(-2)vs. (4.69±0.89) L · min(-1) · m(-2)], GEDI [(780.60±109.30) ml/m2 vs. (784.75± 106.20) ml/m2] and ELWI CC11.61±3.45) ml/kg vs. (11.54±3.56) ml/kg] between the interruption and process of CVVH, as obtained by the pared t-test (all P>0.05). Conclusions The CVVH therapy has no effect on the accuracy and reliability of PiCCO measurement of CI, GEDI and ELWI.

The water-soluble polypeptide drug oxytocin was encapsulated in liposomes by reverse-phase evaporation vesicle method to obtain oxytocin loaded liposomes (OT@LPs) which was further modified with cationic cell penetrating peptide—arginine octamer (R8) to get R8 modified oxytocin loaded liposomes (OT@LPs-R8) which showed enhanced mucoadhesive. The brain targeting efficiency was evaluated preliminarily after nasal administration. OT@LPs-R8 showed a round shape with a particle size distribution of 110.2 ± 7.3 nm, a surface potential as high as +18 mV, a drug loading (62.17 ± 1.88) %, an encapsulation rate (5.85 ± 0.72) %, and stood stable in nasal mucus. After nasal administration, it could significantly prolong the retention and enhance the distribution in the brain with no irritation to the nasal mucosa. The animal experiment in line with the regulations of the Department of Laboratory Animal Science of Fudan University on the ethics of animal experiments had been carried out after passing the review of the Animal Ethics Committee of Fudan University. The results showed nasal administration of OT@LPs-R8 could promote oxytocin directly into the brain from the nose which expected to become a new carrier for delivery of oxytocin to the brain.

Objective To investigate the diagnosis and treatment of septic shock and multiple organ dysfunction syndrome (MODS) following transrectal ultrasound-guided prostate biopsy (TRUSPB). Methods We reported two cases,45 and 46 years old,of septic shock and MODS after TRUSPB from June 1996 to May 2011.10 cases like these two cases in literatures were acquired (3 cases in Chinese and 7 cases in English) from 1991 to 2011,and the causes of severe infections following transrectal prostate biopsy and its prophylactic procedures were discussed as well. Results The two cases,suffered postoperative septic shock and MODS 16 -40 h after being smoothly performed TRUSPB.One patient died four days after surgery and the other improved after five days antibiotic treatment.All the 12 cases had abrupt onsets and deteriorated rapidly,2 cases died and 1 case was performed amputation due to double lower limb gangrene,resulted in high mortality and morbidity.There are many risk factors,such as repeated puncture (4/12),diabetes (3/12),chronic infections (3/12) and used immune suppression (1/12),et al; blood culture was positive in 9 case and E.coli bacteria was the main bacteria(8/9),besides,half of them were multi-drug resistant (4/8) and other 2 cases were ESBLs ( + ) or 1 case was quinolone-resistant repectively.9 cases recovered after actively controlled infection using carbapenem and other treatment. Conclusions Transrectal ultrasound-guided prostate biopsy could cause serious complications such as septic shock,to which more attentions should be paid.Preoperative use of carbapenem should be recommended for patients with repeating biopsy or other risk factors.

Objective To report our surgical experience in treating 19 cases of solitary iliac aneurysms (SIA). Methods The clinical data of 19 consecutive patients with SIA between January 1985 and January 2008 were retrospectively reviewed. There were 18 men and 1 woman, aging from 39 to 77 years ( mean 62 ± 7 years). Results There were 30 SIAs in the 19 patients, including 25 ( 83.3% ) common iliac aneurysms, 4 (13.3%) internal ihac aneurysms and 1 (3. 3% ) external iliac aneurysm. Eleven patients ( 57.9% ) had multiple ancurysms, with 9 patients ( 47.4% ) having bilateral SIA. Two patients had coexistent peripheral vascular occlusive disease. There were 2 patients suffering form ruptured SIA, one was saved by emergency operation and one died before an surgery could be attempted. Seventeen patients underwent successful open aneurysmectomy and artificial graft implantation leaving no ischemic complications of the pelvic organs. One patient with right common iliac aneurysm underwent endovascular repair without endoleak. There was no operative death during porioperative period. The surviving patients remained stable and had good patency of grafts during the follow-up period. Conclusions Early management of SIA is important, CT angiogarphy (CTA) is necessary not only to evaluate the SIAs, but also to detect multiple aneurysms or arterial occlusive disease. Close and long-term follow-up is mandatory for the early detection of the formation of new anearysms.

Objective To investigate the effect of preoperative carbohydrate fluid intake on postoperative insulin resistance and immune function.Methods Sixty elective gastroenteric tumor resection patients were randomly divided into test (n =30) and control (n =30) groups.Control group were fasted before surgery,while test group were given oral carbohydrate before surgery.The blood samples were collected to measure the levels of fasting blood glucose (FBG),fasting insulin (FINS),and cellular immunity (CD3 +,CD4 +,CD8 +,and CD4 +/CD8 +) before operation and 1,3,7 day postoperation,respectively.Homeostasis model assessment (HOMA) was applied to assess the status of insulin resistance.Results Compared to preoperation,the levels of CD4 +,CD4 + / CD8 +,and HOMA-IR at 1 day postoperation in both control and test groups were significantly higher (P ＜ 0.05).Compared to test group,the levels of CD4 +,CD4 +/CD8 +,and HOMA-IR at 1,3 day postoperation in control group were significantly higher (P ＜ 0.05).At the seventh day after surgery,HOMA-IR levels in the test group were returned to the preoperative level (P ＞ 0.05),while the control group was still higher than before surgery (P ＜ 0.05).There were no differences in CD4 + and CD4+/CD8 + at seventh days after surgery between two groups (P ＞ 0.05).Conclusions Preoperative carbohydrate administration may shorten the insulin resistance duration after gastrointestinal cancer surgery,reduce the intensity of insulin resistance,and improve immune function.Thus contributes to the rehabilitation of patients.