Preliminary association of individual different plasma pazopanib concentration with CYP3A4 gene polymorphism / 中国临床药理学与治疗学

AIM: To study the pharmacokinetics (PK) of pazopanib tablets and explore the genetic mechanism of individual differences in drug metabolism primarily. METHODS: Fourteen healthy male subjects were respectively administrated with a single dose pazopanib tablet (200 mg) orally on the day of dosing, and their blood samples were collected from baseline to 96 hours. The serum concentration of pazopanib was measured by LC-MS/MS, the parameters of PK were calculated by winnonlin 6.3 software, and the gene polymorphism of cytochrome P450 3A4 (CYP3A4) was determined by snapshot method. RESULTS: The range of C

Preparation and Quality Evaluation of Bepotastine Besilate Film-coated Tablets / 中国药师

Objective: To prepare bepotastine besilate film-coated tablets, determine the dissolution rate by HPLC, and evaluate the similarity of dissolution curves for self-made tablets and the original tablets. Methods: Bepotastine besilate tablets were prepared by using microcrystalline cellulose, hydroxypropyl cellulose, mannitol, aspartame and magnesium stearate as the accessories. Bepotas-tine besilate film-coated tablets were prepared by using OpadryⅡpremixed spray-coating liquid. The formulation was screened with the angle of repose, disintegration time, content uniformity and dissolution rate as the indices. The coating material amount was screened with the dissolution rate as the index. Results: The optimal formulation of bepotastine besilate film-coated tablet contained bepotastine besilate 5 mg,mannitol 43 mg,microcrystalline cellulose 21. 5mg,aspartame 0. 5 mg,magnesium stearate 0. 5 mg and hydroxypropyl cellulose 15 mg. The optimal weight of coating material was 5% . The self-made tablets and the original tablets had similar dissolution behavior in 4 media including water, hydrochloric acid(pH 1. 2), acetate buffer solution(pH 4. 5) and phosphate buffer solution(pH 6. 8). Conclusion:The self-made tablets have similar dissolution behavior in vitro with the original tablets, and their quality is similar.

Fundamental aspects of synthetic biology / 生物工程学报

Synthetic biology is an emerging interdisciplinary research field. By designing and constructing new or re-designing the existing natural systems, it confers them novel functions, which do not exist in nature. Owing to the predictability and controllability, synthetic biology attracts more and more interest from biologists, physicists, and engineers. Synthetic biology approaches not only can be widely used for biotechnological applications but also can be used to study complex biological systems to address fundamental questions. Here, we reviewed the recent studies following the concept of "build-to-understand", particularly, the studies to understand intracellular network structure, cell physiology, the behavior of multicellular populations, and ecosystems.

Hearing restoration in a deaf animal model with transplantation of adipose-derived mesenchymal stem cells from guinea pigs / 中国组织工程研究

BACKGROUND:Can adipose-derived mesenchymal stem cells be used to treat sensorineural deafness caused by hair celldegeneration and loss? OBJECTIVE:To investigate the effect of adipose-derived mesenchymal stem cells from guinea pigs transplanted via the scala tympani on the recovery from sensorineural hearing in an animal model. METHODS:Intraperitoneal injection of gentamicin was performed to prepare sensorineural deafness models in guinea pigs. Then, adipose-derived mesenchymal stem cells from guinea pig were transplanted via the scala tympani. After 1 and 3 weeks, auditory brainstem responses were detected to observe the hearing variation after adipose-derived mesenchymal stem celltransplantation. Meanwhile, the migration and distribution of EDU-labeled adipose-derived mesenchymal stem cells in the cochlea were traced. RESULTS AND CONCLUSION:After 1 and 3 weeks of implantation, the results from auditory brainstem response showed that the hearing was gradual y improved. At 1 week of implantation, most of the cells were distributed in the perilymph and some cells migrated to the Corti organ and attached to the basement membrane. At 3 weeks of implantation, cells migrated and attached to the basement membrane of Corti organ, furthermore, some cells migrated to the cochlear nerve. The longer the time of implantation, the less cellsurvived. The results indicate that adipose-derived mesenchymal stem cells from guinea pig that are transplanted via the scala tympani can directly migrate and survive ultimately to improve the hearing.

