OBJECTIVETo investigate whether bortezomib can enhance the sensitivity of human prostate cancer (PCa) cells to natural killer (NK) cell-mediated cytotoxicity, and whether it produces the same effect on different PCa cell lines.

METHODSWe treated androgen-dependent PCa LNCaP cells and androgen-independent PCa DU145 cells with bortezomib at the concentrations of 0, 5, 10, 15, 20 and 25 nmol/L for 24, 48 and 72 hours, and then detected the proliferation and apoptosis of the tumor cells by CCK-8 and Annexin V/PI, respectively.

RESULTSThe proliferation rates of the DU145 cells treated with 15, 20 and 25 nmol/L bortezomib were (82.79 +/-2.04)%, (73.59+/- 2.95)% and (74.16+/- 6. 16)% at 48 hours and (71.24+/- 5.30)%, (51.20+/- 2.91)% and (38.02+/- 2.67)% at 72 hours, and those of the LNCaP cells were (77.04+/- 7.74)% , (42.61 +/- 6.62)% and (23.85 +/-6.04)% at 48 hours and (36.45 +/-7.02)%, (14.94 +/-5.76)% and (11.65 +/-5. 87)% at 72 hours, both significantly inhibited as compared with the control group (P <0.05). At 24 hours, the apoptosis rates of the DU145 cells treated with 15, 20 and 25 nmol/L bortezomib were (14.41 +/- 1.32)% , (16.13 +/- 1.55)% and (14.48 +/- 1.42)% , and those of the LNCaP cells treated with 20 and 25 nmol/L bortezomib were (12.77 +/- 1.28)% and (14. 84 +/- 1.65)% , significantly higher than those of the control group (P <0.05) , and the DU145 cells showed an even higher sensitivity to bortezomib than the LNCaP cells. Bortezomib failed to sensitize these two cell lines to NK cell-mediated cytotoxicity in short-term assay, while long-term assay manifested that the apoptosis rates of DU145 and LNCaP cells after treated with 20 nmol/L bortezomib + NK cells were (41.83 +/- 5.06)% and (30.31 +/- 3.62)% , respectively, significantly higher

CONCLUSIONBortezomib enhances the sensitivity of than those after treated with either bortezomib or NK cells alone (P <0.05). PCa cells to NK cell-mediated cytotoxicity and adds to the effect of current cancer therapies, and it is more efficacious for androgen-independent prostate cancer.

Apoptosis ; drug effects ; Boronic Acids ; pharmacology ; Bortezomib ; Cell Line, Tumor ; Cytotoxicity, Immunologic ; drug effects ; Humans ; Killer Cells, Natural ; drug effects ; Male ; Prostatic Neoplasms ; pathology ; Pyrazines ; pharmacology

Congenital Abnormalities ; diagnosis ; therapy ; Ear, External ; abnormalities ; Ear, Middle ; abnormalities ; Humans

BACKGROUND: Surface roughness of implants can directly influence cellular proliferation, differentiation, and gene expression. OBJECTIVE: To observe the early attachment of periodontal ligament cells (PDLCs) to pure titanium with different surface roughness levels, and to study the effect of surface performance on cell differentiation. DESIGN, TIME AND SETTING: Randomized controlled observation/multi-sample comparison study, which was performed at Center of Science and Technology, Gannan Medical College between January 2005 and July 2006. MATERIALS: Pure titanium stick was cut into pieces, of 10 mm diameter and 2 mm thickness, using cutting-off machine, and there were 24 sections in total. Then, the titanium sections were randomly divided into four groups: simple mechanical processing, nitric acid processing, sand blasting processing, and combination group, with 6 sections per group. METHODS: TR240 portable-type surface roughness meter was used in this study. In the simple mechanical processing group, sections were scoured by sand paper alone; in the nitric acid processing group, sections were etched with 65% HNO3 for 1 hour at 100 ℃ after scoured by sand paper; in the sand blasting processing group, sections were sandblasted by 100 μ m AI203 after scoured by sand paper; in the combination group, sections were etched with 65% HNO3 for I hour at 100～C after scoured by sand paper and sandblasted by 100 μ m Al2O3. MAIN OUTCOME MEASURES: Samples were maintained in DMEM for 30 minutes, and the third-passage cells were inoculated. Then, titanium sections were taken out at different time points of 30, 60, 120, 240 minutes, 1, 3, and 7 days. Surface roughness and early attachment of PDLCs were detected under fluorescent microscope. RESULTS: O Quantitative analysis: Surface roughness was (599.5±8.3) nm in the simple mechanical processing group, (406.5 +4.6) nm in the nitric acid processing group, (358.8±11.8) nm in the sand blasting processing group, and (8.7±2.0) nm in the combination group. On the other hand, surface roughness in the simple mechanical processing group was significantly higher Fluorescence observation exhibited that number of PDLCs attaching to pure titanium surface was increased, and the proliferation was greater with the time passing by. in addition, surface roughness of pure titanium was positively associated with number of PDLCs. CONCLUSION: The lighter the surface roughness is, the more the early attachment of PDLCs is, benefiting for cell adhesion and proliferation.

