Chinese medicinal formulae( CMF) were often used in the clinics of traditional Chinese medicine (TCM) which were critical for modernization of Chinese medicine to shed light on the interaction between CMF and biological organisms. In current studies, correlation between system and part, macroscopic actions and microcosmic mechanism, ADME process and pharmacologic actions were often neglected. Thus, we put forward integrative pharmacology, which could integrate the correlation between CMF and biological organisms from multi-levels and multi-dimensional views. Integrative pharmacology would reveal the molecular mechanism of CMF for ailments treatment and screen out effective material systematically, which would be the new paradigm of TCM research.
Absorption ; Computational Biology ; Medicine, Chinese Traditional ; methods ; trends ; Pharmacology ; methods ; trends ; Tissue Distribution

AIM:To examine the efficacy and safety of cryotherapy in the management of Fusarium corneal ulcer.
METHODS: Retrospective contract analysis of the clinical data of 41 patients ( 41 eyes ) who infected with Fusarium corneal ulcer. All of them underwent focal lesion keratectomy combined with amniotic membrane transplantation between January 2010 and May 2013. The cryotherapy treatment group of 22 cases (22 eyes), non-cryotherapy group of 19 cases ( 19 eyes ) . All the cases were followed up for 3 ~12mo. We analyzed the healing of corneal ulcer, corneal neovascularization, postoperative visual acuity, complications and ulcer recurrences.
RESULTS: There were no significant difference for the two groups at the cure rate and the recovery rate, the corneal neovascularization and postoperative visual acuity (P>0. 05). The total effective rate and corneal healing time in cryotherapy group was significantly higher than that in non - cryotherapy group ( P < 0. 05 ). The postoperative visual acuity of two group were higher than that of preoperatively ( P < 0. 05 ). There was no complication occurred in cryotherapy group while there was 1 patient of secondary glaucoma in non-cryotherapy group.
CONCLUSION: Cryotherapy is an effective and safe method for the treatment of Fusarium corneal ulcer.

OBJECTIVETo study the effect of Ti-TiO2 nanotubes with different diameters on the adhesion of fibroblast and osteoblast, and to find which diameter was more favorable for cells' respective adhesion.

METHODSPure titanium sheets were polished and then anodized at different potentials for 1 h with Ti as anode and Pt as cathode. TiO2 nanotubes formed at 1, 5, 10 and 20 V potentials served as experimental groups and polished pure titanium served as control group. Field emission scanning electron microscopy (Fe-SEM) was used to analyze the surface topography. Stained nucleus with Hoechst33342 were used to measure the cell adhesion. The cell shape on the sample surface were analyzed with Fe-SEM.

RESULTSTiO2 nanotube array of different inner diameters from 15 nm to 100 nm were grown on titanium sheets by anodization at potentials from 1 to 20 V. At 30, 60 and 120 min, fibroblast adhesion at nanotubes anodized at 5 V was (141 ± 9), (388 ± 14) and (489 ± 15) respectively, significantly less than any other nanotube surface at the same time (P < 0.01). Nanotubes anodized at 20 V had the least inhibitory effect for fibroblast adhesion with a number of (579 ± 14) at 120 min, and the cell shape was also inhibited. At 30, 60 and 120 min, osteoblast had a significant better adhesion on nanotubes formed at 5 V than it did on any other surface at the same time (P < 0.01), except the control group at 30 min, with the adhesion number of (198 ± 10), (431 ± 10) and (501 ± 10) respectively, and osteoblast had a abundant spread on nanotubes formed at 5 V; while osteoblast adhesion on nanotubes anodized at 20 V was (152 ± 11), (403 ± 9) and (465 ± 12) respectively, less than on any other nanotube surface within the same time (P < 0.05), and the cell shape on the surface changed to be more elongate.

CONCLUSIONSFibroblast adhesion is inhabited more or less on Ti-TiO2 nanotubes of different diameters. Nanotubes formed at 5 V have the most osteoblast adhesion, and inhibit fibroblast adhesion.