Adipose-derived mesenchymal stem cells differentiate into inner ear hair cells in guinea pigs induced by progressive addition of cytokines / 中国组织工程研究

BACKGROUND:Sensorineural hearing loss is mainly caused by missing or damaged hair cells in the inner ear. Application of adipose-derived mesenchymal stem cells to regenerate inner ear hair cells is an effective treatment for hearing loss. OBJECTIVE:To explore the feasibility of in vitro inducing adipose-derived mesenchymal stem cells to differentiate into inner ear hair cel-like cells in guinea pigs. METHODS:Adipose-derived mesenchymal stem cells from guinea pigs were isolated and cultured to the 3rd generation. cellphenotype was detected using flow cytometry. Cytokines were added for induction and differentiation by stages, including epidermal growth factor, basic fibroblast growth factor, insulin-like growth factor-1, al-trans retinoic acid, brain-derived neurotrophic factor, neurotrophin 3. RESULTS AND CONCLUSION:Adipose-derived mesenchymal stem cells of guinea pigs cultured in vitro were fusiform and showed a swirled adherent growth. Passage 3 cells were positive for CDCD29 and CD44, but negative for CD34 and CD45. After induction, the cells were positive for nestin and GFAP positive at early stage;after 10-day continuous induction, the cells expressed Myosin VIIa and Math1, specific markers of hair cells, indicating that cytokines can directly induce adipose-derived mesenchymal stem cells to differentiating into inner ear hair cells in guinea pigs.

The influence of platelet rich plasma gel applied to adipose-derived stem cells repair soft tissue wounds / 重庆医学

Objective To explore the role of ADSCs and PRP in soft tissue defect repairing .Methods Harvest adipose tissue from inguinalis fat pad of SD rats ,isolation ,culture ,and identification the ADSCs through three differentiation method .Take 30 male SD rats about 6-7 weeks old randomly .Randomly selected 12 rats been take blood from heart .Preparation the PRP with modi-fied appel method .To count platelet of whole blood and PRP under microscope .Take the remaining rats .Divided the rat into 3 groups(n=6 in each group) randomly ,of which group A treatment with ADSCs and PRP ;Group B treatment with ADSCs ;Group C treatment whit PRP .Selected one side of skin defect wound for test randomly and the relative side skin defect is for control ,Handle all of the control wound to group D ;Observe the grow th of granulation tissue on the wound surface ;observe the inflammatory sur-rounding and the degree about epithelial .statistical analysis and record the wound size ,and calculation the shrinkage rate of wound in different periods .Record the time of completely healing time .Histologic observation of the wound healing tissue .Results Plate-let counting showed platelet of PRP is 5 .21 times than whole blood .The wound completely healed time :group A (18 .25 ± 1 .44 ) days ,group B(19 .13 ± 1 .28)days ,group C(19 .72 ± 0 .87)days ,group D(22 .31 ± 1 .65) days ,The time of each treatment group and control group was significantly obvious(P< 0 .05) .At 3 ,7 ,11 and 15 days after experimental treatment ,compared with the control group the experiment group of wound contraction rate was significantly obvious (P<0 .05) .Conclusion Application of AD-SCs with PRP can enhance the quality and shorten the wound healing time than used them alone .

Expressions of EOS and COX-2 in nasal polyps in patients with aspirin triad syndrome and its significance / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To explore the regulatory role of COX-2 and aggregation of EOS in the pathogenesis of Aspirin triad syndrome.@*METHOD@#There were 34 patients with ST (group 1), 30 patients with chronic sinusitis and nasal polyps and asthma (group 2), 30 patients with sinusitis (control group). Nasal polyps of 94 patients were obtained in endoscopic sinus surgery,HE staining and immunohistochemical SP staining were performed to detect the distribution of eosinophils(EOS) and the expression of COX-2. Statistical analysis was performed using the SPSS software and then the relationship between their expression and distribution with clinical pathology and pathogenesis was analyzed.@*RESULT@#EOS infiltrated extensively in nasal polyps, and EOS counts in these groups were 80.02 +/- 6.11, 76.62 +/- 5.22, 65.97 +/- 4.78,respectively. The difference between ST group, ATA group and control group are significant (P 0.05) was found between ATA group and control group,ST group and ATA group.@*CONCLUSION@#The difference of EOS infiltration in patients with ST may be associated with an inflammatory response underlying specific clinical manifestations after exposure to non-steroidal anti-inflammatory drugs, and the difference of COX-2 expression in patients with ST may be related to the conversion of metabolic pathway of arachidonic acid and the formation of nasal polyps.

