Organic anion transporting polypeptide 1B1 (OATP1B1) is an important liver-specific uptake transporter, which mediates transport of numerous endogenous substances and drugs from blood into hepatocytes. To identify and investigate potential modulators of OATP1B1 from natural products, the effect of 21 frequently used natural compounds and extracts on OATP1B1-mediated fluorescein methotrexate transport was studied by using Chinese hamster ovary cells stably expressing OATP1B1 (CHO-OATP1B1) in 96-well plates. This method could be used for the screening of large compound libraries. Our studies showed that some flavonoids (e.g., quercetin, quercitrin, rutin, chrysanthemum flavonoids and mulberrin) and triterpenoids (e.g., glycyrrhetinic acid and glycyrrhizic acid) were inhibitors of OATP1B1 with IC50 values less than 16 µmol · L(-1). The IC50 value of glycyrrhetinic acid on OATP1B1 was comparable to its blood concentration in clinics, indicating an OATPlB1-mediated drug-drug interaction could occur. Structure-activity relationship analysis showed that flavonoids had much higher inhibitory activity than their glycosides. Furthermore, the type and length of saccharides had a significant effect on their activity. In addition, we used OATP1B1 substrates fluvastatin and rosuvastatin as probe drugs to investigate the substrate-dependent effect of several natural compounds on the function of OATP1B1 in vitro. Our results demonstrated that the effect of these natural products on the function of OATPlB1 was substrate-dependent. In summary, this study would be conducive to predicting and avoiding potential OATP1B1-mediated drug-drug and drug-food interactions and thus provide the experimental basis and guidance for rational drug use.

Objective To observe effects and mechanisms of insulin on reperfusion injury after cerebral ischemia.Methods Sixty-six male Wistar rats were used in this study.All rats were divided into 3 groups as treated group(A),control group(B) and random sham-operated group(C).Four-vessel occlusion was used to establish global cerebral ischemia reperfusion model in study groups.The treated group were divided into 5 groups(A1-A5) and intraperineally injected with biosynthetic human insulin 2 IU/(kg?d) and 50%glucose 2 g/(kg?d) for 7 days,the blood glucose was monitored in preoperative and postoperative 3,6,12,24 h,and the blood glucose was maintained between 3.5-6.5 mmol/L.These animals of control group were given with saline 2 mL/(kg?d) for 7 days in abdominal cavity.All the rats were killed in the seventh day,brain homogenate was collected for detection of neuron specific enolase(NSE)and nitric oxide(NO).The hippocampus was separated for observation of electronic microscope.Results Concentration of NSE in brain tissue in group C was significantly higher than that of group A and group B,while the level in group A was higher than that of group B.Concentration of NO in group C was lower than that of group A and group B while the level of NO in group A was significantly lower than that of group B.Electron microscope showed that the ultrastructure of sham-operated group was nearly normal,damage degree of hippocampal neuron and gliacyte and capillary was gradually worse from group A1,A2 to A4,the damage degree of group B1,B2 and B4 was serious and there was no difference among them.Conclusion Insulin can really promote recovery of the cerebral injury after ischemia reperfusion.

Organic anion transporting polypeptide 1B1 (OATP1B1) is an important liver-specific uptake transporter, which mediates transport of numerous endogenous substances and drugs from blood into hepatocytes. To identify and investigate potential modulators of OATP1B1 from natural products, the effect of 21 frequently used natural compounds and extracts on OATP1B1-mediated fluorescein methotrexate transport was studied by using Chinese hamster ovary cells stably expressing OATP1B1 (CHO-OATP1B1) in 96-well plates. This method could be used for the screening of large compound libraries. Our studies showed that some flavonoids (e.g., quercetin, quercitrin, rutin, chrysanthemum flavonoids and mulberrin) and triterpenoids (e.g., glycyrrhetinic acid and glycyrrhizic acid) were inhibitors of OATP1B1 with IC50 values less than 16 µmol · L(-1). The IC50 value of glycyrrhetinic acid on OATP1B1 was comparable to its blood concentration in clinics, indicating an OATPlB1-mediated drug-drug interaction could occur. Structure-activity relationship analysis showed that flavonoids had much higher inhibitory activity than their glycosides. Furthermore, the type and length of saccharides had a significant effect on their activity. In addition, we used OATP1B1 substrates fluvastatin and rosuvastatin as probe drugs to investigate the substrate-dependent effect of several natural compounds on the function of OATP1B1 in vitro. Our results demonstrated that the effect of these natural products on the function of OATPlB1 was substrate-dependent. In summary, this study would be conducive to predicting and avoiding potential OATP1B1-mediated drug-drug and drug-food interactions and thus provide the experimental basis and guidance for rational drug use.
Animals ; Biological Products ; CHO Cells ; Cricetulus ; Drug Interactions ; Fatty Acids, Monounsaturated ; pharmacology ; Flavonoids ; pharmacology ; Indoles ; pharmacology ; Inhibitory Concentration 50 ; Organic Anion Transporters ; genetics ; metabolism ; Rosuvastatin Calcium ; pharmacology ; Structure-Activity Relationship

