Objective:To compare the pharmacokinetics and relative bioavailability of rapid oral disintegrating tablet of dimenhydrinate(RODTD) and those of market available tablet of dimenhydrinate(DMH).Methods: Eight healthy volunteers were evenly randomized into 2 groups,one group received RODTD(25 mg) and the other received available market tablet of dimenhydrinate(25 mg).The blood levels of DMH were determined by high performance liquid chromatography(HPLC) before and after drug administration in 2 groups.Chromatography conditions were: Nova-Pak C_(18)as chromatographic column, methanol triethylamine buffer((11),)flow rate: 1.0 ml/min,detection wavelength: 225 nm,and room temperature.The pharmacokinetics and relative bioavailability of RODTD and market available tablets were investigated.Results: The standard curve of DMH in the blank plasma was linear within the range of 5-500 ng/ml,with the regression equation being C=0.004 4 A+4.745 and R~(2)=(0.996.)The limit of detection was 2 ng/ml;the average recovery rate was(90.55?4.69)% and the RSD was 0.041%.The intra-day derivations of 3 different concentrations(low,middle,and high) of plasma were 9.27%,4.93%,and 2.95%,respectively((n=5),) and the inter-day derivations were 9.97%,3.81%,and 3.06%,respectively(n=5).Blood samples(3 ml) were subjected to HPLC assay and significant difference was found between the 2 forms of DMH. The pharmacokinetic parameters of RODTD were: AUC=(602.04?113.82) ng?h?ml~(-1),C_(max)=(95.86?21.28) ng?ml~(-1),and T_(Peak)=(1.8?0.32) h;the pharmacokinetic parameters of market available tablets were:AUC=(342.73?84.96) ng?h?ml~(-1),C_(max)=((46.34?)(10.32)) ng?ml~(-1),and T_(Peak)=(2.65?0.24) h.Statistical analysis showed there was significant difference in the relative bioavailability of 2 forms of DMH(P

Objective: To investigate the role of fibroblast growth factor receptor(FGFR) 1 in endothelial to-mesenchymal transition(EndMT) and epithelial-to-mesenchymal transition(EMT), and to find out a new strategy to study the vascular endothelial function of diabetic renal fibrosis. Methods: Culture media from FRS2 knockdown HMVECs was transferred to HK-2 cells. Western blot and immunofluorescence staining were used to measure EMT markers and key moleculars of transforming growth factor(TGFβ). Results: It was found that the medium from FRS2 siRNA-transfected HMVECs reduced E-cadherin protein levels, increased EMT markers levels, and activated TGFβ signal pathway in HK-2 cells. Conclusion Endothelial FGFR1 deficiency-induced EndMT leads to EMT in neighboring cells in a manner dependent on TGFβ1 signaling. Endothelial cell FGFR1 is an important molecule for maintaining endothelial homeostasis and epithelial homeostasis, and seems to be a key target for anti-diabetic renal fibrosis.

Objective To explore the role of fibroblast growth factor receptor ( FGFR ) 1 in endothelial homeostasis via an induction of microRNA let-7s, with effects on AcSDKP(N-acetyl-seryl-aspartyl-lysyl-proline) and associated mitochondrial biogenesis. Methods Blocking FGFR1 signaling pathway, Western blot and immunofluorescence staining were used to measure mitochondrial fusion ( mitofusin-2, MFN2;optic atrophy protein 1, OPA1 ) and fission ( dynamin-related protein-1, DRP1 ) proteins and mitochondrial biogenesis by MitoTraker Green. Also real-time quantitative PCR(qPCR) was performed to test microRNA let-7' expression. Results FGFR1 signaling pathway was critical for AcSDKP maintaining mitochondrial biogenesis through induction of microRNA let-7b. In endothelial cells, the AcSDKP restored the triple[TGF-β2, interleukin (IL)-1β, tumor necrosis factor (TNF)-α]-suppressed microRNA let-7b-5p expression and associated with mitochondrial biogenesis. Such effect of AcSDKP was lost in either fibroblast growth factor receptor substrate 2 (FRS2) siRNA or neutralizing FGFR1 treated-cells. Similarly, AcSDKP lost its effect on mitochondrial biogenesis in microRNA let-7b-5p inhibitor-treated-cells. In addition, microRNA let-7b-5p mimic reversed the FRS2 siRNA-suppressed mitochondrial biogenesis in endothelial cells. Conclusion These findings demonstrated that FGFR1 is critical for maintaining mitochondrial biogenesis through control of microRNA let-7b-5p in endothelial cells.

