Nanocrystal drugs have many advantages, such as no carrier materials, easy industrialization, diversified dosage forms, and can significantly improve the solubility and bioavailability of insoluble drugs, so many drugs have been on the market. The traditional nanocrystal preparation technology has the problems of low preparation efficiency and process limitation of the smallest achievable particle size. With the progress of pharmaceutical preparation technology, the preparation technology of nanocrystal drugs is constantly improving, and new preparation technologies are constantly emerging. The emergence of new technologies has greatly shortened the process time and makes it possible to prepare nanocrystal drugs with smaller particle diameters. In this paper, the preparation technologies of nanocrystal drugs, especially the new preparation technologies such as high gravity controlled precipitation, microfluidic reaction technology and various combination technologies, are reviewed from three aspects: "Top-down" technology, "Bottom-up" technology and combination technology. This article also prospects the development of new preparation technologies, hoping to provide reference for the related research of nano-preparations.

To compare the pharmacokinetics of syringin, eleutheroside E and isofraxidin after intravenous administration of each monomer and Ciwujia injection. Twenty-four Sprague-Dawley rats were randomly divided into four groups and intravenously administrated with syringin, eleutheroside E, isofraxidin, and Ciwujia injection, respectively. The concentrations of the three components in rat plasma were determined by LC-MS/MS. DAS 2.0 software was applied to calculate the pharmacokinetic parameters while the SPSS 17.0 software was used for statistical analysis. Significant difference (P < 0.05) was found between each monomer and the injection on the main pharmacokinetic parameters such as AUC, CL and t1,/2. Compared with the injection, the group treated with the syringin has obvious decrease in AUC, and increase in CL while the group treated with eleutheroside E has obvious increase in AUC, and decrease in CL The t1/2 of isofraxidin was prolonged in Ciwujia injection. Pharmacokinetic characters of the ingredients in the injection varied greatly from the monomer. Other constituents in the injection may have an impact on the pharmacokinetic profiles of these three components.
Administration, Intravenous ; Animals ; Coumarins ; administration & dosage ; blood ; pharmacokinetics ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Glucosides ; administration & dosage ; blood ; pharmacokinetics ; Lignans ; administration & dosage ; blood ; pharmacokinetics ; Male ; Phenylpropionates ; administration & dosage ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

To establish a method for the determination of cucurbitacin in plasma samples, in order to study the in vivo pharmacokinetic characteristics of cucurbitacin in rats. Rats were intravenously injected with cucurbitacin. With diphenhydramine as the internal standard (IS), the plasma concentrations of cucurbitacin in rat plasma at different time points were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS). With electrospray ionization source, the positive ion detection in the multiple reaction monitoring mode was conducted to determine the ion-pairs for target compound and IS were m/z 503.2/113.1 and m/z 256.0/167.2, respectively. Agilent ZOBAX SB-C18 column (2.1 mm x 50 mm, 1.8 microm) was adopted and eluted with methanol and 0.1% formic acid (55:45), and the flow rate was 0.2 mL x min(-1). DAS 2.0 software was applied to fit the blood concentration and calculate corresponding pharmacokinetic parameters. The rats were intravenously injected with cucurbitacin at the concentration of 3.0 mg x kg(-1). The target blood quality concentration show good linear relations within the range of 10.5-3 150 microg x L(-1) (R2 = 0.996), the lower limit of the standard curve was 10.5 microg x L(-1), and the signal to noise ratio S/N = 12. Intra- and inter-day precisions RSD was less than 6.9% and 14%, respectively; The accuracy RE ranged between 0.20% and 3.7%; The extraction recoveries ranged between 92.7% and 97.1%. Regarding the pharmacokinetic parameters of tail intravenous injection of cucurbitacin, AUC (0-t) was (811.615 +/- 111.578) microg x h x L(-1), (t1/2) was (1.285 +/- 1.390) h, CL was (3.627 +/- 0.487) L x h x kg(-1), and V(d) was (6.721 +/- 7.429) L x kg(-1). In this study, researchers established a simple, accurate, sensitive and highly specific method for determining the blood concentration of cucurbitacin, and reported the in vivo pharmacokinetic characteristics of cucurbitacin in rats for the first time.
Administration, Oral ; Animals ; Cucurbitaceae ; chemistry ; Cucurbitacins ; administration & dosage ; blood ; pharmacokinetics ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Male ; Rats ; Rats, Wistar