Objective To observe the clinical characteristics and prognosis in children with high take -off coronary artery.Methods The clinical characteristics,laboratory examinations and prognosis were retrospectively ana-lyzed in 49 children with high take -off coronary artery who had been admitted to Beijing Children′s Hospital Affiliated to Capital Medical University from April 2009 to December 201 2.Results Among 49 medical records of children with high take -off coronary artery,34 cases were male and 1 5 cases were female,with a mean age of (9.28 ±4.42)years old,and the youngest patient was 1 3 months old,and the oldest patient was 1 7 years and 2 months old.The 64 -section multidetector CT angiography of all patients showed one or both coronary arteries originated from 1 .0 cm higher than the junction area of sinus and aorta,including 38 high take -off of the left coronary artery,7 high take -off of the right coronary artery and 4 high take -off of both coronary arteries.The chief complaints of the patients included chest pain (22 cases,44.90%),chest tightness(1 3 cases,26.53%),declining of exercise tolerance(7 cases,1 4.29%),fatigue (5 cases,1 0.20%),palpitation(3 cases,6.21 %),syncope(1 case,2.04%).Electrocardiogram(ECG)of those pa-tients showed ST -T changes,atrioventricular block,sinus tachycardia,pathological Q -wave,proiosystole and bundle branch block.Ultrasonic cardiogram(UCG)indicated 1 4 patients with the enlarged left ventricle,including 2 patients with ejection fraction lower than 60%.After 1 0 days hospitalization,the anesis of chest pain and chest tightness were significantly different statistically(P <0.05),but there was no significant difference in ECG and UCG.Thirty -nine out of 49 children were followed for 1 year.After 3 months,6 patients with ST -T problem showed normal ST -T segment. After 6 months,1 0 patients with ST -T problem showed normal ST -T segment.After 1 year,1 7 patients with ST -T problem showed normal ST -T segment.Conclusions High take -off coronary artery is a rare malformation of the coronary artery,which can cause myocardial ischemic,leading to multiple clinical manifestations and may result in ECG changes and the left ventricle enlargement.High take -off coronary artery can be confused with myocarditis and myocar-dial lesion clinically.Patients receiving systemic treatment may have their symptoms released,but ECG and UCG may not relieve in a short term.Patients with high take -off coronary artery need long -term observation.

In this study, we prepared various matrices of hydrogel patches and studied their cross-linking mechanism by observing their rheological properties, which could provide theoretical basis and deep technical support for further industrial development of hydrogel patch. Rheology method was used to do the amplitude scanning and single-frequency scanning for various hydrogel matrix, under the condition of oscillation mode of the rheometer. Then the linear viscoelastic region, composite modulus value, as well as changes in slope with time of the composite modulus and phase angle of various hydrogel matrix were analyzed in detail. The results showed that the stability of matrix was mainly determined by hydrogel frame; only in acidic environment, the cross-linking reaction between cross-linker and hydrogel frame can occur; elasticity of matrix can be decreased by organic acid and the effect level was related to the ratio of the number of carboxyl and hydroxyl (-COO(-)/-OH) in adjusters: if the ratio was not equal, the higher -COO(-)/-OH in adjusters would be the less elasticity of matrix decreased; the cross-linking speed of matrix was determined by adjuster, the cross-linking speed of matrix contain different adjusters was ranged in following order: matrix containing tartaric acid > matrix containing lactic acid > matrix containing malic acid > matrix containing citric acid; the cross-linking speed of matrix was not uniform in the whole cross-linking process.