Animals ; Cell Adhesion ; Fibroblasts ; cytology ; ultrastructure ; Mice ; Microscopy, Electron, Scanning ; Nanotubes ; chemistry ; Osteoblasts ; cytology ; ultrastructure ; Surface Properties ; Titanium ; chemistry

Objective To investigate relationship between levels of follicle-sitimulating horomone receptor(FSHR) and ovarian response induced by gonadotropin hormone,and whether the FSHR expression is correlated with in vitro fertilization(IVF) outcome.Methods Granulose cells were collected from 43 women receiving IVF-embryo transplantation(IVF-ET).According to the number of oocyte,the women were divided into three groups: low response(15).The expression intensity of FSHR was measured by immunohistochemistry technique.The expression intensity of FSHR on the granular cell,the embryological and clinical outcomes were compared and analyzed. Results The expression of FSHR was significantly different in three groups with the highest in high response group(P0.05).The FSHR level was positively correlated either with the number of oocyte (r=0.719) or with the serum E2 levels(r=0.516,P0.05). Conclusion Ovarian response to gonadotropin hormone stimulation is correlated with the level of FSHR in the granulose cells.The development of follicles may be influenced by it.

Objective To evaluate the role of mammalian target of rapamycin (mTOR ) in reduction of oxygen-glucose deprivation and restoration (OGD/R )-induced injury to isolated cardiomyocytes by hypoxic preconditioning (HPC) in neonatal rats .Methods Primary cardiomyocytes were obtained from neonatal Sprague-Dawley rats (1-3 days after birth ) ,and seeded in 96-well plates at the density of 1 × 105 cells/ml (200μl/well ) . The cells were randomly divided into 6 groups ( n=6 each ) using a random number table:control group (group C) ,rapamycin group (group R) ,group OGD/R ,rapamycin+OGD/R group (group R+OGD/R);group HPC+OGD/R ,and rapamycin+HPC+OGD/R group (group R+HPC+OGD/R) .Rapamycin (final concentration 20 nmol/L) was added to the culture media and the cells were then incubated for 1 h in group R .In R+OGD/R group ,rapamycin (final concentration 20 nmol/L ) was added to the culture media ,the cells were then incubated for 1 h ,and then OGD/R was performed .In HPC+OGD/R group ,OGD/R was performed immediately after HPC was completed .In R+HPC+OGD/R group ,rapamycin (final concentration 20 nmol/L) was added to the culture media ,the cells were then incubated for 1 h , and then HPC and OGD/R were performed . All the cells were subjected to OGD for 2 h followed by restoration of O2-glucose supply for 3 h to induce OGD/R .HPC was induced by 3 cycles of 10 min hypoxia followed by 30 min reoxygenation .The cell viability (using MTT assay ) and lactic dehydrogenase (LDH) activity in the culture medium were determined .Results Compared with group C ,the cell viability was significantly decreased , and LDH activities in the culture medium were increased in OGD/R , R+OGD/R ,HPC+OGD/R and R+ HPC+OGD/R groups ( P<0.05 ) ,while no significant change was found in the cell viability and LDH activities in R group ( P>0.05) .The cell viability was significantly higher ,and LDH activity in the culture medium were lower in HPC+OGD/R group than in OGD/R group ,and in R+HPC+OGD/R group than in HPC + OGD/R group ( P< 0.05 ) .Conclusion mTOR is involved in HPC-induced attenuation of OGD/R injury to isolated cardiomyocytes in neonatal rats .

The applicator therapy is a unique method to treat infant diarrhea in traditional Chinese medicines and widely applied in clinical practice. Currently, many researchers have proved the rationality of the therapy based on the traditional Chinese medicine mechanism and on the data from clinical practice, but its action mechanism is uncertain at present. In this study, with the assistance of pediatric practitioners, the automated ribosomal intergenic-spacer analysis (ARISA) was adopted to study the effect of the adjuvant therapy with Dingguier umbilical paste on intestinal flora of diarrhea infants, in which Dingguier umbilical paste served as the adjuvant therapy in oral traditional Chinese medicines and fecal samples of infants with different diarrhea symptoms were collected and used as the study materials. The results showed that the adjuvant therapy had a significant effect on the shift of intestinal flora, which was associated with the decrease in the similarity difference to the normal control group and the increase in the number of operational taxonomic units (OTUs) shared with the normal control group. Additionally, adjuvant therapy with Dingguier umbilical paste also showed long action duration and increased OTUs number. These results indicated that Dingguier umbilical paste has the effect in restoring the micro-ecosystem of unbalanced intestinal bacteria. Intestinal flora may be one of major targets for the applicator therapy for the infant diarrhea, but not for the single oral traditional Chinese medicine for infant diarrhea.
Adjuvants, Pharmaceutic ; therapeutic use ; Diarrhea ; drug therapy ; microbiology ; Feces ; microbiology ; Female ; Humans ; Infant ; Intestines ; drug effects ; microbiology ; Male ; Medicine, Chinese Traditional ; methods ; Ointments ; Treatment Outcome ; Umbilicus