BackgroundRetinal pigment epithelial(RPE) cells can secrete platelet-derived growth factor (PDGF) and PDGF receptor(PDGFR).Studies have shown that PDGF plays a key role in the formation of proliferative vitreous retinopathy(PVR). ObjectiveThis study was to investigate the proliferation and apoptosis changes of RPE after blockage of the PDGFR-α expression by antisense oligonucleotide ( ASODN ) in vitro. Methods Human RPE cells strain was cultured in low glucose DMEM with 10％ fetal bovine serum.Logarithmic phase cells were collected and incubated in 96-well plate at the density of 5 × 105 cells/hole.PDGFR-α ASODN was transfected into RPE cells at different concentrations for 48 hours.The cells of the blank control group were regularly cultured without any transfection.The changes of PDGFR-α expression were detected by reverse transcription-polymerase chain reaction(RT-PCR),and the proliferation of RPE was detected by MTT as the A490 value.Hoechst 33258 fluorescence staining was used to determine the apoptosis of RPE.Flow cytometry method (FCM) was applied to detect the change of cell cycle and apoptosis rate of RPE cells. ResultsThe A490 values of RPE cells were 1.45±0.12,1.07±0.06,0.65±0.05 in blank control group,1.0 μmol/L Lipo-ASODN group and 2.0 μmol/L Lipo-ASODN group with the significant difference(P=0.00 ),and that of 1.0 μmol/L Lipo-ASODN group and 2.0 μ mol/L Lipo-ASODN group were significantly lower than the blank control group ( P =0.00,0.00).Hoechst 33258 staining showed that the apoptosis cells were obviously more in Lipo-ASODN group compared with blank control group.PDGFR-α ASODN transfection induced an increase of percentage of RPE cells in G0/G1 phase( F =206.70,P =0.00),and the apoptosis rates in 1.0 μmol/L Lipo-ASODN group and 2.0 μmol/L Lipo-ASODN group were significantly enhanced in comparison with blank control group ( 37.8 ± 1.3 vs 10.5 ± 0.1,61.2 ± 1.9 vs 10.5 ± 0.1 ) ( F =1808.90,P =0.00 ).Expression intensity of PDGFR-α mRNA in RPE cells in Lipo-ASODN groups was lower. ConclusionsBlocking the PDGFR-α expression with ASODN technology can suppress proliferation and induce apoptosis of RPE cells.Intensity of PDGFR-α mRNA expression in RPE cells is ASODN dose-dependent.ASODN targeted to PDGFR-α offers an experimental basis of the gene therapy for PVR.

OBJECTIVETo compare the initial penetration depth of nickel-titanium (NiTi) and stainless-steel (SS) spreader during lateral compaction and the quality of the seal in curved canals.

METHODSForty extracted mandibular premolars with a single curved canal were divided into two groups: no more than 20 degrees and more than 20 degrees based on degree of curvature. All canals were instrumented using a rotary instrumentation technique. NiTi and SS spreaders were used to obturate the canals containing a master cone while the penetration depths were measured. Horizontal sections were cut in 2 and 4 mm from the apex and photographed under stereomicroscope. The percentage of gutta-percha-filled are (PGP) of cross-sections was measured using an image analysis program.

RESULTSIn canals of more than 20 degrees, the penetration depths and PGP of 2 mm from the apex of NiTi spreaders were higher than SS spreader. In canals of no more than 20 degrees, there were no significant difference between them (P > 0.05). At 4 mm from the apex, there was no significant difference between two groups.

CONCLUSIONNiTi spreaders has a higher penetrated depth and obturation density than SS spreaders in severed curved canals.

Gutta-Percha ; Humans ; Nickel ; Root Canal Obturation ; Stainless Steel ; Titanium

OBJECTIVETo determine whether the sonic hedgehog (Shh) signaling could regulate the expression of histone demethylases in the head and neck squamous cell carcinoma(SCC).

METHODSHuman recombinant SHH-N protein or over-expression of the mutant 2 smoothened (M2-SMO) was applied to activate the Shh signaling in tongue squamous cell carcinoma cell line-SCC-6 in this study. Cyclopamine was used to block the Shh signaling in SCC-6. The real-time reverse transcription (RT)-PCR was used to detect the expression of histone demethylases at the mRNA level.