Objectiye To investgate the effects of isoflurane preconditioning on expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) during focal cerebral ischemia-reperfusion (IR) in rats. Methods Thirty male SD rats weighing 250-300 g were randomly divided into 3 groups ( n = 10 each):sham operation group (group S);focal cerebral IR group and isoflurane preconditioning group (group IP). The animals were anesthetized with intraperitoneal pentobarbital 40 mg/kg. In group IR and IP a nylon thread with rounded tip was inserted into right internal jugular vein and threaded cranially until resistance was met. Mid-cerebral artery was occluded (MCAO) for 2 h followed by 24 h reperfusion. In group IP the animals inhaled 2% isoflurane98 % O2 for 1 h once a day for 5 consecutive days at 24 h before MCAO. Neurologic function was assessed and scored and cerebral infarct volume was measured at 24 h of reperfusion. The animals were sacrificed at 24, 48 and 72 h of reperfusion respectively. The right ischemic frontal lobes were removed for determination of TLR4, MyD88and NF-κB expression by Western blot analysis. Results MCAO significantly worsened neurologic function. The neurologic function deficit scores were significantly increased and the TLR4, MyD88 and NF-κB expression were significantly up-regulated in group IR as compared with group S (P ＜ 0.05). Isoflurane preconditioning significantly decreased cerebral infarct volumes and neurologic function deficit scores and down-regulated the expression of TLR4, MyD88 and NF-κB in group IP as compared with group IR ( P ＜ 0.05). Conclusion Isoflurane preconditioning can reduce inflammatory response and focal cerebral IR injury by down-regulating the expression of TLR4and Myd88.

The effects of ultrafine grinding on the dissolution rates of the effective components in Sanjie Zhentong capsule (SZC) were studied in this experiment. Fine and ultrafine powder of SZC intermediates were made by ordinary grinding and ultrafine grinding technology, and then granulated by wet granulation. SZC were prepared by fine powder, ultrafine powder and ultrafine granules, respectively. With resveratrol and loureirin B as investigated indexes, dissolution rates of the four intermediates in SZC were determined by cup method and HPLC. The dissolution rates of resveratrol in SZC prepared by fine powder, ultrafine powder and ultrafine granules were 26.11%, 63.27%, 67.49%, respectively; and the dissolution rates of loureirin B were 7.160%, 20.29%, 23.05%, respectively. The dissolution rate of resveratrol and loureirin B in SZC prepared by ultrafine granules was the best. D90 size of ultrafine grinding was 13.221 μm and could improve the dissolution rates of resveratrol and loureirin B in SZC.
Capsules ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Particle Size ; Silicones ; chemistry ; Solubility ; Technology, Pharmaceutical ; methods

AlM: To explore the inhibiting effect of FTY720 on corneal neovascularization ( CNV) of rat.METHODS: MTT assay and cells scratch were adopted to observe hyperplasia of human umbilical vein endothelial cells ( HUVECs ) and cell migration induced by sphingosine-1-phosphate(S1P) after using FTY720 of different concentration. The effect of FTY720 on CNV induced by S1P in a rat corneal micropocket model was detected. 30SD rats were randomly divided into group A, group B and group C with 10 rats per group. S1P and 0μg, 5μg, and 20μg FTY720 controlled-released particles were implanted into the corneal stroma. The growth of CNV and having pathological examination on 12d after the operation was observed. Findings was analyzed by one-way ANOVA.RESULTS: 10, 102 , 103 , and 104 nmol/L FTY720 and HUVECs co-incubate 72h could inhibit cell proliferation (P < 0. 01 ), 24h after the function of 10, 100nmol/L FTY720, it could inhibit S1P-induced cell migration and the ability of restricting cell proliferation and cell migration was enhanced with increasing concentration of FTY720. On 12d, after rat corneal micropocket controlled-release particles was implanted into groups A, B, C, the CNV area were respectively 10. 05±1. 19, 6. 59±0. 95, 2. 70± 0.68mm2(F=145. 155, P<0. 01), group A and group B was statistically different and this was the same case between group B and group C (P<0. 01).CONCLUSlON:FTY720 can inhibit S1P-induced corneal neovascularization.

