OBJECTIVE: To optimize the formulation of citalopram hydrobromide (CTH ) thermosensitive nasal gel and further evaluate its in vitro properties. METHODS: With gelling temperature and gelling time as evaluating indexes, central composite design-response surface and single factor experimental design method were used to optimize the formulation of CTH thermosensitive nasal gel by using poloxamer 407(F127) and carbomer 940 (CP940) as gel materials. Meanwhile, nasal mucosa permeation enhancer for CTH was then sieved by using Franz diffusion cell and ex vivo sheep nasal mucosa as experimental model. Finally, CTH thermosensitive nasal gel was prepared with cold method and then its in vitro properties was evaluated. In vitro cumulative erosion and cumulative release rate of the drug thermosensitive nasal gel were investigated by membrane-free dissolution method and dialysis membrane method, respectively. Moreover, the effect of temperature and pH on the viscosity of the drug nasal gel formulation was also evaluated. RESULTS: The optimal formulation of the thermosensitive nasal gel consisted of CTH 8.0%, F127 20.27%, CP940 0.17%, DM-β-CD 3.0%, ethylparaben 0.05% and distilled water. The gelling temperature, gelling time and pH of the drug thermosensitive nasal gel were found to be about 32.5 ℃,42 s and 5.0, respectively. The in vitro cumulative erosion and cumulative release percentage were both greater than 90% in 55 min and furthermore there was good linear correlation between these two parameters (r=0.998 6). Additionally, in vitro cumulative release of the drug from the gel formulation was determined to be 92% within 8 h, which conformed to Higuchi kinetic equation. Furthermore, the viscosity of the drug nasal gel was influenced by temperature as well as pH in different extent. CONCLUSION: The optimized formulation of the CTH thermosensitive nasal gel with central composite design-response surface method and single factor design method shows suitable gelling temperature, gelling time, pH value for nasal preparation and obvious in vitro drug sustained release characteristics.

OBJECTIVE: To investigate the pharmacokinetics of citalopram hydrobromide(CTH)thermosensitive nasal gel and further evaluate its brain delivery in rats. METHODS: The concentrations of CTH in rat plasma and brain tissue were determined by HPLC method. With intragastric administration (ig) of CTH solution as control, CTH thermosensitive nasal gel was intranasally given to rats and the concentrations of CTH in plasma and brain tissues were then determined. Moreover, the main pharmacokinetic parameters of CTH in plasma and brain tissues such as tmax, ρmax,relative bioavailability (Fr) and drug targeting efficiency (DTE) were estimated. RESULTS: Main pharmacokinetic parameters of CTH following nasal and ig administration to rats such as tmax and ρmax were 5 and 45 min, 2 152.86 and 589.68 ng•mL-1 in plasma, and 5 and 45 min, 17 660.56 and 1 171.68 ng•g-1 in brain tissue, respectively. Finally, the Fr and DTE of CTH thermosensitive nasal gel were found to be 184.91% and 250.03%, respectively. CONCLUSION: CTH thermosensitive nasal gel may be an ideal non-oral new dosage form with many advantages such as rapid in vivo absorption, high bioavailability and obvious brain delivery characteristics.

At present, cancer is still one of the most serious threats to human health. Despite the wide application of multiple cancer therapies in clinical practice, the therapeutic effects of most cancers are still far from satisfactory. In recent years, the discovery of regulated cell death may be a good first step on the road to treat cancer. Ferroptosis is triggered by lipid peroxidation of unsaturated fatty acids in cell membrane catalyzed by iron ion. It has been widely concerned as an emerging target for cancer therapy. With the booming of biomedical nanotechnology, ferroptosis as an emerging therapeutic target has attracted extensive attention. Here, we review the advance on the intersection of ferroptosis and biomedical nanotechnology. First, the research background of ferroptosis and nano-preparation as well as the feasibility of ferroptosis-based nano-drug delivery systems (nano-DDS) for cancer treatment are presented and analyzed. Then, the strategies for inducing ferroptosis based on nano-DDS are summarized, mainly including: the promotion of Fenton reaction, the inhibition of glutathione peroxidase 4 (GPX-4) and the restriction of the cysteine-glutamate exchange transporter (system Xc^-). Furthermore, the combination therapy strategies based on biomedical nanotechnology induced ferroptosis are also discussed. Finally, we shine the spotlight on the prospects and challenges of ferroptosis-based nanotherapeutics in clinical application.

