Child, Preschool ; Female ; Humans ; Infant ; Male ; Mycophenolic Acid ; adverse effects ; analogs & derivatives ; therapeutic use ; Nephrotic Syndrome ; drug therapy ; Treatment Outcome

OBJECTIVETo prepare coated tablets of glycyrrhetinic acid and hydroxypropyl-beta-cyclodextrin (GTA-HP-beta-CYD) inclusion complex tablets for colon-specific release.

METHODIn order to improve the solubility of GTA, the GTA-HP-beta-CYD inclusion complex was prepared by ultrasonic-lyophilization technique and its formation were characterized by X-ray powder diffraction profiles and infrared spectrometry. The effects of inclusion condition on the inclusion efficiency and stability coefficient of inclusion complex were investigated, respectively. After prepared GTA-HP-beta-CYD tablets by powder direct compression, the pH dependant polymer Eudragit III and/or mixed with Eudragit II were used for further coating materials in fluid-bed coater. The influences of coating weight on the GTA release in different pH conditions were evaluated to establish the method for prepering colon specific delivery tablets with pulsed release properties.

RESULTThe formation of inclusion complexes were proved by X-ray powder diffraction profile and phase solubility curve. The effect of pH value of solvent was played critical role on the preparation of GTA- HP-beta-CYD inclusion complex. And the inclusion efficiency of GTA was 9. 3% and the solubility was increased to 54. 6 times at optimized method. The Eudragit III coated GTA- HP-beta-CYD tablets with coating weight 10% and 16% were showed pH dependant colon specific release profiles with slow release rate. The release profile of tablets coated with the mixture of Eudragit II and Eudragit III (1:2) were indicated typical pH dependant colon specific and pulsed release properties while the coating weight was 17%.

CONCLUSIONThe preliminary method for preparation of colon specific release tablets containing glycyrrhetinic acid with improved solubility was established for further in vivo therapeutic experiment.

2-Hydroxypropyl-beta-cyclodextrin ; Animals ; Colon ; chemistry ; Drug Stability ; Glycyrrhetinic Acid ; chemistry ; pharmacokinetics ; Humans ; Hydrogen-Ion Concentration ; Spectrophotometry, Infrared ; Tablets ; chemistry ; X-Ray Diffraction ; beta-Cyclodextrins ; chemistry ; pharmacokinetics

Background Researches showed that as the non-optical factors,cognitive has certain influence on the regulating system.So accurately experimental design is one of the key steps that evaluates the non-optical factors on regulating system.Objective The present study was to investigate the influence of presenting pattern of target and watching way on the level and amplitude of accommodative fluctuate and to analyze the effect of focus gaze of cognitive on regulating system and the relationship between focus gaze condition under near work and the development of myopia.Methods This study complied with Declaration of Helsinki,and the permission of Ethic Committee and written informed consent was obtained before entering in this trial.Thirty healthy volunteers were included with the mean age (24.80 ± 1.98) years old,equivalent refractive diopter (-1.92 ± 2.02) D and mean cylinder (-0.19±0.58) D.The presenting pattern of the targets was designed as focus gaze and relaxed gaze.The accommodative response and accommodative fluctuation in the complete corrected right eyes for the different targets at the 40 cm under the gazing state was recorded with Grand Seiko WAM 5500 automatic infrared refractor in the experiment.Results The mean accommodative response value was (1.86±0.26) D under the focus gaze and (1.27±0.39) D under the relax gaze,showing a statistically significant difference (t=-8.052,P=0.000).The mean fluctuate value was(0.17±0.06) D under the focus gaze,with a significant lowing in comparison with (0.28±0.17) D under the relax gaze (t =3.600,P =0.001).Conclusions These results demonstrate that the different presenting patterns of sighting target and watching ways of the subjects affect accommodation system.The accommodative response was relatively more accurate with a smaller microwavc moving under the focus gaze condition.