Objective To compare and quantify the determinants in quantitative electroencephalogram(q-EEG) and heart rate variability power spectrum analysis(HRV-PSA) of ketamme(KTM) anesthesia for preschoolers. Methods Seventy four cases were selected and assigned into 3 groups named A(4-5 years), B(5-6 years), C(6-7 years), 22,28,24 cases in every group respectively. All cases were induced with KTM 5 mg /kg intramuscularly and changes of determinants were recorded continuously. If body movement happened, KTM would be injected with 1 mg/kg. Results On pre- anesthesia, BIS in group A was the least among 3 groups, while LF/HF and HRVI were the largest(P

Objective To determine the long term outcomes of laryngomalacia infants with anomalies and to determine the clinical practice guideline for these infants.Methods The charts of infants with moderate to severe laryngomalacia,who were admitted to our hospital between January 2013 and December 2015,were retrospectively reviewed.These infants were divided into two groups,anomaly(A) group(n=37) and non-anomaly (NA) group(n=19).Results Fifty-six cases were enrolled.Infants in A group were older at symptom relief than those in NA group[(10.00±3.56) months vs.(7.89±3.03) months,P＜0.05],and the weight percentiles of infants in A group were lower at 3,6 and 12 months than those in NA group(P＜0.05).There was no statistically significant difference between the two groups on the weights percentiles in infants at 24 months after diagnosis.Five of 37 cases in A group and 3 of 19 cases in NA group had supraglottoplasty.One infant in A group had tracheotomy.Conclusion Both breathing difficulty and development retardations of infants with moderate or severe laryngomalacia could gradually improved with age.There is not enough evidence to support the aggressive supraglottoplasty for infants with anomalies and laryngomalacia.

Objective To investigate the expression of circulating microRNA (miRNA) of rats with hypobaric hypoxia‐induced pulmonary hypertension (HPH) .Methods Commercial rat miRNA microarray was employed to detect and analyze the circulating miRNA profile in the serum samples of Sprague‐Dawley rats with hypobaric hypoxia‐induced HPH and controls .Furthermore ,differentially expressed candidate circulating miRNAs between HPH and control groups were validated by Real‐time quantitative PCR based on the case‐control study ,and receiver operating characteristic curve (ROC ) analysis was used to test the performance of four differentially expressed circulating miRNAs in discriminating HPH and control groups .Results Compared with those in the control group ,13 upregulated miRNAs and 10 downregulated miRNAs were identified in hypobaric hypoxia‐induced HPH rats by using miRNA microarray . And differentially expressed miR‐451 , miR‐505 , let‐7d and miR‐214 were validated by using RT‐PCR .ROC analysis showed that the area under the curve of miR‐451 ,miR‐505 and let‐7d was 0 .979 ,0 .938 and 0 .993 in discriminating HPH and control groups ,respectively .Conclusion The aberrant expression of circulating miR‐451 ,miR‐505 and let‐7d in serum may be correlated with the pathogenesis of HPH .

AIMTo investigate the possible involvement of glutamate(Glu) in the paraventricular nucleus (PVN) in the central regulation of baroreflex.

METHODSThe baroreflex was induced by intravenous injection of phenylephrine in conscious rats, and the extracellular concentration of Glu in the PVN region was measured by microdialysis and high performance liquid chromatography (HPLC) techniques. To determine whether the observed Glu release was involved in the baroreflex, NMDA and non-NMDA receptor antagonists, MK-801 and CNQX, were perfused in the PVN region during baroreflex.

RESULTSDuring baroreflex, the Glu concentration in the PVN region immediately increased to 384.82% +/- 91.77% of basal level (P < 0.01). (2) During baroreflex, direct perfusion of MK-801 and CNQX in the PVN were attenuated the increase of blood pressure and enhanced the decrease of HR (P < 0.01),resulting a significant increase in baroreflex sensitivity (P < 0.01).