Aim To investigate estradiol inhibition of neointimal proliferation after rat carotid artery balloon injury. Methods Eight to ten-week-old SD rats (male,n=21,female,n=21) were divided into intact control(n=7),gonadectomy control(n=7) and estradiol (n=7, gonadectomy)groups in each sex. Left carotid artery was not injured with 2.0 F PTCA balloon until estradiol was injected for three days. Rats were killed 2 wk after injury. Neointimal areas and media area, ratios of intimal areas/media areas were measured with computer. Results Male neointimal areas and ratios of intimal areas /media areas in estradiol group were less than those in intact control group significantly(all P0.05). Conclusions Estrdiol inhibits neointimal proliferation after the gonadectomy in rats undergoing carotid artery balloon injury.

Along with the rapid development of molecular biology, cell biology, genetics, and immunology, there is a new understanding on the pathogenesis of pituitary adenomas. The pathogenesis of pituitary adenomas is considered to be related with gene mutation, growth factors, cell receptors, transcription factors, and cellular signaling pathways.
Adenoma ; genetics ; metabolism ; Humans ; Mutation ; Pituitary Neoplasms ; genetics ; metabolism ; Signal Transduction

Adult ; Aged ; Biomarkers, Tumor ; metabolism ; Carcinoma, Basal Cell ; metabolism ; pathology ; surgery ; Humans ; Keratin-5 ; metabolism ; Keratins ; metabolism ; Male ; Membrane Proteins ; metabolism ; Neoplasm Recurrence, Local ; Prostate ; metabolism ; pathology ; surgery ; Prostatectomy ; Prostatic Neoplasms ; metabolism ; pathology ; surgery

Total mRNA was extracted from lymphocytes separated from the peripheral blood of allergic patients, and then variable region of heavy chain (VH) and variable region of light chain (VL) cDNA library were constructed by RT-PCR. Human scFv templates for rabbit reticulocyte lysate ribosome display were assembled by primers and linker peptide (Gly4Ser)3. mRNA bound in antibody-ribosome-mRNA complexes was recovered using in-situ single primer RT-PCR, and three rounds of anti-IgE scFv DNA were enriched. The target DNA fragments were double enzyme digested and ligated into plasmid pET22b (+), followed by transformation in E. coli Rosseta (DE3). Positive clones were screened using clone PCR, Dot blotting and antigen ELISA. The correct lengths of VH (400 bp) and VL (710 bp) PCR products were obtained. The expected 1,000 bp ribosome display templates were also observed in agarose gel electrophoresis. After three rounds of ribosome display target sequences were effectively enriched, leading to a library of 10(13) members. Antibodies with the highest ELISA value for IgE were generated in the strain pET-IgE-6. A human anti-IgE scFv library was successfully constructed as described herein. Ribosome display using single primer in-situ RT-PCR as the recovery procedure effectively enriched target sequences. Anti-IgE scFv with high affinity and specificity were identified. The prepared human anti-IgE scFv fragment might be self-developed to a lead drug for treating asthma. Our study provides an alternative method for rapid discovery of human antibodies of therapeutic importance.
Amino Acid Sequence ; Antibodies, Anti-Idiotypic ; genetics ; isolation & purification ; Antibody Affinity ; Asthma ; blood ; Base Sequence ; DNA, Complementary ; metabolism ; Escherichia coli ; metabolism ; Humans ; Immunoglobulin Heavy Chains ; genetics ; Immunoglobulin Light Chains ; genetics ; Immunoglobulin Variable Region ; genetics ; Lymphocytes ; chemistry ; Peptide Library ; RNA, Messenger ; isolation & purification ; Recombination, Genetic ; genetics ; Ribosomes ; chemistry ; genetics ; immunology ; Single-Chain Antibodies ; genetics ; isolation & purification ; Transformation, Genetic

OBJECTIVETo analyze the Millard II technique for correcting secondary deformities of unilateral cleft lip.