RESULTSThe data showed that activation of the Shh signaling up-regulated the expression of histone demethylase, lysine-specific demethylase 8 (KDM-8) at the mRNA level by human recombinant SHH-N protein (1.841 ∼ 3.591 fold compare with untreated group; P < 0.01), over-expression of the M2-SMO also increased the expression of KDM-8 (1.358 ∼ 3.013 fold compared with empty vector group; P < 0.05), and after the Shh signaling was blocked by Cyclopamine, the expression of KDM-8 was down regulated (decreased 25.6% ∼ 66.6% compared with control cells, P < 0.05).

CONCLUSIONSHistone demethylase KDM-8 was downstream target gene of Shh signaling in head and neck squamous cell carcinoma cell line SCC-6, and its expression was positively regulated by the Shh signaling.

Carcinoma, Squamous Cell ; genetics ; metabolism ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Head and Neck Neoplasms ; genetics ; metabolism ; Hedgehog Proteins ; metabolism ; Histone Demethylases ; genetics ; metabolism ; Humans ; Mutant Proteins ; metabolism ; RNA, Messenger ; genetics ; Receptors, G-Protein-Coupled ; metabolism ; Recombinant Proteins ; metabolism ; Signal Transduction ; Smoothened Receptor ; Veratrum Alkaloids ; pharmacology

Objective To sum up the therapeutic results of 125 cases of tetralogy of Fallot(TOF),and ex- plore the optimal time and risk factors of opration,as well as perioperative management.Methods One hundred and thirth-one consecutive cases of TOF underwent corrective surgery.There were simple stenosis of infundibular portion in right ventricular outflow tract in 37 cases,stenosis of infundibulum and pulmonary valve in 14 cases,main pul- monary trunk and left/right pulmonary arteries stenosis in 74 cases,and pulmonary atresia in 5 cases.Autologousper- icardial conduit,or with waived were used for right ventricular outflow tract and right ventriculo-pulmonary artery connection.Other anomalies were corrected.Results The surgicalmortality was 4.0 %.The cause of death were se- rious low cardiac output syndrome(3 patients),respiratory function failure(1 patient),pericadial infection(1 pa- tient).Conclusion It is necessary to profonn corrective opration on younger TOF patients.Effetive prophylaxis and control of low cardiac output syndrome and pulmonary complication is a useful strategy.

OBJECTIVETo explore the mid-term surgical results of arterial revascularization for femoro-popliteal arterial occlusive disease (lesion type C and D).

METHODSFrom January 2005 to February 2009, 191 arterial bypass had been performed on 170 patients (21 cases bilateral). There were 108 male and 62 female, age ranged from 45 to 85 years old with an average of 67 years old. The operative indication was claudication in 78 cases, rest pain in 62 cases, ischemic ulcer in 19 cases, and distal tissue necrosis in 11 cases. Arterial angiography were performed on all cases. According to TASC II document, type C lesions were seen in 127 limbs, type D lesions were seen in 64 limbs. Autogenous greater saphenous vein bypass in situ were done on 15 limbs, autogenous greater saphenous vein bypass reversed in 20 limbs, revascularization with artificial prosthesis in 128 limbs, composite grafts consisting of a prosthetic conduit with a distal venous segment in 28 limbs.

RESULTSThere were no 30-day mortality. Follow-up periods ranged 6 to 36 months with an average of (24 + or - 6) months. Seventy-three cases were lost during follow-up periods, follow-up rate was 57% (109/191). Primary patency rate was 84.4% (92/109). The patency rate was 88.2% with artificial prosthesis, 70.8% with greater saphenous vein (in situ or reversed). Secondary patency rate was 89.9%.

CONCLUSIONSArterial revascularization with artificial prosthesis is main treatment for diffused superficial femoral artery occlusive disease (TASC II type C and D lesion) with satisfied surgical results.

Aged ; Aged, 80 and over ; Arteriosclerosis Obliterans ; surgery ; Blood Vessel Prosthesis Implantation ; Female ; Femoral Artery ; surgery ; Humans ; Male ; Middle Aged ; Popliteal Artery ; surgery ; Retrospective Studies ; Saphenous Vein ; transplantation ; Treatment Outcome

Astrocytoma ; genetics ; metabolism ; Brain Neoplasms ; genetics ; metabolism ; Frizzled Receptors ; genetics ; metabolism ; Glioblastoma ; genetics ; metabolism ; Glioma ; genetics ; metabolism ; Humans ; Paraffin Embedding ; RNA, Messenger ; metabolism ; Receptors, G-Protein-Coupled ; genetics ; metabolism ; Signal Transduction ; Wnt2 Protein ; genetics ; metabolism ; beta Catenin ; genetics ; metabolism