·AIM:To present a case of late onset bilateral keratectasis after laser in situ keratomileusis (LASIK) for myopia with rigid gas-permeable contact lenses with a brief review of literature on this subject.·METHODS:A 27-year-old woman underwent bilateral uneventful LASIK for moderate myopia. Preoperative cycloplegic refractions were -5.50/-0.50×50° right eye (OD) and - 4.50/-1.00×15° left eye (OS).Corneal pachymetry was 526μm OD and 541μm OS, Preoperative corneal topography was normal and did not reveal any keratoconus or forme fruste keratoconus.Following the creation of flaps with 160μm plates,ablations of 102μm OD and 86μm OS were performed,estimated to leave residual stromal beds of 264μm OD and 295μm OS.·RESULTS:Twenty-nine months postoperatively,the patient developed bilateral inferior keratectasia of -12.50/-4.00×160° OD and -6.00/- 4.25×125° OS.Visual acuity was reduced in both eyes;the central cornea had steepened; and pachymetry showed central corneal thinning.Keratectasia was diagnosed,and rigid contact lenses were fitted.Three years later,the patient achieved satisfactory visual acuity and all-day lens wear with minimal complications.·CONCLUSION:Late keratectasia may follow LASIK for low to moderate myopia despite a thorough preoperative work-up.Rigid contact lenses can offer a safe,reversible option for improving visual acuity in such patients by delaying or avoiding the need for intracorneal ring segments implanting or penetrating keratoplasty.

Objective: To investigate the effect of electroacupuncture (EA) on cognitive function in D-galactose (D-gal)-induced aging rats, and the correlation between the effect and nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3)-ASC-Caspase-1 signaling pathway. Methods: Forty-six male Sprague-Dawley (SD) rats were randomly divided into a control group (n=10), a model group (n=12), an EA-7 d group (n=12) and an EA-21 d group (n=12). Except the control group, the other three groups received 42 consecutive days of intraperitoneal injection of D-gal to establish aging rat models with cognitive dysfunction. The control group received the same amount of normal saline via intraperitoneal injection. Two EA groups were given EA therapy for 21 consecutive days (began from the 22nd day of modeling) or 7 consecutive days (began from the 36th day of modeling) accordingly at Dazhui (GV 14), Baihui (GV 20), Shenshu (BL 23) and Zusanli (ST 36). After modeling/ intervention, all four groups received behavioral evaluations by Morris water maze (MWM) test, novel object recognition (NOR) test and step-down passive avoidance (SDPA) test followed by the Western blot (WB) detection of the expression levels of hippocampal NLRP3 inflammasome-associated proteins NLRP3, ASC and Caspase-1. Results: MWM (place navigation test, PNT) results showed that the escape latency in the model group was significantly longer than that in the other three groups (P<0.05), and there was no significant difference among the other three groups on the 1st day of the test (P>0.05). From the 2nd day to the 4th day of the test, there was no significant difference between the EA-21 d group and the control group (P>0.05) in the escape latency; the escape latency was significantly shorter in the EA-21 d group than in the model group and the EA-7 d group (P<0.05). MWM (spatial probe test, SPT) results showed that the time spent in the target quadrant was significantly shorter and platform crossover number was significantly lower in the model group than in the other three groups (P<0.05). The time spent in the target quadrant was longer in the EA-7 d group than in the model group (P<0.05), but was shorter than that in the control group and the EA-21 d group (P<0.05). There was no significant difference in the swimming speed among the four groups (P>0.05). NOR results showed that there was no significant difference in the recognition ratio between the EA-7 d group and the EA-21 d group (P>0.05), and the recognition ratio was significantly higher in the two EA groups than in the model group (P<0.05), but was lower than in the control group (P<0.05). SDPA results showed that the electric shock number was higher in the model group than in the other three groups (P<0.05), and the differences among the other three groups were statistically insignificant (P>0.05). The model group had the shortest step-down latency, followed by the EA-7 d group, the EA-21 d group and the control group in order (P<0.05). The WB results indicated that the expression level of NLRP3 was significantly lower in the control group and the EA-21 d group than in the model group and the EA-7 d group (P<0.05). The expression levels of ASC and Caspase-1 were significantly higher in the model group than in the other three groups (P<0.05), and there was no significant difference among these three groups (P>0.05). Conclusion: NLRP3 inflammasome may be involved in the development of cognitive decline in aging rats; 7 consecutive days of EA intervention can partially improve the cognitive impairment in aging rats though the effect is rather limited; 21 consecutive days of EA intervention may improve the learning and memory abilities in aging rats via downregulating the expression levels of NLRP3 inflammasome-associated proteins in hippocampus.

