ABSTACT OBJECTIVE:To study the formation technology of Ibuprofen dropping pills and determine the dissolution in vitro. METHODS:Based on single factor test and with the spherical degree,drug-loading rate and pill weight variation as the evaluated indexes,response surface methodology was employed to screen the ratios of drug to matrix,drug solution temperatures and cryo-genic temperatures in the formation technology,and verification tests were conducted. The dissolution in vitro of the dropping pills prepared by the optimal technology was investigated and compared with that of the preparations sold in the market. RESULTS:The optimal formation technology of Ibuprofen dropping pills was as follows as the ratio of drug to matrix of 1∶6,drug solution temper-ature of 83 ℃ and cryogenic temperature of 7.3 ℃. In the verification tests,the self-made dropping pills demonstrated a spherical degree of 0.945 9,drug-loading rate of 99.82%,pill weight variation of 0.040 28 and drug-loading capacity of 30 mg/pill,with the actual comprehensive score of 0.972 5,deviating from the theoretical one (0.980 0) by 0.771 2%(RSD<1.5%,n=3). The dropping pills prepared had a dissolution rate of 25.36%at 5 min and an accumulated dissolution rate up to 90.12%at 30 min,sim-ilar with the Ibuprofen tablets sold in the market in drug release in vitro (f2=54.91),conforming to a first-order kinetic equation. CONCLUSIONS:The optimized formation technology is simple,stable,feasible and well reproducible,and the dropping pills which are prepared by such technology can release drug quickly.

Objective To investigate the role of cytokines genes expression of liver sinusoidal endothelial cells in liver damage by sepsis.Methods Septic mice models were established with cecal ligation and perforation (CLP), while sham operation group received the same procedure exclusive CLP. The genes expression of TNF?, IL 1? and IL 6 in liver sinusoidal endothelial cells were assessed by RT PCR. Results A significant increase of TNF?, IL 1? genes expression was observed at 3h, and a slight decline at 12h after operation, but still significantly higher than that in the sham group; while IL 6 gene expression showed signficantly higher at 3h and remained at the high level at 12h. Conclusions Liver sinusoidal endothelial cell is an important source of cytokine production in mice with sepsis.

OBJECTIVE:To study the in vitro uptake of Resibufogenin(RBG)lactic acid glycolic acid copolymer-water solu-ble vitamin E (PLGA-TPGS) in human liver cancer HepG2 cells,mouse ascites-type lymphatic metastasis of tumor HCa-F cells, and the toxicity on HepG2 cells. METHODS:RCPTN loading RBG and coumarin-6(C6)were prepared. Fluorescent inverted mi-croscope was used to observe the in vitro uptake by RCPTN HepG2,HCa-F cells. It was divided into negative control group,blank PLGA-TPGS nanoparticles(EPTN)group,5-fluorouracil solution(FS)group,RBG solution(RS)group,RBG/PLGA nanoparti-cles(RPN)group and RPTN group. WST-1 was conducted to investigate the optical density at 450 nm wavelength of HepG2 cells after 24,48,72 h incubated by FS,RS,RPN and RPTN with different final concentrations (1.25,2.5,5,10,20 μg/mL);the cell viability (CV) and half inhibitory concentration (IC50) were calculated. RESULTS:RCPTN distributed around the nucleus of HepG2,HCa-F cells. CV was decreased by RBG concentration increased in RPN group and RPTN group,and decreased by time prolonged;compared with FS group,CV in RPTN group was decreased(P<0.05 or P<0.01). IC50 of HepG2 cells incubated by FS,RS,RPN and RPTN was decreased by time prolonged,ordered by RS>FS>RPN>RPTN;IC50 incubated by RPN and RPTN for 48,72 h was obviously less than that of FS and RS(P<0.05 or P<0.01). CONCLUSIONS:RPTN can deliver RBG in-to HepG2,HCa-F cells,showing inhibition effect on HepG2 cells which is stronger than RPN,RS and FS.

OBJECTIVETo study the gene expression of adhesion molecules in pulmonary and hepatic microvascular endothelial cells during sepsis in mice.

METHODSMale mice were subjected to cecal ligation and puncture (CLP) and microvascular endothelial cells in pulmonary and hepatic tissues were harvested at 3 hours (early sepsis) and 12 hours (late sepsis) after CLP, respectively. Gene expression of the adhesion molecules was assessed by reverse transcription polymerase chain reaction (RT-PCR). Simultaneously, the alterations of myeloperoxidase (MPO) activity in pulmonary and hepatic tissues were also examined.