Objective: To compare the effects of alone and combined administration of nalbuphine and sufentanyl for patient-controlled intravenous analgesia (PCIA) after caesarean section. Methods: From June 2017 to December 2017, 90 women undergoing cesarean section in the Sixth Hospital Affiliated to Shanxi Medical University were selected.They were divided into three groups(with 30 cases in each group) using a random number table: sufentanyl 1.5μg/kg group (group S), nalbuphine 2.0mg/kg group (group N) and nalbuphine 1.0mg/kg+ sufentanyl 1μg/kg group (group NS). In each group tropisetron 6 mg was added, and PCIA solution was then diluted to 10mL in normal saline.Postoperative vital signs, visual analogue scale (VAS) score, the highest Ramsay sedation score, number of self-control analgesia and the occurrence of side effects within 24h after operation were recorded. Results: The highest VAS score within 24h after surgery had statistically significant difference among the three groups [group N (2.66±1.09)points > group S (1.45±0.57)points > group NS (0.90±0.55)points](F=40.11, P<0.05). The Ramsay sedation score among the three groups had no statistically significant difference [group S (2.34±0.61)points, group N (3.13±0.63)points, group NS (2.60±0.72)points] (F=11.00, P>0.05). The number of controlled analgesia among the three groups had no statistically significant difference [group S (0.76±0.69), group N (2.93±0.87), group NS (0.54±0.57)] (F=101.11, P>0.05). The incidence rates of adverse reactions of the three groups were 26.66%(8/30), 16.67%(5/30) and 6.66%(2/30), respecyively, the difference was not statistically significant (P>0.05). Conclusion Combination of nalbuphine and sufentanyl has more significant effect of PCIA after cesarean section than either of the drugs use alone, which is worthy of clinical promotion.

OBJECTIVE To investigate the mechanism of glucose -6-phosphate dehydrogenase （G6PD）-induced sorafenib - resistance in hepatocarcinoma cell based on phoshorylated 3-kinase/protein kinase B （PI3K/Akt）signaling pathway . METHODS Cell lines including hepatocarcinoma cell Huh 7，sorafenib-resistant cell Huh 7-SR，G6PD overexpressed cell Huh 7-G6PD and its control cell Huh 7-CT，and compounds including G 6PD inhibitor （6-Aminonicotinamide，6AN）and sorafenib were used as objects or intervention drugs in these research . CCK8 assay was applied to evaluate cell viability . The protein levels of G 6PD and the phosphorylation levels of PI 3K/Akt signaling pathway were detected by Western blot . Flow cytometry was utilized to investigate cell apoptosis. RESULTS Compared with Huh 7 cells，the protein level of G 6PD was significantly increased in Huh 7-SR cells （P＜ 0.05）. The combination of 6AN and sorafenib reduced cell viability of Huh 7-SR cells （P＜0.01）. However，compared with Huh 7- CT，increased cell viability and decreased cell apoptosis rate were observed in Huh 7-G6PD cells while cells were treated with sorafenib（P＜0.01）. Mechanistically，the phosphorylation levels of PI 3K and Akt were significantly decreased in Huh 7-SR cells that were treated with 6AN（P＜0.05）. Moreover，under the condition of no drug intervention ，the phosphorylation levels of PI 3K and Akt were significantly elevated in Huh 7-G6PD cells when compared with Huh 7-CT（P＜0.01）. CONCLUSION G6PD could induce sorafenib -resistance in hepatocarcinoma cell by activating PI 3K/Akt signaling pathway .