Objective To explore the possibility of repairing injured facial nerve with tissue engineering technology and neural stem cells(NSCs).The complex consisted of NSCs,scaffold and NT-3.NSCs were immature cells with the potential of self-renewal and multiple differentiation to neurons and glial cells.The scaffold with porous surface was made of hyaluronic acid and collagen(HA-Col gel) which degenerate in vivo after transplantation.NT-3 is the signal to promote neurons survival in vitro.Methods NSCs of S-D rat were co-cultured with scaffold and NT-3 in vitro.The two stumps of disconnected facial nerve of rabbit were re-connected with the complex.Electrophysiology and morphology tests were used to examine functional and morphological changes.Results Result] NSCs adhered to the HA-Col gel and survived.Injured facial nerve fixed by NSCs-HA-Col gel-NT-3 complex showed significant improvement in function and anatomical structure.Conclusion Combinative implant of NSCs,HA-Col gel and NT-3 may promote the regeneration of injured facial nerve.

Objective To define the effect and mechanism of hyperkalemic solution on atrial natriuretic peptide (ANP) secretion in rabbits. Methods Eighteen rabbits were selected and the chest was opened under anes-thetization to remove the heart. The left atrium was isolated and fixed in the atrial perfusion system with proper electric stimulation for beating. The following experiments were carried out on beating rabbit atria: ①The atrium was perfused for 60 min to stabilize parameters of ANP secretion and atrial dynamics. The control period (12 min as an experimental cycle) was followed by an infusion of hyperkalemic solution (K+ concentration of hyperkalemic solution was 5.64 mmol/L and the osmolarity of hyperkalemic solution was unchanged) for three cycles, then normal K+ cancentration was recovered for two cycles;②The control period was followed by an infusion of L type Ca2+ channel blocker nifedipine (1.0 μmol/L) for three cycles;③L type Ca2+ channel inhibitor nifedipine (1.0 μmol/L) was infused for 36 rain prior (three cycles) to infusion of hyperkalemic solution. Atrial stroke volume was determined and the ANP secretion was measured by radioimmtmoaasay. Results (1)Hyperkalemic solution increased atrial ANP secretion (P<0.01) and reduced the atrial stroke volume,hut the difference was not statistically significant as compared with that of the control cycle(P>0.05). The recovery trend was to the normal level of ANP secretion and atrial stroke volume was to become normal gradually when solution level recovered to normal ,which was not significantly different from that of the control cycle (P>0.05) ;②Nifedipine (1.0 μmol/L) also increased the atrial ANP secretion (P<0.01 or P <0.05) while decreasing atrial stroke volume (P<0.01 or P < 0.05 ) ; ③Nifodipine (1.0μmol/L) completely blocked the effect of hyperkalemic solution so to increase the ANP secretion (P <0.01 ). Conclusion Hyperkalemic solution significantly increases atrial ANP secretion via extracellular high K+ competitive inhibition of extracellular Ca2+ inflow in beating rabbit atria.

Objective To construct the recombinant plasmid of protein CFP10-MPT48-TB8.4 of Mycobacterium tuberculosis and to investigate the diagnosis potential of this fusion protein in tuberculosis serodiagnosis.Methods The recombinant fusion protein CFP10-MPT48-TB8.4 was expressed, and identified by Western blot.The ELSIA based on the purified fusion protein was done,and used for screening in 230 cases of clinical serum samples including pulmonary tuberculosis patients ( n =150 ),pulmonary disease patients other than tuberculosis (n =70) and health controls (n =103 ).The test result was analyzed by Medcale11.5 software.Results The fusion protein CFP10-MPT48-TB8.4 was successfully expressed with a purity over 95％.Specific immunogenicity of the recombinant protein was confirmed by Western blot.The overall sensitivity and specificity obtained of ELISA were 56.7％ (85/150) and 90.8％ ( 157/173 ),respectively.The specificity was 85.7 ％ (60/70) in non-tuberculosis group and 94.2％ (97/103 ) in healthy group,respectively.Conclusion The recombinant protein of CFP10-MPT48-TB8.4 has a high sensitivity and specificity and may be a potential candidate antigen in tuberculosis serodiagnosis.

Objective To study the etiological effect between the spatial variation of lumbar facet orientation and the degenerative lumbar spondylolisthesis(DLS)in axial,sagittal and coronal plane.Methods 85 patients with DLS at L4 and 110 controlsreceived X-ray and CT scanning.The facet angle at L4-L5 was measured in axial,sagittal and coronal plane.Results Compared with the control group, the DLS-angles were lesser and the difference between the left and right was greater in axial,coronal plane(P <0.05).But were greater in sagittal plane(P <0.05).Conclusion The DLS-angles are more sagittal in axial plane,more level in sagittal plane and more erect in coronal plane.The change of spatial orientation in the facet joint is one of etiological factors of degenerative lumbar spondylolisthesis.