METHODSThe Millard II technique was used to correct secondary deformities of unilateral cleft lip in 42 patients from March of 2003 to September of 2004. Dissection was made between the alar cartilage and skin, and the alar cartilage was suspended.

RESULTSThe postoperative follow-ups with 3 approximately 6 months revealed good results of the symmetrical nostrils and philtrums, prolonged columella nasi, good-shaped cupid's bow, and invisible scar.

CONCLUSIONSThe Millard II technique could be an ideal method to correct secondary deformities of unilateral cleft lip. Releasing and suspending alar cartilage spontaneously at the same time can correct nasal deformity adequately.

Adolescent ; Adult ; Child ; Child, Preschool ; Cleft Lip ; etiology ; surgery ; Female ; Humans ; Male ; Nose ; abnormalities ; Nose Deformities, Acquired ; surgery ; Postoperative Complications ; surgery ; Reconstructive Surgical Procedures ; methods ; Young Adult

OBJECTIVETo explore the effect of fixation of Kirschner needle and thread cancellous bone screw through the sinus tarsi interstice for the treatment of calcaneal fractures.

METHODSFrom January 2009 to December 2012,20 patients with calcaneal fracture were treated by minimally invasive Kirschner wire and threaded cancellous bone screw fixation and bone graft,including 12 males and 8 females with an average age of 39 years old ranging from 21 to 65. Among them, 8 cases were left foot, 12 were right foot. According to Sanders's classification, 8 cases were type II, 10 cases were type III, 2 cases were type IV.

RESULTSAll patients were followed up from 6 to 16 months with an average of 12 months. The incision were healed. Böhler angle were increased from preoperative (17.75 +/- 4.22) degrees to postoperative (26.85 +/- 7.37) degrees (t = 4.308, P = 0.000). Gissane angle were reduced from preoperative (137.05 +/- 24.91) degrees to postoperative (113.75 +/- 13.17) degrees (t = 7.083, P = 0.000). At 3 months after operation, the scores of AOFAS were 85.50 +/- 7.99; the results were excellent in 5 feet and good in 11 feet, fair in 3 feet, and poor in 1 foot.

CONCLUSIONMinimally invasive fixation of Kirschner needle and thread cancellous bone screw fixation is a simple operation, it can get reliable fixation, easy to remove, low cost, less postoperative complications, and it is a good treatment of calcaneal fracture.

Adult ; Aged ; Bone Screws ; Bone Wires ; Calcaneus ; injuries ; surgery ; Female ; Fracture Fixation, Internal ; methods ; Humans ; Male ; Middle Aged

Stem cell factor is an important hematopoietic growth factor. In this study, the human stem cell factor was produced by recombinant E. coli, and the structure and biological activity of the recombinant stem cell factor(rhSCF) was studied. It was indicated that the rhSCF was a uncovalent dimer in phosphate buffer,and had the correct mass spectra, mass peptides spectra, composition of amino acid, N-terminal sequernce, C-terminal sequence and intrachain disulfide linkages, rhSCF alone or synergy with rhG-CSF could mobilze hematopoietic progenitors to blood in monkey.
Animals ; Cell Differentiation ; drug effects ; Cells, Cultured ; Chromatography, High Pressure Liquid ; Haplorhini ; Hematopoietic Stem Cells ; cytology ; drug effects ; Humans ; Recombinant Proteins ; chemistry ; genetics ; metabolism ; pharmacology ; Sequence Analysis, Protein ; Spectrometry, Mass, Fast Atom Bombardment ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Stem Cell Factor ; chemistry ; genetics ; metabolism ; pharmacology