Effects and mechanism of genistein on the proliferation and apoptosis in human nasopharyngeal carcinoma cell lines CNE / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the effects and mechanism of genistein on proliferation inhibition and onset of apoptosis in nasopharyngeal carcinoma cell line CNE.@*METHOD@#Antiproliferative effect of genistein against CNE was tested by MTT method. Apoptotic phenotype of CNE was observed by electron microscope. Cell apoptosis percentage and cell cycle phase distribution of CNE were measured by flow cytometric assay.@*RESULT@#A time dependent and dose dependent proliferation inhibition was demonstrated in CNE, the high potency has the obvious suppression on tumor growth function; Genistein induces nasopharyngeal cancer cell early apoptosis rate but to strengthen along with the density increase, 200 micromol/L group is highest, is 49.9%; and genistein induced a G2/ M cell cycle arrest. The characteristic morphological changes of apoptosis in CNE cells was observed after treated by genistein.@*CONCLUSION@#The time dependent and dose dependent proliferation inhibitory effect of genistein on nasopharyngeal cancer cells. Genistein's mechanism on suppressing effect is probably associated with inducing the cell apoptosis and intervening the cell circle of carcinoma cell. The results provide evidence for the potential usefulness of genistein in the prevention and treatment of human nasopharyngeal carcinoma.

Study of hearing loss in 200 patients with subjective tinnitus / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To analyze the hearing loss profiles in patients with tinnitus, and then provide clinical foundation for further studying the etiology and examination methods of tinnitus.@*METHOD@#Ear specialist examination, acoustic impedance test,normal frequency pure tone audiometry and extended high frequency audiometry were applied to 200 patients with chief complaint of subjective tinnitus.@*RESULT@#Among the 200 tinnitus cases, 123 (61.5%) patients were diagnosed with unilateral tinnitus, 77 (38.5%) patients with bilateral tinnitus and 46 (23.0%) cases with normal hearing. In those patients with unilateral tinnitus, by comparing the hearing threshold of affected side and contralateral side (0.125-8 kHz), the difference was statistically significant (P 10 kHz), the difference between two groups was not statistically significant (P > 0.05). There was significant difference in hearing threshold between tinnitus patients with normal and abnormal hearing in normal frequency (P < 0.05), meantime the detection rate in abnormal hearing group was lower than the normal group.@*CONCLUSION@#Tinnitus can occur in people with normal hearing. Early in tinnitus,further study need be undertaken on whether the audiometry extended high frequency can offer the early evidence of hearing loss for tinnitus patients or not.

Relationship between adult craniofacial structures and development of obstructive sleep apnea-hypopnea syndrome / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To explore the influence of adult craniofacial structures on obstructive sleep apnea hypopnea syndrome (OSAHS).@*METHOD@#This study compared the measurements of the height, body weight,neck circumference, the mallampati oropharyngeal score grading, thyromental distance, thyromental angle, lobule-mental distance, mental-lower lip distance of 50 patients with OSAHS with those of 50 controls.@*RESULT@#Statistical findings showed that OSAHS patients were different from controls in the following ways: (1) higher neck circumference; (2) larger thyromental angle; (3) higher Mallampati scores; (4) higher body mass index; (5) shorter mental-lower lip distance.@*CONCLUSION@#A crowded posterior oropharynx and a steep thyromental plane are associated with OSAHS. The adult craniofacial structures of bony and soft tissue determine the dimension of upper airway during sleep andpaly an important role in the development of OSAHS.

Expression and cytotoxicity of a human interleukin-6 tumor necrosis factor derivative fusion protein (5＇IL6-TNF△) in vitro / 吉林大学学报(医学版)

Objective :To develop an agent that is more active against receptor-bearing target cells without increasing the toxic effect on non-target cells. Methods :By the use of molecular biology techniques,we designed and constructed a fusion protein 5＇IL6-TNF△ by connecting the human interleukin-6 (hIL-6) gene and a human tumor necrosis factor α derivative (TNF△) gene througha synthetic linker sequence followed by subsequent expression in E. Coli. Results: In cytotoxicity assay with myeloma cell line U266, the normal type of 5＇ IL6-TNF△ showed an antitumor activity 3 times higher than that of TNF△;and the antitumor activity of 5＇IL6-TNF△ blocked by IL-6Rwas only 1/30 of that of normal type of 5＇ IL6-TNF△. Meanwhile,the 5＇IL6-TNF△ blocked by an ti-TNF antibody did not show any cytotoxicity to U266 cells. In activity assay with L929 cells ,the toxic effect of the fusion protein was found 1/22 of that of TNF△. Conclusion: The 5＇IL6-TNF△fusion protein might be a useful cytotoxic agent in cancer treatment.