CONCLUSIONGlutamate in PVN is involved in central regulation of baroreflex, which may inhibit baroreflex via ionothopic glutamate receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione ; pharmacology ; Animals ; Baroreflex ; drug effects ; physiology ; Dizocilpine Maleate ; pharmacology ; Excitatory Amino Acid Antagonists ; pharmacology ; Male ; Paraventricular Hypothalamic Nucleus ; physiology ; Rats ; Rats, Wistar

Objective To determine whether cleavage developmentally retarded embryos have not cleaved during a 24 hour period could develop into blastocysts and produce hESC cell lines.Methods A total of 120 such embryos were cultured to blastocyst stage by sequential culture.Blastocysts formation rate and quality of blastocyst were detected under microscope.The relation between blastocyst formation rate and blastomere number,the fragment of blastomere and blastomere symmetry were analyzed by stepwise Logistical regression analysis.Inner cell masses(ICMs)were isolated by immunosurgery.Colonies derived from the ICMs were passed every 4-7 days and the derivatives were passaged and identified.Results A total of 22 blastocysts were obtained from 120 embryos.The blastulation rate was 18.7%.Early blatocyst, blastocyst,full blastocyst,expanded blastocyst,hatching blastoeyst and hatched blastocyst accounted for 5.9%,23.5%,35.3%,23.5%,5.9%,and 5.9% respectively.The grade of ICM and trophoblast was mostly scored C or B.Blastocyst formation rate was related to cell number and blastomere symmetry but not fragment.Immunosurgery resulted in the formation of 7 ICMs and 3 primary colonies,which produced 2 cell lines.The cell lines satisfied the criteria that characterize pluripotent hESC cells.Undifferentiated cells were positive for AKP,SSEA-4,TRA-1-60,and TRA-1-81.It could continue to proliferate in vitro and form embryoid bodies when cultured in suspension.It had capability to form teratoma in SCID mice.Both cell lines had normal karyotypes after 45 and 34 passages respectively.Conclusions Our results suggest that a subset of developmentally retarded embryos can form blastocysts and give rise to hESC cell lines.

Objective To study the expression of KAI1 and CD40 in gastric cancer and their correlation with clinicopathologic features and prognosis.Methods The expression of KAI1 and CD40 of 64 gastric cancer tissues was examinated by S-P immunohistochemieal methods.Results The overall positive rate of KAI1 was 22% in gastric cancer.Expression of KAI1 was positively related to the degree of tumor differentiation,it was negatively related to invasion depth and lymph node metastasis and the tumor clinical stage.The 5-year survival rate of cases with positive expression of KAII was significantly higher than that of cases with negative expression(X~2=42.426,P=0.000).The expression rate of CD40 in gastric cancer tissue was 34%.The expression of CD40 was significantly correlated with metastasis and clinical stage of gastric cancer.The 5-year survival rate of cases with positive expression of CD40 was significantly lower than that of cases with negative expression(X~2=4.841,P=0.028).There is no relationship between KAI1 and CD40 expression in gastric cancer.Conclusion KAI1 is associated with gastric cancer differentiation,invasion and metastasis.CD40 status helps to evaluate metastasis,and predict prognosis of gastric cancer.

Objective To explore the clinical applicating and efficacy of free fibula osteomyocutane- ous flap in mandible defect reconstruction in osteoradionecrosis patients.Methods The mandible defects were reconstructed by free fibula flaps with or without muscle cuff.The soft tissue defects were repaired by skin paddles.Status of osteotomy in fibula and flap survival was recorded.The complication in recipient site and donor site,as well as mouth opening and occlusion were reviewed.Facial contour and chewing function after reconstruction were evaluated.Results Patients were followed up 3-16 months.4 free fibula flaps with muscle cuff and 5 without muscle cuff survived well.The size of mandible defects covered from 6cm to 17cm. And the harvested fibula flaps with length of 8.6-17cm were cut into 3 segments in 2 cases,and 2 segments in 5 cases.Fibula flap was divided into 2 segments and overlapped in 2 cases.No serious complication was oh- served in recipient site and donor site.Satisfying esthetic result and normal occlusiong of heath mandible were obtained in all cases.The degree of mouth opening was 2.5-3.3cm.Fair chewing function was revealed in re- constructive region after prosthesia repaired.Conclusion Free fibula osteomyocutaneous flap is relatively ideal reconstruction material of mandible defect in osteoradionecrosis patients for its high survival rate and well esthetic results.