Objective To discuss the feasibility, efficacy and complications of CT-guided 125I seed implantation for the treatment of lymph node metastasis nearby the iliac vessels.Methods The clinical data of twelve patients with para-iliac vessel lymph node metastasis, who had been treated with CT-guided 125I seed implantation, were retrospectively analyzed. A total of 12 lesions were detected; the diameter ≤6 cm was seen in seven lesions, and the diameter >6 cm was seen in five lesions. Using computer treatment planning system, the source distribution was calculated. Under CT guidance 125I seeds with the activity of 0.4-0.7 mci were implanted into the metastatic lymph nodes with a seed interval of 0.5-1.0 cm. CT scan was performed immediately after implantation to check the distribution of seeds as well as the possible complications. After the treatment, D90 (90%prescription dose received by target volume) was ≥75 Gy in 6 patients and <75 Gy in other 6 patients. Two months after the treatment CT reexamination was employed, and imaging evaluation was conducted according to WHO Response Evaluation Criteria in Solid Tumors. Results CT-guided 125I seed implantation was successfully accomplished in all 12 patients. Two months after the treatment, the evaluation of the therapeutic effect showed that complete remission (CR) was obtained in 0 patient, partial remission (PR) in 8 patients, stable disease in 3 patients and progress disease in one patient;and the total effect rate(CR+PR) was 66.7%. The local control rate was 91.7%. In eight patients the pain that was caused by metastatic lymph nodes was significantly relieved within 1-14 days after 125I implantation treatment. Before the treatment three patients had lower limb edema, and in two of them the lower limb edema was obviously relieved within 1-14 days after the treatment. All patients were followed up for 3-39 months, and the median follow-up time was 11 months. One-year survival rate was 41.7%. No severe complications such as massive hemorrhage, infection, myelosuppression or seed displacement occurred. Conclusion For the treatment of para-iliac vessel lymph node metastasis, CT-guided 125I seed implantation is safe and feasible. Better curative effect may be achieved when the diameter of the metastatic lymph node is<6 cm and the peripheral radiation dose is>75 Gy.

AIM:This study continuously monitors the hemodynamic changes in conscious and anesthetic rats during rapid ascent to high altitude to investigate whether there is difference between the 2 conditions and discuss the rela-ted underlying mechanism.METHODS: Sprague-Dawley rats were randomly divided into conscious group, anesthetic group, anesthetic-5000-control ( A-5000-control) group, anesthetic-5000-aminoguanidine ( A-5000-AG) group, conscious-5000-control ( C-5000-control ) group and conscious-5000-aminoguanidine ( C-5000-AG ) group.The rats in anesthetic group and conscious group were kept in a hypobaric chamber, in which the simulated altitude was increased from 2 260 m to 5 000 m at 2 m/s, and the rats in other 4 groups were at 5 000 m.The system arterial pressure ( Psa) , central venous pressure ( CVP) , heart rate ( HR) and breathing rate ( BR) were directly and continuously displayed and digitally recorded by a high-performance data acquisition (PowerLab 16/35, AD Instruments) at 200 Hz.RESULTS: The HR and BR in the conscious rats were higher and MAP was lower than those in the anesthetic rats obviously.A significant decrease in mean arterial pressure ( MAP) in conscious and anesthetic groups was observed following the increase in the altitude levels, and the net decrease in MAP in conscious group was significantly greater.Additionally, HR in the conscious rats was sig-nificantly lower at 5 000 m than that of the initial level.The rats in C-5000-AG group and A-5000-AG group showed a sig-nificant increase in the arterial pressure after the intravenous injection of AG, a selective inhibitor of inducible nitric oxide synthase ( iNOS) , and no marked change of HR and BR was found.CONCLUSION: Blood pressure and HR decrease during rapid ascent to high altitude, while the change of BR is not obvious.The mechanisms of self-safety would be trig-gered in the early stage of hypoxia, which activates iNOS and then leads to a larger number of nitric oxide.Plentiful NO di-astolizes the vessels to improve the ventilation-perfusion mismatch and lower the blood pressure.When the altitude arise to 5 000 m, even more earlier, a decompensatory stage may occur in the body, leading to decreased HR and blood pressure further more than those in the anesthetic rats.Due to the effects of pentobarbital sodium, the depression of blood pressure requires a lag period and the net decrease in MAP is less than that in the conscious rats.Therefore, hemodynamic changes during rapid ascent to high altitude in conscious rats are more comprehensive and authentic.