Adolescent ; Adult ; Chronic Disease ; Female ; Humans ; Male ; Middle Aged ; Nasal Mucosa ; metabolism ; Rhinitis ; metabolism ; Sinusitis ; metabolism ; Young Adult ; beta-Defensins ; metabolism

In the present study, a risperidone loaded microsphere/sucrose acetate isobutyrate (SAIB) in situ forming complex depot was designed to reduce the burst release of SAIB in situ forming depot and to continuously release risperidone for a long-term period without lagime. The model drug risperidone (Ris) was first encapsulated into microspheres and then the Ris-microspheres were embedded into SAIB depot to reduce the amount of dissolved drug in the depot. The effects of different types of microsphere matrix, including chitosan and poly(lactide-coglycolide) (PLGA), matrix/Ris ratios in microspheres and morphology of microspheres on the drug release behavior of complex depot were investigated. In comparison with the Ris-loaded SAIB depot (Ris-SAIB), the complex depot containing chitosan microspheres (in which chitosan/Ris = 1 : 1, w/w) (Ris-Cm-SAIB) decreased the burst release from 12.16% to 5.80%. However, increased drug release rate after 4 days was observed in Ris-Cm-SAIB, which was caused by the high penetration of the medium to Ris-Cm-SAIB due to the hydrophilie of chitosan. By encapsulation of risperidone in PLGA microspheres, most drugs can be prevented from dissolving in the depot and meanwhile the hydrophobic PLGA can reduce the media penetration effect on the depot. The complex depot containing PLGA microspheres (in which PLGA/ drug=4 : 2, w/w) (Ris-Pm-SAIB) showed a significant effectiveness on reducing the burst release both in vitro and in vivo whereby only 0.64% drug was released on the first day in vitro and a low AUC0-4d value [(105.2± 24.4) ng.mL-1.d] was detected over the first 4 days in vivo. In addition, drug release from Ris-Pm-SAIB can be modified by varying the morphology of microspheres. The porous PLGA microspheres could be prepared by adding medium chain triglyceride (MCT) in the organic phase which served as pore agents during the preparation of PLGA microspheres. The complex depot containing porous PLGA microspheres (which were prepared by co-encapsulation of 20% MCT) (Ris-PPm-SAIB) exhibited a slightly increased AUC0-4d of (194.6±15.8) ng.mL-1d and high plasma concentration levels from 4 to 78 days [Cs(4-78d)=(7.8±1.2) ng.mL-1]. The plasma concentration on 78 day C78d was (9.0 2.5) ng.mL-1 which was higher than that of Ris-Pm-SAIB [C78d= (1.6 ± 0.6) ng.mL-1]. In comparison with Ris-Pm-SAIB, the AUC4-78d of Ris-PPm-SAIB increased from (379.0±114.3) ng.mL-1.d to (465.0 ±149.2) ng.mL-1.d, indicating sufficient drug release from the Ris-PPm-SAIB. These results demonstrate that the risperidone loaded porous PLGA microsphere/SAIB in situ forming complex depot could not only efficiently reduce the burst release of SAIB depot both in vitro and in vivo, but also release the drug sufficiently in vivo, and be capable to continuously release the drug for 78 days.
Chitosan ; Drug Carriers ; Lactic Acid ; Microspheres ; Polyglycolic Acid ; Risperidone ; chemistry ; Sucrose ; analogs & derivatives ; Technology, Pharmaceutical