RESULTSE-selectin mRNA levels markedly increased at 3 hours after CLP in both pulmonary and hepatic microvascular endothelial cells, then they returned to the normal level at 12 hours after CLP. Increases in intercellular adhesion molecule-1 (ICAM-1) mRNA levels were found at 3 hours after CLP in both pulmonary and hepatic microvascular endothelial cells, and these levels became higher at 12 hours after CLP. Adhesion molecule-1 (VCAM-1) mRNA expression of vascular cells also increased significantly at 3 hours and 12 hours after CLP in both pulmonary and hepatic microvascular endothelial cells. The level of VCAM-1 mRNA in hepatic microvascular endothelial cells was higher at 3 hours than that at 12 hours after CLP, while the level of VCAM-1 mRNA in pulmonary microvascular endothelial cells was higher at 12 hours than that at 3 hours after CLP. The MPO activity in pulmonary and hepatic tissues increased at 3 hours after CLP, compared with that of the sham group. They both declined significantly at 12 hours after CLP, but they were still higher than that of the sham group.

CONCLUSIONSThe up-regulation of the gene expression of adhesion molecules in pulmonary and hepatic microvascular endothelial cells is an important step for the migration and accumulation of leukocytes at the site of inflammation, which plays a critical role in organ damage during sepsis. And the contribution of the heterogeneity of endothelial cells in organs' vulnerability during sepsis is worth a further investigation.

Animals ; Endothelium, Vascular ; cytology ; Gene Expression ; Intercellular Adhesion Molecule-1 ; genetics ; Liver ; cytology ; Lung ; cytology ; Male ; Mice ; Peroxidase ; metabolism ; Sepsis ; metabolism ; Up-Regulation ; Vascular Cell Adhesion Molecule-1 ; genetics

OBJECTIVE:To optimize the formulation technology of Ibuprofen sustained-release dropping pill and evaluate its in vitro drug-release characteristics. METHODS:Using stearic acid as sustained-release matrix,polyethylene glycol 6000 as imme-diate-release matrix,melting method was used to prepare the Ibuprofen sustained-release dropping pill. Using the comprehensive scores of roundness,weight difference,drug loading rate,in vitro drug-release time as indexes,drug-matrix mass ratio,liquid tem-perature,condensation temperature,dropping distance as factors,orthogonal test was adopted to optimize the formulation technolo-gy,and verification test was conducted. In media of deionized water,hydrochloric acid solution (pH 1.2),phosphate buffer (pH 4.5,6.8),the in vitro drug-release were compared between self-made sustained-release dropping pill and commercially available Ibuprofen sustained-release capsule,which were fitted for former drug-release behavior. RESULTS:The optimal formulation tech-nology was as follows as mass ratio of ibuprofen-polyethylene glycol 6000-stearic acid of 4.0:15.3:0.7,liquid temperature of 83 ℃,condensation temperature of 8 ℃,and dropping distance of 11 cm. The weight difference of prepared 3 batches of Ibupro-fen sustained-release dropping pill was 2.067%(RSD=1.19%),roundness was 96.73%(RSD=0.28%),drug loading rate was 96.31%(RSD=0.19%),cumulative release rate in 12 h was 93.05%(RSD=0.81%). The f2 values of self-made sustained-re-lease dropping pill and commercially available Ibuprofen sustained-release capsule were greater than 50,the former one fitted more into Higucci equation(r=0.9881-0.9972). CONCLUSIONS:The formulation technology of Ibuprofen sustained-release dropping pill is successfully optimized,and in vitro drug-release behavior of prepared sustained-release dropping pill is similar to commercial-ly available Ibuprofen sustained-release capsule.

Objective To investigate the therapeutic effects of Quercetin (QT)-loaded PLGA-TPGS nanoparticles (QPTN) on solid tumor-bearing mice with HCa-F hepatocarcinoma in vivo.Methods The model of HCa-F hepatocarcinoma solid tumor-bearing mice was established by implanting HCa-F cells into 48 mice.The mice were divided into 6 groups randomly:the negative control,empty PLGA-TPGS nanoparticles,5-Fluorouracil solutions (FS),Quercetin solutions (QTS),QT-loaded PLGA nanoparticles (QPN),and QPTN groups.Each group was treated using tail vein twice a day for 20 days;then,all mice were sacrificed.The increment tumor volumes and tumor growth inhibition rate were counted.Then,tumor specimens were prepared for hematoxylin & eosin (HE) staining and observed under a microscope.Results The results showed that the increment tumor volumes of mice in the QPTN,QPN,and FS groups were significantly smaller than that in the negative control group (P ＜ 0.05 or P ＜ 0.01).The tumor growth inhibition rate of the QPTN group was 59.07％,which was much higher than that of the QTS group (23.94％),the FS group (35.14％),and the QPN group (46.14％).The results of the HE staining on the tumor sections also indicated that the QPTN group showed a better therapeutic outcome compared to the other groups.Conclusion The QPTN has a better therapeutic effect on the model of solid tumor using HCa-F cells-bearing mice than the QPN,QTS,and FS.

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