The nuclear transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) plays a crucial role in maintaining cellular redox homeostasis. The aberrant NRF2 signaling confers enhanced antioxidant capacity, which is linked to tumor progression and therapeutic resistance. The current study investigates the biological effects and molecular mechanism of tribbles homolog 3 (TRIB3), a stress-induced protein, in regulating cell survival and apoptosis in lung cancer. This study first performed the RNA sequencing data analysis with 576 lung adenocarcinoma patients from the cancer genome atlas (TCGA) database. The NRF2- antioxidant response element (ARE) signature was enriched in patients with high TRIB3 expression. Dual-luciferase reporter assay and real-time quantitative polymerase chain reaction (PCR) were used to confirm the effect of TRIB3 on the kelch-like ECH-associated protein-1 (KEAP1)-NRF2 pathway. Abrogation of TRIB3 impaired NRF2 transcriptional activity and reduced the expression of its target genes. Moreover, TRIB3 enhanced NRF2 stability via blocking KEAP1-NRF2 interaction. TRIB3-depletion promoted reactive oxygen species (ROS) production, restrained cell proliferation, and enhanced carboplatin-induced apoptosis. In addition, NRF2 overexpression recovered the tumor inhibition effect of TRIB3-depletion. Consistently, TRIB3 failed to modulate apoptosis in NRF2 depletion cells. In summary, this study shows that TRIB3 inhibits the KEAP1-NRF2 interaction and upregulates the transcriptional activity of NRF2, thereby promoting lung cancer cell proliferation and reducing the sensitivity to chemotherapy. Targeting the TRIB3-NRF2 signal axis may become a new strategy for ROS homeostasis and lung cancer treatment.

AIM To investigate the effects of aqueous extraction at normal temperature,40 ℃,and water boiling on total coumarins extract of Angelicae dahuricae Radix.METHODS For the extracts Ⅰ-Ⅳ obtained by ethanol reflux extraction and three aqueous extraction preprocessing methods,respectively,UV and HPLC were adopted in the content determination of total coumarins and imperatorin,then the powder properties and dissolution rates were compared.RESULTS The contents of total coumarins in four extracts were 3.98％,6.03％,6.81％ and 4.46％,while those of imperatorin were 0.633％,0.540％,0.465％ and 0.155％,respectively.The angles of repose were 48.455°,42.587°,42.689° and 42.024° with the bulk densities of 0.214,0.324,0.316 and 0.354 g/cm3,respectively.Within 100 min,extract Ⅰ demonstrated higher moisture adsorption rate and equilibrium moisture absorption content than the other three extracts.The accumulative dissolution rates of various extracts were much higher than that of medicinal material fine powder within 120 min.CONCLUSION All the three aqueous extraction preprocessing methods can obviously improve the powder properties of total coumarins extract of A.dahuricae Radix and increase the dissolution rate of medicinal material fine powder.

AIM To prepare diosgenin nanosuspensions.METHODS The nanosuspensions prepared by media milling method were solidificated by freeze drying method.With particle size and polydispersity index (PDI) as evaluation indices,stabilizer kind,ratio of diosgenin to stabilizer,ratio of preliminary nanosuspension volume to grinding bead amount,milling time,lyoprotectant kind and its amount as influencing factors,single factor test was applied to screening preparation and solidification processes.The morphology of nanosuspensions was observed,then the particle sizes and polydispersity indices of nanosuspensions and freeze-dried powder were determined.RESULTS The optimal conditions were determined to be 6:1 for ratio of diosgenin to Pluronic F127 (stabilizer Ⅰ),50:1 for ratio of diogenin to sodium dodecyl sulfate (SDS,stabilizer Ⅱ),1:4 for ratio of preliminary nanosuspension volume to grinding bead amount,120 min for milling time,and 8％ PEG-6000 and 2％ mannitol as lyoprotectants.The average particle size and polydispersity index of rod-like or flaky nanosuspensions were (348.1 ±14.2) nm and 0.244 ± 0.059,respectively,which were lower than those of freeze-dried powder.At room temperature,the particle sizes of nanosuspensions and freeze-dried powder remained stable within 35 d and 3 months,respectively.CONCLUSION The physical stability of diosgenin freeze-dried powder is superior to that of its nanosuspensions,which can be used after being reconstituted.